tbuckley/cabot-search huggingface dataset:
Neovascularization in Rats During Urinary Bladder Carcinogenesis Induced by &lt;italic&gt;N&lt;/italic&gt;-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S M Cohen, M Tatematsu, Y Shinohara, K Nakanishi, N Ito
Journal: JNCI Journal of the National Cancer Institute (1980)

Neovascularization in inbred F344 rats during urinary bladder carcinogenesis induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was examined by scanning electron microscopic observation of vascular casts. FANFT was fed to rats at a level of 0.2% of the diet for 6, 10, or 20 weeks, and vascular casts were examined in these rats at those times and after various times on control diets. Similar foci of vascular proliferation (types I and III) were observed after the use of FANFT as previously reported during bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. However, the vascular proliferations were observed to regress as the FANFT-induced epithelial proliferations regressed, similar to the observation of reversible hyperplasias induced by cyclophosphamide or ulceration. Type I vascular foci were present after 6 and 10 weeks, but no vascular lesions were seen through week 20 after these groups of rats were fed the control diet for 4 or more weeks. The epithelial lesions present after 6 and 10 weeks of FANFT feeding also regressed and the mucosa returned to normal as observed by light microscopy. Type III foci were present after 12 weeks and were observed through week 20 when epithelial tumors appeared. Rats fed FANFT for 10 weeks and then the control diet developed hyperplastic epithelial lesions and carcinomas by week 52, whereas those fed FANFT for 6 weeks had normal bladders through 52 weeks.
Response to Letter Regarding Article, “Familial Clustering of Mitral Valve Prolapse in the Community”
Authors: Francesca N. Delling, Jian Rong, Martin G. Larson, Birgitta Lehman, Ewa Osypiuk, Plamen Stantchev, Susan A. Slaugenhaupt, Emelia J. Benjamin, Robert A. Levine, Ramachandran S. Vasan
Journal: Circulation (2015)

We thank Dr Barison and colleagues for their interest in our article. 1In our manuscript, we demonstrate that both parental mitral valve prolapse (MVP) and parental mild, nondiagnostic MVP are associated with increased prevalence of MVP in the offspring in the Framingham Heart Study community.In their letter, Barison et al underline the importance of age when assessing MVP prevalence, stating that MVP is more common among older participants in the offspring or generation 2 (Gen 2) than in the younger generation 3 (Gen 3).Based on published Framingham Heart Study literature, 2 the prevalence of MVP in Gen 2 is 2.4% at their fifth examination cycle.This percentage is slightly higher in the same cohort at their sixth examination cycle (98/3380 or 2.9%) and at their eighth examination cycle (94/2725 or 3.4%; ie, 11 to 17 years after the fifth examination).In addition, in the younger Gen 3 (average age of 40 years at their first examination cycle) the prevalence of MVP is 1.4% (56/4061) and lower than in Gen 2 (average 55-67 years of age at their sixth and eight examination cycles, respectively).Of note, the proportion 49 of 3679 or 1.3% reported in our article is not the prevalence of MVP among all Gen 3 participants, but only that among those with available parental information.Overall, these findings are consistent with an age-related increase in the prevalence of MVP.In addition, reevaluation of MVP status at follow-up examination cycles of Gen 3 may help confirm these initial observations.We agree with Barison et al that only longitudinal data can answer the questions about the echocardiographic progression and long-term prognostic significance of MVP in the community.To date, MVP progression has been shown to be rapid, although previously published data relied on tertiary care samples 3 or nonrandomly selected cohorts. 4arison and colleagues also note the similarities in our article between Gen 3 participants with and without parental MVP with regard to left ventricular size and systolic function.A more direct comparison between MVP/nondiagnostic MVP morphologies and no MVP (rather than between parental and nonparental MVP) in the Framingham Heart Study Gen 2 also showed similar left-sided chamber size and function in the 2 groups. 5These results simply suggest that MVP and nondiagnostic MVP morphologies are related to true valvular disease rather than the consequence of a small, hyperdynamic ventricle.The question whether MVP is primarily a genetically determined disorder with mechanical/electric myocardial involvement is more complex and cannot be answered by our observations.Indeed, additional larger studies are warranted to address the interesting points raised by Barison et al.
Optimizing Sun Protection for Children
Authors: Albert C. Yan, Leslie Castelo-Soccio
Journal: JAMA Pediatrics (2016)

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Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) trial: Comparison of a sequential treatment with irinotecan (CPT-11) plus 5-fluorouracil (5FU)/folinic acid (LV) followed by docetaxel and cisplatin versus a 5-FU/LV regimen as postoperative treatment for radically resected gastric cancer: Tolerability and feasibility of a phase III study.
Authors: E. Bajetta, I. Floriani, M. Di Bartolomeo, R. Labianca, A. Falcone, A. Santoro, R. Casaretti, E. Pasquini, A. Martoni, C. Carlomagno
Journal: Journal of Clinical Oncology (2010)

4018 Background: Although post-operative chemotherapy (CHT) showed small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, optimal CHT regimen remains to be determined. ITACA-S trial is a no-profit, open-label, randomized, multicenter phase III study aimed at compare two adjuvant CHT treatments. Methods: Patients (pts) radically resected for gastric cancer, with ≥D1-lymphadenectomy, node involvement (pN+) or pN0 with pT2b-3-4; within 3-8 weeks after surgery were eligible. Treatment consisted in CPT-11 180 mg/m2 on d1, LV 100 mg/m2 on d1-2, 5-FU 400-600 mg/m2 on d1-2, q 14; for 4 cycles (FOLFIRI regimen) followed by docetaxel 75 mg/m2 on d1, cisplatin 75 mg/m2 on d1, q 21; for 3 cycles (arm A) versus LV 100 mg/m2 on d1-2, 5- FU 400-600 mg/m2 on d1-2, q 14 for 9 administrations (arm B). Primary endpoint was disease-free survival. The superiority hypothesis required 636 events to detect a hazard ratio of 0.80, with 2-sided 5% significance level and a power of 80%. Results: Enrollment started in February 2005 and according to Data&Safety Monitoring Committee advice terminated in August 2009 with 1,106 pts enrolled by 123 Italian centers. 6 pts were excluded for major violations, therefore 1,100 pts (537 arm A/563 arm B) were analyzed. By December 2009 with a median follow-up of 20 months, 367 events, 58% of the number required, occurred. Data on tolerability and compliance are available for 96% of pts. Post-operative treatment was completed in 74% pts (arm A) and 84% pts (arm B). The main grade 3/4 toxicity recorded were neutropenia 45% and 9%, leukopenia 17% and 1%, diarrhea 11% and 3%, asthenia 13% and 3% for arm A and B, respectively. Conclusions: Sequential regimen was associated with a worse tolerability, but showed to be feasible in adjuvant setting. Pts are still being followed-up to assess efficacy. No significant financial relationships to disclose.
Mosaic Study: Actualization of Overall Survival (Os) with 10 Years Follow Up and Evaluation of Braf. By Gercor and Mosaic Investigators
Authors: T. André, A. De Gramont, B. Chibaudel, A. Raballand, A. Duval, T. Hickish, J. Tabernero, J. van Laethem, M. Banzi, E. Maartense, A. Shani, G. Carlsson, W. Scheithauer, D. Papamichael, M. Moehler, S. Landolfi, P. Demetter, S. Dumont, J. Fléjou, A. De Gramont
Journal: Annals of Oncology (2014)
Association of human epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism (plrm) and gender-specific time to tumor recurrence (TTR) in patients (pts) with localized gastric adenocarcinoma (GA).
Authors: E. Y. Lin, P. O. Bohanes, D. Yang, G. Lurje, T. Winder, Y. Ning, E. Ho, L. H. Tang, M. A. Shah, H. Lenz
Journal: Journal of Clinical Oncology (2010)

4093 Background: Overexpression of members of the HER family (HER1-4) is associated with more aggressive GA. Further evidence is accumulating supporting gender-related differences in the risk, development and outcome of GA. Hormone receptors (ER-β) are expressed in the gastrointestinal tract and interact with HER family. Previous studies found plrms in HER1 and ER-β were associated with gender-specific survival in colorectal cancer pts. HER2 (rs1136201) Ile655Val plrm's functionality was shown in breast cell lines with Val-expressing cells exhibiting increase growth capacity. We tested the hypothesis whether germline plrms in HER family genes, including HER1/EGFR (rs11543848; rs45608036), HER2 (rs1136201), HER3 (rs2271189) and HER4 (rs6735267; rs6735626) plrms, may predict gender-specific clinical outcome in localized GA. Methods: Between 1992 and 2008, normal gastric tissues samples were obtained from 137 pts, 83 males and 54 females, with localized GA treated with surgery alone or surgery and adjuvant (radio)-chemotherapy at USC medical facilities (n = 106) or MSKCC (n = 31). The median follow-up was 3.3 years. 61 out of 137 (41%) pts had tumor recurrence, with a probability of 3-year recurrence of 52%. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens and 6 HER gene (HER1-4) plrms were analyzed using a PCR-RFLP or a 5'-end 33p γATP-labeled PCR technique. Results: HER2 Ile655Val plrm is associated with gender-related TTR (P interaction = 0.02). In multivariate analysis, female pts with the low activity HER2 Ile/Ile (n = 32) genotype have longer TTR when compared to Ile/Val or Val/Val (n = 22) genotypes (median TTR = 7.0 vs. 1.5 years; p = 0.018, log-rank test). In male pts, HER2 Ile655Val plrm is not associated with TTR. No association is observed between other tested HER plrms and TTR. Conclusions: This study shows for the first time the functional HER2 Ile655Val plrm as an independent gender-specific prognostic marker in pts with localized gastric cancer. Prospective biomarker- embedded clinical trials are needed to validate our results. No significant financial relationships to disclose.
4-Year Outcome Of 215 Patients With Newly Diagnosed Chronic Myeloid Leukemia (CML) Treated Frontline With Nilotinib In Investigator-Sponsored Studies. A Report From The Gimema CML Working Party
Authors: Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Luciano Levato, Giovanna Rege-Cambrin, Luigiana Luciano, Francesca Palandri, Alfonso Zaccaria, Monica Bocchia, Antonella Russo Rossi, Emilio Usala, Antonella Gozzini, Michele Cedrone, Mario Tiribelli, Elisabetta Abruzzese, Paolo Avanzini, Simona Soverini, Maria Teresa Bochicchio, Nicoletta Testoni, Giuliana Alimena, Fabrizio Pane, Giuseppe Saglio, Giovanni Martinelli, Michele Cavo, Michele Baccarani, Gianantonio Rosti
Journal: Blood (2013)
Oral clodronate for adjuvant treatment of operable breast cancer: Results of a randomized, double-blind, placebo-controlled multicenter trial
Authors: T. Powles, A. Paterson, E. McCloskey, M. Kurkilahti, J. Kanis
Journal: Journal of Clinical Oncology (2004)

528 Background: The bisphosphonate clodronate (Bonefos) may reduce the incidence of bone metastases by inhibiting tumor-induced osteoclastic resorption of bone. Methods: This randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of oral clodronate in 1,069 patients with primary operable stage I-III breast cancer from 1989–2000. Patients received oral clodronate (1600 mg/day) or placebo for 2 years, starting within 6 months of primary treatment (surgery, radiotherapy, and tamoxifen). Ad hoc analyses from this study have been published previously (Powles et al. JCO 2002), and the unpublished protocol-specified results and ad hoc analysis of stage II/III patients are reported here. The protocol-specified primary endpoint was time to first bone metastasis during the 5-year study period. The secondary endpoint was overall survival. These endpoints were analyzed by unstratified Log-rank test and hazard ratio (HR) with 95% CI. Results: Patient demographics were similar between treatment groups. Oral clodronate significantly reduced the risk of bone metastases by 45% in all patients during the medication period (2 years: HR = 0.546, P = 0.031), and by 31% during the study period (5 years: HR = 0.692, P = 0.043) compared to placebo. Similarly, clodronate significantly reduced the risk of bone metastases in patients with stage II/III disease during the medication (2 years: 50%, HR = 0.496, P = 0.020) and study (5 years: 41%, HR = 0.592, P = 0.009) periods. Oral clodronate vs. placebo significantly improved overall survival (23% reduction in risk of death: HR = 0.768, P = 0.048) and survival for stage II/III patients (26% reduction in risk of death: HR = 0.743, P = 0.041). Oral clodronate was well tolerated, with mild-to-moderate diarrhea being the most frequently reported adverse event. Conclusion: In patients with primary operable breast cancer, oral clodronate significantly reduced the risk of bone metastases and significantly improved survival rates during the medication and 5-year study periods compared to placebo. Similar results were seen in stage II/III patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering OY Schering AG Schering AG; Schering Oy Leiras Oy
Biomarker discovery in endometrial carcinoma using novel proteomic methods
Authors: J. A. Borgia, C. Frankenberger, S. E. McCormack, K. A. Kaiser, L. Usha, J. Rotmensch, J. S. Coon
Journal: Journal of Clinical Oncology (2006)

5034 Background: A practical serum-based screening test for endometrial and ovarian carcinomas could greatly improve their early diagnosis, but developing such a test has proved elusive. Herein, we describe methods offering increased statistical power over conventional ‘batch’ analyses, via paired patient serum samples to identify biomarkers specific for uterine endometriod carcinomas (UEA). Methods: Paired serum samples (collected pre- and post- surgery) were prepared from patients undergoing UEA resection. A Ciphergen SELDI-TOF mass spectrometer was used to generate the patient serum proteomic profiles with data acquisition optimized to the 5,000–40,000 m/z (mass) range. Spectra quality was assessed using a specific function within the R-project statistical platform (v2.2.0), whereas data analyses were performed using Bioconductor, an extension of the R statistical platform; all in a blinded manner. Raw spectra were processed as follows: spectra pair normalization, baseline subtraction, and differential peak detection (with calibrated alignment). Aligned peaks were sorted into groups, based on tumor pathology and pre- vs. post-operative specimen type, and compared using a two tailed homoscedastic t-test in Microsoft Excel 2003. Results: Pre- and post-operative serum from 10 patients with UEA had their serum proteomic profiles evaluated for peaks lost after surgery. These values were then compared with a set of ‘normal’ samples (i.e. patients undergoing surgery for benign gynecologic disease). Even with our small sample size we identified 16 serum components that were significantly reduced or absent (p &lt; 0.04) after tumor resection; 10 unique to UEA (p &lt;0.04). From this group, species at m/z values of 4291.9, 4414.2, 5036.1, 9,615.0, and 25,508.8 seem most promising, based on their high level of significance (p &lt; 0.02), for 10/10 patients. Conclusions: These results validate the power of our pre-and post-operative sample sets for the identification of new serum biomarker candidates for UEA. Work is in progress to increase the patient sample size, expand the study to patients with serous uterine and ovarian carcinomas, and identify the reported biomarker candidates via tandem mass spectrometry No significant financial relationships to disclose.
Evaluation of the <i>BRCA</i>1 and <i>BRCA</i>2 mutation prediction models in Japanese patients with breast cancer.
Authors: Reiko Yoshida, Junko Yotsumoto, Chie Watanabe, Seigo Nakamura
Journal: Journal of Clinical Oncology (2014)

46 Background: The breast cancer genetic risk models for predicting BRCA1/2 mutation are widely used before genetic testing. BRCAPRO and Myriad II are common in Europe and America, and KOHBRA BRCA risk calculator (KOHCal) is utilized in the Asian model. However, it is unknown whether these mutation prediction models are useful in Japanese. In this study, we evaluated the accuracy of BRCAPRO, Myriad II and KOHCal in Japanese patients with breast cancer. Methods: We compared sensitivity and specificity with the 10% cut off value in 131 patients with breast cancer who underwent comprehensive BRCA1/2 genetic testing at Showa University Hospital between 2011 to 2014. All patients met the genetic testing criteria of NCCN Guidelines (Genetic/Familial High-Risk Assessment: Breast and Ovarian ver.1 2014) and were received counseling before genetic testing. We assessed validity of each model by constructing receiver operating characteristic (ROC) curves, and evaluating the area under each ROC curve (AUC). The carrier probabilities of BRCA1/2 with Myriad II were calculated using BRCA risk calculator from the Myriad company 1) , with BRCAPRO using the CancerGene software program (version 6.0) from the University of Texas South-western Medical Cernter 2) , and with KOHCal using KOHBRA BRCA risk calculator from the KOHBRA Study website (www.kohbra.kr) 3) . Results: DNA analysis identified 31 deleterious mutations (23.7%) and 10 unclassified variants (7.6%). The sensitivity of KOHcal (87.1%) was higher than BRCAPRO 67.7%) and Myriad II (72.2%) . BRCAPRO (AUC=0.882) had higher diagnostic accuracy than KOHCal (AUC=0.810) and Myriad II (AUC=0.763). KOHCal might be most suitable model to pick up patients for further genetic testing because it’s sensitivity was higher than Myriad II and BRCAPRO, although it had lower specificity than the other. Conclusion: Our results suggest that BRCAPRO and KOHCal are useful in Japanese patients with breast cancer for decision making for further genetic testing for BRCA1/2 mutations.
Expression and epigenetic silencing of <i>ECRG4</i>gene in breast cancer
Authors: F. Fei, Z. Shao
Journal: Journal of Clinical Oncology (2009)

11046 Previous whole-genome expression array studies in our laboratory had shown the expression of ECRG4 (esophageal cancer related gene 4) was significantly down-regulated in primary breast cancer. The present study was undertaken to investigate the expression and epigenetic regulation ofECRG4in human breast cancer cell lines and primary carcinomas. Here we showed that the expression ofECRG4, as measured by quantitative reverse transcription-PCR, was noticeably increased in 3 methylated breast cancer cell lines (MDA-MB-435, Bcap-37, MCF-7), after treated with 5-aza-2’-deoxycytidine - a demethylation agent. Analysis from 16 paired tissue samples revealed expression of ECRG4 was significantly reverse-correlated with methylation (Spearman correlation coefficient r=-0.419, P=0.017). Analysis of 67 additional samples showed that the ECRG4 CpGs island was in high methylation level in 59.7% of cancer tissues compared with 14.9% in tumor adjacent tissues,with an odds ratio of 3.393 (95% CI, 1.912–6.021,P=8.39E-8). And patients with high methylation level had a higher tumor grade. 90% samples were high methylation levels in grade III vs. 50% in grade I-II (95% CI, 1.063–76.213, P=0.033). In conclusion, the inactivation of ECRG4 gene by hypermethylation appears to be a frequent molecular event in development of primary breast cancer and may be involved in the carcinogenesis of this cancer. No significant financial relationships to disclose.
Urbanisation but not biomass fuel smoke exposure is associated with asthma prevalence in four resource-limited settings
Authors: Chelsea Gaviola, Catherine H Miele, Robert A Wise, Robert H Gilman, Devan Jaganath, J Jaime Miranda, Antonio Bernabe-Ortiz, Nadia N Hansel, William Checkley
Journal: Thorax (2015)

<h3>Background</h3> Urbanisation is an important contributor to the prevalence of asthma worldwide, and the burden of this effect in low-income and middle-income countries undergoing rapid industrialisation appears to be growing. We sought to characterise adult asthma prevalence across four geographically diverse settings in Peru and identify both individual and environmental risk factors associated with adult asthma. <h3>Methods</h3> We collected sociodemographics, clinical history and spirometry in adults aged ≥35 years. We defined asthma as meeting one of the three criteria: physician diagnosis, self-report of wheezing attack or use of asthma medications. We used multivariable logistic regression to assess individual and environmental factors associated with adult asthma. <h3>Results</h3> We analysed data from 2953 participants (mean age 55 years; 49% male). Overall asthma prevalence was 7.1%, which varied with urbanisation: highest in Lima (14.5%), followed by urban Puno (4.0%), semiurban Tumbes (3.8%) and rural Puno (1.8%). In multivariable analysis, being male (OR=0.60, 95% CI 0.39 to 0.93) and living at high altitude (OR=0.26, 95% CI 0.16 to 0.42) were associated with lower odds of having asthma, whereas living in an urban setting (OR=4.72, 95% CI 3.15 to 7.23) and family history of asthma (OR=1.83, 95% CI 1.19 to 2.73) were associated with higher odds. Current daily exposure to biomass fuel smoke (OR=1.18, 95% CI 0.70 to 1.91) and smoking (OR=0.99, 95% CI 0.73 to 1.22) were not associated with asthma. <h3>Conclusions</h3> These findings confirm that urbanisation is an environmental risk factor of asthma, questions biomass fuel smoke exposure as an important risk factor and proposes high altitude as possibly protective against the development of asthma.
Private tuberculosis testing is cheaper in India
Authors: Cheryl Travasso
Journal: BMJ (2016)

A report in Lancet Global Health has criticised the high cost and poor availability of the latest tuberculosis (TB) test in countries with a high burden of the disease, but praised an initiative in India for making WHO approved diagnostics available at concessional prices.1

Researchers looked at the availability and cost of the Xpert MTB/RIF test2 in the private sector in 12 high burden countries: Afghanistan, Bangladesh, Cambodia, India, Indonesia, Kenya, Myanmar, Nigeria, Pakistan, the Philippines, Uganda, and Vietnam. 

Xpert MTB/RIF is a rapid automated test that takes less …