tbuckley/cabot-search huggingface dataset:
Breast cancer subtypes in Chinese Americans: A study from the Mount Sinai Health System.
Authors: Camila Masias, Theresa H. Shao
Journal: Journal of Clinical Oncology (2014)

39 Background: Breast cancer has been increasing in many Asian countries, as well as among Asian Americans. While many studies have examined breast cancer subtypes in African American and Caucasian populations, few have looked at tumor subtypes in the Asian population. We aimed to examine breast cancer subtypes in Chinese Americans. Methods: We identified all Chinese patients diagnosed with invasive breast cancers between 2005 and 2012 from the Cancer Registry of Mount Sinai Beth Israel, Mount Sinai St. Luke’s, and Roosevelt Hospitals. The following clinical data were collected for each patient: age at diagnosis, year of diagnosis, largest tumor size (cm), lymph node status, estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Based on ER, PR, and HER2, patients were categorized into three molecular subtypes: 1) Hormone receptor (HR)+ (ER and/or PR positive, HER2 negative), HER2+ and triple negative (TN) (ER, PR, and HER2 negative). Descriptive variables were analyzed using one-way Anova test. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Results: There were 175 Chinese patients diagnosed with invasive breast cancers from 2005 to 2012. Median age at diagnosis was 54 (range 27-90). One hundred fourteen (65%) were HR+, 41 (23%) were HER2+, and 20 (11%) were TN. There were 59 (34%) patients diagnosed at age ≤ 50 and twelve patients (7%) were diagnosed at age &lt; 40. There were more HER2+ and TN breast cancers diagnosed in women age ≤ 50 compared to age &gt; 50, but the difference was not statistically significant. Women in the HR+ group were diagnosed at an older age compared to the other two subgroups (57 ± 12, 52 ± 8, and 52 ± 10 for HR+, HER2+, and TN, respectively, p = 0.036). Patients with TN breast cancers were more likely to have lymph node involvement compared to HR+ or HER2+ patients (p = 0.02). There was a trend of increasing prevalence of HER2+ breast cancer observed in recent years: 18.5% in 2005-2006, 23.8% in 2007-2008, 18.4% in 2009-2010, and 29.8% in 2011-2012. Conclusions: We observed a high proportion of breast cancer among young Chinese Americans as well as an increasing prevalence of HER2+ breast cancer in this population in recent years. Further studies are warranted.
Authors’ reply to Brusasco and colleagues and Quanjer and colleagues
Authors: Francesca Conway, Azeem Majeed, Graham Easton
Journal: BMJ (2016)

In their responses to our article, 1 Brusasco and colleagues and Quanjer and colleagues suggest that current NICE guidelines on the management of chronic obstructive pulmonary disease (COPD) may lead to overdiagnosis in older people and underdiagnosis in younger people because of age related changes in lung function. 2 3
A first-in-human, phase l study to evaluate the dual PI3K/mTOR inhibitor GDC-0980 administered QD in patients with advanced solid tumors or non-Hodgkin's lymphoma.
Authors: S. Dolly, A. J. Wagner, J. C. Bendell, Y. Yan, J. A. Ware, K. E. Mazina, S. N. Holden, M. K. Derynck, J. S. De Bono, H. A. Burris
Journal: Journal of Clinical Oncology (2010)

3079 Background: The PI3K-AKT-mTOR signaling pathway is deregulated in a wide variety of cancers. GDC-0980 is a potent, highly selective, oral, dual inhibitor of class I PI3K and mTOR kinase. GDC-0980 demonstrates broad preclinical activity in breast, ovarian, lung, and prostate cancer models. Methods: This phase I dose escalation study (PIM4604g) for patients (pts) with solid tumors or non-Hodgkin's lymphoma used a 3+3 design. GDC-0980 was given on day 1, followed by 1wk washout to study single-dose pharmacokinetic (PK) and pharmacodynamic (PD) markers. GDC-0980 was then dosed QD on a 3wk on/1wk off schedule. Steady-state PK and PD were evaluated after 1wk of continuous dosing. Objectives were to determine maximum tolerated dose and dose-limiting toxicity (DLT), evaluate PD endpoints (pAKT in platelet-rich plasma [PRP] and optional fluorodeoxyglucose [FDG] uptake via positron emission tomography imaging [PET]), and describe anti-tumor activity. Results: Twelve pts have been enrolled in 4 successive dose-escalation cohorts with dose levels of 2-, 4-, 8-, and 16 mg GDC-0980 daily. The most frequently reported adverse events were nausea (25%), fatigue (50%), diarrhea (42%), and flatulence (25%). No drug-related grade 3 or higher events or DLT have been reported to date. Preliminary PK data suggest dose-proportional increases in Cmax and AUC. Preliminary PD data shows >50% inhibition of pAKT levels assayed in PRP (relative to baseline) following a single dose of 8 mg and higher GDC-0980. Potential signs of antitumor activity have been observed in a mesothelioma pt (previously treated with radiation and cisplatin/pemetrexed) who had a decrease in target lesions of ∼32% by RECIST after one cycle of 8 mg GDC-0980 QD and a soft tissue sarcoma pt who had a decrease in tumor mean SUVmax of ∼31% assessed by FDG-PET after 2 weeks of 16 mg GDC- 0980 QD. Conclusions: GDC-0980 is generally well tolerated up to 16 mg administered orally QD with potential signs of antitumor activity. Preliminary PK data suggest dose-proportional increases in exposure over the dose levels evaluated. Dose-escalation continues and updated data will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Institute of Cancer Research Arno Therapeutics, AstraZeneca, Exelixis, Genentech, GlaxoSmithKline, Merck, Novartis, Pfizer Roche Arno Therapeutics, AstraZeneca, Exelixis, Genentech, GlaxoSmithKline, Merck, Novartis, Pfizer Genentech
P0135 : Impact of vasopressin AVP1A receptor gene polymorphisms on mortality and renal failure in patients with acute decompensation of chronic liver disease
Authors: J.J. Schaapman, A.C. Kerbert, J.J. van der Reijden, A. Amoros Navarro, M. Pavesi, B. van Hoek, V. Arroyo, M. Bernardi, G. Soriano, M.-V. Catalina, P. Aguilar, H.W. Verspaget, M.J. Coenraad
Journal: Journal of Hepatology (2015)
Common variation in atrial fibrillation: navigating the path from genetic association to mechanism
Authors: Nathan R. Tucker, Sebastian Clauss, Patrick T. Ellinor
Journal: Cardiovascular Research (2016)

Atrial fibrillation (AF) is the most common cardiac arrhythmia with well-established clinical and genetic risk components. Genome-wide association studies (GWAS) have identified 17 independent susceptibility signals for AF at 14 genomic regions, but the mechanisms through which these loci confer risk to AF remain largely undefined. This problem is not unique to AF, as the field of functional genomics, which attempts to bridge this gap from genotype to phenotype, has only uncovered the mechanisms for a handful of GWAS loci. Recent functional genomic studies have made great strides towards translating genetic discoveries to an underlying mechanism, but the large-scale application of these techniques to AF has remain limited. These advances, as well as the continued unresolved challenges for both common variation in AF and the functional genomics field in general, will be the subject of the following review.
A Secreted Slit2 Fragment Regulates Adipose Tissue Thermogenesis and Metabolic Function
Authors: Katrin J. Svensson, Jonathan Z. Long, Mark P. Jedrychowski, Paul Cohen, James C. Lo, Sara Serag, Serkan Kir, Kosaku Shinoda, Julia A. Tartaglia, Rajesh R. Rao, Alain Chédotal, Shingo Kajimura, Steven P. Gygi, Bruce M. Spiegelman
Journal: Cell Metabolism (2016)
The final analysis of a multicenter randomized controlled trial of gemcitabine (G) alone versus gemcitabine and S-1 combination therapy (GS) in patients with unresectable advanced pancreatic cancer (PC): GEMSAP study.
Authors: H. Isayama, Y. Nakai, T. Sasaki, N. Sasahira, K. Hirano, T. Tsujino, M. Tada, M. Omata, K. Koike
Journal: Journal of Clinical Oncology (2011)

4040 Background: A pilot study of GS showed good results with median TTP of 10.0 months and OS of 20.4 months in unresectable PC (Oncology.2009;77:300-3). The aim of this study was to compare GS combination therapy to G monotherapy (UMIN-CTR 000000498). The first analysis at September 2009 showed significantly longer progression-free survival in GS (5.4 months) than in G (3.6 months) (presented at ASCO 2010). Overall survival was analyzed in this final analysis. Methods: Patients (pts) were randomized 1:1 to G (gemcitabine 1,000 mg/m2 30min i.v. day 1, 8, 15, repeated every 4 weeks) or to GS (G 1,000 mg/m2 30 min i.v. day1, 15 and S-1 40 mg/m2 p.o. twice daily days 1-14, every 4 weeks). Eligible pts had unresectable locally advanced or metastatic pancreatic cancer without any prior treatment and ECOG PS 0-2. Results: Between July 2006 and February 2009, 106 pts were enrolled in 6 hospitals. At the time of this final analysis, 2 pts in G and 4 pts in GS were still alive. The median age, 67 and 63, male, 62% and 79%, PS=0, 60% and 58%, locally advanced, 25% and 28% in G and GS, respectively. S-1 was introduced as second line chemotherapy in 58% patients after failure of G. Median OS was 8.8 months (95%CI, 7.0-10.6) in G and 13.5 month (95%CI, 7.8-16.3) in GS (HR 0.72, 95%CI 0.48-1.07, p=0.104), and 1-year survival rate was 30.2% in G and 52.8% in GS (p=0.031). Conclusions: The addition of S to G demonstrated significantly higher 1-year survival rate with 4.7 months increase in median OS. Though this increase in survival was not statistically significant because of the small sample size, GS may be the standard chemotherapy in advanced pancreatic cancer.
Resveratrol regulates ECM remodeling in lung fibrosis
Authors: Nikica Mise, Isis E. Fernandez, Oliver Eickelberg
Journal: European Respiratory Journal (2014)

Sirtuin 1 (SIRT1) is a protein deacetylases that is involved in regulation of cell metabolism, stress response and aging. Resveratrol, a polyphenol found in wines, it has been described as a potent activator of SIRT1 enzyme. Several studies have shown that resveratrol treatment can prevent progression of wide variety of age-associated diseases, including the pulmonary diseases. Therefore, we aim to investigate the mechanism by which SIRT1 might regulate the development and progression of lung fibrosis.  Bleomycin-treated mice were gavaged with saline or with resveratrol daily. At the day 14 all mice were sacrificed, lung function was measured and lung tissues were excised and processed for further analysis. The results have shown increased survival rate of resveratrol-treated animals, as well as significantly improved lung function. Resveratrol treatment markedly reduced levels of fibrotic markers such as fibronectin, collagen I and collagen IV. Furthermore, our data have demonstrated that resveratrol treatment increased levels of autophagy markers LC3BII and Atg5. We have also shown that resveratrol-induced autophagy in human primary fibroblasts is SIRT1-dependent. Overexpression of SIRT1 in lung epithelial cells and fibroblast, increased expression of LC3BII and promoted formation of autophagosomes. Importantly, SIRT1 silencing led to increased deposition of extracellular matrix (ECM) proteins even in the presence of resveratrol.  Taken together, these data provide evidences that resveratrol treatment decreases ECM deposition by regulation of autophagy and that this process is SIRT1-dependent. It is possible to hypothesize that SIRT1 expression and activity play a critical role during development of lung fibrosis.
Detection of ovarian cancer-specific gene by differentially expressed gene polymerase chain reaction prescreening and direct DNA sequencing
Authors: J. Kim, J. H. Pak, W. H. Choi, J. Y. Kim, W. D. Joo, D. Y. Kim, D. S. Suh, Y. M. Kim, Y. T. Kim, J. H. Nam
Journal: Journal of Clinical Oncology (2007)

21106 Background: To detect the genes differentially expressed in the ovarian cancer, we analysed the genes in the ovarian cancer and normal ovary by differentially expressed gene(DEG) PCR using the RNA extracted from the both tissues. We examined the relationship between the specific genes of ovarian cancer and pathogenesis of ovarian cancer. Methods: Differentially expressed genes were screened by ACP-based PCR. Differentially expressed bands were extracted from agarose gel, and then directly sequenced. Finally we determined the clinical importances of differentially expressed genes. Results: Some genes were overexpressed in the ovarian cancer tissue than normal ovary, such as plexin B1(PLXNB1), aminoacylase 1(ACY1), solute carrier family 25 protein(SLC25A5), triosephosphate isomerase 1(TPI 1), poliovirus receptor-related 3 protein(PVRL 3), clusterin, LY6/PLAUR domain containing 1 protein(LYPDC 1). And other five genes were more expressed in the normal ovary than ovarian cancer, such as ribosomal protein L11 and L23, tenascin XB (TNXB), complement component 1 and actin alpha 2. Conclusions: Clusterin was highly expressed in the tissue from ovarian cancer, which was identified with anti- or proapoptotic activity regulated by calcium homeostasis in prostate, breast and colorectal cancers. And it suggests the possibility that regulation of clusterin activity provides the prospect of breaking down cancer cells‘ resistance to apoptosis in the ovarian cancer. Ribosomal protein L11 and L23 was highly expressed in normal ovary, which plays an important role in regulating the stability and function of the p53 tumor suppressor protein. It suggests that suppression of ribosomal protein L11 may act an important role in proliferation of ovarian cancer and over-expression of ribosomal protein L11 may act an important role in cell cycle arrest in the treatment of the ovarian cancer. No significant financial relationships to disclose.
Pyothorax-associated lymphoma: Description of the first two cases detected in Italy
Authors: S Ascani, M Piccioli, S Poggi, A Briskomatis, G B Bolis, F Liberati, R Frongillo, C Caramatti, G Fraternali-Orcioni, B Gamberi, P L Zinzani, S Lazzi, L Leoncini, J O'Leary, P P Piccaluga, S A Pileri
Journal: Annals of Oncology (1997)
Early assessment of a population-based breast cancer screening program
Authors: L. Cortesi, V. E. Chiuri, S. Ruscelli, V. Bellelli, R. Negri, I. Rashid, C. Cirilli, E. Gallo, M. Federico
Journal: Journal of Clinical Oncology (2005)

1018 Background: The reduced mortality rate from breast carcinoma among women offered screening mammography is usually observed after 10 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening. Methods: All cases of breast cancer diagnosed in the Province of Modena between years 1996 and 2000 in women aged from 50 to 69 years, identified through the Modena Cancer Registry were linked to the data-base of the screening mammographic program (SMP), allowing the identification of cases with invasive or in situ breast cancer diagnosed in women attending or not the SMP. Stage of disease and treatment information were obtained from clinical records. All the events occurred up to June 30, 2003 were retrieved by experienced monitors. Five-year overall and event-free survival were the principal end-points of the study. Results: Between January 1,1996 and December 31, 2000, 1058 new breast cancer were detected among women aged 50–69 residents in the Province of Modena. 55% of cases were detected through the screening program. The screen-detected tumors had smaller size (13 vs 19 mm, p<0.0001) were more likely to have a pathologically confirmed negative nodal status (81% vs 62%, p<0.0001), a low histologic grade (25% vs 21%, p< 0.0001), a low proliferative activity (74% vs 61%, p<0.0001), and a positive hormonal status (84% vs 73%, p=0.02). In addition, breast conservative surgery was performed in 75% of SMP participants and in only 54% of non participants. The 5-year estimated survival rate was 94% for women with screen-detected breast cancer and 84% for those with not screen-detected breast cancer (p=0.0001). The rate of 5-year event free survival was 89% and 75% for the SMP attenders and non attenders, respectively (p=0.0001). Conclusions: Our data demonstrate a better prognosis of screen-detected breast cancers in terms of five-year overall and event-free survival, which represent an earlier measure of the efficacy of a population based breast cancer screening program. Finally, a population-based cancer registry is a relevant tool in the evaluation of the program itself. No significant financial relationships to disclose.
Are cancer patients utilizing complementary therapies? A URCC CCOP study
Authors: J. Yates, G. Morrow, K. Mustian, M. Hofman, P. Bushunow, P. J. Flynn, R. Rosenbluth, J. Atkins
Journal: Journal of Clinical Oncology (2004)

8157 Background: There is an increasing interest in complementary therapies (CT) among health care patients. CT may positively influence perceived health and disease processes, however CT usage is not well documented among cancer patients. Methods: Cancer patients (N=750) were surveyed on CT usage within two weeks of completing standard treatments. Results: Analyses revealed that, 91% (N=677) of patients surveyed reported using at least one CT since diagnosis. Data suggest that women were more likely to use CT than men (p≤.01). Of the patients surveyed, 68% (N=460) were female, 54% (N= 362) were diagnosed with breast cancer, 17% (N= 114) with genitourinary cancer, 39% (N= 262) of patients received chemotherapy, 35% (N= 235) radiation therapy and 26% (N= 173) both. CTs most frequently used by patients were prayer (85%; N= 578), relaxation (66%; N= 447), and exercise (53%; N= 356), with 46% (N= 315) of these patients utilizing 2 or 3 CTs. Ninety percent (N= 613) of patients who used CT perceived their health status as good, very good, or excellent. There were no significant differences in perceived health status between patients using and not using CT. Of the patients using CT, 51% (N=346) told their oncologist, 27% (N=186) told their primary physician, and 17% (N=114) told both about at least one treatment, however 81% (N= 550) did not discuss all the CTs they were using with either physician. Conclusions: These data suggest that cancer patients are using CT, however patients may not discuss them at all or fully with their physician. Communication will alleviate potential effects resulting from CT usage and treatments. Further research needs to assess effective ways of gathering information about CT usage during treatment in cancer patients. Supported, in part, by NCI PHS grant U10 CA37420 and by ACS grant RSG-01–071-PBP No significant financial relationships to disclose.
Development of Multiple Features of Antigen-Induced Asthma Pathology in a New Strain of Mast Cell Deficient BALB/c-KitW-Sh/W-Sh Mice
Authors: Joseph D. Hernandez, Mang Yu, Riccardo Sibilano, Mindy Tsai, Stephen J. Galli
Journal: Journal of Allergy and Clinical Immunology (2016)
Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry
Authors: Joan Sweeney, Chris C Patterson, Andrew Menzies-Gow, Rob M Niven, Adel H Mansur, Christine Bucknall, Rekha Chaudhuri, David Price, Chris E Brightling, Liam G Heaney
Journal: Thorax (2016)

<h3>Objective</h3> To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma. <h3>Design</h3> Cross-sectional observational study. <h3>Setting</h3> The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry. <h3>Participants</h3> Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)—severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control). <h3>Main outcome measures</h3> Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group. <h3>Results</h3> 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p&lt;0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p&lt;0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p&lt;0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p&lt;0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p&lt;0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified. <h3>Conclusions</h3> Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.
A detailed analysis of the risk factors influencing local and distant breast cancer recurrence during adjuvant endocrine therapy
Authors: J. Houghton
Journal: Journal of Clinical Oncology (2007)

562 Background: The ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC; ISRCTN18233230 ) trial compared the efficacy and safety of 5 years’ anastrozole, tamoxifen, or combination as adjuvant therapy for 9366 postmenopausal women with early invasive breast cancer. Here, risk factors influencing local and distant recurrences during the trial, independent of trial treatment, are assessed. Methods: The influence of standard baseline factors such as hormone receptor status, nodal involvement, tumor size, grade and age were evaluated on both local and distant recurrence rates. The use of other treatments (adjuvant chemotherapy, radiotherapy) and surgical status (mastectomy and axillary surgery) were also included. In addition, weight, body mass index, hysterectomy and prior hormone- replacement therapy were added. Cox models were used to analyze events by prognostic factors, and subsequently adjusted by country, before the production of confirmatory models. Results: For both local and distant recurrence, the highest risk correlated with poorer tumor differentiation, larger tumor size, increased nodal involvement and a negative hormone receptor status (see table ). While surgical status also affected the risk of developing a recurrence, previous treatments were less important, but residence in the USA showed a significant advantage. No association was seen with hysterectomy or weight for any recurrence. Conclusions: Although the pattern of risk varied for local and distant recurrence, tumor grade, size, and nodal involvement were the strongest risk factors for both. In comparison, the impact of previous treatments on hazard risk was lower. These data from a large international clinical trial confirm that women with less differentiated or larger tumors, and those with involved nodes, are at an increased risk of recurrence. [Table: see text] [Table: see text]