tbuckley/cabot-search huggingface dataset:
Abstract P4-13-02: BRCA1/2 founder mutations among high-risk HBOC patients from Northeast of Brazil
Authors: Ivana L Nascimento, Gabriela ES Felix, Camila A Sandes, Taisa B Machado-Lopes, Thais F Bomfim, Roberto Meyer, Maura Romeo, Betania Toralles, Kiyoko A Sandes
Journal: Cancer Research (2015)

Abstract Background: Genetic susceptibility to Hereditary Breast and Ovarian Cancer (HBOC) syndrome could be test by the screening of BRCA1 and BRCA2 genes. Thus, knowing that each population has its degree of heterogeneity and the Brazilian population is one of the most heterogeneous of the world, we aimed to verify the frequency of BRCA1/2 founder mutations in high-risk HBOC patients from Bahia, the biggest State of the Northeast of Brazil. Methods: It was analyzed the DNA of 98 unrelated high-risk HBOC patients, considering the criteria of NCCN v.1.2010. These patients were tested for the next founder mutations: BRCA1 c.211A&amp;gt;G (Galician), BRCA1 943ins10 (African), BRCA1 3450del4 (Hispanic) and BRCA2 c.5946_5946delT (Portuguese) by sequencing or PCR/RFLP. All positive results were confirmed by two sequencing reactions. The genetic ancestry was analyzed with a panel of 10 ancestry informative markers (AIMs). The clinical and epidemiological data were collected during the genetic counseling and were analyzed in Epi InfoTM 7, while the frequency of the AIMs was analyzed in GENEPOP, and in ADMIX95 the genetic admixture was estimated. Results: All patients had personal and/or familial history of breast and/or ovarian cancer. Most of the patients self-reported as mulatto (61.23%), followed by black (21.43%), white (10.20%) and others (7.14%). The African, Amerindian and European ancestry contribution estimated were 35.33%, 11.31% and 53.35% respectively (R2 = 0.998). Two mutations were detected the BRCA1 3450del4 in five patients (4.90%) and the BRCA1 c.211A&amp;gt;G in two patients (2.04%). All patients with these mutations were from State of Bahia and self-reported as mulatto or white. Any carrier declared as Spanish descendant. Conclusion: Although the Portuguese settled Brazil, here it was observed that this population seems to have high Spanish ancestry contribution, due to the high frequency of the BRCA1 3450del4 and c.211A&amp;gt;G (6.94%). It is also interestingly the absence of BRCA1 943ins10, because the State of Bahia has the higher rate of African-descendants in Brazil and most of the patients exhibited these physical traits (mulatto and black, 82.65%). Thus, high-risk patients from that region of Brazil could be screening first for the BRCA1 3450del4 and BRCA1 c.211A&amp;gt;G, where it has a founder effect. Citation Format: Ivana L Nascimento, Gabriela ES Felix, Camila A Sandes, Taisa B Machado-Lopes, Thais F Bomfim, Roberto Meyer, Maura Romeo, Betania Toralles, Kiyoko A Sandes. BRCA1/2 founder mutations among high-risk HBOC patients from Northeast of Brazil [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-13-02.
A Phase I Study of Estramustine, Weekly Docetaxel, and Carboplatin Chemotherapy in Patients with Hormone-Refractory Prostate Cancer
Authors: William K. Oh, Elizabeth Hagmann, Judith Manola, Daniel J. George, Timothy D. Gilligan, Joseph O. Jacobson, Matthew R. Smith, Donald S. Kaufman, Philip W. Kantoff
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To define the maximal tolerated dose, safety, and efficacy of docetaxel, carboplatin, and estramustine in patients with hormone-refractory prostate cancer (HRPC). Methods: Patients with HRPC received docetaxel for 3 weeks, followed by a rest week. Docetaxel (20, 25, 30, 36, or 43 mg/m2) was given on days 2, 9, and 16 of a 28-day cycle. Patients also received estramustine (140 mg p.o. three times daily on days 1-5, 8-12, and 15-19) and carboplatin [area under the curve, AUC (5) or (6) on day 2]. Results: Thirty patients were treated. Five patients received carboplatin [AUC (6)] but experienced delayed thrombocytopenia. After a protocol amendment, 25 subsequent patients received carboplatin [AUC (5)]. Median age was 64 years. Median prostate-specific antigen (PSA) was 117 ng/mL. Fifty-three percent received prior ketoconazole and 10% had mitoxantrone. No dose-limiting toxicities were noted. Although maximal tolerated dose was not reached, docetaxel dose escalation was stopped at 43 mg/m2. Significant myelosuppression was not seen until the highest dose level, when seven and four patients experienced grade 3 and 4 toxicities, respectively. Among all patients, PSA declines of ≥50% occurred in 63%. At the recommended phase II dose, PSA declines of ≥50% occurred in 75% (95% confidence interval, 43-95). Four of 14 (29%) patients with measurable disease had partial responses. Median survival was 14.6 months. Conclusions: Estramustine, docetaxel, and carboplatin are well tolerated and active in HRPC. Myelosuppression is the primary toxicity. The recommended phase II dose of docetaxel is 43 mg/m2 combined with estramustine and carboplatin. PSA declines were seen at every dose level.
miR-221/222 Are Involved in Response to Sunitinib Treatment in Metastatic Renal Cell Carcinoma
Authors: Heba W Z Khella, Henriett Butz, Qiang Ding, Fabio Rotondo, Kenneth R Evans, Peter Kupchak, Moyez Dharsee, Ashraf Latif, Maria D Pasic, Evi Lianidou, Georg A Bjarnason, George M Yousef
Journal: Molecular Therapy (2015)

Sunitinib is a multitargeting tyrosine kinase inhibitor used for metastatic renal cancer. There are no biomarkers that can predict sunitinib response. Such markers are needed to avoid administration of costly medication with side effects to patients who would not benefit from it. We compared global miRNA expression between patients with a short (≤12 months) versus prolonged (>12 months) progression-free survival (PFS) under sunitinib as first-line therapy for metastatic renal cell carcinoma. We identified a number of differentially expressed miRNAs and developed miRNA statistical models that can accurately distinguish between the two groups. We validated our models in the discovery set and an independent set of 57 patients. Target prediction and pathway analysis showed that these miRNAs are involved in vascular endothelial growth factor (VEGF), TGFβ, and mammalian target of rapamycin (mTOR)-mediated signaling and cell-cell communication. We tested the effect of these miRNAs on cellular proliferation and angiogenesis. We validated the negative correlation between miR-221 and its target, VEGFR2.miR-221 overexpression was associated with a poor PFS while its target, VEGFR2 was associated with longer survival. Gain of function experiments showed that miR-221 and miR-222 decreased angiogenesis and cellular proliferation in human umbilical vein endothelial cells (HUVEC) while increasing cellular proliferation in ACHN cells. miRNAs represent potential predictive markers for sunitinib response.
GSTP1 and MC1R in melanoma susceptibility
Authors: R.A. Sturm
Journal: British Journal of Dermatology (2012)

Conflicts of interest None declared. Funding sources No external funding. The glutathione S‐transferase enzymes (GSTs) are important in the detoxification of reactive free radical oxygen species formed as a by‐product of melanin synthesis in melanocytes and following ultraviolet radiation (UVR) exposure of the skin. Of considerable interest to genetic epidemiologists has been the observation that the GST gene family is highly polymorphic, with GSTM1 deleted in approximately 50% and GSTT1 in 20% of European‐descendent populations. This complete loss of enzyme function from these two genes in the nullizygous state has been recognized as candidate risk factors for a number of medical conditions, including melanoma susceptibility.1 There are nonsynonymous codon changes within the GSTP1 protein but no copy number variation reported. The MC1R gene is also highly polymorphic with variant RHC alleles associated with red hair,2 fair skin, sun sensitivity and high rates of skin cancer.3 It was the first low‐penetrance gene recognized that could, dependent upon sun exposure, increase an individual’s risk of developing melanoma. In addition to MC1R RHC variants leading to compromised tanning ability and the switching of melanin towards the less photoprotective red‐yellow pheomelanin, they are also now known to be involved in regulating the DNA damage response of melanocytes to UVR.4, 5
TNF-α sensitizes HL-60 cells to DMSO-induced differentiation
Authors: Eun-Mi Noh, Young-Rae Lee, Jong-Suk Kim, Myung-Kwan Han, Myung Ju Ahn, Se Hoon Park, Dong Bok Shin, Jae Hoon Lee, Jinny Park
Journal: Cancer Research (2007)

4386   Tumor necrosis factor-α (TNF-α) induces monocyte differentiation in HL-60 human myeloid leukemia cells. We investigated the effects of TNF-α on the susceptibility of human myeloid leukemia HL-60 cells to dimethyl sulfoxide (DMSO). TNF-α sensitized HL-60 cells towards the induction of differentiation in response to DMSO. The DMSO-induced cell cycle arrest and differentiation of HL-60 cells were enhanced more by DMSO plus TNF-α than by DMSO alone. However, TNF-α alone had no significant effect on the differentiation of HL-60 cells. The enhancement of DMSO-induced HL-60 differentiation by TNF-α was offset by pyrrolidine dithiocarbamate, a strong inhibitor of nuclear factor (NF)-κB inhibitor, indicating that the synergistic effect of TNF-α and DMSO on the differentiation of HL-60 cells is mediated by cellular NF-κB. These results suggest that TNF-α in combination with DMSO may be a useful agent in treatment models of leukemia.
207. Micro RNAs as Novel siRNA Shuttles
Authors: Ryan Boudreau, Haibin Xia, Beverly L. Davidson
Journal: Molecular Therapy (2004)

Top of pageAbstract
Huntington's disease (HD) and Spinocerebellar ataxia type I (SCA1) are two of a class of dominant, neurodegenerative diseases caused by a polyglutamine (polyQ) expansion. The mutation confers a toxic gain of function to the protein, with polyQ length predictive of age of onset and disease severity. There is no curative or preventative therapy for HD or SCA1, supporting the investigation of novel strategies. In other work, we showed that gene silencing by RNA interference (RNAi) can be achieved in vitro and in vivo by expressing short hairpin RNAs (shRNAs) specific for mRNAs encoding ataxin-1 or huntingtin. Currently, strong, constitutive polIII promoters (U6 and H1) are used to express shRNAs, which are subsequently processed into functional small interfering RNAs (siRNAs). However, strong, constitutive expression of shRNAs may be inappropriate for diseases that take several decades to manifest. Moreover, high-level expression may be unnecessary for sustained benefit, and in some systems may induce a non-specific interferon response leading to global shut-down of gene expression. We therefore investigated the use of polII-expressed microRNAs (miRNAs) as siRNA shuttles as an alternative strategy. Due to their endogenous nature, miRNA backbones may prevent the induction of the interferon response. Using human mir-30 as a template, we designed miRNA shuttles that upon processing by dicer would release siRNAs specific for ataxin-1. Constructs containing polII-expressed miRNA shuttles with embedded ataxin-1-specific siRNAs were co-transfected into cells with GFP-tagged ataxin-1, and gene silencing was assessed by fluorescence microscopy and western analysis. We observed dramatic and dose-dependent gene silencing relative to non-specific miRNAs carrying control siRNAs. This polII-based expression system exploits the structure of known miRNAs and supports tissue-specific as well as inducible siRNA expression, and thus, serves as a unique and powerful alternative to dominant neurodegenerative disease therapy by RNAi.
Leukocyte depletion of random single-donor platelet transfusions does not prevent secondary human leukocyte antigen-alloimmunization and refractoriness: a randomized prospective study
Authors: K Sintnicolaas, M van Marwijk Kooij, HC van Prooijen, BA van Dijk, WL van Putten, FH Claas, VM Novotny, A Brand
Journal: Blood (1995)
Commentary
Authors: Nanette Mutrie
Journal: British Journal of Sports Medicine (2000)

Objectives-To explore, using qualitative methods, the concept of exercise dependence.Semistructured interviews were undertaken with subjects screened for exercise dependence and eating disorders.Methods-Female exercisers, four in each case, were allocated a priori to four groups: primary exercise dependent; secondary exercise dependent, where there was a coincidence of exercise dependence and an eating disorder; eating disordered; control, where there was no evidence of either exercise dependence or eating disorder.They were asked about their exercise and eating attitudes and behaviour, as well as about any history of psychological distress.Their narratives were taped, transcribed, and analysed from a social constructionist perspective using QSR NUD*IST.Results-Participants classified as primary exercise dependent either showed no evidence of exercise dependent attitudes and behaviour or, if they exhibited features of exercise dependence, displayed symptoms of an eating disorder.Only the latter reported a history of psychological distress, similar to that exhibited by women classified as secondary exercise dependent or eating disordered.For secondary exercise dependent and eating disordered women, as well as for controls, the narratives largely confirmed the a priori classification.Conclusions-Where exercise dependence was manifest, it was always in the context of an eating disorder, and it was this comorbidity, in addition to eating disorders per se, that was associated with psychological distress.As such, these qualitative data support the concept of secondary, but not primary, exercise dependence.
Antimicrobial activity of bismuth subsalicylate on<i>Clostridium difficile</i>,<i>Escherichia coli</i>O157:H7, norovirus, and other common enteric pathogens
Authors: Adam M Pitz, Geun Woo Park, David Lee, Ying L Boissy, Jan Vinjé
Journal: Gut Microbes (2015)

Previous studies have shown bismuth subsalicylate (BSS) has antimicrobial properties, but few studies have addressed the mechanism of action. Furthermore, following BSS ingestion other bismuth salts form throughout the gastrointestinal tract including bismuth oxychloride (BiOCl) that also act upon enteric pathogens. To further understand the antimicrobial activity of bismuth in infectious diarrhea, the antimicrobial effect of BSS and BiOCl on Clostridium difficile, Salmonella, Shigella, Shiga toxin-producing Escherichia coli strains and norovirus (NoV) were measured. Bacterial enteric pathogens in pure culture or in human fecal material were exposed to 35mg/ml BSS or BiOCl with or without a vehicle suspension. BSS and BiOCl treated samples were quantified and visualized by transmission electron microscopy. To measure the effect on NoV, reduction of infectious murine NoV (MNV), a surrogate for human NoV, and Norwalk virus RNA levels were measured by viral plaque assay and RT-qPCR, respectively. BSS and BiOCl reduced bacterial growth by 3–9 logs in all strains with majority resulting in populations of <10 cfu/ml within 24 h. Similar results were found when fecal material was included. Microscopy images detected bismuth on bacterial membranes and within the bacterial organisms at 30 min post-treatment. At 8.8mg/ml BSS and BiOCl reduced infectivity of MNV significantly by 2.7 and 2.0 log after 24 h of exposure. In addition, both BSS and BiOCl slightly reduced the level of Norwalk replicon-bearing cells suggesting that bismuth may inhibit NoV in vivo. Collectively, our results confirm and build on existing data that BSS has antimicrobial properties against a wide-range of diarrhea-causing pathogens.
Early Manifestations of Rheumatic Infections in Young Children
Authors: C. C. Mclean
Journal: Annals of Internal Medicine (1932)

Article1 May 1932Early Manifestations of Rheumatic Infections in Young ChildrenC. C. MCLEAN, M.D., F.A.C.P.C. C. MCLEAN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-11-1357 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe early manifestations of rheumatic infections in children are characterized by an insidious onset. Such children are pale, easily fatigued, have poor appetites and are not gaining in weight as they should. Many complain of slight pains in the legs, feet or joints. There is often stiffness of limbs or neck. Digestive disturbances with paroxysmal abdominal pains are common. There is a change in disposition. The children become irritable, nervous, peevish and are easily frightened. Often there is a failure in mental concentration and they begin to drop objects and at times have difficulty in writing. There may be slight...References1 Heart disease and its prevention, Am. Heart Assoc., 1928, Series No. 4, 4-6. Google Scholar2 DROLET GJ: Heart disease: the outstanding health problem. New York Tuberculosis and Health Assoc., 1926, Bull. 7, 18-22. Google Scholar3 WYCKOFFLINGG JC: Statistical studies bearing on problems in the classification of heart disease. 2. Etiology in organic heart disease, Am. Heart Jr. 1926, l, 446-448. CrossrefGoogle Scholar4 MUNLY WC: Problems in the prevention and relief of heart disease, Am. Jr. Pub. Health., 1928, xviii, 1098-1100. CrossrefGoogle Scholar5 STERLING B: Statistics in registration area in United States, 1928. Congressional Record, U. S. Gov't. Printing Office, Washington, 1931 (60690-7403), 44. Google Scholar6 FEER E: Pediatrics, First Eng. ed., 1922, 707. Google Scholar7 RIESMANSMALL DJC: Rheumatic fever; clinical manifestations, etiology and treatment, Ann. of Int. Med., 1929, ii, 637-639. Google Scholar8 COOMBS CF: The diagnosis and treatment of rheumatic heart disease in its early stages, Brit. Med. Jr., 1930, i, 227-229. CrossrefGoogle Scholar9 STILL CF: Common disorders and diseases of childhood, Fifth ed., 1927, 576-78. Google Scholar10 MCLEAN CC: Early rheumatic infections of childhood, Arch. of Ped., 1929, xlvi, 657-59. Google Scholar11 SCHLOSS OM: The normal percentage of the different variations of leukocytes in infants and children, Arch. Int. Med., 1910, vi, 638-40. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Birmingham, Alabama*Read before the Chattahoochee Valley Medical and Surgical Association, Radium Springs, Ga., July 14, 1931. Received for publication, October 22, 1931. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1932Volume 5, Issue 11Page: 1357-1366KeywordsAbdominal painArthralgiaAttentionChildrenPediatric infectionsStiffnessWeight gain ePublished: 1 December 2008 Issue Published: 1 May 1932 PDF downloadLoading ...
Chemical Induction of Neoplasms in the Kidney of Rana pipiens
Authors: Edith Strauss, G. M. Mateyko
Journal: Cancer Research (1964)

Summary  Five organic compounds were injected directly into the kidney of Rana pipiens in an attempt to induce frog renal adenocarcinomas. Under general anesthesia open surgery facilitated the examination of the kidneys and insured a tumor-free condition. The following—3,4-benzpyrene (BP), 5,7-dimethyl-1,2-benzacridine (DMBA), and 3-methylcholanthrene (MC)—had to be discontinued because of toxic effects. p-Aminoazobenzene (AB), and 1,2,5,6-dibenzanthracene (DBA) were well tolerated so that their effects could be evaluated. Ninety-five frogs were given injections of AB or DBA, out of which 62 lived longer than 3 weeks, the minimum time-span found to be required for a neoplastic kidney response.  At autopsy, white nodules were seen in the kidneys of 48 frogs; other organs, primarily the liver and lungs, were also frequently nodular. Histological examination of 37 animals showed that fifteen had developed typical renal adenocarcinomas, more than a threefold tumor incidence compared with the highest spontaneous tumor occurrence so far encountered under similar environmental conditions. Of these, three frogs demonstrated adenocarcinomas unilaterally on the injected kidney, and twelve kidneys revealed bilateral tumors. The tumor incidence was higher in females than in males. Histological and histochemical findings corresponded to those previously observed in the Lucke tumor.
Promoter hypermethylation of the neurofilament heavy chain gene in human esophageal cancer
Authors: Xiaofei Chang, Myoung Kim, Keishi Yamashita, Jin Baek, Yutaka Tokumaru, Chulso Moon, David Sidransky
Journal: Cancer Research (2007)

2860  Epigenetic silencing of tumor suppressor genes in neoplasia has been recognized as a common mechanism of cancer development. Genes which exhibit frequent cancer-specific methylation may have tumor suppressive activities and hold value as biomarkers for cancer diagnosis. Pharmacological unmasking in esophageal squamous cell carcinoma (ESCC) cell lines uncovered the neurofilament heavy chain (NEFH) gene as a candidate methylated gene. NEFH expression was silenced in ESCC cell lines and reactivated by the demethylating agent, 5-aza-2’-deoxycytidine. Quantitative methylation-specific PCR detected NEFH promoter hypermethylation in 34/70 (48.5%) primary human ESCC and absent or minimal levels in normal corresponding tissues. Moreover, overexpression of NEFH in ESCC cell lines effectively inhibited the formation of cell colonies (44% compared to control vector). NEFH silencing may, thus, provide a selective growth advantage during ESCC tumorigenesis. Furthermore, NEFH methylation shows promise as a biomarker for ESCC due to its common occurrence and high cancer cell specificity.