Cellular Mechanism Of Action
While ADT was being developed clinically for use in patients with prostate cancer, others were investigating the mechanism by which suppression of androgens improves disease control. There was conjecture about the clinical benefit of ADT being a result of cytoreduction or debulking of disease prior to radiation therapy, while others surmised a synergy between ADT and radiation therapy at the cellular level.
In men, the majority of circulating testosterone is produced by leydig cells in the testes following stimulatory signals produced by the pituitary, LH and FSH. The remainder of testosterone is produced by the adrenal gland, derived from circulating steroid hormone precursors . Once produced, testosterone is transported protein-bound to the target cell where it is metabolized intracellularly by 5-reductase to the super-active metabolite, dihydrotestosterone . DHT binds its cognate receptor, the AR, which subsequently dimerizes and is translocates into the nucleus where it conducts its DNA-directed functions, including transcriptional regulation of target genes .
The critical importance of AR-signaling for prostate cancer growth is further highlighted in the context of castrate resistant prostate cancer, prostate cancer that grows despite androgen levels being suppressed to castrate levels. In these patients, exogenous selection pressure stimulates resistance to ADT through multiple pathways.
Immune Checkpoint Inhibitor Therapy
Immune checkpoint inhibitor therapy has shown clinical benefit in a number of solid tumors , but unfortunately these observations have not been replicated in patients with mCRPC . Factors such as low tumor mutational burden , loss of tumor suppressors , low prevalence of DDR genetic defects, and silencing of major histocompatibility complex-1 expression may all contribute to mCRPCs relative lack of response to ICI therapy . Two early phase-3 studies of the anti-cytotoxic T lymphocyte-associated protein-4 antibody ipilimumab both failed to meet their primary endpoint of improved OS however, recent studies investigating the efficacy of the programmed death-1 inhibitor pembrolizumab have shown promising responses in patients with mCRPC. In a single-site cohort of 48 patients with mCRPC treated with pembrolizumab, 17% had50% PSA decline with 8% having90% PSA decline as best response . These exceptional responders were found to have molecular changes , TMB-high, and mutation in LRP1b), which predispose to anti-PD-1 responses.
Completed and ongoing clinical trials investigating different ICI agents in patients with mPC have been summarized . Although monotherapy ICIs have not been successful, there are many ongoing trials to combine ICIs with standard chemotherapies or targeted therapies in order to improve clinical outcomes.
Table 3 Ongoing clinical trials investigating the administration of immune checkpoint inhibitor agents in patients with mPC
Gene Depletion Of Mdm4 Reduces Prostate Cancer Cell Viability
To determine how prostate cancer cells would respond to precision tools that target MDM4 at the gene level, we used CRISPR-Cas9 and two sgRNAs targeting distinct sequences of MDM4 in prostate cancer cell lines. Compared with a negative-control sgRNA , viability of 4 different prostate cancer cells was reduced by about 5080% in response to MDM4 depletion after 12 days in culture. Altogether, we concluded that MDM4 regulates enzalutamide resistance, and that targeting MDM4 through either chemical or genetic approaches significantly attenuated the viability of prostate cancer cell lines. Our observations indicate that antagonizing MDM4 in metastatic CRPCs that harbour wild-type p53 is an attractive precision strategy. MDM4 antibodies and were used together for immunoblotting experiments done in Extended Data Fig. .
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Chief Executive Officer Director
Mr. McGarrity has more than 25 years of experience in the healthcare industry with a unique combination of device, diagnostics and biotechnology experience. Michael was most recently the CEO of Sterilis Medical. Prior to Sterilis Michael was the CEO of Nanosphere , a nanotechnology-based molecular diagnostics company, where he engineered an operational and strategic turnaround that resulted in its successful sale to Luminex in 2016. Prior to Nanosphere, McGarrity spent 13 years at Stryker Corporation . McGarrity served in leadership roles in sales and marketing and led Stryker into new growth markets such as post-operative pain management, surgical fluid waste management and interventional pain management. He also had executive general management responsibility for a newly created business unit focused on interventional spine pain management. Michael received a Bachelor of Arts degree from the University of Notre Dame and began his career in commercial banking.
Better Togethersupporting Your Prostate Completely
While these two powerful prostate formulas offer significant long-term benefits on their own, research shows they work better when used together. ProstaCaid is shown to work synergistically with PectaSol-C, resulting in up to 40% greater benefits for prostate cellular health when the two are used together, compared to either product alone.*
Achievingand maintaining optimal prostate health doesnt have to be complicated. At ecoNugenics, its our mission to deliver the most effective, research-based formulas and natural health solutionslike ProstaCaid and PectaSol that make a difference in how you feel, especially as you age. Prioritize your total-body wellness with complete prostate support.
Eliaz, I, et al.Altern Ther Health Med.2018 Sep 24:26-32. InformedHealth.org . Cologne, Germany: Institute for Quality and Efficiency in Health Care 2006-. How does the prostate work? 2011 Feb 15 .Available from: https://www.ncbi.nlm.nih.gov/books/NBK279291/
Jiang J, Eliaz I, Sliva D. Integr Cancer Ther. 2013 Mar 12:145-52.
Keizman D, Frenkel M, Peer A,et al. Journal of Clinical Oncology.201937:15_suppl,e16609-e16609/
Swiner C. What is the prostate? Whats normal? Web MD. Nov 18, 2020. Accessed May 24, 2021. https://www.webmd.com/men/prostate-enlargement-bph/what-is-the-prostate
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Ginger Phytochemicals Inhibit Prostate Cancer Cell Proliferation
We have previously shown that GE is non-toxic and inhibits prostate cancer growth both in vitro and in vivo. Since the major bioactive constituents of ginger are gingerols and shogaols, the antiproliferative activity of GE could be attributed to these components of ginger extract, viz., 6G, 8G, 10G and 6S. Thus, we first determined the half-maximal growth inhibitory concentration for GE and its phytochemicals in prostate cancer, PC-3 cells. To this end, we used an in vitro cell proliferation assay, MTT, to quantify the percent survival of PC-3 cells in the presence of test agents. The IC50 values obtained were 75 M for 6G, 10 M for 8G, 50 M for 10G, 4 M for 6S , and 250 g/ml for GE, . The carbon chain length of ginger phytochemicals has been reported to play a role in the differential potencies of the gingerols and shogaols . On similar lines, the results observed in our study showed a variability of IC50s in the context of prostate cancer cells. In addition, our data suggested a significant difference in the IC50 values of ginger constituents compared to whole ginger extract. As evident from , the constituent ginger phytochemicals were more potent than GE.
Clinical Synergy Mens Essential Plus 180 Caps
$41.95
Statements regarding dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease or health condition.
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- Over 46 Potent Essential Ingredients: EcoNnugenics Mens Longevity Essentials Plus is a potent multivitamin and multimineral supplement packed with essential vitamins, minerals, herbs and antioxidants for daily wellness for men of all ages
- Superior Proprietary Blend: Our formulas proprietary blends include Vitamins A, B6, B12, C, D3 and E, Thiamin, Calcium, Biotin, Niacin, Riboflavin, Folic Acid, Iodine, Magnesium, Zinc, Selenium, Copper, Chromium, Molybdenum, Potassium, L-Taurine & more
- Promotes Daily Mens Health: This dietary supplement contains an advanced multivitamin complex to provide men with extra support for liver, prostate, metabolic, endocrine, cardiovascular, vitality and immune health*
- Natural, Hypoallergenic, Non-GMO, Vegan Safe: This formula is prepared with the highest quality herbal ingredients, under conditions that meet or exceed Good Manufacturing Practices . Natural, hypoallergenic and vegan-friendly
- Professionally Formulated by Dr. Isaac Eliaz: Mens Longevity Essentials Plus is professionally formulated in the USA by a leading authority of integrative medicine & cellular health, Dr. Isaac Eliaz M.D., L.Ac., founder of ecoNugenics.
Safety Information
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Tumour Blood Flow For Prediction Of Pca Aggressiveness
The coherency between quantitative TBF and PCa aggressiveness is being established, and the present results are in line with our previous publications . However, the potential clinical role of quantitative TBF is undetermined in PCa management. The results of TBF measurement with Rb complements other studies using quantitative pharmacokinetic analysis of the dynamic contrast-enhanced series of MRI, which found an improvement in the PPV of mpMRI for primary local staging of PCa . Meanwhile, the studies using the simpler qualitative analysis of the dynamic contrast-enhanced series generally report more limited additional value of the Gadolinium contrast examination . Hence, there could be an unexploited potential in the quantitative pharmacokinetic analysis of prostate dynamic contrast-enhanced MRI at selecting which patients to biopsy, as absolute quantification of perfusion with DCE MRI might provide comparable information to perfusion PET. In PET studies on other cancers though, low blood flowhigh metabolism mismatch, which is essentially a sign of hypoxia, was found to be the best predictor of tumour grade, treatment response, and/or survival .
Clinical Synergy Complete Prostate Health
CHAKRA ACTIVATION CHART
Suggested Use:
Note: For regular prostate support, one should take this product for 3 months to see full benefits. For those with a serious prostate condition, it is highly recommended to use along with Clinical Synergy Pecta-Sol. Together they have shown clinically to improve severe prostate conditions by 79% over 6 months .
Clinical Synergy® Complete Prostate Health is a comprehensive formula providing 33 beneficial ingredients including highly prized botanical compounds, botanically enhanced mycelium from organically grown medicinal mushrooms, vitamins, minerals and specialty nutrients. These standardized botanical extracts provide optimal concentrations of active ingredients.
This proprietary blend is clinically shown to promote healthy urinary flow in men. It targets hormone balance, liver, and immune defense along with prostate cellular health for complete support.*
- Supports Prostate Cell Health*
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- Helps Balance Hormones*
Clinical Synergy® Complete Prostate Health is developed by renowned clinician, author and researcher, Isaac Eliaz, MD, MS, LAc, who has formulated multi-targeted products and protocols which are recommended worldwide as effective, research-based solutions for today’s most critical health concerns.
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Localized Intermediate Risk Prostate Cancer
Proven effective for metastatic and high-risk, locally advanced prostate cancer, the use of ADT in combination with definitive radiation therapy was extended to patients with intermediate risk disease. Because survival in these patients is years to decades, short-term ADT was evaluated in these patients, rather than long-term ADT, in order to optimize the risk-benefit ratio by minimizing unwanted acute and chronic toxicities.
The role of ADT combined with definitive radiation therapy for intermediate risk prostate cancer was evaluated in three landmark clinical trials. RTOG 94-08 demonstrated that for patients with low- and intermediate-risk prostate cancer, short term ADT improved outcomes at 10 years, with the largest benefit in the intermediate risk group . While TROG 96.01 confirmed that 6 months of ADT was superior to 3 months of ADT for patients with intermediate and high-risk prostate cancer . Focusing on the unfavorable intermediate risk group , DAmico demonstrated that 6 months of ADT improved overall survival, prostate cancer-specific mortality and all-cause mortality . However, the 15-year follow-up suggested that in the subset of patients with moderate-to-severe comorbidities, the addition of ADT significantly increased overall mortality and cardiac mortality .
Independent Director Representing Regine Slagmulder Bv
Dr. Regine Slagmulder is a partner and full professor in management accounting & control at Vlerick Business School. Previously, she worked as a strategy practice consultant at McKinsey & Company. She also previously worked as a professor of management accounting at INSEAD and at the University of Tilburg. She serves. as an independent director and chair of the audit committee on the board of the investment company Quest for Growth. and of Ekopak , both listed on Euronext. Dr. Slagmulder graduated in civil electrotechnical engineering and industrial management from the University of Ghent, after which she took a management doctorate at Vlerick Business School. As part of her research activities, she was a research fellow attached to INSEAD, Boston University and the P. Drucker Graduate Management Center at Claremont University .
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Preparation Of Ginger Extract And Ginger Standards
GE was prepared as described previously . Briefly, fresh ginger was obtained from a local farmers market, and grated ginger was then soaked in methanol for 4 consecutive days. The supernatant collected daily was pooled together, concentrated in vacuo , and freeze-dried to a solid form. GE and the standard stock solutions of gingerol phytochemicals were prepared at a concentration of 100 mg/ml and 10 mM, respectively, in DMSO. All experiments were performed using a single batch of GE in order to avoid batch-to-batch variation and maximize constancy. However, the variation among different batches of ginger extracts was determined based upon the quantitative values of 6, 8, 10 gingerols.
Androgen Deprivation Therapy And Radiation Therapy For Prostate Cancer: The Mechanism Underlying Therapeutic Synergy
Catherine S. Spina
Department of Radiation Oncology, Columbia University Medical Center , , USA
Correspondence to:
Abstract: Androgen deprivation therapy , combined with definitive radiation therapy, is the standard of care for locally advanced prostate cancer. Here, we describe the clinical development of ADT for prostate cancer, from the initial report of surgical castration for palliation of metastatic prostate cancer through the accumulated evidence derived from seminal randomized clinical trials confirming the benefit of ADT for patients treated with definitive radiation therapy. Though the positive impact of ADT on clinical outcomes is widely accepted, the synergistic relationship between ADT and radiation therapy remains underappreciated. Hence, we offer a review of select pre-clinical and clinical data from a growing body of evidence elucidating the mechanism by which ADT and radiation therapy behave synergistically. Collectively, the evidence outlined herein underscore the clinical importance of combined ADT and radiation therapy and the rationale for its effectiveness.
Keywords: Radiation prostate cancer androgen deprivation therapy synergy
Submitted May 08, 2018. Accepted for publication May 18, 2018.
doi: 10.21037/tcr.2018.05.42
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Selenium And The Prostate
The most robust results of the NPC Trial come from the recent analyses of the complete trial data for prostate cancer incidence, the diagnosis of which was confirmed by analysis of prostate-specific antigen in the plasma . These analyses show that, for men with PSA values #4ngml1, Se treatment was associated with a 65% reduction in prostate cancer risk . In addition, after a finding of elevated PSA, men in the Se-treated group were 40% as likely to undergo biopsy as those in the placebo group . , suggested that this difference may indicate a bias against the detection of prostate cancer in the Se-treated group, but no data were presented to test that speculation. For men entering the trial with PSA > 4ngml1, there was no significant effect of treatment , nor did Se treatment reduce elevated PSA values or affect the clinical stage or incidence of advanced prostate cancers. These findings would suggest a protective effect of Se treatment against early stage of carcinogenesis however, there was no indication that Se treatment affected the stage of prostatic disease among men with that diagnosis. In contrast, found that Barrett’s oesophagus subjects with relatively high serum Se levels had reduced risks to developing high-grade dysplasia.
What Are The Ingredients In Complete Uricare Capsules And How Are They Beneficial
Complete Uricare contains several natural ingredients chosen for their benefits for urinary health and synergistic action.
A reputable pumpkin seed extract . Pumpkin seeds have been used for centuries in Central America to treat nephritis and disorders of the urinary system such as incontinence. The German Commission E recognises pumpkin seeds for their ability to relieve symptoms of irritable bladder and for treating problems with micturition . Studies have confirmed that supplementing with pumpkin seed extract provides relief from these problems .
The pumpkin seed extract in this formulation is combined with a soy germ extract under the brand name Go-Less®. This blend of pumpkin seed and soy germ extracts has been clinically studied for its benefits for the urinary system and in particular the bladder. Suitable for both men and women, it promotes regulation of bladder movements and prevents irritation caused by various factors such as the bladder compression that often accompanies an enlarged prostate.
Angelica . Angelica is a medicinal plant used for centuries to relieve gastrointestinal spasms, bloating and problems of the urinary system. Pharmacological tests have shown it to be powerfully antiseptic due to its high content of furanocoumarins, phytosterols and essential oil. It has an inhibitory effect on urease, an enzyme found in certain yeasts and pathogenic bacteria, including the dreaded Helicobacter pylori.
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What Additional Measures Can Be Combined With Taking Complete Uricare
- Drink plenty of fluid to maintain a good urinary flow.
- Dont wait too long to go to the toilet: retaining urine in the bladder for too long gives bacteria more opportunity to multiply and travel back up.
- Go to the toilet straight after sexual intercourse.
- Drink cranberry juice regularly if you suffer from frequent urinary tract infections: a number of meta-analyses have demonstrated cranberry juices ability to significantly reduce repeat infections .
- Reduce your consumption of coffee, alcohol and caffeinated drinks: these compounds particularly irritate the bladder.
- Try consuming nettles and horsetail . These two plants are recognised by the Commission E for treating bacterial infections of the bladder and urethra.
- Reduce consumption of sugary foods and meat, both of which have an adverse effect on the bacterial composition of stools and promote urinary infections.
- Combine Complete Uricare with other herbs such as black radish, ginger, artichoke or milk thistle, and other supplements available to buy at Supersmart such as Prosta-Friendly 250 mg if your problems are prostate-related, Cran-Max® 500 mg, if youre prone to urinary tract infections or U-Tract Forte, a supplement formulated to relieve occasion urinary discomfort and sensitivity.
Buy Complete Uricare capsules to support urinary health.