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Nathan Goodyear

Going viral: a review of replication-selective oncolytic adenoviruses - PMC - 0 views

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    The plurality of this article is around the concept of oncolytic therapy; yet, the article mentions the documentation of a influenza induced spontaneous remission of leukemia.
Nathan Goodyear

Book Review: New Books: Spontaneous Regression of Cancer, 1967 - 0 views

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    Second book, written by Everson and Cole
Nathan Goodyear

Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with... - 0 views

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    Study shows that gastrointestinal epithelial dysfunction is found in autism. This would play a critical role in systemic inflammation and would contribute to ASD symptoms through the gut-brain connection.
Nathan Goodyear

EHP - Bisphenol A Exposure during Adulthood Causes Augmentation of Follicular... - 0 views

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    Bisphenol A shown to disrupt ovarian estrogen production from exposure in adults.  The point of this that is important is that BPA, a xenoestrogen, can infact disrupt physiologic hormone production in adults, and contribute to ovarian failure.  BPA, itself, is 1,000 fold weaker than E2, yet it disrupts ovarian function.
Nathan Goodyear

Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty ac... - 0 views

  • The most convincing evidence for beneficial effects of omega-3 PUFA is to be found in mood disorders. A meta-analysis of trials involving patients with major depressive disorder and bipolar disorder provided evidence that omega-3 PUFA supplementation reduces symptoms of depression. Furthermore, meta-regression analysis suggests that supplementation with eicosapentaenoic acid may be more beneficial in mood disorders than with docosahexaenoic acid,
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    Omega-3 beneficial in depression and bi-polar clients
Nathan Goodyear

Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Andro... - 0 views

  • in male obesity basal and LH-stimulated androgen levels are reduced and inversely correlated with circulating leptin
  • functional leptin receptors are present in rodent Leydig cells
  • it is conceivable that in males high leptin concentrations may have a direct inhibitory effect(s) on Leydig cell function.
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  • insulin is an important inhibitor of the synthesis of SHBG
  • no correlation between leptin and SHBG levels
  • SHBG reduction in obesity is a minor determinant of lowered androgen levels
  • SHBG can explain only up to 3% of the correlation
  • testicular T de novo production is impaired in obese men and that leptin seems to be the best hormonal predictor of this blunted response to LH stimulation
  • The low basal 17-OH-P levels found in massively obese men are consistent with a global impairment of Leydig cell steroidogenic function in this group of subjects.
  • These findings indicate that obese men have a FM-related defect in the enzymatic conversion of 17-OH-P to T, which is revealed by hCG stimulation.
  • Other studies have investigated the adrenal function in male obesity and have shown that basal cortisol and 17-OH-progesterone levels tend to decrease with the increase in the degree of obesity
  • High E2 can inhibit the expression and activity of the 17,20-lyase and may be responsible for this steroidogenic lesion
  • However, stimulated E2 levels were not higher in the obese than in controls, excluding the fact that the lower androgen response was due to an increased aromatization of T to E2 and that estrogens have a major role in the observed defect of 17,20-lyase activity in obese men.
  • the percentage increase in the 17-OH-progesterone to T molar ratio paralleled the increase in leptin levels of obese men
  • Multiple regression analysis indicated that the best hormonal predictor of the obesity-related reduction in T and FT basal levels and androgen changes after hCG stimulation was serum leptin concentration
  • insulin has no negative influences on androgen production in obese men
  • insulin is known to have stimulatory actions on T production that have been demonstrated in obese and normal weight men (57) and in Leydig cells in culture
  • the negative correlation between insulin and basal T can be partly explained by the inhibitory action of insulin on SHBG production
  • hypogonadal men have higher circulating leptin levels compared with hypogonadal patients under effective androgen substitution therapy
  • The impaired androgen response to LH stimulus was due to a defect in the enzymatic conversion of 17-OH-progesterone to T, which was disclosed by a leptin-related increase in 17-OH-progesterone to T ratio
  • Estrogens, which are inhibitory modulators of LH pulsatility and bioactivity
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    Leptin appears to be a good marker of low Testosterone.  This study proposes that the mechanism of action is potentially 2 fold: first, a decrease in LH release by leptin (kisspeptin?) and 2nd, a directed decrease in Testosterone production by the leydig cells in the testes.
Nathan Goodyear

Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in ... - 0 views

  • Rigvir is a 2 ml frozen solution
  • ECHO-7 virus strain, Picornaviridae family, Enterovirus genus, Enteric Cytopathic Human Orphan (ECHO) type 7, group IV, positive-sense single-stranded RNA virus
  • a few side effects were reported, for example subfebrile temperature (37.5°C for a couple of days), pain in the tumour area, sleepiness and diarrhoea
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  • In this retrospective study, however, there was no record of any untoward side effect from Rigvir treatment or its discontinuation
  • Early observations of tumour regressions after virus infections have been published starting from the late 19th century
  • The present results show that in substage IB, IIA, IIB and IIC melanoma patients, Rigvir administration after surgery significantly (P<0.05) prolongs survival compared with patients who were managed according to current published guidelines
  • no value higher than grade 2 was recorded in Rigvir-treated patients. This is in contrast to most other cancer therapies, where grades 3 and 4 are frequently observed
  • Administration of virus induces the formation of neutralising antibodies that might potentially influence the efficiency of Rigvir
  • In 94 healthy adult participants tested, the titres were found to be low (1 : 20 to 1 : 62) 39,40. When tested in 155 adult cancer patients who had not been treated with Rigvir, neutralising antibodies against ECHO-7 were detected in ∼50% of the patients
  • the presence of ECHO-7 antibodies was shown to increase with age in children and level off to a plateau of around 75% in adults
  • Rigvir is an immunomodulator that affects both the humoral, antibody-mediated, and the cellular immune systems
  • neutralising antibodies do not affect efficacy when local or regional administration is used
  • it reduces the viability of melanoma, as well as pulmonary, gastric, pancreatic, bone, and breast cancer cell cultures
  • It is oncolytic in melanoma and rectum cancer patients
  • shown to improve the 5-year survival in rectum cancer patients
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    RIGVIR shown to improve survival against standard therapy in stage IB, IIA, IIB, and IIC in malignant melanoma patients in retrospective study. Side effects are minimal. Neutralizing antibodies are an area to watch that likely effects individual outcome beyond that of the type of cancer
Nathan Goodyear

Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on g... - 0 views

  • Cisplatin and 5-FU or CAP (cisplatin, doxorubicin, and cyclophosphamide) regimens can be used for combination chemotherapy
  • patients with advanced salivary gland malignancy treated with the CAP regimen achieved partial response (PR) or stable disease (SD) rates of 67% (8 out of 12 patients)
  • Agents commonly given as monotherapy for treating ACC are cisplatin, mitoxantrone, epirubicin, vinorelbine, paclitaxel, and gemcitabine. However, few of these agents have shown efficacy
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  • single agent mitoxantrone or vinorelbine were recommended as reasonable choices
  • ACC is subdivided into 3 histological groups based on solid components of the tumor including cribriform, tubular, and solid
  • Cribriform and tubular ACCs usually exhibit a more indolent course, whereas the solid subtype is associated with worse prognosis
  • ACC consists of two different cell types: inner luminal epithelial cells and outer myoepithelial cells
  • epithelial cells express c-kit, cox-2 and Bcl-2
  • myoepithelial cells express EGFR and MYB
  • a balanced translocation of the v-myb avian myeloblastosis viral oncogene homolog-nuclear factor I/B (MYB-NFIB) is considered to be a signature molecular event of ACC oncogenesis
  • As a transcription factor, MYB is known to modulate multiple genetic downstream targets involved in oncogenesis, such as cox-2, c-kit, Bcl-2 and BclX
  • Various signaling cascades are essential for cancer cells to survive and grow. The PI3K/Akt/mTOR pathway is one of them
  • This pathway regulates cell survival and growth and is upregulated in many cancers
  • Mutations in genes associated with DNA repair are frequently found in familial cancer syndromes, such as hereditary breast-ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC, also called Lynch syndrome) and Li-Fraumeni syndrome [30, 31]. These mutations were also reported in non-hereditary cancers
  • 70% of ACC samples (58 of 84) were found to have genetic alterations in the MYB/MYC pathway, indicating that changes in this pathway are crucial in ACC pathogenesis
  • The second most frequently mutated pathway was involved in chromatin remodeling (epigenetic modification), a pathway that includes multiple histone related proteins, and was altered in 44% of samples
  • C-kit
  • VEGF, iNOS and NF-κB were noted to be highly expressed in ACC cells as compared to normal salivary gland cells
  • members of the SOX family, such as SOX 4 and SOX10, are overexpressed in ACC
  • FABP7 (Fatty acid binding protein 7) and AQP1 (Aquaporin 1) tend to be overexpressed in ACC cell lines
  • considerable variability in HER2 overexpression ranging from 0–58% in patients with ACC
  • the study with cetuximab and concurrent chemoradiation or chemotherapy showed the highest ORR (total 43%, 9.5% CR and 33% PR), but this regimen was only given to the EGFR positive patients
  • Cancer immunotherapy can be classified into 3 major groups. Active immunization using anti-tumor vaccines to induce and recruit T cells, passive immunization based on monoclonal antibodies, and adoptive cell transfer to expand tumor-reactive autologous T cells ex vivo and then reintroduce these cells into the same individual
  • LAK cells showed cytotoxicity against ACC cells
  • cytokine-induced cell apoptosis and the cytotoxic effect of the LAK cells contributed to tumor regression
  • molecular finding of the MYB-NFIB fusion gene has the greatest potential to target what appears to be a fundamental event in disease pathogenesis
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    good review of adenoid cystic carcinoma
Nathan Goodyear

Cancer immunotherapy with low-dose interleukin-2 subcutaneous administration: potential... - 1 views

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    high dose melatonin and low-dose IL-2 in wide variety of solid tumors found tumor regression in 17 of 82 patiens (21%).  Four of these were complete remission and 13 were Partial.
Nathan Goodyear

Statins use and coronary artery plaque composition: Results from the International Mult... - 0 views

  • Statin use is associated with an increased prevalence and extent of coronary plaques possessing calcium
  • As compared with individuals not taking statins, those taking statins possessed a significantly higher prevalence of obstructive CAD, as well as higher numbers of vessels with obstructive CAD
  • non-calcified plaques (NCP)
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  • non-calcified (NCP), mixed (MP), or calcified (CP) plaque
  • statin use was each associated with a significantly higher prevalence of NCP, MP and CP
  • statin use was associated with increased presence of MP [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.27–1.68, p < 0.001] and CP (OR 1.54, 95% CI 1.36–1.74, p < 0.001], but not NCP
  • statin use was associated with increasing numbers of coronary segments possessing MP and CP but not associated with increasing numbers of coronary segments possessing NCP
  • North America, Europe and Asia
  • A total of 6673 individuals (2413 on statin therapy and 4260 not on statin therapy) comprised the study population
  • we identified a strong association of statin use to coronary artery plaque features
  • statin use was associated with a differentially increased prevalence and extent of MP and CP
  • one potential unifying hypothesis is that rather than regression of coronary plaque, statins may contribute to the conversion of coronary plaque constituents, perhaps by conversion of NCP to plaque possessing calcium
  • Coronary computed tomographic angiography (CCTA)
  • Statin use was associated with a higher frequency of severe coronary artery stenoses as well as numbers of coronary vessels with obstructive CAD
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    Study finds statin therapy associated with increased coronary plaque with calcium.
Nathan Goodyear

Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces susta... - 0 views

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    Low-dose vinblastine found to be anti-angiogenic.
Nathan Goodyear

Vitamin C may reduce the duration of mechanical ventilation in critically ill patients:... - 0 views

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    Meta-analysis finds that vitamin C shortened ventilation time by 25% in critical ill.
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