obesity has also been linked to preferential estrogen metabolism via the 16-alpha-hydroxylation pathway; thus,
a prediction of the mechanism by which obesity could increase breast cancer risk would be through a lowering of the 2:16 ratio
in favor of the 16 pathway
Group items matching
in title, tags, annotations or url
14More
Urinary estrogen metabolites in women at high risk for breast cancer - 0 views
carcin.oxfordjournals.org/...1532.full
breast cancer CA estrogen metabolism 2:16 OHE 2-OH-estrone 16-alpha-OH-estrone
shared by Nathan Goodyear on 10 May 12
- No Cached
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Our data show a significant association between alcohol use, defined as at least one drink per day or an average of seven per week, and 2:16 OHE ratio
- ...10 more annotations...
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An alcohol-induced rise in estrogens as a consequence of alcohol catabolism in the liver has been reported
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The only study that looked at the association between alcohol and wine consumption in healthy women did not report a clear association
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smoking has been reported to increase induction of the 2-hydroxylation metabolic pathway (24). However, the few epidemiological studies conducted on healthy women showed no difference in estrogen metabolites with smoking status (22) or smoking dose (20), in line with our findings.
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Family history of a first-degree family member with breast cancer confers a 2- to 4-fold risk of developing breast cancer
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Estrogen metabolism occurs through enzymes whose activity is determined by the presence of specific genetic polymorphisms, thus can be defined as unique to each individual.
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the metabolism is also influenced by a number of environmental factors, which change over a lifetime
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significantly lower 2:16 OHE ratio in women who have known breast cancer risk factors compared with healthy women
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There was an additional significant association specifically with BMI and alcohol use, which also supports the evidence that these factors affect estrogen metabolism
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Profiling estrogen metabolites may identify women who are more likely to develop breast cancer within a population of women with known risk factors
18More
Growth Inhibition of Ovarian Tumor-Initiating Cells by Niclosamide | Molecular Cancer T... - 0 views
mct.aacrjournals.org/...1703.long
Niclosamide Tumor-initiation cells TIC ovarian cancer cancer CSC cancer stem cells
shared by Nathan Goodyear on 16 Apr 18
- No Cached
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Ovarian cancer is the most lethal gynecologic malignancy and the fifth-most cause of overall cancer death of women in developed countries
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An increasingly accepted cancer stem cell hypothesis regards tumors as caricatures of normal organs, possessing a hierarchy of cell types, at various stages of aberrant differentiation, descended from precursor tumor-initiating cells (TIC) cells that are highly resistant to conventional cytotoxics
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Significant changes of gene expression in 2,928 genes were identified after niclosamide treatment for different time periods
- ...14 more annotations...
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uncoupling of mitochondrial oxidative phosphorylation is believed to be its anti-helminthic mechanism of action
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we hypothesized that niclosamides antagonistic effects on OTICs could, in part, be due to its disruption of metabolism
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Our results showed that genes participating in protein complexes of oxidative phosphorylation were downregulated
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niclosamide treatment resulted in a more than 20% increase in reactive oxygen species (ROS) in cultured OTICs
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niclosamide, which has proved to be safe and effective for the past 2 decades against numerous parasites, inhibited OTIC growth both in vitro and in vivo
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niclosamide represses metabolic enzymes responsible for bioenergetics, biosynthesis, and redox regulation specifically in OTICs, presumably leading to mitochondrial intrinsic apoptosis pathways, loss of tumor stemness, and growth inhibition
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Niclosamide was reported to inactivate NF-κB, causing mitochondrial damage and the generation of ROS, leading to apoptosis of leukemic stem cells
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mTOR was reported to maintain stemness properties of HSCs by inhibiting mitochondrial biogenesis and ROS levels (39), implying that mTOR inhibitors (such as niclosamide) may interfere with mitochondria and various metabolic pathways in TICs via disruption of antioxidant responses
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We observed Wnt hyperactivity in OTICs, in agreement with previous hypotheses of Wnt inhibitor effectiveness as an ovarian cancer therapy
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ovarian carcinogenesis, the cell-to-cell signaling pathway Notch (8), were also suppressed by niclosamide (data not shown). These results agree with another recent niclosamide study in leukemia (49), and it has been widely hypothesized that disruption of Notch signaling may represent a highly effective therapy for ovarian and other solid tumors, via its essentiality to maintaining TIC stemness
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Niclosamide, common anti-parasitic medication, inhibits cellular metabolism and increases ROS; both of which provide powerful anti-proliferative, anti-cancer treatment mechanism in TICs. Powerful target therapy for cancer stem cells. Also shown to inhibit Wnt stimulated oncogenes survivin and c-Myc, disrupts Notch signaling, inactivates NF-kappaBeta, and inhibits mTOR-signaling. This has been found in in vitro and in vivo studies.
1More
Sex Steroids and Prostate Carcinogenesis Integrated, Multifactorial Working Hypothesis - 0 views
www.ncbi.nlm.nih.gov/...PMC2821822
prostate cancer estradiol Testosterone aromatase hormone hormones
shared by Nathan Goodyear on 23 Sep 13
- No Cached
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The genesis of cancer is complex. To simply say that cancer is genetic is both niave and uninformed. This study displays the complexity of the timing of hormones and cancer genesis. This rat study found that Estradiol added to Testosterone increased "markedly". Estrogen plays a role in the genesis of prostate disease. However, this varies among individuals. The response of prostate cancer to estradiol appears to change according to the progression of the cancer.
1More
Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program fo... - 0 views
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low aggressive prostate cancer followed conservatively results in low mortality rate in study. The study is significant in that it followed 1,298 men up to 18 years and found reclassification to "lethal" grade prostate cancer to be only 5.9%. This challenges long held dogma that the first approach to cancer is to cut it out. For those with low aggressive prostate cancer, conservative approaches i.e. observation, can be employed.
7More
PLOS ONE: Microbial Dysbiosis in Colorectal Cancer (CRC) Patients - 0 views
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differences in the colon microbiota in individuals with colon cancer versus those with a normal colonoscopy
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qPCR revealed significant elevation of the Bacteroides/Prevotella population in cancer patients that appeared to be linked with elevated IL17 producing cells in the mucosa of individuals with cancer.
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Bacteroides genus populations and more specifically those of Bacteroides fragilis, have recently been shown to produce a metalloprotease in colon cancer patients, but not in controls [12] suggesting this species sub population might favor carcinogenesis
- ...3 more annotations...
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It is noteworthy that among the many mechanisms that may mediate associations between microbiota and human health [21]–[22], pro-inflammatory and immune cell activation in colon mucosa are of great importance in relation to malignancy
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B. fragilis has been shown to induce mucosal regulatory T-cell responses in the intestine involving TH17 cell recruitment in experimental models
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the elevations of Bacteroides in the stool and/or IL17 immunoreactive cells in the normal mucosa appear to be promising sensitive markers
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A relationship between dysbiosis and colon cancer appears to be present. Particularly an increase in Bacteroidetes and Prevotella species were found in those with colon cancer versus those without. An inflammatory up regulation of IL-17 appears to be involved. Whether this is a cause or effect is yet to be determined, but the presence of elevated Bacteroidetes species with increased IL17 could be used as sensitive biomarkers.
21More
Anemia in cancer - 0 views
- ...17 more annotations...
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mild (10 g/dl—normal), moderate (8–10 g/dl), severe (6.5–8 g/dl) and life threatening (<6.5 g/dl or unstable patient) anemia
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Cancer itself can directly cause or exacerbate anemia either by suppressing hematopoiesis through bone marrow infiltration or production of cytokines that lead to iron sequestration, or by reduced red blood cell production
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in inflammatory anemia, iron deficiency should be defined by a low transferrin saturation of <20%, ferritin levels of <100 ng/ml and a low reticulocyte hemoglobin concentration of <32 pg
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Other cytokines, such as interleukin-6 (IL-6), IL-1 and interferon-γ, have also been shown to inhibit erythroid precursors in vitro [9], albeit to a lesser extent
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In inflammation, from whatever cause, IL-6 induces the liver to produce hepcidin. Hepcidin decreases iron absorption from the bowel and blocks iron utilization in the bone marrow
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nephrotoxic effects of particular cytotoxic agents such as platinum salts can also lead to the persistence of anemia through reduced Epo production by the kidney
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Currently two options are at the disposal of the clinician for the treatment of anemia in cancer patients: transfusion of packed red blood cells and the use of erythropoiesis-stimulating agents (ESAs)
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Transfusion of 1 unit of packed red blood cells has been estimated to result in an increase in the hemoglobin level of 1 g/dl in a normal-sized adult
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Recent concerns regarding the risk of thromboembolism in patients treated with ESA have been corroborated by the meta-analyses conducted by Tonnelli and Bennett
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Great review of anemia in Cancer: 1) blood loss 2) increased RBC loss 3) decreased RBC production Cancer infiltration of marrow can reduce hematopoiesis. Inflammatory cytokines can reduce hematopoiesis. Inflammatory cytokines can block Fe absorption. Chemo and radiation can cause anemia--particularily platinum based therapies.
26More
In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epitheli... - 0 views
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we functionally validated a potent EOC oncogene, KPNB1, and showed its clinical relevance to human EOC
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a well-established antiparasitic drug, ivermectin, has antitumor effects on EOC through its inhibition of KPNB1
- ...22 more annotations...
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Sequencing revealed that almost all tumors (96%) had mutations in TP53, which serves as a major driver of this cancer
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Low-prevalence but statistically significant mutations in nine other genes including NF1, BRCA1, BRCA2, RB1, and CDK12 were also identified, but the majority of genes were mutated at low frequency, making it difficult to distinguish between driver and passenger mutations
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KPNB1 inhibition via any of three KPNB1 siRNAs or importazole treatment induced apoptosis in human EOC cell lines (Fig. 3 A–F and Fig. S4), and was accompanied by an increase in the expression levels of the proapoptotic proteins BAX and cleaved caspase-3
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Stable overexpression of KPNB1 in SKOV3 and OVCAR3 (Fig. S6) significantly accelerated cell proliferation/survival (Fig. 5 A–C), confirming that KPNB1 functions as an oncogene in EOC
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KPNB1 overexpression significantly decreased caspase-3/7 activity (Fig. 5D), in addition to the expression levels of cleaved caspase-3 and BAX proteins (Fig. 5E). KPNB1 overexpression also decreased p21 and p27 protein levels (Fig. 5E), as opposed to their increase by KPNB1 inhibition
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Patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1
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ivermectin treatment suppressed cell proliferation/viability in a dose-dependent manner (Fig. 7A), indicating that it exerts an antitumor effect on EOC
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we found that ivermectin synergistically reduced cell proliferation/viability in combination with paclitaxel in human EOC cells
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Single treatment of ivermectin or paclitaxel reduced tumor growth in nude mice, but, notably, combination treatment of ivermectin and paclitaxel almost completely suppressed tumor growth
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ERBB2, is amplified and overexpressed in many cancers, including breast (31), ovary (31), colon (32), bladder (33), non-small-cell lung (34), and gastric cancer (35), and is a poor prognostic factor in certain cancer types
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Increased KPNB1 protein levels have been reported in several cancers, including cervical cancer (42), hepatocellular carcinoma (43), and glioma (44), suggesting KPNB1’s oncogenic potential in these tumor types
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our findings suggest that KPNB1 might serve as a master regulator of cell cycle by regulating several cell cycle-related proteins, including p21, p27, and APC/C family members
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higher and/or more-frequent doses of ivermectin than currently approved for humans are well tolerated in humans
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none of the mice in this study treated with the effective dosage of ivermectin for in vivo anticancer therapy showed severe adverse event
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we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC cell lines than either drug alone
17More
Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking m... - 0 views
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Accumulating evidence suggests that niclosamide targets multiple signaling pathways such as nuclear factor-kappaB (NF-kB), Wnt/β-catenin, and Notch, most of which are closely involved with cancer stem cell proliferation
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The transcription factor NF-κB has been demonstrated to promote cancer growth, angiogenesis, escape from apoptosis, and tumorigenesis
- ...13 more annotations...
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Niclosamide blocked TNFα-induced IκBα phosphorylation, translocation of p65, and the expression of NF-κB-regulated genes
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The Wnt signaling pathway plays fundamental roles in directing tissue patterning in embryonic development, in maintaining tissue homeostasis in differentiated tissue, and in tumorigenesis
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The Notch signaling pathway plays important roles in a variety of cellular processes such as proliferation, differentiation, apoptosis, cell fate decisions, and maintenance of stem cells
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niclosamide potently suppresses the luciferase activity of a CBF-1-dependent reporter gene in both a dose-dependent and a time-dependent manners in K562 leukemia cells
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niclosamide treatment abrogated the epidermal growth factor (EGF)-stimulated dimerization and nuclear translocation and transcriptional activity of Stat3, and induced cell growth inhibition and apoptosis in several types of cancer cells (e.g. Du145, Hela, A549) that exhibit relatively higher levels of Stat3 constitutive activation
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Niclosamide is active against cancer cells such as AML and colorectal cancer cells, not only as a monotherapy but also as part of combination therapy, in which it has been found to be synergistic with frontline chemotherapeutic agents (e.g., oxaliplatin, cytarabine, etoposide, and daunorubicin)
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Because niclosamide targets multiple signaling pathways (e.g., NF-κB, Wnt/β-catenin, and Notch), most of which are closely involved with cancer stem cells, it holds promise in eradicating cancer stem cells
21More
Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer - 0 views
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Previous studies from our laboratory have demonstrated that pharmacological ascorbate is cytotoxic to pancreatic cancer cells while normal cells are resistant
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Ascorbate-induced cytotoxicity is mediated by the formation of H2O2 during the oxidation of ascorbate
- ...17 more annotations...
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Under steady-state conditions, intracellular GSH is maintained at millimolar concentrations, which keeps cells in a reduced environment and serves as the principal intracellular redox buffer when cells are subjected to an oxidative stressor including H2O2 (26). Glutathione peroxidase (GPx) activity catalyzes the reduction of H2O2 to water with the conversion of GSH to glutathione disulfide (GSSG). Under steady-state conditions, GSSG is recycled back to GSH by glutathione disulfide reductase using reducing equivalents from NADPH. However, under conditions of increased H2O2 flux, this recycling mechanism may become overwhelmed leading to a depletion of intracellular GSH (27, 28).
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ascorbate radiosensitization can create an overwhelming oxidative stress to pancreatic cancer cells resulting in oxidation/depletion of the GSH intracellular redox buffer, resulting in cell death.
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Treatment with the combination of ascorbate + IR significantly delayed tumor growth compared to controls or ascorbate alone
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Ascorbate + IR also significantly increased overall survival compared to controls, IR alone or ascorbate alone
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Glutathione is a measurable marker indicative of the oxidation state of the thiol redox buffer in cells. In severe systemic oxidative stress, the GSSG/2GSH couple may become oxidized, i.e. the concentration of GSH decreases and GSSG may increase because the capacity to recycle GSSG to GSH becomes rate-limiting
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This suggests that the very high levels of pharmacological ascorbate in these experiments may have a pro-oxidant toward red blood cells as seen by a decrease in the capacity of the intracellular redox buffer
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These data support the hypothesis that ascorbate radiosensitization does not cause an increase in oxidative damage from lipid-derived aldehydes to other organs.
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Our current study demonstrates the potential for pharmacological ascorbate as a radiosensitizer in the treatment of pancreatic cancer.
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pharmacological ascorbate enhances IR-induced cell killing and DNA fragmentation leading to induction of apoptosis in HL60 leukemia cells
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pharmacological ascorbate significantly decreases clonogenic survival and inhibits the growth of all pancreatic cancer cell lines as a single agent, as well as sensitizes cancer cells to IR
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Hurst et al. demonstrated that pharmacological ascorbate combined with IR leads to increased numbers of double-strand DNA breaks and cell cycle arrest when compared to either treatment alone
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The combination of ascorbate and IR provide two distinct mechanisms of action: ascorbate-induced toxicity due to extracellular production of H2O2 that then diffuses into cells and causes damage to DNA, protein, and lipids; and radiation-induced toxicity as a result of ROS-induced damage to DNA. In addition, redox metal metals like Fe2+ may play an important role in ascorbate-induced cytotoxicity. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of H2O2; labile iron can also react with H2O2. Recently our group has demonstrated that pharmacological ascorbate and IR increase the labile iron in tumor homogenates from this murine model of pancreatic cancer
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we demonstrated that ascorbate or IR alone decreased tumor growth, but the combination treatment further inhibited tumor growth, indicating that pharmacological ascorbate is an effective radiosensitizer in vivo
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data suggest that pharmacological ascorbate may protect the gut locally by decreasing IR-induced damage to the crypt cells, and systemically, by ameliorating increases in TNF-α
1More
High dose intravenous vitamin c and metastatic pancreatic cancer: Two cases - 0 views
www.oatext.com/ancreatic-cancer-Two-cases.php
pancreatic cancer cancer IV vitamin c vitamin c alternative cancer treatment alternative medicine
shared by Nathan Goodyear on 31 Jan 18
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50More
Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2... - 0 views
www.nature.com/...s41698-017-0044-8
cancer cancer stem cells liver cancer vitamin C IV vitamin C oncology
shared by Nathan Goodyear on 30 Jan 18
- No Cached
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Chen et al. have revealed that ascorbate at pharmacologic concentrations (0.3–20 mM) achieved only by intravenously (i.v.) administration selectively kills a variety of cancer cell lines in vitro, but has little cytotoxic effect on normal cells.
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Ascorbic acid (the reduced form of vitamin C) is specifically transported into cells by sodium-dependent vitamin C transporters (SVCTs)
- ...41 more annotations...
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differential sensitivity to VC may result from variations in VC flow into cells, which is dependent on SVCT-2 expression.
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high-dose VC significantly impaired both the tumorspheres initiation (Fig. 4d, e) and the growth of established tumorspheres derived from HCC cells (Fig. 4f, g) in a time-dependent and dose-dependent manner.
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The antioxidant, N-acetyl-L-cysteine (NAC), preventing VC-induced ROS production (a ROS scavenger), completely restored the viability and colony formation among VC-treated cells
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Interestingly, the combination of VC and cisplatin was even more effective in reducing tumor growth and weight
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Consistent with the in vitro results, stemness-related genes expressions in tumor xenograft were remarkably reduced after VC or VC+cisplatin treatment, whereas conventional cisplatin therapy alone led to the increase of CSCs
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Interestingly, at extracellular concentrations greater than 1 mM, VC induces strong cytotoxicity to cancer cells including liver cancer cells
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we hypothesized that intravenous VC might reduce the risk of recurrence in HCC patients after curative liver resection.
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Intriguingly, the 5-year disease-free survival (DFS) for patients who received intravenous VC was 24%, as opposed to 15% for no intravenous VC-treated patients
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In this study, based on the elevated expression of SVCT-2, which is responsible for VC uptake, in liver CSCs, we revealed that clinically achievable concentrations of VC preferentially eradicated liver CSCs in vitro and in vivo
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Additionally, we found that intravenous VC reduced the risk of post-surgical HCC progression in a retrospective cohort study.
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Three hundred thirty-nine participants (55.3%) received 2 g intravenous VC for 4 or more days after initial hepatectomy
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As the key protein responsible for VC uptake in the liver, SVCT-2 played crucial roles in regulating the sensitivity to ascorbate-induced cytotoxicity
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we also observed that SVCT-2 was highly expressed in human HCC samples and preferentially elevated in liver CSCs
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we revealed that VC treatment dramatically reduced the self-renewal ability, expression levels of CSC-associated genes, and percentages of CSCs in HCC, indicating that CSCs were more susceptible to VC-induced cell death
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as a drug for eradicating CSCs, VC may represent a promising strategy for treatment of HCC, alone or particularly in combination with chemotherapeutic drugs
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In HCC, we found that VC-generated ROS caused genotoxic stress (DNA damage) and metabolic stress (ATP depletion), which further activated the cyclin-dependent kinase inhibitor p21, leading to G2/M phase cell cycle arrest and caspase-dependent apoptosis in HCC cells
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we demonstrated a synergistic effect of VC and chemotherapeutic drug cisplatin on killing HCC both in vitro and in vivo
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Intravenous VC has also been reported to reduce chemotherapy-associated toxicity of carboplatin and paclitaxel in patients,38 but the specific mechanism needs further investigation
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Our retrospective cohort study also showed that intravenous VC use (2 g) was related to the improved DFS in HCC patients after initial hepatectomy
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several clinical trials of high-dose intravenous VC have been conducted in patients with advanced cancer and have revealed improved quality of life and prolonged OS
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high expression (grade 2+/3+) of SVCT-2 was in agreement with poorer overall survival (OS) of HCC patients (Fig. 1c) and more aggressive tumor behavior
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these data suggest that SVCT-2 is preferentially expressed in liver CSCs and is required for the maintenance of liver CSCs.
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pharmacologic concentrations of plasma VC higher than 0.3 mM are achievable only from i.v. administration
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The viabilities of HCC cells were dramatically decreased after exposure to VC in dose-dependent manner
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These results verify that VC inhibits tumor growth in HCC PDX models and SVCT-2 expression level is associated with VC response
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qPCR and IHC analysis demonstrated that expression levels of CSC-associated genes and percentages of CSCs in PDXs dramatically declined after VC treatment, confirming the inhibitory role of VC in liver CSCs
44More
Hyperthermia as an immunotherapy strategy for cancer - 1 views
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After antigen uptake at tumor sites, APCs have the ability to create a robust response by entering lymphoid compartments and programming lymphocytes
- ...36 more annotations...
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Hyperthermia differs fundamentally from fever in that it elevates the core body temperature without changing the physiological set point
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mor cells [2]. Although significant cell killing could be achieved by heating cells or tissues to temperatures > 42°C for 1 or more hours, the application, measurement and consistency of this temperature range within the setting of cancer clinical trials
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mild temperature hyperthermia (ie, within the fever-range, 39–41°C)
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moderate hyperthermia (41°C)
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Hsps ensure appropriate post-translational protein folding, and are able to refold denatured proteins, or mark irreversibly damaged proteins for destruction
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the ability of fever-range hyperthermia to induce reactive immunity against tumor antigens through DCs and NK-cells is likely mediated by Hsps
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Hsps support the malignant phenotype of cancer cells by not only affecting the cells’ survival, but also participating in angiogenesis, invasion, metastasis and immortalization mechanisms
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Hsps released from stressed or dying cells activate dendritic cells (DCs), transforming them into mature APCs
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In theory, fever-range hyperthermia may take advantage of tumor cell Hsps by inducing their release from tumor cells and augmenting DC priming against tumor antigens
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In several models of hyperthermia, heat-treated tumors exhibited improved DC priming and generation of systemic immunity to tumor cell
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hyperthermia alone can enhance antigen display by tumor cells, thus rendering them even more susceptible to programmed immune clearance
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Hsps may exert an adjuvant effect by bolstering MHC class II and co-stimulatory molecule expression by DCs
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thermal ablation of liver tumors in particular has demonstrated an ability to potentiate immune responses [57, 58] and elicit robust T-cell infiltrates at ablation sites
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specific Hsp, Hsp70, directly inhibits apoptosis pathways in cancer cells, as demonstrated in human pancreatic, prostate and gastric cancer cells
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Cross-priming is the ability of extracellular Hsps complexed to tumor peptides to be internalized and presented in the context of MHC class I molecules on APCs, thus allowing potent priming of CTLs against tumor antigens
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It has been reported that Hsps are generated from necrotic tumor cell lysates, but not from tumor cells undergoing apoptosis
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tumor cells exposed to hyperthermia in the heat shock range (42°C for 4h) prior to lysing, DC activation and cross-priming were significantly enhanced with the application of heat
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Due to the ability of Hsps to activate DCs directly by chaperoning tumor antigens upon their release [28], it is possible that both local and regional immune stimulation can be achieved with hyperthermia.
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support the use of hyperthermia as an inducer of Hsps to serve as ‘danger signals’, activating antitumor immune responses
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whole-body hyperthermia not only augments immune responses, but also stimulates the migration of skin-derived DCs to draining lymph nodes
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In mice treated with fever-range whole-body hyperthermia, tumor growth was significantly inhibited and NK-cell infiltration increased
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exposure to fever-range hyperthermia resulted in improved endogenous NK-cell cytotoxicity to several cancer types
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The combined effects of hyperthermia on lymphoid tissue endothelium and lymphocytes can promote immune surveillance and increase the probability of naive lymphocytes leaving the circulation and encountering their cognate antigen displayed by DCs in lymphoid organs.
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In independent clinical studies, whole-body hyperthermia resulted in a transient decrease in circulating lymphocytes in patients with advanced cancer [12, 94, 99, 100], a finding which mirrored observations in animal models in which lymphocyte entry into lymph noeds was increased following hyperthermia treatment [93]. Enhanced recruitment of lymphocytes to lymphoid tissues may be exploited in the treatment of malignancies.
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The initial tumor antigen presentation and initiation of clonal expansion of CTLs transpires in the lymph nodes and cannot take place outside this specialized compartment
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the ability of DCs present in the lymph nodes to stimulate an anti-tumor immune response is critical
1More
ERβ Inhibits Proliferation and Invasion of Breast Cancer Cells - 0 views
endo.endojournals.org/...4120.long
ER-beta estrogen receptor beta estrogen receptor beta breast cancer ER
shared by Nathan Goodyear on 23 Nov 12
- No Cached
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Estrogen Receptor Beta shown to inhibit growth and spread of breast cancer cells. So, ER-beta should be evaluated to not only prevent/slow the growth of breast cancer, but to prevent the spread of breast cancer. This study proposes that the loss of ER-beta is a seminal event in the development of breast cancer.
1More
ERβ inhibits proliferation and invasion of breast cancer cells - 0 views
www.ncbi.nlm.nih.gov/...PMC2040491
ER alpha ER beta ER-alpha ER-beta hormones cancer breast cancer prostate cancer ovarian cancer colon cancer
shared by Nathan Goodyear on 05 Jan 17
- No Cached
19More
Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among P... - 0 views
cancerres.aacrjournals.org/...696.full
estrogen metabolites estrogen metabolism ER estrogen receptors ROS hormones cancer breast cancer
shared by Nathan Goodyear on 07 Oct 15
- No Cached
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both 2- and 4-catechol estrogen metabolites bind to the ER with affinities comparable with estradiol, 4-catechol estrogen metabolites have lower dissociation rates than estradiol and an enhanced ability to upregulate ER-dependent processes
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2-catechol estrogen metabolites act as either weak mitogens (39) or weak inhibitors of cell proliferation
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While 16α-hydroxyestrone binds to the ER with lower affinity than estradiol, it binds covalently (41) and leads to a constitutively activated ER
- ...15 more annotations...
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4-hydroxyestradiol and 16α-hydroxyestrone increasing proliferation and decreasing apoptosis in a manner similar to estradiol; however, these effects were achieved only at concentrations 10-fold higher than estradiol (39). In contrast, 2-hydroxyestradiol did not have substantial proliferative or antiapoptotic effects
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In our study, the associations with both 2-hydroxyestrone and 16α-hydroxyestrone were nonsignificantly inverse and we did not observe a consistent trend or significant associations between the 2-hydroxyestrone:16α-hydroxyestrone ratio and breast cancer risk
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Ratios of the 3 hydroxylation pathways were not significantly associated with risk although the 2:16-pathway and 4:16-pathway ratios were suggestively inversely associated
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Catechol estrogens can be oxidized into quinones and induce DNA damage directly through the formation of DNA adducts, or indirectly via redox cycling and generation of reactive oxygen species
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the oxidized forms of the catechol estrogens differ in their ability to damage DNA through adducts, with oxidized 2-catechols forming stable and reversible DNA adducts and oxidized 4-catechols forming unstable adducts, which lead to depurination and mutations
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2- and 4-catechols have been shown to produce reactive oxygen species and induce oxidative DNA damage
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While the catechol estrogens have estrogenic and genotoxic potential, the methylated catechol estrogens, which are catechol estrogens with one hydroxyl group methylated, have been hypothesized to lower the risk of breast cancer
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The suggested mechanisms are indirect, by decreasing circulating levels of catechol estrogens and thereby the opportunity for catechols to exert genotoxic or proliferative effects, or direct, by inhibiting tumor growth and inducing apoptosis
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the balance between phase I (oxidation) and phase II (methylation) metabolism of estrogen may be important in hormonally related cancer development.
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Despite the estrogenic and genotoxic potential of many of the estrogen metabolites, we only observed a significantly increased breast cancer risk with one estrogen metabolite, 17-epiestriol, which has particularly strong estrogenic activity and binds to both ERα and ERβ with an affinity comparable with estradiol
1More
The impact of vitamin D in breast cancer: genomics, pathways, metabolism - 0 views
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Good review of data on vitamin D, Vitamin D receptors and cancer risk. Studies have shown that low Vitamin D levels are associated with increased cancer risk and that higher vitamin D levels are associated with reduced cancer risk. The ability to fully map out vitamin Ds role in the physiology is probably difficult due to the heterogeneity of cancer development and physiology.
15More
Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor,... - 0 views
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the MAF precursor activity of prostate cancer patient Gc protein is lost or reduced, because their serum Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells
- ...11 more annotations...
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As GcMAF therapy progressed the MAF precursor activity of all five patients increased and their serum Nagalase activity decreased inversely
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As GcMAF therapy progressed, the MAF precursor activity increased with a concomitant decrease in serum Nagalase activity
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as GcMAF therapy progressed, serum Nagalase activity decreased and, concomitantly, tumor burden decreased
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annual computed tomographic scans of these patients confirmed them being tumor recurrence-free for the 7 years
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undifferentiated cells were killed rapidly during the first few weeks, and the differentiated cells were killed slowly in the remaining GcMAF therapeutic period
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In patients without tumor resection, however, although serum Nagalase activity decreased as GcMAF therapy progressed, their PSA values remained unchanged. The result suggests that the PSA derived from tumor-bearing prostate did not change while tumor burden decreased. Because tumor-induced inflammation in the noncancerous prostate tissues causes secretion of PSA [38], the PSA produced from these inflamed noncancerous prostate tissues cannot be changed by the decrease in tumor burden
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Advanced cancer patients have high serum Nagalase activities, resulting in no macrophage activation and severe immunosuppression that explain why cancer patients die with overwhelming infection
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Prognostic utility of serum α-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients
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GC-MAF levels exist in inverse relationship to nagalase. In this study of men with prostate cancer, weekly GCMAF injections reduced Nagalase activity to levels found in healthy controls suggesting tumor free. The dose was 100 ng/week. Nagalase is a protein that suppresses GC-MAF production and thus is immunosuppressive.
11More
The current state and future perspectives of cannabinoids in cancer biology - 0 views
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The activation of each of them leads to an inhibition of adenylyl cyclase via G proteins (Gi/o), which in turn activates many metabolic pathways such as mitogen‐activated protein kinase pathway (MAPK), phosphoinositide 3‐kinase pathway (PI3K), cyclooxygenase‐2 pathway (COX‐2), accumulation of ceramide, modulation of protein kinase B (Akt), and ion channels
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Action of THC in human organism relies on mimicking endogenous agonists of CB receptors—endocannabinoids
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The upregulated expression of CB receptors and the elevated levels of endocannabinoids have been observed in a variety of cancer cells (skin, prostate, and colon cancer, hepatocellular carcinoma, endometrial sarcoma, glioblastoma multiforme, meningioma and pituitary adenoma, Hodgkin lymphoma, chemically induced hepatocarcinoma, mantel cell lymphoma)
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concentration of endocannabinoids, expression level of their receptors, and the enzymes involved in their metabolism frequently are associated with an aggressiveness of cancer
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CB2 receptor contributes to human epidermal growth factor receptor (HER2) pro‐oncogenic signaling and an overexpression of CB2 increases susceptibility for leukemia development after leukemia viral infection
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Many cannabinoids, ranging from phytocannabinoids (THC, CBD), endocannabinoids (2‐arachidonoylglycerol, anandamide), to synthetic cannabinoids (JWH‐133, WIN‐55,212‐2), have shown ability to inhibit proliferation, metastasis, and angiogenesis in a variety of models of cancer
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Despite some inconsistent data, the main effect of cannabinoids in a tumor is the inhibition of cancer cells’ proliferation and induction of cancer cell death by apoptosis
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CB1 and CB2 receptor agonists stimulate apoptotic cell death in glioma cells by induction of de novo synthesis of ceramide, sphingolipid with proapoptotic activity
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Testosterone replacement therapy and the risk of prostate cancer - 0 views
www.ncbi.nlm.nih.gov/...PMC4814970
Testosterone testosterone therapy saturation theory cancer prostate cancer male hormones
shared by Nathan Goodyear on 01 Oct 16
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When the level of circulating androgen is below normal, some androgen receptors are inactive, and the secondary downstream effects are decreased. Once androgen receptors within the prostate are saturated, however, increasing testosterone will no longer have an effect
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Only the subset of individuals with pretreatment testosterone level <250 ng dl−1 had PSA level correlating with free and total testosterone level
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none of the men stopped testosterone supplementation due to prostate cancer recurrence, and none demonstrated cancer progression
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PSA level did transiently rise in one patient; however, none exceeded a PSA of 1.5 ng ml−1 to raise concern for biochemical recurrence
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after 19 months on TRT, 10 hypogonadal patients with a history of undergoing a radical retropubic prostatectomy for prostate cancer had no PSA recurrence and had statistically significant improvements in serum total testosterone and hypogonadal symptoms
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Similarly, Kaufman and Graydon14 examined case records of seven hypogonadal men who had undergone curative RP with symptoms of hypogonadism and low serum testosterone levels treated with testosterone replacement. No biochemical or clinical evidence of cancer recurrence was noted
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In a much larger case series, Khera et al.15 reviewed the records of 57 men who received TRT following RP. After an average of 36 months following RP, testosterone replacement was initiated and followed for an average of 13 months. Mean testosterone values rose significantly and once again, there was no increase in PSA values and, therefore, no diagnosed biochemical recurrence
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Four of the patients in the treatment group were found to have cancer recurrence, compared with eight in the control group