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Nathan Goodyear

Meta-Analysis of BRCA1 and BRCA2 Penetrance - 0 views

www.ncbi.nlm.nih.gov/...PMC2267287

BRCA 1 BRCA 2 SNPs single nucleotide polymorphisms cancer breast cancer ovarian cancer

shared by Nathan Goodyear on 18 Sep 17 - No Cached
  • The resulting cumulative risks by age 70 years are as follows: breast cancer risk of 55% (95% CI, 50% to 59%) for BRCA1 and 47% (95% CI, 42% to 51%) for BRCA2 mutation carriers;and ovarian cancer risk of 39% (95% CI,34% to 45%) for BRCA1 and 17% (95% CI,13% to 21%) for BRCA2 mutation carriers
  • Nathan Goodyear on 18 Sep 17
     
    good meta-analysis and discussion of the heterogenous penetrance of BRCA1 and BRCA2.  This study found lower penetrance compared to previous studies i.e. 55% breast cancer risk and 39% ovarian cancer risk in BRCA1
Nathan Goodyear

Modifiers of Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: Systematic Review and Me... - 0 views

www.ncbi.nlm.nih.gov/...PMC4081625

BRCA BRCA 1 BRCA 2 breast cancer ovarian cancer cancer

shared by Nathan Goodyear on 18 Sep 17 - No Cached
  • Nathan Goodyear on 18 Sep 17
     
    good review of how the different variables influcence the penetrance of BRCA1 and BRCA2.  Not all BRCA1/2 patients will express the same and environment plays a role.
Nathan Goodyear

Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers | Annals of Onc... - 0 views

academic.oup.com/...s-of-cancer-risk-for-BRCA1-and

SNPs epigenetics BRCA 1 BRCA 2 cancer breast cancer ovarian cancer

shared by Nathan Goodyear on 17 Sep 17 - No Cached
  • Nathan Goodyear on 17 Sep 17
     
    BRCA are actually SNPs. Great up to date review on the risks of BRCA1 and BRCA1 and the SNPs involved.
Nathan Goodyear

Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective c... - 0 views

www.thelancet.com/...fulltext

breast cancer cancer BRCA 1 BRCA BRCA 2 mastectomy

shared by Nathan Goodyear on 17 Jan 18 - No Cached
  • Nathan Goodyear on 17 Jan 18
     
    New study casts doubt on survival benefit from bilateral mastectomy in women with BRCA1 or BRCA 2 breast cancer.   Of concern also, only 14% of women had genetic testing done with most occurring at the time of diagnosis.  It is very likely that these women had significant family history that could have been identified if genetic testing was performed earlier.  
Nathan Goodyear

Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers - 0 views

www.ncbi.nlm.nih.gov/...PMC1242151

cancer BRCA BRCA 1 BRCA 2 weight loss weight obesity women breast cancer

shared by Nathan Goodyear on 18 Sep 17 - No Cached
  • Nathan Goodyear on 18 Sep 17
     
    normal weight and weight loss in women 18-30 with BRCA1 decrease risk penetrance.
Nathan Goodyear

Hormone Therapy and the Risk of Breast Cancer in BRCA1 Mutation Carriers - 0 views

www.ncbi.nlm.nih.gov/...PMC2556701

hormones hormone therapy cancer breast cancer BRCA BRCA 1

shared by Nathan Goodyear on 18 Sep 17 - No Cached
  • Nathan Goodyear on 18 Sep 17
     
    Hormone therapy in postmenopausal women with BRCA1 have decreases breast cancer risk.
Nathan Goodyear

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epitheli... - 0 views

www.pnas.org/E7301

Ivermectin cancer ovarian cancer oncogene oncogenes

shared by Nathan Goodyear on 20 Mar 18 - No Cached
  • we functionally validated a potent EOC oncogene, KPNB1, and showed its clinical relevance to human EOC
  • a well-established antiparasitic drug, ivermectin, has antitumor effects on EOC through its inhibition of KPNB1
  • EOC has high intertumor and intratumor heterogeneity at the molecular and epigenetic levels
  • ...22 more annotations...
  • the mortality rate of EOC has not been significantly changed for several decades
  • Sequencing revealed that almost all tumors (96%) had mutations in TP53, which serves as a major driver of this cancer
  • 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
  • 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
  • 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
  • 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
  • KPNB1 functions as an antiapoptotic and proproliferative oncogene in EOC.
  • Patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1
  • KPNB1 acts as an oncogene in human EOC and represents a promising therapeutic target.
  • ivermectin treatment suppressed cell proliferation/viability in a dose-dependent manner (Fig. 7A), indicating that it exerts an antitumor effect on EOC
  • ivermectin also induced apoptosis
  • ivermectin increased the expression levels of BAX, and cleaved PARP, as well as p21 and p27
  • KPNB1 inhibition is responsible for the antitumor effect of ivermectin
  • we found that ivermectin synergistically reduced cell proliferation/viability in combination with paclitaxel in human EOC cells
  • 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
  • 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
  • KPNB1 was the second-highest-ranked gene identified in our screen
  • 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
  • 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
  • higher and/or more-frequent doses of ivermectin than currently approved for humans are well tolerated in humans
  • none of the mice in this study treated with the effective dosage of ivermectin for in vivo anticancer therapy showed severe adverse event
  • we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC cell lines than either drug alone
  • Nathan Goodyear on 20 Mar 18
     
    Ivermectin found to be pro-apoptotic for the epithelial ovarian cancer oncogene, KPNB1 in in Vivo study.  This effective anti-parasitic drug inhibits the KPNB1 oncogene.
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