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Mobilizing serum factors and immune cells through exercise to counteract age-related changes in cancer risk.
Hwang, JH, McGovern, J, Minett, GM, Della Gatta, PA, Roberts, L, Harris, JM, Thompson, EW, Parker, TJ, Peake, JM, Neubauer, O
Exercise immunology review. 2020;:80-99
Abstract
An increasing body of evidence suggests that age-related immune changes and chronic inflammation contribute to cancer development. Recognizing that exercise has protective effects against cancer, promotes immune function, and beneficially modulates inflammation with ageing, this review outlines the current evidence indicating an emerging role for exercise immunology in preventing and treating cancer in older adults. A specific focus is on data suggesting that muscle- derived cytokines (myokines) mediate anti-cancer effects through promoting immunosurveillance against tumourigenesis or inhibiting cancer cell viability. Previous studies suggested that the exercise-induced release of myokines and other endocrine factors into the blood increases the capacity of blood serum to inhibit cancer cell growth in vitro. However, little is known about whether this effect is influenced by ageing. Prostate cancer is the second most common cancer in men. We therefore examined the effects of serum collected before and after exercise from healthy young and older men on the metabolic activity of androgen-responsive LNCaP and androgen-unresponsive PC3 prostate cancer cells. Exercise-conditioned serum collected from the young group did not alter cell metabolic activity, whereas post-exercise serum (compared with pre-exercise serum) from the older men inhibited the metabolic activity of LNCaP cancer cells. Serum levels of candidate cancer-inhibitory myokines oncostatin M and osteonectin increased in both age groups following exercise. Serum testosterone increased only in the younger men postexercise, potentially attenuating inhibitory effects of myokines on the LNCaP cell viability. The data from our study and the evidence in this review suggest that mobilizing serum factors and immune cells may be a key mechanism of how exercise counteracts cancer in the older population.
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2.
Endogenous molecular-cellular hierarchical modeling of prostate carcinogenesis uncovers robust structure.
Zhu, X, Yuan, R, Hood, L, Ao, P
Progress in biophysics and molecular biology. 2015;(1):30-42
Abstract
We explored endogenous molecular-cellular network hypothesis for prostate cancer by constructing relevant endogenous interaction network model and analyzing its dynamical properties. Molecular regulations involved in cell proliferation, apoptosis, differentiation and metabolism are included in a hierarchical mathematical modeling scheme. This dynamical network organizes into multiple robust functional states, including physiological and pathological ones. Some states have characteristics of cancer: elevated metabolic and immune activities, high concentration of growth factors and different proliferative, apoptotic and adhesive behaviors. The molecular profile of calculated cancer state agrees with existing experiments. The modeling results have additional predictions which may be validated by further experiment: 1) Prostate supports both stem cell like and liver style proliferation; 2) While prostate supports multiple cell types, including basal, luminal and endocrine cell type differentiated from its stem cell, luminal cell is most likely to be transformed malignantly into androgen independent type cancer; 3) Retinoic acid pathway and C/EBPα are possible therapeutic targets.
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3.
[Genistein in chemoprevention and treatment].
Tarkowski, M, Kokocińska, M, Latocha, M
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2013;(199):54-7
Abstract
Genistein is a natural compound which occurs in Asian diet, rich in soy products. It has a wide spectrum of activity, expressed both in protecting cells from malignant transformation, reducing proliferation of tumor cells and stimulating apoptosis. In the other hand, genistein also prevents from some of the side effects manifesting in menopausal estrogen deficiency also being a good research object in this field. It has been shown, among others effect of genistein on: the level of free radicals and reactive oxygen species in the body, the metabolism of carcinogenic factors, cell cycle progression, initiation of apoptosis, angiogenesis, inflammatory processes and immune response. To achieve the desired therapeutic effect it is crucial to determine genistein dose titration in order to obtain an appropriate concentration in the tissues of phytohormone and duration of therapy.
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4.
Targeted therapeutic approaches for hormone-refractory prostate cancer.
Stavridi, F, Karapanagiotou, EM, Syrigos, KN
Cancer treatment reviews. 2010;(2):122-30
Abstract
Prostate cancer is one of the leading causes of cancer related death in men, and remains incurable in the metastatic setting. Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state due to cumulative genetic alterations in tumour cells or the microenvironment. Docetaxel represents the first chemotherapeutic agent with a small survival benefit for metastatic hormone-refractory prostate cancer (HRPC). In an attempt to improve survival benefit, several novel drugs targeting specific pathways involved in cell signaling, proliferation, angiogenesis, apoptosis and immune modulation are currently under investigation either as single agents or in combination with cytotoxic drugs. Clinical trials evaluate the inhibition of prostate cancer cells growth by targeting the nuclear receptor of vitamin D alongside cytotoxic therapy. Angiogenesis inhibitors as well as epidermal growth factor receptor blockage are also under clinical investigation in several combinations. Immunomodulatory agents and autologous dendritic cells or allogenic whole cell vaccines have progressed up to phase III trials. New drugs targeting bone microenvironment or apoptotic and proliferation pathways may enhance antitumour activity of chemotherapy in HRCP. Given the complexity of mechanisms underlying prostate cancer progression, future therapeutic strategies should rely on multidisciplinary approaches, thus exploiting newer molecular targets in concert with immunotherapy and cytotoxic chemotherapy. Here, we review the latest clinical evidence regarding the use of novel agents in HRPC.
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5.
Prostate cancer prevention by short-term anti-androgens: the rationale behind design of pilot studies.
Oliver, T, Lorinez, A, Cuzick, J
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer. 2009;:195-205
Abstract
This paper sets out to review evidence that low-grade prostate inflammation is a precursor of prostate cancer development and the mechanisms by which it may account for the more than 50 years natural history from first infection to cancer. Though as yet there is no clear-cut specific associated infection, there is clear evidence that some sexually acquired infections damage the prostate and increase serum PSA with slow recovery back to normal. The demonstration that low-level solar exposure is protective provides a possible mechanism due to vitamin D's known benefit through action to boost macrophage-mediated immune surveillance. This observation and data demonstrating that non-steroidal anti-inflammatory drugs (NSAIDs) protect against prostate cancer provide the justification for trials of these two agents combined with short course intermittent anti-androgen therapy in populations at high risk of prostate cancer.
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6.
[A critical assessment of phytotherapy for prostate cancer].
Perabo, FG, von Löw, EC, Siener, R, Ellinger, J, Müller, SC, Bastian, PJ
Der Urologe. Ausg. A. 2009;(3):270-1, 274-83
Abstract
Prostate cancer patients increasingly use complementary and alternative medicines to support the body's immune system in addition to conventional treatment to minimize morbidity associated with conventional treatment, to enhance the quality of life, and ultimately in the hope to cure cancer when conventional treatment fails. As there is a large variety of phytomedicines promoted as potential treatment for prostate cancer, the aim of this review was to differentiate between preventive and therapeutic approaches and evaluate which phytochemicals might be suited for therapy of prostate cancer. Therefore, preclinical in vitro and in vivo data as well as clinical trials with phytosubstances such as genistein, lycopene, epigallocatechin gallate, resveratrol, and mistletoe were assessed. The presented data show that at present there is no clinical evidence that phytochemicals might have a therapeutic use in prostate cancer in relation to reduction of tumor progression or improved survival. The question about an improved immune function or quality of life remains open. Potentially the use of phytochemicals could play a role in a preventive setting.
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7.
Zinc for prostate disease and other conditions: a little evidence, a lot of hype, and a significant potential problem.
Moyad, MA
Urologic nursing. 2004;(1):49-52
Abstract
Dietary and supplemental zinc, especially in excess, has received much attention in numerous alternative medicine resources. There is a small amount of medical evidence that zinc may alleviate some mostly rare medical conditions (such as Wilson's disease). However, in prostate conditions, such as BPH, large concentrations of zinc are found in the prostate gland. Excess intake of zinc, especially with individual supplements, has the potential to encourage the growth of prostate conditions from BPH to cancer. In fact, one large study found a significantly higher risk of advanced prostate cancer in men consuming large intakes of these supplements. Large doses of zinc can inhibit the benefits of bisphosphonate drugs, increase testosterone level, increase cholesterol, reduce levels of "good cholesterol" or HDL, and can promote immune dysfunction. More research is needed in this area, but in the meantime, the time seems more than ripe to discourage or immediately discontinue the intake of larger concentrations of zinc for most individuals until adequate research resolves this controversial issue.
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8.
Is obesity a risk factor for prostate cancer, and does it even matter? A hypothesis and different perspective.
Moyad, MA
Urology. 2002;(4 Suppl 1):41-50
Abstract
Measurement of obesity is not as simple as its definition. Currently, several methods of measuring obesity are used in clinical studies. Skinfold thickness, crude weight, lean body mass (LBM), body mass index (BMI), and waist-to-hip ratio (WHR) are some of the more popular methods, but each contains its inherent strengths and flaws. In general, the results of the largest studies on prostate cancer and obesity have not been conclusive. One of the largest studies found an inverse relation to prostate cancer in the youngest age groups. The age and duration of obesity or any rapid changes in weight gain, along with other unhealthy exposures, may have some relation to prostate cancer incidence and mortality. Early intrinsic or extrinsic exposure to estrogen or estrogenlike compounds may provide a protective effect. The timing and duration of a higher estrogen and/or lower testosterone exposure may have a beneficial or detrimental impact on the prognosis of an established prostate tumor. Negative exposures over time such as low levels of sex hormone-binding globulin (SHBG), a greater exposure to growth factors, elevated insulin levels, greater sympathetic activity, higher cholesterol levels, immune system dysfunction, inadequate diets, smoking status, and other factors may be associated with an increased risk of prostate cancer and other diseases. Obesity may also be associated with other cancers for similar and different reasons. For example, morbidity and mortality from postmenopausal breast cancer, colon, kidney, and other cancers are potentially associated with obesity. Other comorbidities such as cataracts, coronary heart disease, diabetes, erectile dysfunction, hypertension, and others are also associated with obesity. The 2 largest prospective studies on BMI and overall mortality have also demonstrated the substantial negative impact of excess weight on society. Prostate cancer risk and obesity need further research to establish if a true association exists, but at this time, does it really matter? Overall, the profound adverse effect of being obese on general health is dramatic, and this is what clinicians and patients need to remember.