tbuckley/cabot-search huggingface dataset:
Abstract 4735: Examining known diabetes risk variants for association with prostate cancer in a multiethnic population
Authors: Kevin M. Waters, Daniel O. Stram, Iona Cheng, Frederick R. Schumacher, Lynne R. Wilkens, Kristine R. Monroe, Laurence N. Kolonel, Brian E. Henderson, Loïc Le Marchand, Christopher A. Haiman
Journal: Cancer Research (2010)

Abstract Epidemiologic studies have found evidence of an inverse association between diabetes status and prostate cancer risk. Recently genome-wide association studies of these two diseases have identified a single risk allele at the HNF1B locus that is associated with both diseases along with two risk loci (JAZF1 and THADA) that have been associated with both diseases through distinct unlinked variants. We, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study, explored the hypothesis that common genetic variation may explain, in part, the inverse association between type II diabetes and prostate cancer, by examining known diabetes risk variants for their association with prostate cancer. Our study consists of men from a prostate cancer case-control set of 2,707 cases and 2,438 controls from five racial-ethnic groups (African American, European American, Latino, Japanese American, and Native Hawaiian) of the Multiethnic Cohort. The allelic discrimination assay was used to genotype 21 diabetes risk variants from 18 loci identified by genome-wide association studies. Unconditional logistic regression was used to examine these alleles for association with prostate cancer risk. In ethnic-pooled analysis, we did not find evidence of an association with prostate cancer for the diabetes risk alleles in either of the two loci previously associated with prostate cancer (JAZF1, rs864745, OR 1.01, 95% CI 0.92-1.10; THADA, rs7578597, OR 1.11, 95% CI 0.97-1.27). An allele (rs7961581) in the TSPAN8 locus, which has been shown to be positively associated with diabetes risk had a protective association with prostate cancer at a nominally statistically significant level (OR 0.88, 95% CI 0.80-0.97, p=7.8×10-3). Except for the risk allele at HNF1B (allele G of rs4430796), which we previously reported to be associated inversely with prostate cancer, we found no evidence of an association with prostate cancer for the diabetes risk loci at JAZF1 and THADA despite other independent alleles at these loci being associated with prostate cancer. In summary, we found an association between the TSPAN8 allele and prostate cancer risk that needs to be replicated in larger populations. Resequencing and fine-mapping studies to identify causal alleles in large association studies will be important in exploring the role of common risk variants in the inverse association between diabetes and prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4735.
Abstract 4489: Clinical specimen-based investigatory study of biomarkers for gastric cancer
Authors: Takashi Oshima, Chikara Kunisaki, Shinichi Hasegawa, Hidetaka Ono, Shinichi Fujii, Tsutomu Sato, Roppei Yamada, Norio Yukawa, Yasushi Rino, Munetaka Masuda, Toshio Imada
Journal: Cancer Research (2012)

Abstract Objectives: We have identified potential biomarkers for gastric cancer using a cDNA bank on the basis of mRNA extracted from frozen specimens of gastric cancer tissue and adjacent normal gastric mucosa. We report currently available results. Methods: The study group comprised 227 patients in whom 5 or more years had elapsed since gastrectomy. The disease stage was IB in 29 patients, II in 66, III in 103, and IV in 29. Among the 139 patients who postoperatively received fluoropyrimidines, 97 with stage II or III disease were given adjuvant chemotherapy with S-1. A total 104 genes were selected on the basis of the results of comprehensive DNA microarray analysis, extraction from serial analysis of gene expression (SAGE) libraries, and preclinical and other studies of potential targets for molecular-targeted therapy. The relative expression levels of these genes in gastric cancer tissue and adjacent normal mucosa from each patient were measured by a quantitative polymerase chain reaction assay using the cDNA bank described above, and the relations between clinicopathological factors and outcomes were examined. Results: In patients who underwent gastrectomy, high expression of matrix metalloproteinase-9 (MMP9), insulin-like growth factor receptor 1 (IGF-R1), and apolipoprotein E (APOE) genes were associated with significantly worse outcomes. In patients with stage II or III disease who received adjuvant chemotherapy with S-1, high expression of IGF-R1, thymidylate synthase (TS), and regenerating IV (Reg IV) genes were associated with significantly worse outcomes. Conclusions: MMP9, IGFR-1, and APOE gene expression levels were suggested to be useful prognostic factors in patients who underwent gastrectomy for gastric cancer. In patients with stage II or III disease who received adjuvant chemotherapy with S-1, IGF-1R, TS, and Reg IV gene expression levels were suggested to be useful prognostic factors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4489. doi:1538-7445.AM2012-4489
Do isolated cells (pN0i+) in the sentinel lymph node change the post-operative management in breast cancer?.
Authors: C Charles, S Alran, Y De Rycke, I Malka, V Fourchotte, M Falcou, M Berry, M Benamor, Y Kirova, J Pierga, X Sastre, B Sigal-Zafrani, RJ Salmon
Journal: Cancer Research (2009)

Abstract Abstract #206 Background: immunohistochemical (IHC) analysis of the sentinel lymph node (SLN) allows detection of occult metastases not routinely diagnosed by conventional techniques. There is, however, no consensus concerning the post-operative management of those patients with IHC-positive (pN0i+) nodes: should one re-operate, change the medical treatment or alter the irradiation fields?&amp;#x2028; Patients and methods: 2692 patients with early invasive breast cancer underwent conservative treatment with SLN biopsy between 2000 and 2006. SLN were evaluated with frozen section followed by serial-section HES and IHC if HES showed no tumour cells. Lymph node staging followed the accepted pTNM classification: pN0, pN0i+ (≤ 0.2mm, IHC+), pNmi (0.2-2mm) and pN1a (&amp;gt; 2mm). In 1506 patients with T1pN0 tumours : 143 were pN0i+, that is 10%. We compared the post-operative management of pN0 patients, who had no completion axillary dissection (CAD), to those pN0i+ who did. All positive SLNs underwent CAD according to our institutional protocol.&amp;#x2028; Results: 15 of 143 (10.5%) pN0i+ patients showed metastases in their CAD; a single node in 10 cases, 2-3 in 4 and &amp;gt; 3 in one patient. Univariate analysis showed chemo- and hormono-therapy to be more frequently administered in pN0i+ (24.5% vs. 77.6%) compared to pN0 (9.1% vs. 55.8%) patients; p &amp;lt; 0.0001. Irrespective of the result of CAD, pN0i+ patients had significant modifications in their fields of lymphatic irradiation at the internal mammary (43.6% vs. 23.5%), supra-clavicular (40.9% vs. 21.5%) and sub-clavicular (13.5% vs. 3.7%) areas; p &amp;lt; 0.0001. Other predictive factors showed a similar pattern including age &amp;lt; 50 years (31.5% vs. 18.6%), tumour size bigger (1.51cm vs. 1.16 cm) and lymphovascular invasion (27.5% vs. 11.6%); p &amp;lt; 0,0001. After multivariate analysis, the sole decisive factor for chemotherapy between the two groups was the presence of nodal metastasis in CAD. The duration of this study is, however, insufficient to comment on the long-term implications for pN0i+ patients.&amp;#x2028; Discussion: immunohistochemistry alone plays a decisive role in favour of chemotherapy in N+ supplementary AD in only 10% of pN0i+ (15/143) patients. However, this concerns only 1% (15/1506) of those undergoing IHC so may have significant resource implications and other factors were found to be more influential. Moreover, pN0i+ patients underwent additional lymphatic irradiation, to all 3 fields, more frequently. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 206.
A multicenter, randomized trial of long-acting octreotide (LAR) in the treatment of chemotherapy-induced diarrhea (CTID)
Authors: S. Rosenoff, N. Gabrail, R. Conklin, J. Hohneker, W. Berg, J. Hedrick, G. Warsi, J. Benedetto, W. Zhu, L. Anthony
Journal: Journal of Clinical Oncology (2004)

8109 Background: Diarrhea is a common side effect of chemotherapy and can be dose-limiting in some patients (pts). Severe diarrhea often results in chemotherapy delay and/or dose-reduction, potentially reducing the overall therapeutic benefit of treatment. Octreotide, a synthetic octapeptide analogue of somatostatin, has been shown to be effective in controlling CTID in previous studies and has been recommended in guidelines for the treatment of CTID (Wadler et al, JCO 16:1998). The long-acting formulation of octreotide (Sandostatin LAR® Depot) is administered by monthly injection. This trial was designed to study the effects of two dosages of LAR, 30mg and 40mg, in pts with a history of CTID. Methods: 150 pts were planned to be enrolled. Pts with active or recent CTID and scheduled for chemotherapy were randomly assigned to receive up to 6 doses of either 30mg or 40mg of LAR via IM injection. The first 2 doses were given 7–14 days apart with subsequent treatment delivered q 28d. AEs, QOL, and pt diaries were collected. Results: An interim analysis was performed after 118 pts were enrolled and 81 pts had received at least 2 doses of LAR. There were no statistically significant differences between the two dose-groups in age, sex, race, weight, primary tumor type or chemotherapy regimens. 80.5% were being treated for colorectal carcinoma with 50% receiving 5-FU/LV +/- CPT-11. 49% of the pts entered the study with their most recent episode of diarrhea being grade III/IV by NCI-CTC. At the interim analysis the overall incidence of grade III/IV diarrhea while on study treatment was 38% (n=39) and 33% (n=42) for pts on 30 mg and 40 mg LAR respectively at Dose 2, and was 36% (n=28) and 43% (n=28) for pts on 30 mg and 40 mg LAR respectively at Dose 3. Conclusions: Accrual of the scheduled 151 pts has been completed at 43 US sites. Assessment of LAR 30 mg and LAR 40 mg in the management of recurrent CTID awaits further follow-up. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corporation
Pattern of growth of a gastric inflammatory fibroid polyp with PDGFRA overexpression
Authors: K. Yamashita, Y. Arimura, T. Tanuma, T. Endo, T. Hasegawa, Y. Shinomura
Journal: Endoscopy (2011)

A 73-year-old man with esophageal varices due to hepatitis C virus-induced cirrhosis has been followed by endoscopy since 1994. When a smooth, flat elevation first appeared in the gastric antrum in 2004 ([Fig. 1 a]), our provisional diagnosis was gastric verrucosa.
Abstract 5214: Development of a microfiltration system for the improved detection and viable capture of metastatic circulating tumor cells
Authors: Ramdane Harouaka, Mingda Zhou, Jiayun Zhang, Waleed J. Khan, Siyang Zheng
Journal: Cancer Research (2011)

Abstract The ability of metastatic cancer to release cells that travel through the circulatory system and invade different parts of the body accounts for over 90% of cancer related deaths. The fundamental challenge with detecting these circulating tumor cells (CTCs) in blood samples is the fact that they are so rare, with only a few tumors cells occurring among billions of blood cells. Since tumor cells are almost always significantly larger and more rigid than normal blood cells, size based separation has been demonstrated to be an effective method for CTC capture and enrichment. While useful for detection, size based techniques apply concentrated stresses that affect the viability of captured cells. We have incorporated novel spring structures into our microfilter design that mitigate the stresses experienced by CTCs during filtration to encourage their health and survival. The geometric design and filtration pressures have been optimized to maximize capture efficiency, enrichment against white blood cells, and tumor cell viability. This was achieved through repeated filtrations using a model system of fluorescently labeled cells from various established tumor cell lines spiked into healthy donor blood. The viability of captured cells has been confirmed through exclusion dye testing, and through the proliferation and culture of captured cells directly on the filter surface. The successful capture and primary culture of viable CTCs from clinical patient samples will allow unprecedented analysis and genetic testing of the cells directly responsible for metastasis. This could provide the basis for externally testing tumor cell response to a variety of anticancer drugs without having to expose a patient to the unnecessary cost and toxic effects of chemotherapy, thereby improving patient outcomes through the development of personalized treatment plans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5214. doi:10.1158/1538-7445.AM2011-5214
Abstract 2767: Effect of obesity on glutamine levels after L-asparaginase
Authors: Steven D. Mittelman, Nancy Hart, Lana Tom, Diandra Nuno, Anna Butturini
Journal: Cancer Research (2010)

Abstract L-asparaginase is used as a first-line agent in the treatment of acute lymphoblastic leukemia (ALL). It is believed to act primarily via depletion of the non-essential amino acid asparagine (ASN), since ALL cells are unable to synthesize sufficient ASN to meet their high metabolic demands. However, there is evidence that the depletion of glutamine (GLN) by L-asparaginase might also be important in its anti-leukemia activity. We have previously shown that children who are obese at the time they are diagnosed with high-risk ALL have a 50% higher chance of relapse. Since adipose tissue is known to produce GLN, the present study was designed to test whether obese subjects diagnosed with high-risk ALL would have less suppression of GLN after an injection of PEG-Asparaginase than their lean counterparts. Four lean (BMI 35 ± 19 %ile, 2 male/2 female) and 3 obese (BMI 98 ± 1 %ile, 2 male/1 female) adolescents with new diagnosis of high-risk ALL were studied so far. Amino acid levels were measured by HPLC in the CHLA clinical laboratory prior to and at weekly interval after injection of PEG-Asparaginase (2500 IU/m2). One lean subject received the drug intravenously, the remainder intra-muscularly. The other drugs used in induction were vincristine, daunomycin and prednisone, per CCG 1961 protocol, not on study. No dose adjustments were made based on obesity. Prior to treatment, there were no differences in plasma ASN (44.3±17.2 vs. 42.5±17.3 μM obese vs. lean, p=0.90) or GLN (539±78 vs. 567±247 μM, obese vs. lean, p=0.85) levels between groups. Two weeks after treatment, ASN levels were suppressed to ≤2 μM in both groups. In contrast, GLN levels after PEG-Asparaginase were different in obese vs. lean patients: in the obese patients, GNL level significantly increased by the second week after treatment (709±111 μM, p=0.02 vs. week 0) while no significant changes were detected in lean subjects (509±141 μM, p=0.36 vs. week 0). The change in GLN level from week 0 to 2 was +170±43 and −58±107 μM in obese and lean subjects, respectively (p=0.02). Thus, obesity appears to affect GLN levels after a single injection of PEG-Asparaginase. The differences in plasma GLN levels might reflect larger differences in GLN levels in the local leukemia microenvironment (e.g. bone marrow, adipose tissue). Although the clinical significance of this observation is limited by the small patient sample, these data highlight the need for further studies to investigate the role of obesity on the efficacies of chemotherapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2767.
Brexit would protect NHS from US interference, campaigners claim
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The NHS would be protected from a major trade deal with the United States if the United Kingdom were to leave the European Union, campaigners have said.

At the launch of the Vote Leave group’s Save Our NHS campaign held in London on 6 April, campaign organisers warned of the growing control and influence the European Union would have over the NHS if the country voted to remain in the union in June’s EU referendum.

However, these claims have been strongly rejected by pro-EU campaigners, who labelled them as “scaremongering” and said that the NHS would be protected from trade deals.

David …
Primary Care Geriatrics: A Case-Based Learning Program.
Journal: Annals of Internal Medicine (1984)

REVIEWSaccomplish breadth sacrifices depth.For example, while his expressions of concern about the value of nocturnal penile tumescence as a diagnostic indicator in erectile failure disorders are interesting and provocative, they are not complete.There is considerably more literature in this area to validate the importance of this procedure than that to which the author has given attention.The same can be said for several other areas.On balance, however, the author has taken the better tactic in providing a comprehensive view of the field rather than an intensive view of any particular area.Moreover, his conclusions, even in those areas which are not comprehensively reviewed, represent the current state of the art in almost all instances.
Abstract 284: Aspirin, NSAIDs, statins and risk of lung cancer: Gene by drug interaction
Authors: EunMi Chun, Mi-Sun Lee, Kofi Asomaning, John C. Wain, Rebeccal Heist, Li Su, David C. Christiani
Journal: Cancer Research (2011)

Abstract Lung cancer remains the leading cause of cancer-related mortality. Chemoprevention strategies have been developed to prevent lung cancer. Epidemiologic studies have shown that use of chemopreventive drugs may decrease cancer risk due to their pleiotropic effects. However, the effects of aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and statins use have not been examined in terms of lung cancer. Therefore, we aimed to investigate the effects of aspirin, NSAIDs, and statins use on reduction in the risk of lung cancer. We further examined whether genetic polymorphisms in several metabolic pathway genes modify these effects. The study population consisted of 1,582 lung cancer patients and 816 controls from the Massachusetts General Hospital (MGH). Controls were recruited from healthy friends and non-blood related family members, usually spouses of lung cancer cases or of other cases of from the cardiothoracic service. of several groups of hospital patients. SNPs were assessed in genes involved in phase II (GSTs, NAT2, EPHX, and NQO1), DNA repair (ERCC1, ERCC2, and XRCC1), DNA methylation (MTHFR C677T and A1298C), and angiogenesis (VEGF +936C&amp;gt;T, -460T&amp;gt;C, and +405G&amp;gt;C) pathways. We used logistic regression models to estimate the odds ratios (OR), adjusting for covariates including age, gender, smoking status, and pack-years. After adjustment for covariates, the use of statins and aspirin were significantly associated with a lower risk of lung cancer [OR 0.74, 95% confidence interval (CI) 0.56 to 0.97 for statins and OR 0.36, 95% CI 0.27 to 0.47 for aspirin, respectively], whereas an opposite effect was seen with NSAIDs. Significant effect modifications were found by NQO1 gene polymorphisms with the use of statins (OR 0.57, 95% CI 0.40 to 0.80 for CC versus OR 1.21, 95% CI 0.74 to 1.99 for CT or TT, P for interaction = 0.03) and by GSTP1 with aspirin use (OR 0.23, 95% CI 0.15 to 0.35 for AA versus OR 0.46, 95% CI 0.32 to 0.67 for AG or GG, P for interaction = 0.04). Our results indicate that statins and aspirins use may attenuate in the risk of lung cancer and genetic polymorphic genes may modify these associations. Further large scale studies are needed to confirm our findings and to screen for other genes that modify the relation. Supported by NIH grants CA704386, CA92824, and CA90578. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 284. doi:10.1158/1538-7445.AM2011-284
P2-01-22: Characterization of Four ER-Negative Breast Primary Tumor Dissociated Cultures as a Model for the In Vitro and In Vivo Study of Tumorigenesis, Metastasis and Angiogenesis.
Authors: K Drews-Elger, JA Brinkman, SJ Dean, D El-Ashry
Journal: Cancer Research (2011)

Abstract ER negative breast cancers comprise a subtype of tumors for which there are few therapies with successful response. Currently, the use of established cell lines has allowed detailed molecular and cellular studies on cancer mechanisms ranging form stem cells to proliferation, from tumorigenesis to invasion and metastases, and from tumor suppressors to oncogenes. But while cell lines provide a source of homogeneous, propagatable material, a drawback of this model is that most breast cancer cell lines are derived from metastatic lesions that may harbor additional mutations and have little resemblance with the primary tumor of origin. Additionally, the continuous passage of these cells over the last 20-plus years has given rise to well-established differences in growth rate, hormone receptor status, karyotype and clonogenicity. Our purpose here was to characterize four primary dissociated tumor (DT) cell cultures from ER- breast tumors, the establishment of which we had previously described, to determine if they could provide more accurate models for both in vitro and in vivo studies. These four DT cultures (DT16, DT22, DT25 and DT28) display a triple negative phenotype and were characterized by their genomic profile by the PAM50 predictor analysis as belonging to the basal (DT22, DT25 and DT28) and luminal B (DT16) subtypes. Of those cultures for which primary tumor sample was available, microarray gene expression profiling and cell line clustering analysis show the primary tumor and dissociated culture cluster together and to similar breast tumors. Interestingly, of the three basal DT cultures, DT22 clusters with Claudin-low tumors and cell lines. We have established that each of these 4 DTs are tumorigenic in the NOD/SCID mouse model, and are now assessing their metastatic potential. DT16 generated metastases in 25% of the mice (6 out of 24; two in liver, four in lymph node). DT22 generated highly vascularized tumors, which may provide a relevant model for study of the in vivo vascular recruitment process. In addition, we have analyzed and characterized the role of pivotal signaling pathways often deregulated in breast cancer such as EGFR, P-MAPK, PI3k/mTOR, p53, TGFb, Hedgehog, Notch, and Wnt in both the 2D culture as well as in sections of xenograft samples. Given that the scope of primary tumor heterogeneity and consequently the early stages of breast tumorigenesis are under-represented by current in vitro models in breast cancer research, the use of these DT cell cultures could more accurately recapitulate the disease in both the in vitro and in vivo settings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-22.