11 steps treatment to cancer

Abstract:

Our cells as a complex machinery have many different survival skills. The cancer cells represent innovative forms to multiply themselves. Due the cancer cell versatility, we can understand that they can’t have enough time and conditions to reorganize themselves in a novel cell survival alternative vias, hence multiple approaches should surround these possibilities to force them, in the most complete possible way, to either triggers apoptose or be immediately annihilated by the immunological system, and in case of those approaches fails, resort to the old-fashion methods such as traditional chemotherapic drugs, surgery, radiotherapy, that in this project these procedures are left as a last resource, due the life risks, low survival and lifespan, as well as sequels which most of them represents.

We support an adaptive clinical trial project where exist an integration with those approaches, although this may sacrifice a higher research specificity, unfocusing and making variables, for the people may not be sacrificed, and that is why, we support in this clinical trail project, a new wider protocol and not isolated approaches.

We present a protocol with 11 (eleven) steps divided in 2 (two) major parts:

Basic Preliminary Treatments – 1) Detoxification; 2) Colostrum; 3) Parasites; 4) Probiotics; 5) Nutrition, mainly an anti-inflammatory one, that may be at least over grown cancer control; 6) Psycotherapy; 7) Physiotherapy;

We propose that these trials may be done at common healthcare centers, before leading patients to more specialized treatments, which would decrease costs, increase speed, prepare the patient’s health to be ready for later treatments and also would eliminate some cases decreasing the number of patients in the queue.

For the second part, we would have treatments primarily utilizing conjugated immunotherapy – 8) dendritic cells (Dcs) culture and re-infusion; 9) Tumor Infiltrated Lymphocytes (TILs) and 10) NK with an incentive strategy for better tumorigenic cell visibility.

At this high risks of oncological treatments (HROT) paradigm transition, towards immunotherapy, fourth pillar of cancer treatments. The lack of scientific update, has leading, at least in Brazil, forwarding to new treatments and in most cases of lower invasiveness as the last chance, the last resort for the patient that has refused traditional treatment, or for those that in most of time has given up hope by the doctors (in Brazil is used, “undeceived by the doctors” expression, for those who have few chances to survive), these patients are many times with a lot of sequels and comorbidities due the HROT side effects. At this same part of this new associated immunotherapy method, the research will look for the possibles genetics fragility relations that allowed the illness development.

After the 7 preliminary steps, will occur a repetition of the same tests, as we call Enhanced Biopsy, which will allows hundreds of effects observations, specially epigenetics, as well as quantity and quality comparisons of DCs, TILs and NKs.

The propose has by adaptive principle utilize more traditional treatments like chemotherapies, surgeries ad radiotherapies, of high invasiveness HROT as a last resort of the oncology practice, exception for those cases where the efficacy percentage of these approaches are promising, and when the chances are very low, so, in these cases, it must be totally honest with the patient and lead him/her to a clinical trial of higher specific efficiency.

Introdução

O sistema imunológico atua como uma orquestra de sinalizações frente as ameaças externas e internas, e os ataques se caracterizarem por muitos eventos ocorrendo ao mesmo tempo. Percebemos que quando interleucinas incentivam um tipo de ameaça pode ocorrer ao mesmo tempo a inibição outro tipo de ataque [1][2], e que a presença de várias ameaças e comorbidades confundem suas tarefas como ocorre em casos de vários virus[3] sepse[4] sepse pós-operatória [5] interleucina IL-6 acima da mediana como preditivo de mortalidade[6] [7] comorbidades nosocomiais[8] depressão[9][10] Esta situação fica evidenciada em estudos que apontam menor sobrevida de pacientes de câncer com comorbidades[11] o que aumenta em idosos[12]. Neste trabalho defendemos que diminuir o turbilhão de cascatas eliminando comorbidades pro inflamatórias e ao mesmo tempo inibitórias , principalmente aquelas que estarão competindo com ataque ao tumor, são tarefas fundamentais de preparo e de eliminação de efeitos imunológicos cruzados e inibitórios sob diferentes ataques, com objetivo de minimizar ao máximo possibilidade desta sobrecarga a memória de trabalho imunológico. Propomos alguns passos preliminares e fundamentamos os mesmos como prováveis de estar aumentando tarefas de ataques e diminuindo a eficiência de ataque mais específico ao tumor, em uma ordem estrategicamente coordenada para que ao fim tenhamos um organismo com menores focos inflamatórios para poder ter melhor garantia de eficiência em incentivo de reações mais específicas.

Referências

1. ↑ Diehl, Sean; Rincón, Mercedes (1 de dezembro de 2002). «The two faces of IL-6 on Th1/Th2 differentiation». Molecular Immunology. Proceedings from the Autumn Immunology Conference (2001): Regulators of Immune Function. 39 (9): 531–536. ISSN 0161-5890. doi:10.1016/S0161-5890(02)00210-9 

2. ↑ Nakanishi, K.; Yoshimoto, T.; Tsutsui, H.; Okamura, H. (2001). «Interleukin-18 regulates both Th1 and Th2 responses». Annual Review of Immunology. 19: 423–474. ISSN 0732-0582. PMID 11244043. doi:10.1146/annurev.immunol.19.1.423 

3. ↑ Hotchkiss, Richard S.; Storch, Gregory A.; Green, Jonathan M.; Shannon, William D.; Deych, Elena; Brooks, Terrence L.; Pachot, Alexandre; Brownstein, Bernard H.; Sato, Bryan (11 de junho de 2014). «Reactivation of Multiple Viruses in Patients with Sepsis». PLOS ONE (em inglês). 9 (6): e98819. ISSN 1932-6203. PMC PMC4053360 Verifique |pmc= (ajuda). PMID 24919177. doi:10.1371/journal.pone.0098819 

4. ↑ Ward, Peter A.; Delano, Matthew J. (4 de janeiro de 2016). «Sepsis-induced immune dysfunction: can immune therapies reduce mortality?». The Journal of Clinical Investigation (em inglês). 126 (1): 23–31. ISSN 0021-9738. doi:10.1172/JCI82224 

5. ↑ Blache, J. L.; Moutardier, V.; Houvenaeghel, G.; Delpero, J. R.; Brun, J. P.; Sannini, A.; Merlin, M.; Mokart, D. (1 de junho de 2005). «Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): early markers of postoperative sepsis after major surgery». BJA: British Journal of Anaesthesia (em inglês). 94 (6): 767–773. ISSN 0007-0912. doi:10.1093/bja/aei143 

6. ↑ Naffaa, Mohammad; Makhoul, Badira F.; Tobia, Amjad; Kaplan, Marielle; Aronson, Doron; Saliba, Walid; Azzam, Zaher S. (1 de setembro de 2013). «Interleukin-6 at discharge predicts all-cause mortality in patients with sepsis». The American Journal of Emergency Medicine. 31 (9): 1361–1364. ISSN 0735-6757. doi:10.1016/j.ajem.2013.06.011 

7. ↑ Angus, Derek C.; Delude, Russell L.; Krichevsky, Alexander; Fine, Jonathan; Pinsky, Michael R.; Yealy, Donald M.; Weissfeld, Lisa A.; Fink, Mitchell P.; Kong, Lan (13 de agosto de 2007). «Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis: Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study». Archives of Internal Medicine (em inglês). 167 (15): 1655–1663. ISSN 0003-9926. doi:10.1001/archinte.167.15.1655 

8. ↑ Hotchkiss, Richard S; Monneret, Guillaume; Payen, Didier (1 de março de 2013). «Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach». The Lancet Infectious Diseases. 13 (3): 260–268. ISSN 1473-3099. doi:10.1016/S1473-3099(13)70001-X 

9. Dowlati, Yekta; Herrmann, Nathan; Swardfager, Walter; Liu, Helena; Sham, Lauren; Reim, Elyse K.; Lanctôt, Krista L. (1 de março de 2010). «A Meta-Analysis of Cytokines in Major Depression». Biological Psychiatry. Cortical Inhibitory Deficits in Depression. 67 (5): 446–457. ISSN 0006-3223. doi:10.1016/j.biopsych.2009.09.033

10. ↑ Kelley, Keith W.; Johnson, Rodney W.; Freund, Gregory G.; O'Connor, Jason C.; Dantzer, Robert (2008). «From inflammation to sickness and depression: when the immune system subjugates the brain». Nature Reviews Neuroscience (em inglês). 9 (1): 46–56. ISSN 1471-0048. doi:10.1038/nrn2297 

11. ↑ Extermann, Martine (2007). «Interaction between Comorbidity and Cancer». Cancer Control (em inglês). 14 (1): 13–22. ISSN 1073-2748. doi:10.1177/107327480701400103 

12. ↑ Extermann, Martine (2007). «Interaction between Comorbidity and Cancer». Cancer Control (em inglês). 14 (1): 13–22. ISSN 1073-2748. doi:10.1177/107327480701400103 

Introduction

The immune system acts as a signaling orchestra against external and internal threats, and attacks are characterized by many events occurring at the same time, so in this paper we argue that reducing the swirl of cascades eliminating pro-inflammatory comorbidities, especially those that will be competing. with tumor attack, are fundamental tasks of preparation and elimination of cross and inhibitory immunological effects under different attacks. We have established some preliminary steps and ground them as likely to hinder more efficient attacks on the tumor, in a strategically coordinated order so that eventually we have an organism ready for more specific treatments.

Preliminary measures are: 1) Detoxification and Cleansing 2) Colostrum Administration 3) Helminth and Parasite Elimination 4) Probiotic Replacement 5) Mainly anti-inflammatory nutraceutical strategies that control cancer growth and are inhibitory of alternative pathway strategic points 6) Psychotherapy 7) Physiotherapies. These preliminary approaches can be done in clinics in an "open" clinical trial system or in spas taking the patient to a multidisciplinary treatment center, following these pre-treatment guidelines prior to referral to a specialized cancer center, so that it has a greater chance of success in more specific treatments and longer survival.

Such measures become even more appropriate in Brazil due to the long queues [1] [2] , which are diminished by the rapid mortality of many aggressive and high-risk treatments, often administered to patients with comorbidities that should be eliminated beforehand. of the same. These measures are likely to be welcomed by a desperate and sometimes disillusioned audience who are destined to die under the mold of collectivist cancer culture . [3]

Immunotherapy should take place after doing these preliminaries we call "homework," because maintaining people's health should be the main focus of health systems in Brazil, where the highest spending of $ 117 billion in 2018 [4] as well as previous years, it has been with the last years of its population's life [5] [6] which clearly demonstrates a neglect of quality of life, disease prevention and low productivity than an assisted population in this way will represent. Knowing how to deal with the main maintenance system of our health, is the strategy that can predict the debacle that will represent the increasing proportion of elderly in the Brazilian [7] and worldwide [8], to increase productivity and decrease the natural tendency of immune weakening in old age. These preliminary measures should be part of the culture and primary goals of primary care posts, as they represent a gateway to thousands of diseases other than cancer.

Part of the immune system acts by attacking more foreign bodies (innate) and part by acting more by attacking our own defective cells (CD8 + adaptive system). NK cells are an exception to this rule because they act against a variety of external and internal threats, as well as the fact that innate and adaptive system leukocytes participate simultaneously in presentations or stimuli that may or may not benefit attack on foreign bodies or cells. " very "defective and replicating (cancerous) and / or virus infected.

The main route of attack occurs through the adaptive system where macrophage-dendritic cells (long-fingered) phagocyte a cancer cell and segment into small pieces of around 30 nucleotides (9 to 11 amino acids) their proteins to present MHC class 1 system. CD8 + cells in the lymph node (lymph nodes) that identify the abnormality by becoming active, multiplying and going to the site of inflammation to check the attack and multiply further to accomplish the task.

If all goes like this, the cancer is battling, but halfway there are usually many stones and comorbidities that can disrupt CD8 +, including the time factor, because the attack system must be short-lived so as not to affect the body and therefore inhibitory systems. act to curb the attack and that is why several anti-inhibitory drugs have been developed (eg MSD pembrolizumab anti PD-1 and Roche atezolizumab anti PD-L1).

These inhibitors have generated high success rates in phase I and II, III and IV clinical trials, and various types of cancer immunotherapy linked to TILs, DCs, NK, Mabs, oncolytic viruses, vaccines, using ACT therapies and / or using inhibitors. checkpoint to prolong the attack on tumors [9] , has been shown to be advantageous strategies for combating various cancers and has earned Nobel Prize to James P. Allison, chair of immunology at MD Anderson Cancer Center in the United States, and professor of Kyoto's Tasuku Honjo immunology, establishing in this striking and glorious way, immunotherapy as the fourth pillar in official cancer treatment options [10] [11]

Due to the high degree of repetition of culture protocols of DCs, TILs, NK, MABs (dendritic cells, infiltrated lymphocytes, Natural Killer, Mabs), in immunotherapeutic assays, we observed the need to establish protocols common to several types of cancer, with Preliminary clinical approaches for several clinical trials, called project immuno2019-2025brasil, hoping to contribute to the improvement of immunotherapeutic strategies.

The scientific advance seen in the transition from the oncological paradigm characterized by chemotherapies, radiotherapies, transplants and surgeries (often very risky and averaging around 2% efficiency for 5-year survival [12] ) to use strategies with a higher degree of survival . Specificity of immunotherapy requires an update and workforce in oncology today, which needs to be updated, where the junction of doctors and researchers linked to immunology has become crucial. We believe that we can contribute to foster this update by publishing articles, conference abstracts, and explaining methodologies of various immunotherapy clinical trials, especially adaptive (encouraged by the FDA).

Brazil faces several difficulties for fluent technological and scientific development to take place, among them, we highlight in relation to clinical trials. Starting with the low proportion of doctors, the insufficient number of doctors for the Brazilian population (1.85) occupying 75th place [13] and being poorly distributed [14] , which was reflected even in the drop in child mortality [15 ] [16] with the implementation of the program more doctors who imported thousands of doctors from Cuba [14] leaves them no time to devote themselves to clinical research, with the physician being the main figure in the clinical trial principles established by the Declaration of Helsinki [ 17] .

The cost of clinical research is already considered very high in developed and capitalized countries ($ 300 million to $ 1.5 billion), in Brazil this becomes even more unreachable [18]. An inexperienced academic culture for the application of scientific knowledge in clinical trials, with researchers working far from the doctor, with a much more theoretical curriculum that overloads students and teachers to perform duties, passing subjects quickly that will be decorated and forgotten, which is not allows a system of attraction of innovative projects. The reliance on research from foreign laboratories that are almost the only ones to afford the expensive clinical phases; receiving little and insufficient support from Brazilian funding agencies such as BNDS. Given this scenario, the results regarding clinical trials related to immunotherapy in Brazil were numerically quite humble [19] as well expressed by Dr. Cecilia Ferreira da Silva:

"In this study, only nine clinical trials with monoclonal antibodies and oncology bio-drugs were identified between 2003 and 2012 in Brazil. The types of cancer involved - colorectal, gastric, non-Hodgkin's lymphoma, melanoma, non-small cell lung and renal - have high incidence rates in the country, justifying this research. However, the number of trials is below the necessary, given the importance of this class of antineoplastics. It should be noted that there was no trial for breast or prostate cancer, those with the highest incidence in females and males, respectively, in Brazil "(...)" Two trials were terminated early " [20] [21] [22]

Spending is mainly on chemotherapy, which is what the system can do. "The volume of treatment and cancer spending in Brazil is increasing exponentially, but still falling short of needs. Between 1999 and 2015, spending on treatment (excluding promotion and prevention) increased from R $ 470 million to R $ 3.3 billion in nominal values1 [1], ie a seven-fold increase over a 16-year period. chemotherapy " [23] , which could be invested in immunotherapy given its most promising results.

In order to have a scientific update, it is necessary to explain step by step the methodologies used and to train multidisciplinary teams and oncologists in their handling, informing the details of these challenging some related advances. This project foresees several initiations of immunotherapy trials since it is done the preliminaries that we call "homework", seeking with this:

1) Eliminate the possibility of prior necessary approaches to the innate immune system and prepare the patient for treatment under focus of the adaptive immune system, since we see comorbidities acting in conjunction with most cancer cases, such as the hypothesis that TH1-to-TH2 shift occurred in the administration of dewormer that resulted in cancer cure in several reported cases following the popular Joe Tippens case [24]

2) Improve the amount and quality of second biopsy TILs to ensure that the second stage (ACT) is more likely to succeed in clonal expansion;

3) Observe results especially by looking at PD-L1 / PD1, CTLA4 / B7 and others inhibitors, helping to decide on approaches using more appropriate Mabs

4) Complementary treatment by opting for factors more associated with apoptosis induction and / or cell repair mechanisms through appropriate clinical choice within a variety of approaches.

5) interact, contribute or try to direct actions that the immune system is taking on patients.

6) Give the patient greater survival and quality of life.

FDA-Encouraged Adaptive Clinical Trial

Bayesian adaptive trials [25] (considering variables and uncertainties) are being preferred for several reasons where flexibility is a solution in each particular universe of each patient. This way research can better work your data by flexing solutions that are not provided for in a fixed system.

reducing cost and time factor. Although the concept of adaptive clinical trials has been round for the past 40 years, there is still a lack of uniformity and understanding of the subject. This review highlights important adaptive projected methodologies and covers regulatory positions on this issue. "[26] [27] [28] .

With the advancement of clinical trials by 2018 [29] , we can see greater clinical versatility, food and drug use in adaptive trials [30] . and greater respect for the necessary flexibility

Sequence of Treatment Steps

ET PRELIMINARY APAS

It is always good to note that there may be cases of tumor remission already in preliminary stages and attention should be paid to larger tumors that when they shrink provide too much fatty material that can clog kidneys, liver, generate thrombosis [31] and other sequelae. Therefore, any treatment against tumors, especially large and solid tumors [32] , use known natural or synthetic antithrombotic and diuretic protocols as a function of the fat generated by the accumulation of dead cancer cells, or by metastatic thrombosis where thrombin, aggregates platelets and prevents immune system access to the metastatic cell and further stimulates fibrin production [33]

There are natural diuretics such as Ginkgo biloba, Vitex montevidensis, Campomanesia xantocarpa and Allophylus edulispicão [34] , costus spicatus (monkey cane), and phytotherapics in general such as avocado, stone break, artichoke, leather hat and others. . Peeled lemon can be frozen to break cell walls and facilitate its absorption. After it must be shaved for use, lemon is also powerful astringent for fat. Green tea catechins inhibit vascular endothelial growth factor receptor phosphorylation [35] . Green tea catechins as new antitumor and antiangiogenic compounds [36] [37] [38] [39]. "demonstrated some anticoagulant and / or antiplatelet action, often detecting and isolating their active principles, and generating hypotheses about how they act, either at some point in the coagulation cascade or exerting their action on platelet aggregation, becoming an alternative. In antithrombotic treatment, among these we find many of the ancient uses.Who has recognized several medicinal plants through various publications, as to the therapeutic actions disclosed, such as: Aloe vera, Astragalus, Chamomile, Echinacea purpura, Garlic, Ginger, Valerian, Ginkgo. biloba, Ginseng and Plantago ovata " [40]

Anticoagulants

One of the protocols in cancer treatments is anti-thrombotics and diuretics that help prevent liver and kidney clogging by the presence of too much protein and fat generated by cell death. When acting on lymphocytes acting in conjunction with macrophages, the effect is less devastating than attack necrosis caused by chemotherapies and radiotherapies, but even so, despite lower doses it is always prudent to have more dead cells. in the blood. For both the list of medicines are:

Step 1 - Detoxification

Hodgkin's lymphoma is characterized by malignant cells that pass the lymph nodes (mainly B cells) and may be caused by the very common Epstein-Barr virus (EBV), and if its problem is very variable or not host response? where did he come from? of a fish? From any food? Either way, food detox can be a good start to treatment for this and many other cases.

Hodgkin's lymphoma may also be related to mercury [41] of dental openings. [42] Detoxification becomes critical as it decreases and points in directions, funneling through the results, around a more enlightening response to what has been going on. Many ways to detoxify are highly related to enhancements and increased immune system performance. Exercise [43] selenium supplementation [44] sauna and complementary medicines. [45]

A number of diseases and cancer are directly related to heavy metals and poisoning such as cadmium [46] , mercury and others. "There were 28 studies of liver cancer showing positive association to exposure to aflatoxin, air pollution, polycyclic aromatic hydrocarbons, asbestos, and paint chimneys occupation" [47] . Cassileth, a physician at Memorial Sloan-Kettering Cancer Center , published the book The Complete Guide to Complementary Therapies in Cancer Care Bowel Cleansing Using Colon Therapy [48] [49] , [50] Liver Cleansing Using Diverse Protocols like Dr. Hulda Clarck's , the use of liver cleansing such as curcumin [51] [52]of "naturally occurring selected epigenetic modulators, namely: butyrate, curcumin, (-) - epigallocatechin-3-gallate, resveratrol, romidepsin and trichostatin A" [53] , prawns ( costus spicatus ), artichoke, parsley ( Petroselinum crispum) ), ozone therapy, thermal shock saunas, etc., represent a basic approach that can remove causal factors from cancer or are in any way related to its progress. Because the innate and specific defense system has difficulties with toxins, evidence attests that not only "life begins with a healthy bowel" [54] but any treatment should eliminate these toxins first.

Step 2 - Colostrum

The use of transfer factors (TF) [55] [56] such as cow colostrum from the region where the patient inhabits, or where acquired the disease so that viral and microorganism variations according to regions [57] [58]do not allow to lose the specificity of immune defense in the multiplication of antibodies more specific those geographical variations that are challenged (term used in immunology referring to pathogen exposure to obtain an immune reaction) and produce antibodies with higher affinity allowing a better immune response and higher concentration of TILs in the second or first biopsy if there has already been such awareness about the use of this valuable natural remedy available free of charge to all farmers and dairy farmers who play the same pigs and dogs, and that companies cleverly has sought to defend patents on forms of their use [59]. Use of cow colostrum from the region where you live, or from the partner region to eliminate difficulties linked to the normal functioning of the immune system, especially when the patient is more allergic, such as those born from cesarean section that carry the rest. more allergies than other people in their lives [60] [61] [62] [63] .

We reason that ultimately those who have made antibodies and immune communications are basically rabbits, rats, horses, cows, goats, etc. They are our best immunological drug industry including more specific vaccines, viral variations in each region and each time. Using colostrum as a basic immunological tool will probably yield superior results that we risk acting on an immune system not well prepared for the possible attacks that host has been suffering.

Step 3 - Parasites

The hypothesis that the TH1 to TH2 shift occurred in dewormer administration that resulted in cancer cure in several reported cases following the popular Joe Tippens case [24]piqued our interest along with similar remarks. Elimination of helminths that deflect and inhibit TH1 cancer attacks by prioritizing the TH2 attack and eosinophil recruitment are basic preliminaries necessary above all to avoid interleukin stimulus diversion to attack other pathogens rather than cancer (TH2 vs TH1 in helminths, for example), and could be done preliminarily prior to referral to a specialist treatment center; for such simpler and easier preparation and attempts would save time, care, resources, and increase the efficiency of further treatment, save even in the hypothesis that even before such a need we may have notice of remission or that the patient is already free. of the tumor in the preliminary phase.

Step 4 - Probiotic Approach

The relationship of biota with lymphocyte activity [64] (Erickson, 2000) [65] paves the way for understanding the cause and solution of many types of cancer and disease. There is an immune system relationship with our biota and also a biota relationship with the emergence of various types of cancer. Through these two observations we realize that replacing commensal strains in patients will be eliminating causes for the return of cancer and comorbidity factors in its maintenance and origin.

Sanitation and sanitation can both eradicate diseases and promote diseases linked to resistant strains and lack of competition of microorganisms in an analogous species of microbiological pest that develops most in the absence of competitors. The etiological relationship with various types of tumor is widely documented in relation mainly to the intestinal biota, but we can also perceive its relationship to the oral, esophageal, intestinal and stomach biota [66] [67]

"In this intricate chain of local factors, in addition to the action of smoking and drinking, the mucosal alterations as well as the role of the fungi should be considered, given their importance, due to their high nitriding power in the possible malignant transformation. not fully elucidated. Thus, the fungal action should be better evaluated as to its role, even if supporting in the etiology of oral neoplasms ".

Bibliographic reviews discuss "the impact of microbiota on cancer initiation, development and progression in different types of human cells" [68] [69] . Our culture, both in the academic world that extends to the popular world, proves to be deficient in solely caring for cleanliness, hygiene, bactericides and antibiotics, without worrying about replenishing strains of high-powered commensal bacteria to compete with isolated harmful strains. human health that end up resisting these devices more and more possessing all territory without competitors causing even more diseases [70] [71] .

Our knowledge of the microbial composition of the intestinal ecosystem is rapidly expanding with the introduction of molecular techniques. Differences in intestinal microbiota composition and their relationship between health and atopy or inflammatory bowel disease have been repeatedly reported. Recent data on inflammatory bowel disease suggest reduced diversity and temporal instability of the intestinal microecosystem (15).[72] .

Step 5 - Nutraceutical and Phytotherapeutic

Although detoxification contains nutritional and phytotherapeutic aspects, these encompass an even larger universe. According to research (Anand, P, 2008) [73] "Only 5-10% of all cancer cases can be attributed to genetic defects, while the remaining 90-95% have their roots in the environment and lifestyle." Reviews reiterate that the origin of cancer is more linked to metabolism and that only caloric restrictions (ketogenic diets and assisted calorie fasts like the Russians do) associated with anti-glucose and glutamine drugs could be excellent strategies [74] . Lifestyle and food use aspects are an important factor in the prevention and treatment of many cancers (Reboredo-Rodríguez, 2018) [75]. It therefore becomes neglect with the complementary factors during treatment, which may represent their low efficiency.

Several studies indicate a close link between immunological activity and food, probiotics, psychotherapies and physiotherapies. [76] [77] [78] [79] [80] [81] [82] Therefore, in order to have better lymphocyte quality and quantity, some studies demonstrate the close relationship between activity and quantity of white cells acting with various stimulatory measures. Therefore we realize that before and during good nutraceutical orthomolecular supplementation, use inflammatory response modulating foods to control tumor growth [83] and anticancer diets [84] (Beliveau, Gingras, et al., 2003-2018) [85][86] [87] [88] [89] or calorie-restricted ketogenic diets , use Dr Ornish's method [90] [91] [92] [93] with exercise (if such a possibility exists), sonotherapy methods [94 ]with earplugs [95], psychotherapy, intestinal, oral commensal biota replacement, various immune stimuli such as heat shock (which can be localized), and multidisciplinary stimuli and physiotherapies, perform therapeutic apheresis separating lymphocytes before and after, remove biopsy before and after to verify improvement approaches of infiltrated TIL samples. Just as we have seen in the literature better chances of cure by some percentage using these strategies, in this context we estimate that our ACT TILs will be more active to accomplish their task, while such initiatives may contribute to our patients' longer survival and quality of life. of trials under these directives as well as in Chinese medicine [96] .

Dr Thomas N Seyfrield recently even teased in the title of the article "Provocative Question: Should Ketogenic Metabolic Therapy Be the Standard of Care for Glioblastoma?" where it advocates nutritional therapy as far more efficient than usual for treating brain tumors [97]. In the same vein an independent researcher in Brazil named Fábio Henrique Amaral de Almeida developed a series of studies called "biomolecular cell engineering", in this study he identifies the failure of aconitase enzyme as a crucial point in the genesis of cancer because it creates the need for the pathway. alternative to citrate formed in the first phase of the Krebs cycle, now inactivated by the lack of the aconitase enzyme, which would generate food for the pentose pathway that would feed the main base that triggers cell duplication. The nutritional metabolic approaches that work these etiological beginnings of alternative ways altering the configuration of the functioning of the cell, would bring the possibility already in the preliminary phase to solve the problem?

A huge dispute is taking place in the scientific and medical world where non-economically viable research (those that do not yield patents with exclusive isolation) participate in expensive sponsored clinical phases, are commonly referred to as alternative medicine that is extremely marginalized in the ordering, approval and payment process. by their use, even though principles and clinical and scientific criteria point to them as less risky and more promising measures.

"Following the emergence of modern antineoplastic therapy, the medical community is divided into two opposing fields, one of them stating the absolute need to use isolated or synthesized chemical compounds for efficient patient care and the other that advocates alternative cancer therapies, particularly those based on cancer. natural sources, including plant extracts It seems, in fact, that the two fields are reconcilable: while natural sources, plant extracts or juices play a healing and protective role, drugs represent the ultimate possibility of inhibiting or reversing tumor development. " [98]

Supplements have an infinite range of stimuli, so which suitable stimulus which genetic and proteomic need is the challenge to systematize which supplement will be most useful in a given approach.

IL-22, for example, regenerates the Thymus [99] , and when it is poorly coded it is associated with gastric cancer [100] (probably due to the thymus not maturing and / or eliminating lymphocytes, and consequently leaving them unfit for both. In this case, if the person supplemented with IL-22 [101] , he could solve his problem (if the NGS test for this defect in IL-22 coding genes were defective?) for leukemia in general?

An important point in this context is to diminish effects of autoimmune diseases by inhibiting PD1 / TCLA-4 and therefore several measures should seek to contain such effects [102] . Food and medicinal plants have been identified in thousands of research studies as containing potent active ingredients in the fight against cancer [103] linoleic acid (Kesley, 2007) [104] (Dmitri, 2015) [105] .

There are numerous foods and supplements [106] that modulate the inflammatory response and enhance immune activity such as PO supplementation that can make the cancer cell more visible [107] . These aspects are important both to prevent cancer proliferation and to ensure better IS efficiency . What signs of apoptosis or growth can be modulated or suppressed by nutraceuticals such as lemon peel ( citrus limon ) that prevents proliferation of gastric cancer further induces apoptosis. [108]What supplements can be expected to correct cancer cell metabolism? What role do CFM-recognized antioxidants play in their ultimate resolutions in cancer cells? Because we perceive some positive expectation for certain metabolic, but not to the point of becoming pillars of an approved treatment option, we categorize them here as measures that help the quality and quantity of biopsy TILs, and improve patients' quality of life, ensuring their survival. and response to treatments elected as most effective.

In addition, article 7 of the resolution of the Federal Council of Medicine, determines as to the treatments proposed by Orthomolecular practice:

"I) nutritional and lifestyle correction; II) drug replacement of nutrient deficiencies, according to article 2; III) therapeutic use of vitamins, minerals, fatty acids or amino acids with the purpose of modulating oxidative stress" "; IV) Removal of minerals when in excess (eg iron, cadmium) or toxic minerals (eg lead, mercury, aluminum) [109] ".

and extra-cellular complements that communicate between cells ( Gap Junctional ) [110] [111] [112] and their relationship to Oncologic Immunotherapy as valuable preliminary and necessary tools during treatments.

Step 6 - Neurotransmitter Psychotherapeutic Approach

Emotional trauma and positive events often define the tendency for breast cancer survival or death [113] . The case of Judy Perkins's successful ACT therapy [114] [115] calls our attention for the increase in quality of life during the period she decided to say goodbye to life, strolling and doing "everything she wanted." We estimate that this period where the photos indicate walks, smiles, pleasure and detachment with concerns that no longer mattered, had a positive effect on your metabolism, immune system and the quality and quantity of TILs, and this contributed to the success of your treatment. .

In practice we know superficially about psychosomatic effects as we try to understand some principles of how cell components communicate so quickly through our limitations discussed in 3D chemical and electrical models. But this mystery still hovers under the most basic questions and even more so when we try to map the conversations between neurons and T cells. Anyway it occurs and we need to attend to what we perceive even poorly. Observing psychological [116] [117] [118] [119] , social, neurological [120] [121] , and even metaphysical aspects called "spiritual" in the person becomes critical because our T lymphocytes obey neurons ( Candace Pert) [122] , so all treatment will depend on familiar aspects, thoughts, positivism, joy, gift, flowers, reconciliations, nourishment, supplements and even what we call "spirituality" will play a role in stimulating lymphocytes. Their activity has been observed to be low in depressed people. Even so, this protocol seems to supersede this aspect a little, because we can follow the activated ones multiplying, and depending on the success of psychotherapeutic approaches, as Freud repeated, if healing will occur.

It is recommended [123] to pay attention to methods that may be used for emotional trauma, familial aspects [124] , neurological aspects, psychiatric, psychological, spiritual, sacred-related aspects, guilt, more metaphysical aspects, psychosomatic effect, placebo effect, dialogue. between neuron and T cells, thanatology,

Since T cells have memory and talk, we say they have some kind of brain that seeks to control the wills of the living being in relation to pleasure, homeostasis, and balance. The neurotransmitter aspects studied since Dr. Candice Pert, following conversations through informational molecules of neurons to T lymphocytes, commanders of the immune response, which greater weight has been evaluated with the influence of psychological and neurological aspects as fundamental in the treatment, recovery and maintenance of treatments [125] [126] [127] [128]

Step 7 - Physical Therapy Approach - Inhibiting Cancer Growth and Increasing Immunological Activity

Which physical therapy actions are best indicated to contribute to the improvement of biopsy and cancer treatment complement? Which questionnaire will determine the best actions for each type of condition?

Defining which physical therapy aids can be of great value for many aspects of treatment. Often some aspects of the patient need intervention that will make a big difference to the good response of other treatments, especially when it comes to increased immune activity.

Its accompanying function is mediated by facilitating protein folding and maintaining the innate structures and functions of its client proteins when cells undergo homeostatic challenges. In addition, HSPs are involved in a number of important cellular processes, such as protein assembly, secretion, transport, protein translocation and degradation, and regulation of transcription factors, especially the refolding of unfolded proteins.[129]

Autohemo-ozone therapy decreases serum levels of inflammatory cytokines [130] [131] which inhibits cancer growth, and is associated with some chemotherapies [132] . "Tumor growth is suppressed after treatment with ozonated water as the amount of CDDP (cisplatin) reaching the tumor increases when intra-tumor blood perfusion is increased due to ozonated water. Thus, administration of ozonates to water can be a new therapeutic approach to address current concerns about antitumor treatment [133] . "

STEP 8 - Cultivation and Re-infusion of DCs Dendritic Cells, TILs, NK Infiltrated Tumor Lymphocytes, and Increased Tumorigenic Incentive Strategy

Cultivating dendritic cells (DCs) that can be stimulated monocytes taken from peripheral blood [134] [135] and TILs (Tumor-infiltrating lymphocytes) taken from biopsies [136] [137] , along with the encouragement of NK [138] represent three efficient joint therapeutic actions.

They removed NK cells from mice and found tumor growth [139] , the same occurs shortly after surgeries which weaken and depress the performance of NKs [140]. An environment conducive to tumor growth and development [141] . This is just an example of what can happen if you do not check all the variables included in a treatment. In the present paper we intend to "circumvent" several of these possibilities through preliminary and post-treatment approaches that we deem necessary to increase survival, the efficiency of the main elected treatment (s), and the reduction of relapses.

After removal of human biopsies use ACT for all TILs of all patients containing them; Those presenting TILs in the first biopsy of diagnosis or in the second comparative biopsy after breeding system should belong to two cultivation processes. According to clinical criteria, we should map possibilities of using biopsy removal before and after to compare efficiency of epigenetic stimuli. Several stimuli should occur 3 days before withdrawal as temperature alternation using ice in place to increase TILS, autohemoozonotherapy and herbal medicine.

As an adaptive assay, check the culture, at the same time apply PBLs by removing peripheral blood and training ex vivo lymphocytes and then multiplying them and / or alternating training / infusion.

Patients who have problems or lack of TILs, take biomarker tests (MSD offered for free [142] ) and with PD1, TCLA-4 expression, compare and monitor the possibility of multiplying TILs and decide whether or not to apply checkpoint inhibitors. several manufacturers like Pembrolizumab from MSD, in training or directly if there is a positive track record for a particular case. If not applied with selective carriers, check the mechanical possibility of applying "Mab" and then remove now infiltrated TILs for cultivation; then make partial or total leukapheresis, so select only those matured for the specific cancer and return to the blood, thus avoiding autoimmune diseases and side effects.

Selectively apply other types of inhibitors as per randomized small group outcome studies.

Modify some plasmid dendritic cells to recognize and present mutated epitopes from cancer cells to T cells.

With negative results, the assay allows conjugations of Caelyx low-invasiveness chemotherapy, capecitabine (Xeloda), Glivec, to make associations and / or not to use new surgeries, chemotherapies and radiotherapies according to clinical case analysis.

Separating infiltrated lymphocytes from biopsies (TILs), then multiplying TILs and training unspecified lymphocytes to attack cancer. Multiply them using lymphocyte culture (Kit) or healthy and tested ox serum + interleukins + radiated peripheral blood (which is the standard method in lymphocyte culture). In pathogen-controlled culture, test in place of a "clean room" probiotic system with competitors and use antibiotics for fungi and bacteria that may be natural, such as nettle extract, barbatimon, etc.), depending on the sensitivity of the candidate strains and verified on the substrates. and handling variants.

One "clean" room option could be calculated using propolis-coated lymphocyte cell culture hosting system to become aseptic without losing the ideal temperature which should be 37 ° C. We will try to multiply by mimicking the bee system. Follow up to see if lymphocytes are multiplying and attacking small biopsies in vitro. During the process use checkpoint stimuli gradually realizing their effects in vivo.

"Treatment of metastatic melanoma patients with autologous tumor infiltrating lymphocytes (TIL) shows robust and reproducible clinical responses in clinical trials conducted at various specialized centers worldwide [143] [144] [145] [146] "

As we see the success of ACT immunotherapies already in clinical phase I and II by 2018: "Foster Cell Therapy (ACT) using T-cells derived from tumor infiltrating lymphocytes (TIL) or T cells genetically engineered to express tumor recognition receptors has emerged as a potent and potentially curative therapy for many cancers.Many ACT-based therapies have recently entered the late phase clinical trial, with several T-cell therapies already reaching regulatory approval for the treatment of patients with B-cell malignancies. review, we briefly summarize the principles of adoptively transferred T cells for cancer treatment " [147] . See Spectacular Sunday report on Juddy Perkins case [148]. Bibliographic review 2014: Exploring the healing potential of adoptive T-cell therapy for cancer [149] . ACT with over 50% efficiency for melanoma in 2012 [150] . Improvement of ACT - 2018 [151] . 90% efficiency of car-t in ALL [152] .

The report of the scientific publication, where there was a report of cure of breast cancer by multiplying the biopsy T lymphocytes in a culture medium due to their insufficient number is very encouraging, of the 3 treated patients one was totally healed, one died of complications. Linked to Infectious (Lymphocyte Culture Needs This Extreme Caution or Did Judy Perkins Perform Immune Enhancement Protocol Before?).

When lymphocytes attack a cancer cell, they memorize that cell and multiply by passing their memory to daughter cells, doubling themselves with the same memory, and the result is an increase in the number of soldiers who will attack that particular cell type.

STEP 9 - Checkpoint Inhibitors in Clinical Trials I, II, and III

In the last two years alone, more than 500 clinical trials using PD-1 and PD-L1 have been performed on thousands of patients. And the use of PD-1 / PD-L1 inhibitors have been approved for treating various types of cancer. Selective delivery of drugs to cancer cells has been a concern that avoids side effects [153] , the goal being to prevent other healthy cells from being tapped. We used a selective delivery system using phosphoethanolamine [154] [155] [156] , as in the delivery function with approved drug approval from ANVISA [157] [158] [159] linked to the buffered factor of attraction of a specific cancer, thus having dual affinity for selective delivery thus reducing the chances of side effects.

The Checkpoint between PD-1 and PD-L1 (Programmed Cell Death Protein) where PD-1 is the Receptor, and PD-L1 is the ligand (effector). There are proteins in the immune system that regulate their activation or inactivation. These proteins turn the defense cells on and off. Or as well expressed by oncologist Felipe Ades;

"Its normal function in the body is to bind immune cells to fight infection and then turn off when the infection is healed and the cells are no longer needed" [160] . " It happens that some cancers use this route to block the immune response of the patient and continue to grow" [161].

Success with checkpoint inhibitors has been widely reported [162] [163] [164]. Monoclonal prostate cancer [165] .

In this study we evaluated pembrolizumab, nivolumab, atezolizumab, durvalumab and avelumab. But only pembrolizumab was singled out as superior to chemotherapy [166] [167]. Here we compared 3 pembrolizumab, atezo and nivolumab [168] [169] [170]

Oncologist says 50% of patients with high PDL1 rate treatment is efficient

Here pembrolizumab has demonstrated efficacy only in individuals with mismatch-repair sorafenib + vorinostat system deficiency (chemotherapeutic) increased anti PD1 effect for pancreatic adenocarcinoma [171] [172]

STEP 10 - Referral or Software Innovation

With NGS tests in hand and software suggestions like "oncomine", here are the most promising treatment options given to the patient who has not responded to the steps so far established.

Overcoming Some Difficulties

Some difficulties related to side effects, durability, risks in lymphocyte culture, quality and quantity of TILs (tumor infiltrating lymphocytes) have been exposed in the literature [173] , thus diminishing the efficiency of this approach. Adaptive clinical trials use the ACT technique of separating TILs and then multiplying them in culture using interleukins IL-2, IL-17, IL-22, or using gene therapy to increase their amount [174] . Cultivation of CD8 + can be done through multi-vendor kits in a clean room with interleukins and radiated peripheral blood as food and incentive in order to replace them by infusion into the patient.

We hope to overcome some difficulties regarding the quality and quantity of matrix TILs, side effects and durability by testing some nutraceutical, probiotic, psycho-therapeutic, physiotherapeutic and genetic engineering epigenetic strategies to 1) increase the chances of immune response 2) Use of prolongation of attack without damaging tissues due to the person's body's readiness to support the increased attack time approach 3) Control cancer cell proliferation through inflammation modulators and antioxidants while patient awaits ACT or NGS-based decision. 4) Reduce side effects through strategies that increase attack specificity 5) Educate the patient in their lifestyle regarding preliminary approaches promoting durability of treatment, longer survival, less stress, and even cost savings on commuting. 6) Complete immunological information by means of colostrum compatible with viral variations and microorganisms and helminths in target regions. 7) Detoxify the patient so that possible causative agents are eliminated as much as possible and do not cause relapses due to their presence.

In the phase cycle, in order not only to depend on the multiplication of "Tils" taken from the first biopsy of the diagnosis, remove monocytes and stimulate them to become DCs, by therapeutic apheresis (leukapheresis) or "bead magnetic" to sensitize them with fragmented biopsy. Check patients with large PD1 [175] , CTLA-4 or CD152 [176] expression to elect those who will most need PD1 / PD-L 1,2,3,4 (pembrolizumab, nivolumab, atezolizumab, durvalumab checkpoint inhibitors) , avelumab ...) each having better indications according to cancer type, along with biopsy, so that when cultured army is reinfused longer attack the tumor along with those encouraged by the new presentations of DCs.

The major concern with checkpoint inhibitors, for example, is that most patients do not respond to PD-1 immunotherapy, and some patients experience adverse events [177] . [178] We can see that attack inhibitory ligand expression such as PD1 -PD-L1 and CTLA-4-B7They are adaptive systems that protect the body from long-term inflammation, as well as mechanisms expressed in tolerances where attack cells are inhibited. This system ultimately benefits tumors. In this work, besides introducing the concept of biopsy improvement and quality of life of the patients involved, we will test strategies that optimize the short attack time to cancer cells so that they do not have time to run out and are inhibited looking for deadline. maximum every 21 days [179] , studying the inflammatory behaviors that trigger inhibition.

Advantages of Oral Cancer Immunotherapy

Because it is more exposed, it allows better examinations, larger studies, has the potential to be better treated when we consider the head as much more sensitive to more aggressive treatments. Our project started at the premises of CGDB - Goiano Center for Boca Diseasesfrom the Faculty of Dentistry - UFG, specifically during the NL (Free Nucleus of Studies of Mouth) oral cancer classes, where we see the same pessimistic picture of traditional treatments and the opportunity to have biopsy exams available. We then consulted with the UFG immunology specialists to verify the possibility of applying the TIL culture technique and in view of the needs and difficulties presented, we consulted the participation and help of the head of clinical cancer research of the Araújo Jorge hospital , Dr Ruffo de Freitas Junior , so we can proceed with the prior design of our actions, as has happened with several oral cancer research centers. [180]. As in these phase II trials 200 patients [181] and in more than 20 trials including phase III [182] . We realize that several other parallel and similar clinical studies may arise due to the multi-center of those involved, demonstrating the repetition of similar protocols with some variations and / or optimizations that each type of cancer requires.

Genetic Entropy and Polymerase I and III

The hypothesis that the rapidity of cancer cell multiplication comes from several stages that have been deleted, modified and simplified by commands of alternative energy capture and replication pathways should be clarified in the genetic and proteomic mapping, realizing the absence of proteins and factors. of silencing when comparing healthy and cancerous tissue. The speed of a malignant cancer suggests uncontrolled action independent of the consequences of imperfection (since polimesare I is by nature only doing gross repairs and delegating more careful repairs to polymerase III, P53 and others). the defect would be the very systematic "neglect" of polymerase I, the defect when it makes minor repairs,

John C Sanford, inventor of the GeneGun technique [183] released in 2005 the book "Entropy Genetic" that analyzes 5000 human diseases, has published along with a cloud of scientists on genetic entropy and points out:

• 1. The impending chaos of cells decreasing gene pool of derived populations, deleted genes, deleteriously mutated and passed on, etc. [184]

• 2. The present negative charge accumulation of deleterious genes that conservative mechanisms have not been able to eliminate (eg natural selection) [185] [186]

• 3. Its "glorious" past as machinery with no deleterious mutational defects and no need for adaptive energy and informational spending.

We can then calculate from the perspective of this line of research on genetic entropy (as a tendency to disorder) [187] how the cell was designed and / or held important information that today its lack or alteration causes disease and cancer [188] . and to study in denisova maps the weight of inbreeding in the incidence of cancer [189] , and Neanderthals, and in different ethnicities, where there is useful corrective information that in a given DNA is altered or missing.

The complete map of what the cell was like before it suffered from entropy of genetic information and deleterious gene accumulation [190] in both individuals and populations [191]. If the cell has been undergoing such adaptations in life and throughout the history of DNA, we estimate that its accelerated replication is only part of this adaptive system which, in seeking survival pathways, blinds itself to the consequences of becoming a cancer cell. Or if the alternative pathways that the cell uses today had aspects not only possessed in the past, it makes us reflect both ways of understanding and greater possibilities of managing the problem by looking at the past from a planning perspective that studies the cell as a engineered machine. This perspective has repercussions on the fathers of modern science and on an increasing number of publications. [192] [193] [194] [195] [196] [197] [198] [199][200] [201] [202] [203] [204] [205] [206] [207] [207] and tell us that the attack system and the entire cell system were designed by a "Design" and that the The accumulation of defects demonstrated by JC Sanford and Crabtree [209] shows us that our most efficient solutions should try to understand their most complex, sophisticated, efficient initial programming and with the least negative charge for deleterious mutation accumulation.

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34. ↑ Wang, Tzu-Fei; Li, Ang; Garcia, David (May 1, 2018). Managing thrombosis in cancer patients . Research and Practice in Thrombosis and Haemostasis. 2 (3): 429–438. ISSN  2475-0379 . doi : 10.1002 / rth2.12102 

35. ↑ Pires, Vanessa Arânega (2014). «Effect of the vitex montevidensis plant on experimental atherosclerosis: an approach on the development of a herbal medicine in Brazilian industry» . UFSC Institutional Repository 

36. Y Lamy, Sylvie; Gingras, Denis; Béliveau, Richard (January 15, 2002). «Green tea catechins inhibit vascular endothelial growth factor receptor phosphorylation» . Cancer Research. 62 (2): 381–385. ISSN  0008-5472 . PMID  11809684 

37. ↑ Demeule, Michel; Michaud-Levesque, Jonathan; Annabi, Borhane; Gingras, Denis; Boivin, Dominique; Jodoin, Julie; Lamy, Sylvie; Bertrand, Yanick; Béliveau, Richard (2002). Green tea catechins as novel antitumor and antiangiogenic compounds . Current Medicinal Chemistry. Anti-Cancer Agents. 2 (4): 441–463. ISSN  1568-0118 . PMID  12678730 

38. ↑ Gingras, Denis; Béliveau, Richard (2011). «Colorectal cancer prevention through dietary and lifestyle modifications» . Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society. 4 (2): 133–139. ISSN  1875-2284 . PMC  3170421  . PMID  21909875 . doi : 10.1007 / s12307-010-0060-5 

39. ↑ Durko, Anke; Malecka-Panas, Ewa (2014). Lifestyle Modifications and Colorectal Cancer . Current Colorectal Cancer Reports. 10 : 45–54. ISSN  1556-3790 . PMC  3950624  . PMID  24659930 . doi : 10.1007 / s11888-013-0203-4 

40. ↑ Mehta, Mamta; Shike, Moshe (2014). Diet and physical activity in the prevention of colorectal cancer . Journal of the National Comprehensive Cancer Network: JNCCN. 12 (12): 1721–1726. ISSN  1540-1413 . PMID  25505213 

41. ↑ Fuentes Salas, María Colombina; Palomo González, Iván (Prof Guía) (2006). Platelet Antiaggregates of Natural Origin (in Spanish) 

42. ↑ Rice, Kevin M .; Walker, Ernest M .; Wu, Miaozong; Gillette, Chris; Blough, Eric R. (2014). Environmental Mercury and Its Toxic Effects . Journal of Preventive Medicine and Public Health. 47 (2): 74–83. ISSN  1975-8375 . PMC  3988285  . PMID  24744824 . doi : 10.3961 / jpmph.2014.47.2.74 

43. ↑ Zanager, Afaf Mohamed (2019). "Mercury leaching from dental amalgam fillings and its association with urinary zinc ' (in English) 

44. Ut Dutra, Patricia Maria Lourenço; Pinto, Veronica Salerno; Silva, Silvia Amaral Gonçalves da; Earth, Rodrigo (2012). «Effect of exercise on the immune system: response, adaptation and cellular signaling» . Brazilian Journal of Sports Medicine. 18 (3): 208–214. ISSN  1517-8692 . doi : 10.1590 / S1517-86922012000300015 

45. ↑ Teixeira, Angelica de Paula (2019). «Dietary selenium supplementation and its effect on semen quality of clowns» . UFPR Institutional Digital Repository 

46. Ros Barros, Nelson Filice de; Otani, Marcia Aparecida Padovan (March 2011). «Integrative Medicine and the construction of a new model in health» . Science & Public Health. 16 (3): 1801–1811. ISSN  1413-8123 . doi : 10.1590 / S1413-81232011000300016 

47. ↑ Broekhoven, Francine van (June 27, 2019). Breast Health Handbook and Medical Thermography: Healthy Happy Breasts . [Sl]: Balboa Press. ISBN  9781982215101 

48. ↑ VoPham, Trang (March 1, 2019). Environmental Risk Factors for Liver Cancer and Nonalcoholic Fatty Liver Disease . Current Epidemiology Reports. 6 (1): 50–66. ISSN  2196-2995 . doi : 10.1007 / s40471-019-0183-2 

49. ↑ Kim, Jeong Wook; Lee, Jong Jin (July 1, 2015). «Successful Removal of Hard Sigmoid Fecaloma Using Endoscopic Glue Injection» . The Korean Journal of Gastroenterology (in Korean). 66 (1): 46–49. ISSN  1598-9992 . doi : 10.4166 / kjg.2015.66.1.46  ! CS1 maintenance: Unrecognized language ( link )

50. Ne Manne, Janaki R .; Rangu, Venu M .; Motapothula, Uma Maheswara R .; Hall, Matthew C. (May 2012). «A crunching colon: rectal bezoar caused by pumpkin seed consumption» . Clinical Medicine & Research. 10 (2): 75–77. ISSN  1554-6179 . PMC  3355739  . PMID  22031478 . doi : 10.3121 / cmr.2011.1016 

51. ↑ Bethune, Robert; Abdalkoddus, Muhammad; Smith, Radford Arran James (May 14, 2018). «Large bowel obstruction in a 27-year-old woman caused by a sigmoid faecal bolus» . Case Reports. 2018 : bcr – 2018–224811. ISSN  1757-790X . PMID  29764832 . doi : 10.1136 / bcr-2018-224811 

52. ↑ Pal, Suman; Bhattacharyya, Sankar; Choudhuri, Tathagata; Datta, Goutam K; Das, Tanya; Sa, Gaurisankar (January 1, 2005). 'Amelioration of immune cell number depletion and potentiation of depressed detoxification system of tumor-bearing mice by curcumin' . Cancer Detection and Prevention. 29 (5): 470–478. ISSN  0361-090X . doi : 10.1016 / j.cdp.2005.05.003 

53. Óp López-Lázaro, Miguel (2008). «Anticancer and carcinogenic properties of curcumin: Considerations for its clinical development as a chemopreventive and chemotherapeutic agent» . Molecular Nutrition & Food Research. 52 (S1): S103 – S127. ISSN  1613-4133 . doi : 10.1002 / mnfr.200700238 

54. ↑ Schnekenburger, Michael; Dicato, Mario; Diederich, Marc F. (2019). "Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?" . Cancer. 125 (10): 1612–1628. ISSN  1097-0142 . doi : 10.1002 / cncr.32041 

55. ↑ Broekhoven, Francine van (June 27, 2019). Breast Health Handbook and Medical Thermography: Healthy Happy Breasts . [Sl]: Balboa Press. ISBN  9781982215101 

56. ↑ Andruškienė, Jurgita; Kirkutis, Algimantas; Chizhov, Alexey Ya (2016). 'PERSPECTIVES IN THE APPLICATION OF IMMUNOCORRECTOR - TRANSFER FACTOR ™ IN IMMUNOPROPHYLAXIS PROGRAMS AND IMMUNOREHABILITATION' . Rehabilitacijos mokslai: slauga, kineziterapija, ergoterapija (in English). 2 (15). ISSN  2538-8673 . doi : 10.33607 / rmske.v2i15.703 

57. ↑ Aiguo Wu; Guangren, Duan (2006). «PMID Observer Design of Linear Systems Descriptor» . IEEE 2007 Chinese Control Conference. ISBN  9787811240559 . doi : 10.1109 / chicc.2006.4347343 

58. Iro Ribeiro, Simone G .; Martin, Darren P .; Lacorte, Cristiano; Simões, Isabella C .; Orlandini, Deborah RS; Inoue-Nagata, Alice K. (May 31, 2007). «Molecular and Biological Characterization of Tomato chlorotic mottle virus Suggests that Recombination Underlies the Evolution and Diversity of Brazilian Tomato Begomoviruses» . Phytopathology. 97 (6): 702–711. ISSN  0031-949X . doi : 10.1094 / PHYTO-97-6-0702 

59. Ul Schulz, Thomas F .; Calabrò, Maria-Luisa; Hoad, Julian G .; Carrington, Christine VF; Matutes, Estella; Catovsky, Daniel; Weiss, Robin A. (October 1, 1991). «HTLV-1 envelope sequences from Brazil, the Caribbean, and Romania: Clustering of sequences according to geographic origin and variability in an antibody epitope» . Virology. 184 (2): 483–491. ISSN  0042-6822 . doi : 10.1016 / 0042-6822 (91) 90418-B 

60. ↑ Transfer factor preparations and associated methods , May 2, 2006, consulted August 1, 2019 

61. ↑ Silva, Paulo Manuel Marques; Rodrigues, Sílvia Manuela Leite (December 2017). "Eutocic delivery versus elective cesarean section and the incidence of pathologies in children up to 2 years old" . Nursing Journal Reference. serIV (15): 83–90. ISSN  0874-0283 . doi : 10.12707 / RIV17051 

62. ↑ Bager, P. (2011). «Birth by caesarean section and wheezing, asthma, allergy, and intestinal disease» . Clinical & Experimental Allergy. 41 (2): 147–148. ISSN  1365-2222 . doi : 10.1111 / j.1365-2222.2010.03635.x 

63. Iao Xiao, Jin-zhong; Shimizu, Toshiaki; Aisaka, Kohzo; Kuhara, Tetsuya; Katayama, Takane; Mitsuyama, Eri; Odamaki, Toshitaka; Katsumata, Noriko; Satoh, Takumi (June 18, 2019). «Neonatal oral fluid as a transmission route for bifidobacteria to the infant gut immediately after birth» . Scientific Reports. 9 (1). 8692 pages. ISSN  2045-2322 . doi : 10.1038 / s41598-019-45198-9 

64. ↑ Kim, Kyung Won; Hong, Soo-jong; Kim, Kyu-Earn; Sohn, Myung Hyun; Kim, Woo Kyung; Lee, So Yeon; Yu, Jinho; Kim, Hyo Bin; Kim, Byoung Ju (September 1, 2011). Prevalence of Allergic Diseases in Children according to Mode of Delivery . Pediatric Allergy and Respiratory Disease (in Korean). 21 (3): 197–206. ISSN  1225-679X . doi : 10.7581 / pard.2011.21.3.197  ! CS1 maintenance: Unrecognized language ( link )

65. ↑ Umesaki, Yoshinori; Okada, Yasushi; Matsumoto, Satoshi; Imaoka, Akemi; Setoyama, Hiromi (August 1, 1995). «Segmented Filamentous Bacteria Are Indigenous Intestinal Bacteria That Activate Intraepithelial Lymphocytes and Induce MHC Class II Molecules and Fucosyl Asialo GM1 Glycolipids on the Small Intestinal Epithelial Cells in the Ex-Germ-Free Mouse» . Microbiology and Immunology. 39 (8): 555–562. ISSN  0385-5600 . doi : 10.1111 / j.1348-0421.1995.tb02242.x 

66. ↑ Erickson, Kent L .; Hubbard, Neil E. (February 1, 2000). Probiotic Immunomodulation in Health and Disease . The Journal of Nutrition. 130 (2): 403S – 409S. ISSN  0022-3166 . doi : 10.1093 / jn / 130.2.403S 

67. ↑ Meir, Juliane; Hartmann, Elena; Eckstein, Marie-Therese; Guiducci, Eva; Kirchner, Florian; Rosenwald, Andreas; LeibundGut-Landmann, Salome; Perez, J. Christian (2018). Identification of Candida albicans regulatory genes governing mucosal infection . Cellular Microbiology. 20 (8): e12841. ISSN  1462-5822 . PMID  29575428 . doi : 10.1111 / cmi.12841 

68. ↑ Börnigen, Daniela; Ren, Boyu; Pickard, Robert; Li, Jingfeng; Ozer, Enver; Hartmann, Erica M .; Xiao, Weihong; Tickle, Timothy; Rider, Jennifer (2017). «Alterations in oral bacterial communities are associated with risk factors for oral and oropharyngeal cancer» . Scientific Reports. 7 (1). ISSN  2045-2322 . doi : 10.1038 / s41598-017-17795-z 

69. Hang Zhang, Han; Sun, Litao (July 1, 2018). «When human cells meet bacteria: Precision medicine for cancers using the microbiota» . American Journal of Cancer Research. 8 (7): 1157-1175. ISSN  2156-6976 

70. ↑ Kernbauer, Elisabeth; Ding, Yi; Cadwell, Ken (November 19, 2014). «An enteric virus can replace the beneficial function of commensal bacteria» . Nature 516 (7529). ISSN  0028-0836 . doi : 10.1038 / nature13960 

71. ↑ Guarner, Francisco (November 1, 2007). Hygiene, microbial diversity and immune regulation . Current Opinion in Gastroenterology. 23 (6): 667–672. ISSN  0267-1379 . doi : 10.1097 / MOG.0b013e3282eeb43b 

72. ↑ Jiang, Wei; Wang, Xiaqiong; Zeng, Benhua; Liu, Lei; Late, Aubry; Wei, Hong; Han, Jiahuai; MacDonald, H. Robson; Tschopp, Jurg (October 21, 2013). «Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes» . Journal of Experimental Medicine. 210 (11): 2465–2476. ISSN  0022-1007 . PMID  24062413 . doi : 10.1084 / jem.20122490 

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75. Y Seyfried, Thomas N .; Shelton, Laura M. (January 27, 2010). Cancer as a metabolic disease . Nutrition & Metabolism. 7 (1). 7 pages. ISSN  1743-7075 . doi : 10.1186 / 1743-7075-7-7 

76. Bor Reboredo-Rodríguez, Patricia; Varela-López, Alfonso; Forbes-Hernandez, Tamara Y .; Gasparrini, Massimiliano; Afrin, Sadia; Cyanciosi, Danila; Zhang, Jiaojiao; Manna, Piera Pia; Bompadre, Stefano (August 6, 2018). «Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases» . International Journal of Molecular Sciences. 19 (8). 2305 pages. doi : 10.3390 / ijms19082305 

77. Ish Ornish, Dean; Weidner, Gerdi; Fair, William R .; Marlin, Ruth; Pettengill, Elaine B .; Raisin, Caren J .; Dunn-Emke, Stacey; Crutchfield, Lila; Jacobs, F. Nicholas (2005). «Intensive lifestyle changes may affect the progression of prostate cancer» . The Journal of Urology. 174 (3): 1065-1069; discussion 1069–1070. ISSN  0022-5347 . PMID  16094059 . Doi : 10.1097 / 01.ju.0000169487.49018.73 

78. Ish Ornish, Dean; Magbanua, Mark Jesus M .; Weidner, Gerdi; Weinberg, Vivian; Kemp, Colleen; Green, Christopher; Mattie, Michael D .; Marlin, Ruth; Simko, Jeff (June 17, 2008). «Changes in prostate gene expression in men undergoing intensive nutrition and lifestyle intervention» . Proceedings of the National Academy of Sciences of the United States of America. 105 (24): 8369-8374. ISSN  0027-8424 . PMID  18559852 . doi : 10.1073 / pnas.0803080105 

79. ↑ Campbell, T. Colin (2017). Cancer Prevention and Treatment by Wholistic Nutrition . Journal of Nature and Science. 3 (10). ISSN  2377-2700 . PMID  29057328 

80. ↑ "Natural Products in anticancer therapy" . Current Opinion in Pharmacology. 1 (4): 364–369. August 1, 2001. ISSN  1471-4892 . doi : 10.1016 / S1471-4892 (01) 00063-7 

81. ↑ «Isoxazoline containing natural products as anticancer agents: A review» . European Journal of Medicinal Chemistry. 77 : 121–133. April 22, 2014. ISSN  0223-5234 . doi : 10.1016 / j.ejmech.2014.02.063 

82. ↑ Anticancer polysaccharides from natural resources: A review of recent research . Carbohydrate Polymers. 90 (4): 1395–1410. November 6, 2012. ISSN  0144-8617 . doi : 10.1016 / j.carbpol.2012.07.026 

83. O Guo, B .; Wang, Y .; Sun, X .; Tang, K. (2008). «Bioactive natural products from endophytes: A review» . Applied Biochemistry and Microbiology. 44 (2): 136–142. ISSN  0003-6838 . doi : 10.1134 / s0003683808020026 

84. Y Lamy, Sylvie; Ouanouki, Amira; Béliveau, Richard; Desrosiers, Richard R. (March 10, 2014). 'Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation' . Experimental Cell Research. 322 (1): 89–98. ISSN  1090-2422 . PMID  24326154 . doi : 10.1016 / j.yexcr.2013.11.022 

85. ↑ Gingras, Denis; Béliveau, Richard (2011). «Colorectal cancer prevention through dietary and lifestyle modifications» . Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society. 4 (2): 133–139. ISSN  1875-2284 . PMC  3170421  . PMID  21909875 . doi : 10.1007 / s12307-010-0060-5 

86. ↑ Annabi Borhane; Lord-Dufour, Simon; Vézina, Amélie; Béliveau, Richard (2012). Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent . Drug Target Insights. 6 : 1–11. ISSN  1177-3928 . PMC  3329184  . PMID  22523472 . doi : 10,4137 / DTI.S9442 

87. Y Lamy, Sylvie; Akla, Naoufal; Ouanouki, Amira; Lord-Dufour, Simon; Béliveau, Richard (August 1, 2012). «Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6 / STAT3 pathway» . Experimental Cell Research. 318 (13): 1586–1596. ISSN  1090-2422 . PMID  22522122 . doi : 10.1016 / j.yexcr.2012.04.004 

88. ↑ Michaud-Levesque, Jonathan; Bousquet-Gagnon, Nathalie; Béliveau, Richard (May 1, 2012). «Quercetin abrogates IL-6 / STAT3 signaling and inhibits glioblastoma cell line growth and migration» . Experimental Cell Research. 318 (8): 925–935. ISSN  1090-2422 . PMID  22394507 . doi : 10.1016 / j.yexcr.2012.02.017 

89. É Ché, Christian; Yang, Gaoqiang; Thiot, Carine; Lacoste, Marie-Claude; Currie, Jean-Christophe; Demeule, Michel; Regina, Anthony; Béliveau, Richard; Castaigne, Jean-Paul (April 8, 2010). New Angiopep-modified doxorubicin (ANG1007) and etoposide (ANG1009) chemotherapeutics with increased brain penetration . Journal of Medicinal Chemistry. 53 (7): 2814–2824. ISSN  1520-4804 . PMID  20210346 . doi : 10.1021 / jm9016637 

90. Ry Perry, Marie-Claude; Demeule, Michel; Regina, Anthony; Moumdjian, Robert; Béliveau, Richard (2010). Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts . Molecular Nutrition & Food Research. 54 (8): 1192-1201. ISSN  1613-4133 . PMID  20087857 . doi : 10.1002 / mnfr.200900277 

91. Ish Ornish, DM; Lee, KL; Fair, WR; Pettengill, EB; Carroll, PR (2001). «Dietary trial in prostate cancer: Early experience and implications for clinical trial design» . Urology. 57 (4 Suppl 1): 200-201. ISSN  1527-9995 . PMID  11295627 

92. At Frattaroli, Joanne; Weidner, Gerdi; Dnistrian, Ann M .; Kemp, Colleen; Daubenmier, Jennifer J .; Marlin, Ruth O .; Crutchfield, Lila; Yglecias, Loren; Carroll, Peter R. (2008). «Clinical events in prostate cancer lifestyle trial: results from two years of follow-up» . Urology. 72 (6): 1319-1323. ISSN  1527-9995 . PMID  18602144 . doi : 10.1016 / j.urology.2008.04.050 

93. Ish Ornish, Dean; Weidner, Gerdi; Fair, William R .; Marlin, Ruth; Pettengill, Elaine B .; Raisin, Caren J .; Dunn-Emke, Stacey; Crutchfield, Lila; Jacobs, F. Nicholas (2005). «Intensive lifestyle changes may affect the progression of prostate cancer» . The Journal of Urology. 174 (3): 1065-1069; discussion 1069–1070. ISSN  0022-5347 . PMID  16094059 . Doi : 10.1097 / 01.ju.0000169487.49018.73 

94. ↑ Daubenmier, Jennifer J .; Weidner, Gerdi; Marlin, Ruth; Crutchfield, Lila; Dunn-Emke, Stacey; Chi, Christine; Gao, Billy; Carroll, Peter; Ornish, Dean (2006). «Lifestyle and health-related quality of life of men with prostate cancer managed with active surveillance» . Urology. 67 (1): 125–130. ISSN  1527-9995 . PMID  16413347 . doi : 10.1016 / j.urology.2005.07.056 

95. ↑ Neuendorf, Rachel; Wahbeh, Helane; Chamine, Irina; Yu, Jun; Hutchison, Kimberly; Oken, Barry S. (2015). «The Effects of Mind-Body Interventions on Sleep Quality: A Systematic Review» . Evidence-Based Complementary and Alternative Medicine: eCAM. 2015 . 902708 pages. ISSN  1741-427X . PMC  4487927  . PMID  26161128 . doi : 10.1155 / 2015/902708 

96. ↑ Hu, Rong-Fang; Jiang, Xiao-Ying; Chen, Junmin; Zeng, Zhiyong; Chen, Xiao Y .; Li, Yueping; Huining, Xin; Evans, David JW (October 6, 2015). Non-pharmacological interventions for sleep promotion in the intensive care unit . The Cochrane Database of Systematic Reviews (10): CD008808. ISSN  1469-493X . PMID  26439374 . doi : 10.1002 / 14651858.CD008808.pub2 

97. ↑ Guo, Qiujun; Li, Jie; Lin, Hongsheng (2015). «Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Immunosuppressive Microenvironment» . BioMed Research International. 2015 : 1–12. ISSN  2314-6133 . doi : 10.1155 / 2015/261620 

98. Y Seyfried, Thomas N .; Shelton, Laura; Arismendi-Morillo, Gabriel; Kalamian, Miriam; Elsakka, Ahmed; Maroon, Joseph; Mukherjee, Purna (April 25, 2019). «Provocative Question: Should Ketogenic Metabolic Therapy Become the Standard of Care for Glioblastoma?» . Neurochemical Research. ISSN  1573-6903 . doi : 10.1007 / s11064-019-02795-4 

99. ↑ Levitsky, Dmitri O .; Dembitsky, Valery M. (2015). Anti-Breast Cancer Agents Derived from Plants . Natural Products and Bioprospecting. 5 (1): 1–16. ISSN  2192-2195 . PMC  4327996  . PMID  25466288 . doi : 10.1007 / s13659-014-0048-9 

100. ↑ Pan Bin; Wang, Dong; Li, Lingling; Shang, Longmei; Xia, Fan; Zhang, Fan; Zhang, Ying; Gale, Robert Peter; Xu, Mengdi (June 10, 2019). «Interleukin-22 accelerates thymus regeneration via Stat3 / Mcl-1 and decreases chronic graft-versus-host disease in mice after allotransplants» . Biology of Blood and Marrow Transplantation. ISSN  1083-8791 . doi : 10.1016 / j.bbmt.2019.06.002 

101. ↑ Qin, Shan-yu; Yang, Xian-wen; Luo, Wei; Chen, Mei; Liu, Zhi-ling; Su, Si-biao; Jiang, Hai-xing (2015). Association of interleukin 22 polymorphisms with gastric cancer risk . Tumor Biology. 36 (3): 2033–2039. ISSN  1010-4283 . doi : 10.1007 / s13277-014-2810-3 

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103. ↑ Hindawi. «Complementary and Alternative Therapy of Rare Inflammatory / Autoimmune Diseases» . www.hindawi.com. Consulted on November 19, 2018 

104. ↑ Granchi, Carlotta (5 September 2018). 'ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism' . European Journal of Medicinal Chemistry. 157 : 1276-1291. ISSN  1768-3254 . doi : 10.1016 / j.ejmech.2018.09.001 

105. ↑ Kelley, Nirvair S .; Hubbard, Neil E .; Erickson, Kent L. (December 1, 2007). Conjugated Linoleic Acid Isomers and Cancer . The Journal of Nutrition. 137 (12): 2599–2607. ISSN  0022-3166 . doi : 10.1093 / jn / 137.12.2599 

106. ↑ Levitsky, Dmitri O .; Dembitsky, Valery M. (February 1, 2015). Anti-Breast Cancer Agents Derived from Plants . Natural Products and Bioprospecting. 5 (1): 1–16. ISSN  2192-2209 . PMC  4327996  . PMID  25466288 . doi : 10.1007 / s13659-014-0048-9 

107. Inha Sinha, Niharika; Meher, Biswa Ranjan; Naik, Prajna Paramita; Panda, Prashanta Kumar; Mukhapadhyay, Subhadip; Maiti, Tapas K; Bhutia, Sujit K (March 1, 2019). «P73 induction by Abrus agglutinin facilitates Snail ubiquitination to inhibit epithelial to mesenchymal transition in oral cancer» . Phytomedicine. 55 : 179–190. ISSN  0944-7113 . doi : 10.1016 / j.phymed.2018.08.003 

108. ↑ Tan, Loh Teng Hern; Chan, Kok-Gan; Pusparajah, Priyia; Lee, Wai-Leng; Chuah, Lay-Hong; Khan, Tahir Mehmood; Lee, Learn-Han; Goh, Bey-Hing (January 23, 2017). "Membrane Lipid Targeting the Potential Cancer Cure?» . Frontiers in Pharmacology. 8 . ISSN  1663-9812 . doi : 10.3389 / fphar.2017.00012 

109. ↑ Cho, Somi Kim; Kang, Hye Rim; Hyun, Ho Bong; Moon, Jeong Yong; Osman, Ahmed (September 30, 2016). «The chloroform fraction of citrus limon leaves inhibits human gastric cancer cell proliferation via induction of apoptosis» . Journal of Applied Biological Chemistry. 59 (3): 207–213. ISSN  1976-0442 . doi : 10.3839 / jabc.2016.036  ! CS1 maintenance: Unrecognized language ( link )

110. ↑ “CFM RESOLUTION No. 1” . www.portalmedico.org.br. Consulted on November 17, 2018 

111. ↑ Trosko, James E. (2019). «Cancer Prevention and Therapy of Two Types of Junctional Intercellular Communication – Deficient Gap" Cancer Stem Cell "» . Cancers. 11 (1). 87 pages. doi : 10.3390 / cancers11010087 

112. Ón Ramón y Cajal, Santiago; Hernández-Losa, Javier; Moliné, Teresa; Martinez-Marti, Alexandre; Temprana-Salvador, Jordi; Romagosa, Cleofé; Montero, Maria Ángeles; Sansano, Irene; Aasen, Trond (2019). "Insight into the Role and Regulation of Gap Junction Genes in Lung Cancer and Identification of Nuclear Cx43 as a Putative Biomarker of Poor Prognosis ." Cancers. 11 (3). 320 pages. doi : 10.3390 / cancers11030320 

113. Ern Tabernero, Arantxa; Pogoda, Kristin; Mesnil, Marc; Maria D. Mayán; Kameritsch, Petra; Graham, Sheila V .; Leithe, Edward; Aasen, Trond (2019). Connexins in cancer: bridging the gap to the clinic . Oncogene. 38 (23): 4429–4451. ISSN  1476-5594 . doi : 10.1038 / s41388-019-0741-6 

114. ↑ Heikkinen, Sanna; Miettinen, Joonas; Pukkala, Eero; Koskenvuo, Markku; Malila, Nea; Pitkäniemi, Janne (June 1, 2017). «Impact of major life events on breast-cancer-specific mortality: A case fatality study on 8000 breast cancer patients» . Cancer Epidemiology. 48 : 62–69. ISSN  1877-7821 . doi : 10.1016 / j.canep.2017.03.008 

115. D Feldman, Steven A .; Goff, Stephanie L .; Rosenberg, Steven A .; Robbins, Paul F .; Somerville, Robert P .; Trebska-McGowan, Katarzyna; Jia, Li; Gartner, Jared; Todd Prickett (2018). «Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer». Nature Medicine. 24 (6): 724–730. ISSN  1546-170X . doi : 10.1038 / s41591-018-0040-8 

116. ↑ Radvanyi, Laszlo G. (2018). Targeting the cancer mutanome of breast cancer . Nature Medicine. 24 (6): 703–704. ISSN  1546-170X . doi : 10.1038 / s41591-018-0065-z 

117. Enc Lorenc, Ava; Feder, Gene; MacPherson, Hugh; Little, Paul; Mercer, Stewart W .; Sharp, Deborah (October 15, 2018). «Scoping review of systematic reviews of complementary medicine for musculoskeletal and mental health conditions» . BMJ open. 8 (10): e020222. ISSN  2044-6055 . doi : 10.1136 / bmjopen-2017-020222 

118. ↑ Benedetti, Fabrizio; Mayberg, Helen S .; Wager, Tor D .; Stohler, Christian S .; Zubieta, Jon-Kar (November 9, 2005). Neurobiological Mechanisms of the Placebo Effect . Journal of Neuroscience. 25 (45): 10390-10402. ISSN  0270-6474 . PMID  16280578 . doi : 10.1523 / JNEUROSCI.3458-05.2005 

119. ↑ Wahbeh, Helane; Haywood, Ashley; Kaufman, Karen; Zwickey, Heather (2009). «Mind-Body Medicine and Immune System Outcomes: A Systematic Review» . The open complementary medicine journal. 1 : 25–34. ISSN  1876-391X . PMC  3516431  . PMID  23227136 . doi : 10.2174 / 1876391X00901010025 

120. ↑ Neuendorf, Rachel; Wahbeh, Helane; Chamine, Irina; Yu, Jun; Hutchison, Kimberly; Oken, Barry S. (2015). «The Effects of Mind-Body Interventions on Sleep Quality: A Systematic Review» . Evidence-Based Complementary and Alternative Medicine: eCAM. 2015 . 902708 pages. ISSN  1741-427X . PMC  4487927  . PMID  26161128 . doi : 10.1155 / 2015/902708 

121. ↑ Wahbeh, Helane; Haywood, Ashley; Kaufman, Karen; Zwickey, Heather (2009). «Mind-Body Medicine and Immune System Outcomes: A Systematic Review» . The open complementary medicine journal. 1 : 25–34. ISSN  1876-391X . PMC  3516431  . PMID  23227136 . doi : 10.2174 / 1876391X00901010025 

122. ↑ Benedetti, Fabrizio; Mayberg, Helen S .; Wager, Tor D .; Stohler, Christian S .; Zubieta, Jon-Kar (November 9, 2005). Neurobiological Mechanisms of the Placebo Effect . Journal of Neuroscience. 25 (45): 10390-10402. ISSN  0270-6474 . PMID  16280578 . doi : 10.1523 / JNEUROSCI.3458-05.2005 

123. Ert Pert, Candace B. (2002). «The wisdom of the receptors: neuropeptides, the emotions, and bodymind. 1986 ' . Advances in Mind-Body Medicine. 18 (1): 30–35. ISSN  1470-3556 . PMID  12523304 

124. ↑ «PsycNET» . psycnet.apa.org. Consulted on July 31, 2019 

125. Ome Gomez, Scarlett Lin; Komenaka, Ian; Schwab, Richard; Kroenke, Candyce H .; Tao, Li; Unkart, Jonathan T.; Martínez, María Elena (2017). «Prognostic significance of marital status in breast cancer survival: A population-based study» . PLOS ONE. 12 (5): e0175515. ISSN  1932-6203 . PMC  5419505  . PMID  28475579 . doi : 10.1371 / journal.pone.0175515 

126. ↑ Neuendorf, Rachel; Wahbeh, Helane; Chamine, Irina; Yu, Jun; Hutchison, Kimberly; Oken, Barry S. (2015). «The Effects of Mind-Body Interventions on Sleep Quality: A Systematic Review» . Evidence-Based Complementary and Alternative Medicine: eCAM. 2015 . 902708 pages. ISSN  1741-427X . PMC  4487927  . PMID  26161128 . doi : 10.1155 / 2015/902708 

127. ↑ Neuendorf, Rachel; Wahbeh, Helane; Chamine, Irina; Yu, Jun; Hutchison, Kimberly; Oken, Barry S. (2015). «The Effects of Mind-Body Interventions on Sleep Quality: A Systematic Review» . Evidence-Based Complementary and Alternative Medicine. 2015 : 1–17. ISSN  1741-427X . doi : 10.1155 / 2015/902708 

128. ↑ Mao, Dan; Feng, Lei; Gong, Hui (November 18, 2018). "The Antitumor and Immunomodulatory Effect of Yanghe Decoction in Breast Cancer is Related to the Modulation of the JAK / STAT Signaling Pathway ." Evidence-Based Complementary and Alternative Medicine. 2018 : 1–9. ISSN  1741-427X . doi : 10.1155 / 2018/8460526 

129. ↑ Wahbeh, Helane; Haywood, Ashley; Kaufman, Karen; Zwickey, Heather (2009). «Mind-Body Medicine and Immune System Outcomes: A Systematic Review» . The open complementary medicine journal. 1 : 25–34. ISSN  1876-391X . PMC  3516431  . PMID  23227136 . doi : 10.2174 / 1876391X00901010025 

130. ↑ Chatterjee, Suman; Burns, Timothy F. (September 15, 2017). Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach . International Journal of Molecular Sciences. 18 (9). ISSN  1422-0067 . PMC  5618627  . PMID  28914774 . doi : 10.3390 / ijms18091978 

131. ↑ Li, Lian-Yun; Ma, Ruo-Lan; Du, Liqin; Wu, An-Shi (2017). «Ozonated autohemotherapy modulates serum levels of inflammatory cytokines in gouty patients» . Open Access Rheumatology: Research and Reviews. 9 : 159–165. ISSN  1179-156X . PMC  5565251  . PMID  28860878. doi : 10.2147 / OARRR.S119749 

132. ↑ Biedunkiewicz, B .; Tylicki, L .; Nieweglowski, T .; Burakowski, S .; Rutkowski, B. (January 1, 2004). «Clinical efficacy of ozonated autohemotherapy in hemodialyzed patients with intermittent claudication: an oxygen-controlled study» . The International Journal of Artificial Organs. 27 (1): 29–34. ISSN  0391-3988 . PMID  14984181 

133. ↑ Wu, Xiaona; Liu, Xiaoyan; Huang, Huai; Li, ZhenSheng; Xiong, TieGen; Xiang, Wei; Liu, Liu; Tao, Zhang (November 2, 2018). «Effects of major ozonated autoheamotherapy on functional recovery, ischemic brain tissue apoptosis and oxygen free radical damage in the rat model of brain ischemia» . Journal of Cellular Biochemistry. ISSN  1097-4644 . doi : 10.1002 / jcb.27978 

134. Oda Kuroda, Kohei; Yamashita, Masamiti; Murahata, Yusuke; Azuma, Kazuo; Osaki, Tomohiro; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Okamoto, Yoshiharu (September 1, 2018). «Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment» . Experimental and Therapeutic Medicine. 16 (3): 1597–1602. ISSN  1792-0981 . doi : 10.3892 / etm.2018.6415 

135. ↑ Banchereau, Jacques; Steinman, Ralph M. (1998). Dendritic cells and the control of immunity . Nature 392 (6673): 245–252. ISSN  0028-0836 . doi : 10.1038 / 32588 

136. ↑ Barillet, S .; Fattal, E .; Mura, S .; Tsapis, N .; Pallardy, M .; Hillaireau, H .; Kerdine-Römer, S. (February 14, 2019). Immunotoxicity of poly (lactic-co-glycolic acid) nanoparticles: influence of surface properties on dendritic cell activation . Nanotoxicology. 0 (0): 1–17. ISSN  1743-5390 . doi : 10.1080 / 17435390.2018.1564078 

137. ↑ Weinberg, Andrew D .; Bell, Richard B .; Leidner, Rom; Miranda, Noel F. de; Verdegaal, Els ME; Grunkemeier, Gary; Chang, Shu-Ching; Fox, Bernard A .; Bulk, Jitske van den (February 1, 2019). Abstract A186: A new strategy for identifying and expanding CD8 TILs in human solid tumors . Cancer Immunology Research. 7 (2 Supplement): A186-A186. ISSN  2326-6066 . doi : 10.1158 / 2326-6074.CRICIMTEATIAACR18-A186 

138. Uma Schumacher, Ton NM; Haanen, John BAG; Zippelius, Alfred; Mertz, Kirsten D .; Monkhorst, Kim; Hummelink, Karlijn; Braber, Marlous van den; Voabil, Paula; Bruijn, Marjolein of (February 1, 2019). "Abstract B050: Identification of PD-1T TILs and CXCL13 determinants for response to anti-PD-1 treatment using human tumor explants ." Cancer Immunology Research. 7 (2 Supplement): B050 – B050. ISSN  2326-6066 . doi : 10.1158 / 2326-6074.CRICIMTEATIAACR18-B050 

139. Mann Waldmann, Thomas A .; Roederer, Mario; Creekmore, Stephen P .; Yovandich, Jason L .; Shih, Joanna H.; Peer, Cody J .; Figg, William D .; Hsu, Jennifer; Perera, Liyanage P. (January 1, 2019). «IL-15 by continuous iv infusion to adult patients with solid tumors in a Phase I trial induced dramatic NK cell subset expansion» . Clinical Cancer Research: clincanres.3468.2018. ISSN  1078-0432 . doi : 10.1158 / 1078-0432.CCR-18-3468 

140. ↑ Dunn, Gavin P .; Old, Lloyd J .; Schreiber, Robert D. (2004). The Immunobiology of Cancer Immunosurveillance and Immunoediting . Immunity. 21(2): 137–148. doi : 10.1016 / j.immuni.2004.07.017 

141. Er Auer, Rebecca C .; Kennedy, Michael A .; Angka, Leonard; Baxter, Katherine E .; Market, Marisa (2019). «The Potential for Immunotherapy Cancer in Targeting Surgery-Induced Natural Killer Cell Dysfunction» . Cancers. 11 (1). 2 pages. doi : 10.3390 / cancers11010002 

142. ↑ Chammas, Roger; Onuchic, Ana Claudia (March 19, 2010). «Cancer and the tumor microenvironment» . Journal of Medicine. 89 (1): 21–31. ISSN  1679-9836 . doi : 10.11606 / issn.1679-9836.v89i1p21-31 

143. ↑ "MSD offers free biomarker test for patients with gastric cancer - KEYTRUDA (PEMBROLIZUMADE) APPROVED IN ANVISA FOR MELANOMA, LUNG AND urothelial (bladder)» . MSD Offers Free Biomarker Test for Gastric Cancer Patients - KEYTRUDA (PEMBROLIZUMADE) APPROVED FOR MELANOMA, LUNG AND UROTELIAL (BLADDER) TEST ~ RM Consult. Consulted on November 18, 2018 

144. ↑ Rohaan, Maartje W .; van den Berg, Joost H.; Kvistborg, Pia; Haanen, John BAG (October 3, 2018). Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option . Journal for Immunotherapy of Cancer. 6 (1). 102 pages. ISSN  2051-1426 . doi : 10.1186 / s40425-018-0391-1 

145. ↑ Radvanyi, Laszlo G. (2018-06). Targeting the cancer mutanome of breast cancer . Nature Medicine. 24 (6): 703–704. ISSN  1078-8956 . doi : 10.1038 / s41591-018-0065-z   Check date at: |data=( help )

146. Acha Zacharakis, Nikolaos; Chinnasamy, Harshini; Black, Mary; Xu, Hui; Lu, Yong-Chen; Zheng, Zhili; Pasetto, Anna; Langhan, Michelle; Shelton, Thomas (2018-06). «Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer» . Nature Medicine. 24 (6): 724–730. ISSN  1078-8956 . doi : 10.1038 / s41591-018-0040-8   Check date at: |data=( help )

147. ↑ Wu, Richard; Forget, Marie-Andrée; Chacon, Jessica; Bernatchez, Chantale; Haymaker, Cara; Chen, Jie Qing; Hwu, Patrick; Radvanyi, Laszlo G. (2012-3). «Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook» . Cancer Journal (Sudbury, Mass.). 18 (2): 160–175. ISSN  1540-336X . PMC  PMC3315690  Check |pmc=( help ). PMID  22453018 . doi : 10.1097 / PPO.0b013e31824d4465   Check date at: |data=( help )

148. ↑ Met, Özcan; Jensen, Kasper Mølgaard; Chamberlain, Christopher Aled; Donia, Marco; Svane, Inge Marie (September 5, 2018). Principles of adoptive Cell therapy in cancer . Seminars in Immunopathology. ISSN  1863-2300 . PMID  30187086 Check |pmid=( help ). doi : 10.1007 / s00281-018-0703-z 

149. ↑ Spectacular Sunday (June 17, 2018), Researchers cure breast cancer patient through immunotherapy , consulted November 18, 2018 

150. In Hinrichs, Christian S .; Rosenberg, Steven A. (2014-1). "Exploiting the curative potential of adoptive T-cell therapy for cancer" . Immunological Reviews. 257 (1): 56–71. ISSN  1600-065X . PMC  PMC3920180  Check |pmc=( help ). PMID  24329789 . doi : 10.1111 / imr.12132   Check date at: |data=( help )

151. ↑ Wu, Richard; Forget, Marie-Andrée; Chacon, Jessica; Bernatchez, Chantale; Haymaker, Cara; Chen, Jie Qing; Hwu, Patrick; Radvanyi, Laszlo G. (2012-3). «Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook» . Cancer Journal (Sudbury, Mass.). 18 (2): 160–175. ISSN  1540-336X . PMC  PMC3315690  Check |pmc=( help ). PMID  22453018 . doi : 10.1097 / PPO.0b013e31824d4465   Check date at: |data=( help )

152. ↑ Tang, Li; Zheng, Yiran; Melo, Mariane Bandeira; Mabardi, Llian; Castaño, Ana P .; Xie, Yu-Qing; Li, Na; Kudchodkar, Sagar B .; Wong, Hing C. (2018-9). Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery . Nature Biotechnology. 36 (8): 707–716. ISSN  1546-1696 . PMC  PMC6078803  Check |pmc=( help ). PMID  29985479 . doi : 10.1038 / nbt.4181   Check date at: |data=( help )

153. ↑ Oluwole Olalekan O .; Davila, Marco L. (12 2016). 'At The Bedside: Clinical review of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies " . Journal of Leukocyte Biology. 100 (6): 1265-1272. ISSN  1938-3673 . PMID  27354412 . doi : 10.1189 / jlb.5BT1115-524R   Check date at: |data=( help )

154. ↑ «Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level» . Cancer Letters. 290 (2): 192–203. April 28, 2010. ISSN  0304-3835 . doi : 10.1016 / j.canlet.2009.09.010 

155. ↑ «Phosphoethanolamine induces caspase-independent cell death by reducing the expression of C-RAF and inhibits tumor growth in human melanoma model» . Biomedicine & Pharmacotherapy. 103 : 18–28. July 1, 2018. ISSN  0753-3322 . doi : 10.1016 / j.biopha.2018.03.135 

156. ↑ Mosque, Orange, Angela (July 1, 2016). "Potential antitumor effect of synthetic phosphoethanolamine in experimental tumor models" . Consulted on November 18, 2018 

157. Una Luna, Arthur Cássio de Lima; Hail, Greice Kelle Viegas; Son, Otaviano Mendonça Ribeiro; Chierice, Gilberto Orivaldo; Neto, Salvador Claro; Cuccovia, Iolanda Midea; Maria, Durvanei Augusto (April 18, 2016). Potential antitumor activity of novel DODAC / PHO-S liposomes . International Journal of Nanomedicine. 11 : 1577-1591. ISSN  1176-9114 . PMC  4841408  . PMID  27143880 . doi : 10.2147 / IJN.S90850 

158. ↑ Ataie-Kachoie Parvin; Pillai, Krishna; Badar, Samina; Akhter, Javed; Morris, David Lawson (2018). «Monepantel considerably enhances the therapeutic potentials of PEGylated liposomal doxorubicin and gemcitabine in ovarian cancer: in vitro and in vivo studies» . American Journal of Cancer Research. 8 (10): 2064-2075. ISSN  2156-6976 

159. Uc Trucco, Matteo M .; Meyer, Christian F .; Thornton, Katherine A .; Shah, Preeti; Chen, Allen R .; Wilky, Breelyn A .; Carrera-Haro, Maria A .; Boyer, Lillian C .; Ferreira, Margaret F. (2018). "A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas" . Clinical Sarcoma Research. 8 . 21 pages. ISSN  2045-3329 . doi : 10.1186 / s13569-018-0107-9 

160. Uns Munster, Pamela; Krop, Ian E .; LoRusso, Patricia; Ma, Cynthia; Siegel, Barry A .; Shields, Anthony F .; Molnár, István; Wickham, Thomas J .; Reynolds, Joseph (October 1, 2018). 'Safety and pharmacokinetics of MM-302, HER2-targeted antibody-liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study' . British Journal of Cancer. 119 (9): 1086-1093. ISSN  1532-1827 . doi: 10.1038 / s41416-018-0235-2 

161. ↑ «anti-PD1 | Felipe Ades MD PhD - Oncologist . drfelipeades.wordpress.com. Consulted on November 19, 2018 

162. ↑ Barclay, Jonathan; Creswell, Joanne; Leon, Juan (May 1, 2018). Cancer immunotherapy and the PD-1 / PD-L1 checkpoint pathway . Archivos Espanoles Of Urology. 71 (4): 393–399. ISSN  0004-0614 . PMID  29745928 

163. ↑ Cantero-Cid, Ramón; Casas-Martin, José; Hernández-Jiménez, Enrique; Cubillos-Zapata, Carolina; Serrano worm, Hannibal; Avendaño-Ortiz, José; Casarrubios, Marta; Montalbán-Hernández, Karla; Villacañas-Gil, Ignacio (October 3, 2018). "PD-L1 / PD-1 crosstalk in colorectal cancer: are we targeting the right cells?" . BMC cancer. 18 (1). 945 pages. ISSN  1471-2407 . doi : 10.1186 / s12885-018-4853-0 

164. ↑ Marginean, Emerald Celia; Melosky, Barbara (January 15, 2018). «Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II-The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer . Archives of Pathology & Laboratory Medicine. 142 (1): 26–34. ISSN  1543-2165 . PMID  29120224 . doi : 10.5858 / arpa.2017-0041-RA 

165. ↑ Alsaab, Hashem .; Sau, Samaresh; Alzhrani, Ramie; Tatiparti, Katyayani; Bhise, Ketki; Kashaw, Sushil K .; Iyer, Arun K. (2017). PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome . Frontiers in Pharmacology. 8 . ISSN  1663-9812 . doi : 10.3389 / fphar.2017.00561  ! CS1 maintenance: Unrecognized language ( link )

166. ↑ Cancer, Cleveland Clinic. 'Sipuleucel-T - Chemotherapy Drugs - Chemocare' . chemocare.com. Consulted on November 19, 2018 

167. ↑ Stenehjem, David D .; Tran, Dao; Nkrumah, Michael A .; Gupta, Shilpa (2018). 'PD1 / PDL1 inhibitors for the treatment of advanced urothelial bladder cancer' . OncoTargets and Therapy. 11 : 5973-5989. ISSN  1178-6930 . doi : 10.2147 / OTT.S135157 

168. ↑ Marginean, Emerald Celia; Melosky, Barbara (January 15, 2018). «Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II-The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer . Archives of Pathology & Laboratory Medicine. 142 (1): 26–34. ISSN  1543-2165 . PMID  29120224 . doi : 10.5858 / arpa.2017-0041-RA 

169. ↑ Abdel-Rahman, Omar; Oweira, Hani; Giryes, Anwar (December 12, 2018). «Health-related quality of life in cancer patients treated with PD- (L) 1 inhibitors: a systematic review» . Expert Review of Anticancer Therapy. 18 (12): 1231–1239. ISSN  1744-8328 . doi : 10.1080 / 14737140.2018.1528146 

170. Fel Dr. Felipe Ades MD PhD - Oncologist (August 8, 2017), Dr. Felipe Ades - Pembrolizumab as a first-line treatment for lung cancer , consulted November 19, 2018 

171. In Klein, Sarah; Ziello, Jennifer; Speranza, Maria; Gokhale, Prafulla; Kirschmeier, Paul; Crosby, Katherine; Freeman, Gordon; Reardon, David (May 1, 2018). 'PD-1 blockade activates conventional CD4 T cells and innate immune response during glioblastoma eradication' . The Journal of Immunology. 200 (1 Supplement): 57.9–57.9. ISSN  0022-1767 

172. ↑ Booth, Laurence; Roberts, Jane Lisa; Poklepovic, Andrew; Dent, Paul (August 24, 2018). Prior exposure of pancreatic tumors to [sorafenib + vorinostat] enhances the efficacy of an anti-PD-1 antibody . Cancer Biology & Therapy: 1–13. ISSN  1538-4047 . doi : 10.1080 / 15384047.2018.1507258 

173. ↑ Cancer, Cleveland Clinic. 'Sipuleucel-T - Chemotherapy Drugs - Chemocare' . chemocare.com. Consulted on November 19, 2018 

174. ↑ Duan, Xiaopin; Chan, Christina; Lin, Wenbin (2019). 'Durch Nanopartikel vermittelter immunogener Zelltod ermöglicht und verstärkt die Immuntherapie gegen Krebs' . Angewandte Chemie (in German). 131 (3): 680-691. ISSN  1521-3757 . doi : 10.1002 / ange.201804882 

175. ↑ Rocha, Flavia Gomes de Goes (July 28, 2010). «Evaluation of the bicistronic retroviral vector Endostatin and interleukin-2 encoder For use in anti-tumor gene therapy» 

176. Ang Fang, Wenfeng; Chen, Ying; Sheng, Jin; Zhou, Ting; Zhang, Yaxiong; Zhan, Jianhua; Liu, Lin; Huang, Jiaxing; Peng, Peijian (2017). "Association between PD-L1 Expression on Tumor-Infiltrating Lymphocytes and Overall Survival in Patients with Gastric Cancer" . Journal of Cancer. 8 (9): 1579–1585. ISSN  1837-9664 . doi : 10.7150 / jca.18729 

177. ↑ Buchbinder, Elizabeth I .; Desai, Anupam (2016). CTLA-4 and PD-1 Pathways . American Journal of Clinical Oncology. 39 (1): 98–106. ISSN  0277-3732 . doi : 10.1097 / COC.0000000000000239 

178. Genética "Gene Cancer Therapy: Studies Show Good Remission Rates But Strong Side Effects ." www.abrale.org.br. Retrieved July 6, 2019 

179. ↑ «Combination of treatments controls cancer without causing negative effects» . Jornal.usp.br. Retrieved July 6, 2019 

180. ↑ Cancer therapy , February 10, 2017, consulted July 3, 2019 

181. ↑ Economopoulou, Panagiota; Perisanidis, Christos; Giotakis, Evaggelos I .; Psyrri, Amanda (2016). «The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications» . Annals of Translational Medicine. 4 (9). ISSN  2305-5839 . PMC  4876265  . PMID  27275486 . doi : 10.21037 / atm.2016.03.34 

182. ↑ "Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Human Papillomavirus-Associated Cancers - Full Text View - ClinicalTrials.gov» (in English) 

183. ↑ Economopoulou, Panagiota; Perisanidis, Christos; Giotakis, Evaggelos I .; Psyrri, Amanda (2016). «The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications» . Annals of Translational Medicine. 4 (9). ISSN  2305-5839 . PMC  4876265  . PMID  27275486 . doi : 10.21037 / atm.2016.03.34 

184. ↑ Sanford, John C. (1990). Biolistic plant transformation . Physiologia Plantarum (in English). 79 (1): 206–209. ISSN  1399-3054 . doi : 10.1111 / j.1399-3054.1990.tb05888.x 

185. ↑ Montañez, George; Marks II, Robert J .; Fernandez, Jorge; Sanford, John C. (April 10, 2013). «Multiple Overlapping Genetic Codes Profoundly Reduce the Probability of Beneficial Mutation» . SCIENTIFIC WORLD: 139–167. ISBN  9789814508711 . doi : 10.1142 / 9789814508728_0006 

186. ↑ Nelson, Chase W .; Sanford, John C. (April 10, 2013). «Computational Evolution Experiments Reveal the Net Loss of Genetic Information Despite Selection» . SCIENTIFIC WORLD: 338–368. ISBN  9789814508711 . doi : 10.1142 / 9789814508728_0014 

187. Is Peischl, Stephan; Dupanloup, Isabelle; Foucal, Adrien; Jomphe, Michèle; Bruat, Vanessa; Grenier, Jean-Christophe; Gouy, Alexandre; Gilbert, KJ; Gbeha, Elias (2018). «Relaxed Selection During a Recent Human Expansion» . Genetics 208 (2): 763–777. ISSN  1943-2631 . PMC  5788536  . PMID  29187508 . doi : 10.1534 / genetics.117.300551 

188. ↑ Shepard, Samuel S .; Nelson, Chase W .; Gryder, Berkley E. (2013). Biosemiotic Entropy of the Genome: Mutations and Epigenetic Imbalances Resulting in Cancer . Entropy. 15 (1): 234–261. doi : 10.3390 / e15010234 

189. Fl Hayflick, Leonard (December 12, 2007). "Entropy Explains Aging, Genetic Determinism Explains Longevity, and Undefined Terminology Explains Misunderstanding Both ." PLoS Genetics. 3 (12). ISSN  1553-7390 . PMC  2134939  . PMID  18085826 . doi : 10.1371 / journal.pgen.0030220 

190. J Ujvari, Beata; Klaassen, Marcel; Raven, Nynke; Russell, Tracey; Vittecoq, Marion; Hamede, Rodrigo; Thomas, Frederic; Madsen, Thomas (March 28, 2018). Genetic diversity, inbreeding and cancer . Proc. R. Soc. B (in English). 285 (1875). 20172589 pages. ISSN  0962-8452 . PMID  29563261 . doi : 10.1098 / rspb.2017.2589 

191. ↑ Fu, Wenqing; O'Connor, Timothy D .; Jun, Goo; Kang, Hyun Min; Abecasis, Goncalo; Leal, Suzanne M .; Gabriel, Stacey; Rieder, Mark J .; Altshuler, David (January 10, 2013). Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants . Nature 493 (7431): 216-220. ISSN  1476-4687 . PMC  3676746  . PMID  23201682 . doi : 10.1038 / nature11690 

192. Is Peischl, S .; Dupanloup, I .; Kirkpatrick, M .; Excoffier, L. (2013). «On the accumulation of deleterious mutations during range expansions» . Molecular Ecology. 22 (24): 5972-5982. ISSN  1365-294X . doi : 10.1111 / mec.12524 

193. He Behe, Michael J .; Snoke, David W. (October 1, 2004). «Simulating evolution by gene duplication of protein features that require multiple amino acid residues» . Protein Science: The Publication of the Protein Society. 13 (10): 2651–2664. ISSN  0961-8368 . PMC  2286568  . PMID  15340163 . doi : 10.1110 / ps.04802904 

194. He Behe, Michael J. (December 1, 2010). «Experimental evolution, loss-of-function mutations, and" the first rule of adaptive evolution "» . The Quarterly Review of Biology. 85 (4): 419–445. ISSN  0033-5770 . PMID  21243963 

195. ↑ Kuhn, Joseph A. (January 1, 2012). Dissecting Darwinism . Proceedings (Baylor University. Medical Center). 25 (1): 41–47. ISSN  0899-8280 . PMC  3246854  . PMID  22275784 

196. ↑ Lonnig WE; Saedler, H. (December 31, 1997). "Plant transposons: contributors to evolution?" . Gene. 205 (1-2): 245–253. ISSN  0378-1119 . PMID  9461398 

197. ↑ Lonnig, Wolf-Ekkehard (2004). «Http://www.sensortime.com/loennig-dygmosoic-e.htm» . http://ressign.com/review_books_04/b_04/b04.htm37/661 (2) ed. Kerala, India: Max-Planck-Institute for Plant Breeding Research, Carl-von-Linné-weg 10. 50829 Cologne, Germany. ISBN  81-7736-231-3 . Consulted on June 7, 2019   External link at |titulo=( help )

198. Eld Sheldon, Robert B .; Hoover, Richard B. (August 28, 2008). Cosmological evolution: spatial relativity and the speed of life . 7097 . doi : 10.1117 / 12.802195.short 

199. ↑ Denton, Michael (1986). Evolution: A theory in crisis (PDF). [Sl]: Adler & Adler. pp. 368 pages. ISBN  091756152X . Consulted on November 18, 2018 

200. On Denton, Michael J .; Marshall, Craig J .; Legge, Michael (December 7, 2002). «The protein folds as platonic forms: new support for the pre-Darwinian conception of evolution by natural law» . Journal of Theoretical Biology. 219 (3): 325–342. ISSN  0022-5193 . PMID  12419661 

201. U Zuñiga, Jorge G. (2018). «The evolution of the complete biochemical systems» . revista.ucr.ac.cr (in spanish). VOL. 57 NUMBER 147 (2018): PHILOSOPHY MAGAZINE. Consulted on November 18, 2018 

202. ↑ Washington., Biological Society of; Washington., Biological Society of; Washington., Biological Society of; Institution., Smithsonian; Institution., Smithsonian (2004). Proceedings of the Biological Society of Washington . v. 117 (2004). ISSN  0006-324X 

203. ↑ Weber, Bruce H. (May 31, 2013). Towards a General Biology: Emergence of Life and Information from the Perspective of Complex Systems Dynamics . SCIENTIFIC WORLD. Biological Information. ISBN  9789814508711 . doi : 10.1142 / 9789814508728_0024 

204. ↑ 1950-, Marks, Robert J., II (Robert Jackson), ([2013]). Biological information - new perspectives: proceedings of a symposium held May 31, 2011 through June 3, 2011 at Cornell University . [Hackensack] New Jersey: World Scientific. ISBN  9789814508728 . OCLC  847526859 

205. ↑ «Emergence of Life and Biological Selection from the Perspective of Complex Systems Dynamics | Request PDF » . ResearchGate. Consulted on November 18, 2018 

206. ↑ Grubesich, Fabio. "THE ORIGINS OF ORDER Self-Organization and Selection in Evolution" (in English) 

207. ↑ Meester, Ronald (September 1, 2009). Simulation of biological evolution and the NFL theorems . Biology & Philosophy. 24 (4): 461–472. ISSN  0169-3867 . PMC  2837227  . PMID  20234823 . doi : 10.1007 / s10539-008-9134-x . Consulted on November 18, 2018 

208. ↑ Ax, Douglas D .; Dixon, Brendan W .; Lu, Philip (June 4, 2008). «Stylus: A System for Evolutionary Experimentation Based on a Protein / Proteome Model with Non-Arbitrary Functional Constraints» . PLoS ONE. 3 (6): e2246. ISSN  1932-6203 . PMC  2405935  . PMID  18523658. doi : 10.1371 / journal.pone.0002246 

209. ↑ «Model and Laboratory Demonstrations That Evolutionary Optimization Works Well Only If Preceded by Invention - Selection Itself Is Not Inventive». BIO-Complexity. 2015 (0). December 22, 2015. ISSN  2151-7444 

210. Ab Crabtree, Gerald R. (January 1, 2013). «Our fragile intellect. Part I » . Trends in Genetics. 29 (1): 1–3. ISSN  0168-9525 . PMID  23153596 . doi : 10.1016 / j.tig.2012.10.002  ! CS1 maintenance: Unrecognized language ( link )