Диета против рака

Голландский врач Корнелиус Моэрман (умер в 1988 г. в 95 лет) разработал эффективный метод лечения рака (диету), признанный Минздравом страны. Диета основана на овощах, фруктах и зерновых.

Опухоль замораживают при -40

В клинике урологии МГУ им.Сеченова опухоль замораживают аргоном при -40, затем размораживают гелием. Онкоклетки гибнут от перепада температур

Раннее старение зависит от ДНК

Ранний запуск часов старения во многом зависит от такой химической модификации ДНК, как метилирование, к такому выводу пришли ученые из университета Эдинбурга

Беспроводной протез восстановит зрение в тяжелых случаях

Ученые разработали протез сетчатки, используя нанопровода и беспроводные электронные системы.

В России слепому установили бионический глаз

Впервые слепому установили комплекс из очков с видеокамерой, блоком обработки сигнала и электростимулятором

В НИИ Робототехники и технической кибернетики (РФ) создали устройство очистки крови от раковых клеток

Очистка от онкоклеток происходит за счет искусственной циркуляции крови, которая нагревается до 43 градусов. В кровоток добавляют химиопрепараты

 

Стрессы провоцируют метастазирование

Стресс вызывает рост метастазов

Доказано научно, что стрессы имеют прямое влияние на развитие раковых метастазов. Ученые изучали влияние стрессовых механизмов- различных гормонов (адреналина, норадреналина, кортизола) на метастазирование.

А это, по мнению кандидата медицинских наук Сергея Кацалапа, может быть подсказкой, почему временной промежуток между 2 и 4 стадиями рака нередко быстро сокращается.

И у больных со 2 стадией за несколько месяцев неожиданно появляются метастазы, несмотря на проведенное лечение.

По мнению доктора, которое он высказал в группе Facebook, «хирургическое лечение усиливает имеющийся уже стресс у пациента с раком, это и есть наиболее вероятная причина быстрого прогрессирования заболевания от стадии 2 до стадии 4.

Вероятно, одной из важнейших задач в лечении онкологических заболеваний является снижение уровня стресса пациента».

Ниже приводим часть вышеупомянутой научной работы, изданной US National Library of Medicine National Institutes of Health.

 

«Impact of stress on cancer metastasis»

Myrthala Moreno-Smith, Susan K Lutgendorf, and Anil K Sood

Abstract

The influence of psychosocial factors on the development and progression of cancer has been a longstanding hypothesis since ancient times. In fact, epidemiological and clinical studies over the past 30 years have provided strong evidence for links between chronic stress, depression and social isolation and cancer progression.

By contrast, there is only limited evidence for the role of these behavioral factors in cancer initiation. Recent cellular and molecular studies have identified specific signaling pathways that impact cancer growth and metastasis. This article provides an overview of the relationship between psychosocial factors, specifically chronic stress, and cancer progression.

Keywords: cancer, catecholamine, metastasis, signaling pathway, stress

The major cause of death from cancer is metastasis that is resistant to conventional therapy . Primary neoplasms are biologically heterogeneous and the process of metastasis consists of a series of sequential and selective steps that few cells can successfully complete. The outcome of cancer metastasis depends on multiple interactions between metastatic cells and homeostatic mechanisms that are unique to a given organ micro environment .

Therefore, the treatment of metastasis should be targeted not only against cancer cells, but also against the host factors that contribute to and support the progressive growth and survival of metastatic cancer cells. Clinical and epidemiological studies over the last 30 years have identified psychosocial factors including stress, chronic depression and lack of social support as risk factors for cancer progression .

Whereas evidence for the role of psychosocial factors in cancer initiation is limited and some-what contradictory, support is stronger for links between psychological factors such as stress, depression and social isolation and disease progression . Chronicity of negative affect, as manifested by depressed mood or hopelessness, appears to have stronger relationships with outcomes than do stressful events, suggesting that sustained activation of negative affective pathways may provide the strongest links to cancer progression.

Moderators of stress, such as social support, have been frequently studied with respect to cancer outcomes. Social support refers to an individual’s perceived satisfaction with social relationships and is thought to play a major role in buffering psychological and biological stress responses .

Several studies have linked high levels of social support to improved clinical outcomes in cancer patients. For example, in breast cancer patients, social support has been related to longer survival in several large-scale studies, although negative findings were noted in some studies . Collectively, emerging evidence has shown stress and specific psychosocial factors to be associated with key elements of the metastatic cascade in both animal and human models. In this article, we review the biological processes affected by chronic stress and the related pathways and discuss implications for cancer management.

Effects of stress on cancer metastasis

Metastasis is a complex process that requires several steps to be successful, including angiogenesis, proliferation, invasion, embolization and evasion of immune system surveillance. Growth of a tumor beyond 1 mm in size requires vascularization of the tumor, which also provides a method for dissemination of metastatic cells.

Moreover, a tumor cell must gain the ability to break off from the main tumor, invade through the basement membrane and embolize into the bloodstream. The cell then arrests in capillary beds and must be able to extravasate from the bloodstream and adhere to parenchymal tissues. The cell must also evade immune system surveillance.

Once settled, the metastatic cell interacts with its new microenvironment to grow and ultimately develop its own blood supply. Cells that fail to acquire any one of these characteristics cannot metastasize and the cascade is aborted. Increasing evidence shows that the stress response can affect many parts of this cascade. Here, we examine cellular and molecular findings relating stress to processes implicated in cancer progression and metastasis.

Main steps in the formation of a metastasis

The process of cancer metastasis consists of sequential selective steps. The outcome of each step is influenced by the interaction of metastatic cells with homeostatic factors. Failure of a tumor cell to complete any step effectively terminates the process. Therefore, the formation of clinically relevant metastases represents the survival and growth of unique subpopulations of cells that pre-exist in primary tumors.

(A) Cellular transformation and tumor growth. (B) Extensive vascularization must occur if a tumor mass exceeds 1–2 mm in diameter. The synthesis and secretion of angiogenic factors establish a capillary network from the surrounding host tissue. (C) Migration and invasion of the host stroma by some tumor cells occurs by several parallel mechanisms. Lymphatic channels offer very little resistance to penetration by tumor cells and provide the most common route for tumor cell entry into the circulation.

(D) Next, detachment and embolization of single tumor cells or aggregates occurs; most circulating tumor cells are rapidly destroyed. (E) After cancer cells have survived the circulation, they become trapped in the capillary beds of distant organs by adhering either to capillary endothelial cells or to the subendothelial basement membrane. (F) Extravasation then occurs, probably by mechanisms similar to those that operate during invasion. (G) Proliferation within the organ parenchyma completes the metastatic process. To continue growing, the micrometastasis must develop a vascular network and evade destruction by host defenses. The cells can then invade blood vessels, enter the circulation and produce additional metastases.

Proliferation & growth of primary tumors & metastases

Tumor growth at the primary site initially depends on nutrient and oxygen diffusion. Subsequently, at metastatic sites, signals from autocrine, paracrine and/or endocrine pathways influence tumor cell proliferation, with growth dependent on the net balance of positive and negative signals.

There are limited data regarding the direct effects of stress hormones on cell proliferation. Most data suggest that catecholamines suppress proliferation of normal cells such as keratinocytes, which may contribute to impaired wound healing in the context of stress. The effects of stress-related hormones on cancer cell proliferation may depend on the type of substance and tumor type. In mammary tumors, activation of ADRBs has been related to accelerated tumor growth.

The cAMP responsive element-binding (CREB) protein is an important transcription factor activated by multiple signal transduction pathways in response to external stimuli, including stress hormones. Several studies have revealed a role for the CREB family of proteins in tumor cell proliferation, migration, angiogenesis and inhibition of apoptosis. However, in other models, catecholamines appear to inhibit tumor cell proliferation, a process that may be mediated by ADRAs.

Pifl and colleagues found that NE inhibited neuroblastoma cell growth, primarily in cells expressing the DA transporter. In cells with DA uptake, the share of G0/G1 populations of cells was significantly increased after treatment with NE. In prostate carcinoma, treatment with agents that induce cAMP, such as E, isoproterenol, forskolin and dibutyryl cAMP, result in acquisition of neuroendocrine characteristics by epithelial prostate cancer cells.

The neuroendocrine characteristics were manifested by dense core granules in the cytoplasm, the extension of neuron-like processes, loss of mitogenic activity and expression of multiple neuroendocrine markers. The presence of these neuroendocrine cells has been linked to poor prognosis in prostate cancer patients. Interestingly, the neuroendocrine cells have minimal proliferative activity, but these cells provide paracrine stimuli for the proliferation of surrounding cancer cells. Among epithelial tumors, some decrease in proliferation may be reflective of a more invasive phenotype.

Effects of GC hormones on cancer cell proliferation have also been reported. Zhao and colleagues observed that cortisol and its metabolite cortisone stimulated the growth of prostate cancer cells in the absence of androgens and increased the secretion of prostate-specific antigen.

These cells had a mutated androgen receptor, indicating that cortisol promoted androgen-independent growth of prostate cancer cells. Simon and coworkers examined the effects of several steroid hormones on human mammary carcinoma cells and found that physiological concentrations of GCs enhanced proliferation by nearly twofold . The role of GC hormones in the context of other neuroendocrine hormones remains to be studied with regard to its effects on proliferation.

Stress effects on the immune response

It is known that the CNS, the endocrine system and the immune system interact with each other, and thus changes in any one system may have downstream effects in the other systems. The CNS modulates immunity both through release of GCs via the HPA axis as well as via the release of catecholamines through the autonomic nervous system.

Several factors involved in the stress response are involved in activating or blunting the immune response, which may play a role in allowing tumor cells to escape detection and immune cell elimination. In contrast to chronic/long-term stress that suppresses/dysreg ulates immune function, an acute/short-term fight or fight stress can enhance innate immunity.

A recent report has described that short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma. Therefore, the physiological fight or fight response and its adjuvant-like immunoenhancing effects may provide a novel mechanism to promote or increase immune system-mediated tumor detection/elimination.

T helper (Th) cells are crucial for the development of an immune response by activating antigen-specific effector cells and recruiting cells of the innate immune system, such as macrophages and mast cells. There are two predominant Th-cell subtypes: Th1 and Th2. While Th1 cells directly kill tumor cells via release of cytokines that activate death receptors on the tumor cell surface, Th2 cells favor a predominantly humoral response. Th2 immunity may be enhanced by stress hormones (catecholamines and GCs) increasing a shift from predominantly Th1 to Th2 cells. This shift is thought to better enable tumor cells to evade immune surveillance.

T helper 17 cells play an active role in inflammatory and autoimmune diseases; however, recent studies suggest a potential impact of Th17 on tumors. Kryczek and colleagues have shown that the levels of Th17 cells were significantly increased in peripheral blood, ascite fluid and tumor tissues in human ovarian, renal and pancreatic carcinomas. Similarly, the proportion of Th17 cells in peripheral blood of gastric cancer patients was significantly higher than in healthy donors (6.7 ± 3.7 vs 1.8 ± 1.1%; p < 0.01).

Moreover, patients with advanced disease had an even higher percentage of Th17 cells than patients with lower-stage disease or healthy controls. It is known that CD4+, CD25+, FoxP3+ and other additional regulatory T cells (Tregs) are elevated in cancers. Tregs play a crucial role in tumor immune pathogenesis and tumor immune therapeutic efficacy. Recent human cancer trials suggest that depleting Tregs may be clinically beneficial.

Conclusion

In modern lifestyle societies, chronic stress has been associated with the pathogenesis of many diseases, including cancer. Chronic stress results in the activation of specific signaling pathways in cancer cells and the tumor microenvironment, leading to tumor growth and progression. Elucidation of these pathways is essential for the development of novel approaches to block the deleterious effects of stress biology on cancer growth and metastasis.

Future perspective

Contemporary lifestyles and the environment of modern societies appear to be particularly inducive of stress-related disorders. With respect to cancer pathogenesis, there is growing and compelling mechanistic evidence for biological and clinical implications of psychosocial and biobehavioral influences.

However, despite significant progress in the past decade, further research is needed in order to understand how stress hormones modulate the interplay between tumor and stromal cells in the tumor microenvironment, resulting in regulation of signaling pathways with important implications for cancer progression.

These studies may offer new alternatives for treatments based on behavioral and pharmacological approaches. β-blockers have been shown to block many of the deleterious effects of stress. While some clinical studies have demonstrated lower cancer incidence among patients treated with β-blockers, in others, the cancer risk was neutral. Other potential targets in the tumor microenvironment are STAT-3 and VEGF, since these factors are differentially increased in tumors.

Since stress mediators not only affect tumor growth but also many related physiological processes, it will be important to identify additional pathways that could alter the efficacy of chemo- or immuno-modulatory therapy. The role of environmental factors on cancer progression remains poorly defined.

Interestingly, a recent report described that an enriched environment in mice was able to decrease tumor growth and also to increase cancer remission. In this mouse model, hypothalamic brain-derived neurotrophic factor was selectively upregulated by the enriched environment, suggesting that genetic or environmental activation of this brain-derived neurotrophic factor–leptin axis may have therapeutic significance for cancer.

Similarly, the role of stress-related immuno-suppression in promoting tumor immune escape mechanisms has been poorly studied and represents an exciting new area of investigation. Finally, the complex interplay between biobehavioral pathways and socioeconomic and cultural stressors merits further study in diverse populations. As cancer therapy moves towards being more patient specific, it will be crucial to define the behavioral and/or pharmacological interventions that are most likely to benefit individual patients.

Executive summary

■ Collective evidence points to a prominent role for chronic stress in cancer growth and metastasis.

■ Sympathetic nervous system and hypothalamic–pituitary–adrenal axis activation, along with related hormones, have functionally and biologically significant impacts on the tumor microenvironment.

■ β-adrenergic receptor signaling pathways directly affect cancer cells. Stress hormones (e.g., norepinephrine and epinephrine) stimulate angiogenesis, cell migration and invasion, leading to increased tumor growth and progression.

■ Dopamine retards tumor growth by inhibiting angiogenesis.

■ Glucocorticoids inhibit chemotherapy-induced cancer cell apoptosis and promote cancer cell survival.

■ Integrated pharmacological and biobehavioral interventions are being developed to target neuroendocrine dynamics in the tumor microenvironment and create more successful cancer therapies.

 

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