tbuckley/cabot-search huggingface dataset:
Abstract 3414: Ethnic disparities in breast cancer survival in Sarawak, Malaysia
Authors: Hyuna Sung, C.R. Beena Devi, Jennifer Guida, Tieng Swee Tang, William F. Anderson, Xiaohong R. Yang
Journal: Cancer Research (2016)

Abstract Introduction: There are three distinct South-East Asian ethnic groups in Sarawak, Malaysia (Chinese, Malay, and natives) whose breast cancer incidence rates and the distribution of tumor subtypes were reported to be significantly different. It remains unclear whether survival varies among breast cancer cases in these ethnic groups. We aimed to evaluate the relationship between survival and ethnicity when taking into account tumor characteristics. Methods: We analyzed incident breast cancer cases who were enrolled and treated in Sarawak General Hospital, Malaysia, between 1992 and 2014. The association of ethnicity with survival (relapse-free survival and overall survival) was evaluated using multivariate Cox-proportional hazard model. Subgroup analysis was conducted for each tumor subtype defined by hormone receptor (HR+, ER+ or PR+; HR-, ER- and PR-) and HER2 status (HR+/HER2-, HR+/HER2+, HR-/HER2-, and HR-/HER2+). Results: Among 2,758 eligible cases (median follow-up years, 2.90 years), there were 636 deceased and 423 relapsed cases. While there was no significant difference in disease recurrence, overall survival varied significantly by ethnicity. Compared with Chinese women, Malay women had a higher proportion of mortality (HR = 1.50; 95% CI = 1.14-1.96; P = 0.0037). This disparity remained significant only among cases with HR+ tumors (HR = 1.91; 95% CI = 1.17-3.11; P = 0.0091 among HR+/HER2-; HR = 2.74; 95% CI = 1.30-5.77; P = 0.0079 among HR+/HER2+). There was no difference in survival between Chinese and native women overall or stratified by subtype. Conclusions: Our results showed that Malay women experienced worse survival compared to Chinese women particularly among cases with HR+ tumors. Future studies are needed to clarify the underlying factors for this association in order to develop intervention strategies to reduce disparity. Citation Format: Hyuna Sung, C.R. Beena Devi, Jennifer Guida, Tieng Swee Tang, William F. Anderson, Xiaohong R. Yang. Ethnic disparities in breast cancer survival in Sarawak, Malaysia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3414.
Hepaticoplasty prevents cholangitis after pancreaticoduodenectomy in patients with small bile ducts
Authors: Masahide Hiyoshi, Takashi Wada, Yuki Tsuchimochi, Takeomi Hamada, Koichi Yano, Naoya Imamura, Yoshiro Fujii, Atsushi Nanashima
Journal: International Journal of Surgery (2016)
Abstract 849: Improved geometric deconvolution of bulk tumor genomic data
Authors: Theodore Roman, Lu Xie, Russell Schwartz
Journal: Cancer Research (2016)

Abstract We develop new methods for improved computational deconvolution of clonal populations from heterogeneous bulk genomic data. Deconvolution methods have become an important tool in resolving intratumor heterogeneity from bulk tumor genomic data, but prevailing methods are still able only to resolve only coarse-grained approximations of true clonal substructure. We seek to improve a genomic deconvolution strategy called “simplicial complex inference” that is designed to take advantage of similarity between the clonal subpopulations of single tumors or tumor regions to better infer portraits of those clonal subpopulations and their distribution across tumor samples. We evaluate the method through application to DNA copy-number (CN) data from a 472-tumor ovarian cancer (OV) panel and a 408-tumor lung squamous small cell carcinoma (LUSC) panel from The Cancer Genome Atlas (TCGA). We deconvolved the OV data into a mixture of six clonal models, two per data sample, each interpreted as a consensus copy number profile of one recurring progression stage found in a subset of OV samples. We analyzed the resulting models for enrichment of labels derived from RNASeq-based subtyping (Verhaak et al., 2013), revealing significant correspondence by chi-squared test between tumor subclusters identified by the deconvolution and OV subtypes (p = 0.0168). We further analyzed the clonal models to identify regions of significant amplification or loss, which we tested for enrichment of gene ontology (GO) terms and pathway terms through the DAVID toolkit. Ontological analysis showed significant enrichment for GO terms connected to genetic regulation and proliferation including “DNA binding,” “DNA packing,” and “protein-DNA complex” (p &amp;lt; 0.001). The LUSC data was partitioned into nine clonal models, three per sample. A log-rank test showed significant correspondence between mixture subclustering and survival for LUSC patients (p &amp;lt; 0.001). Regions of significant CN gain or loss identified in the clonal models were found by DAVID to be significantly enriched for pathway terms including “Cytokine network” (p = 0.0025) and “Cytokines and Inflammatory Response” (p = 0.0043). These findings suggest that more sophisticated models of clonal population structures can enhance our ability to deconvolve heterogeneous tumor genomic data and lead to better inference of clonal substructure. Citation Format: Theodore Roman, Lu Xie, Russell Schwartz. Improved geometric deconvolution of bulk tumor genomic data. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 849.
Abstract CT091: A neoadjuvant co-clinical trial in triple-negative breast cancer patients with genomic discovery analysis
Authors: Foluso O. Ademuyiwa, Shunqiang Li, Jingqin Luo, Tracy Skinner, Jason Hoshower, Cynthia X. Ma, Katherine Weilbaecher, Michael Naughton, Leonel Hernandez-Aya, Elaine R. Mardis, Matthew J. Ellis
Journal: Cancer Research (2016)

Abstract Background: Patients with TNBC who do not achieve a pathologic complete response (pCR) or near pCR have high rates of relapse, due to chemotherapy resistance, within the first few years after their diagnosis. Molecular biomarkers predictive for chemotherapy sensitivity are lacking. This ongoing trial is evaluating carboplatin and docetaxel in the neoadjuvant setting to determine whether these drugs will increase the pCR rate compared to historical controls. Correlative studies include exome and transcriptome sequencing on samples acquired from patients as a means to decipher the genomic architecture and clonal evolution of those who achieved a pCR compared to those who did not. The simultaneous development of patient derived xenografts (PDX) from host tumors is also planned. Methods: Patients with clinical stage 2 or 3 histologically confirmed TNBC will receive six cycles of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 every 3 weeks, followed by definitive surgery. Forty-one eligible patients will be treated according to this protocol, permitting us to attain a power of 83% to detect our expected pCR rate of 54% compared to the historical 35% rate, based on a two-sided exact binomial test at the 4.8% significance level. Eligibility: tumor size at least 2 cm, adequate organ and bone marrow function, no bilateral or inflammatory breast cancer, no invasive cancer within 5 years, ECOG performance status of ? 2, no prior sentinel lymph node biopsy. Tissue collection for xenografting and correlative studies will occur at baseline, at cycle 1 day 3, and at surgery. The primary objective is to determine the pCR rate, defined as the absence of invasive cancer in breast or nodes at definitive surgery. Secondary and exploratory objectives include xenografting rates, evaluation of mutational signatures of chemotherapy resistance and response, and comparison of chemotherapy responses between patients and their xenografts. The study was activated on 7/7/2014 and is still recruiting. Twenty (48.8% of planned 41) patients have been enrolled and have had baseline tissue banked. Fourteen patients have completed protocol therapy. Three patients have tissue at all 3 time points (9 samples), and are presently being studied by exome and transcriptome sequencing. Citation Format: Foluso O. Ademuyiwa, Shunqiang Li, Jingqin Luo, Tracy Skinner, Jason Hoshower, Cynthia X. Ma, Katherine Weilbaecher, Michael Naughton, Leonel Hernandez-Aya, Elaine R. Mardis, Matthew J. Ellis. A neoadjuvant co-clinical trial in triple-negative breast cancer patients with genomic discovery analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT091.
Evaluation of a Technology to Support a Translational Diabetes Prevention Intervention
Authors: David G. Marrero
Journal: Diabetes Care (2016)

Diabetes is now one of the greatest threats to our public health. There are now over 26 million Americans with diabetes, which exert considerable social and fiscal impact (1). More disturbingly, there are now more than 86 million people in the U.S. with prediabetes, a metabolic condition that significantly increases risk for developing type 2 diabetes (1,2). Fortunately, there is now substantial evidence that this risk can be significantly reduced by lifestyle interventions that result in modest reductions in weight and increased physical activity (3,4). Thus, there have been increasing efforts to translate these interventions into programs that can be more readily accessed by the public, and there is growing evidence that many are effective in producing weight loss that is associated with risk reduction (5). Unfortunately, many people, particularly low-income and minority populations, find it difficult to commit to a weight-loss intervention that requires structured attendance at specific venues (5,6). This has given rise to investigators trying new approaches for diabetes prevention, including the application of mobile technology, which is the basis of the study reported by Fischer et al. (7) in this issue of Diabetes Care .

The Diabetes Prevention Program (DPP), a multicenter study of strategies to prevent type 2 diabetes in high-risk individuals, demonstrated that modest …
Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering
Authors: Yu Zhang, Di Zhang, Qian Li, Jing Liang, Luyang Sun, Xia Yi, Zhe Chen, Ruorong Yan, Guojia Xie, Wanjin Li, Shumeng Liu, Bosen Xu, Lei Li, Jianguo Yang, Lin He, Yongfeng Shang
Journal: Nature Genetics (2016)
-82 A>G promoter polymorphism in the gene of human macrophage elastase (MMP-12) as a risk factor for COPD and bronchial asthma
Authors: Tanya Tacheva, Dimo Dimov, Elina Aleksandrova, Atanas Koychev, Maya Gulubova, Tatyana Vlaykova
Journal: European Respiratory Journal (2014)

Matrix metalloproteinases (MMP) are a large family of zinc-dependent proteolytic enzymes which have a pivotal role in many physiological and pathological conditions due to their ability to cleave the proteins of extracellular matrix and other biologically active proteins. MMP-12 (macrophage elastase) has been shown to be important in abnormal airway inflammation and tissue remodelingin COPD and Bronchial asthma (BA). At least 2 functional polymorphism in the promoter regions of  MMP12  have been described as the more common A allele of  MMP12  -82 A>G SNP was associated with higher gene expression. In the current study we aimed to explore the possible role of  MMP12  -82 A>G SNP in development of COPD and BA. We genotyped 119 control individuals, 167 patients with COPD and 58 with BA for  MMP12  -82A>G SNP using PCR-RFLP. The genotype distribution showed statistically significant differences between controls (AA-63.9%, AG-35.5%, GG-0.8%) and patients with COPD (AA-77.8%, AG-19.8%, GG-2.4%, p=0.010) and with BA (AA-86.2%, AG-13.8%, GG-0%, p=0.008). The obtained genotype distributions determined 1.99- fold lower risk of developing COPD (OR=0.50, 95% CI 0.30-0.85, p=0.009) and 3.53-fold lower risk of developing BA (OR=0.28, 95% CI 0.13-0.64, p=0.002) for the carriers of G allele genotypes (AG+GG) compared to the carriers of AA genotype. Based on our results we suggest that the more common A allele and AA genotype of MMP12 -82 A>G promoter polymorphism may be considered as risk factors for developing of COPD and bronchial asthma, possibly by enhancing airway wall degradation and injury due to increased levels of macrophage elastase in carriers of AA genotype.
Ipilimumab for recurrent glioblastoma: A single-institution case series.
Authors: Jethro Lisien Hu, Padmanee Sharma, John Yu, Keith L. Black, Jeremy David Rudnick
Journal: Journal of Clinical Oncology (2014)

e13010 Background: The anti-CTLA-4 monoclonal antibody ipilimumab is a potent immune modulator. Ipilimumab is FDA-approved for advanced-stage melanoma, and evidence of preclinical activity has been shown in experimental glioma models. However, experience treating glioblastoma patients with ipilimumab is limited. Methods: In this single-institution case series, we identified 5 patients with recurrent glioblastoma who were treated with ipilimumab between June 2012 to August 2013. Risks, benefits, and alternatives of this off-label therapy were discussed with each patient. Results: Age at treatment ranged from 48 to 66 years; 4 patients were male, 1 female. Number of infusions ranged from 1 to 5. Four patients received a 3 mg/kg dose per infusion; 1 patient received 2 doses at 10 mg/kg. Number of recurrences prior to starting ipilimumab ranged from 1 to 4. Four patients received additional treatment in conjunction with ipilimumab, including 3 who received bevacizumab. Time to progression was 1 month for 2 patients, 2.7 mo for 1 patient, and 6 months for 1 patient. One patient is still recurrence-free 19 months from initial treatment. This patient underwent repeat resection 3 months following treatment initiation, but no evidence of progressive disease was found. Increased granzyme B expression, suggestive of an immune response, was found on immunohistochemistry. Serum flow cytometry studies in this patient demonstrate an increasing percentage of memory and effector T-cells over time. Autoimmune-related adverse effects were seen in all 5 patients, including 2 incidences each of grade 2 rash, colitis, and hypothyroidism. One patient experienced transient grade 2 encephalitis following the first infusion. The only possible grade 3 toxicity was an episode of epilepsy partialis continua that responded to steroids. All toxicities resolved with either steroids or hormone supplementation. Conclusions: This single-institution case series highlights the potential use and adverse effect profile of ipilimumab for patients with recurrent glioblastoma. Though optimal dose and use of ipilimumab have yet to be defined, early immune response studies are encouraging. A clinical trial that incorporates ipilimumab treatment is planned to open shortly.
Case 38-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Mortimer J. Buckley, Benjamin Castleman
Journal: New England Journal of Medicine (1971)

Presentation of CaseA 66-year-old man entered the hospital because of abdominal pain and rectal bleeding.He had been well until nine years previously, when intermittent claudication developed. Two years later an aortic endarterectomy was performed, and an aortofemoral knitted Dacron bifurcation graft was inserted, extending from a level just beneath the origin of the renal arteries to the common femoral arteries. Three years before admission the left limb of the bypass graft became occluded, and thrombectomy of the graft and of the left femoral artery was performed, followed by a lumbar sympathectomy. Two months later he was readmitted because . . .
Abstract 1337: Exploration of 2-aryl fused thiophene analogs as selective inhibitors of MEK5
Authors: Patrick T. Flaherty, Dhruv Shah, Mohit Gupta, Thomas Wright, Jane E. Cavanaugh, Matthew E. Burow
Journal: Cancer Research (2016)

Abstract In several cancers intermediate enzymes in the MAPK cascades are up-regulated and may represent adaptive changes giving these cancers a competitive metabolic edge over normal cells. Additionally these alterations may induce resistance to previously useful chemotherapeutic agents. The enzyme MEK5, a component of the MEK5/ERK5 cascade, is up-regulated in several cancer types including triple negative breast cancer and prostrate cancers. Our group has previously described the synthesis and testing of anthranillic acid derived compounds and their ring constrained analogs. To explore chemical functional group tolerance and preference on the central arene ring by MEK5, a series of fused-thiophene ring variations, obtainable by the Gewald reaction were prepared and tested. These compounds were examined at 10 μM with MDA-MB-231 cells treated with EGF to induce MEK1/2 and MEK5 phosphorylation. Western blot analysis using IR-tagged antibodies against pERK1/2, pERK5, ERK1/2, or ERK5 was used to determine total and relative inhibition of MEK-mediated phosphorylation of respective pERK products. Incubation with PD0325901 resulted in full suppression of both pERK1/2 and pERK5. For the variations explored, several novel compounds were identified that resulted in no inhibition in the formation of pERK1/2 and 70% inhibition of pERK5. This establishes a new structural class of selective Type III inhibitors of MEK5 that are more amenable to structural variation, facilitating additional structure activity relationship studies. Citation Format: Patrick T. Flaherty, Dhruv Shah, Mohit Gupta, Thomas Wright, Jane E. Cavanaugh, Matthew E. Burow. Exploration of 2-aryl fused thiophene analogs as selective inhibitors of MEK5. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1337.
Evaluation of the combined expression of chemokine SDF-1α and its receptor CXCR4 as a marker for prognosis in gastric cancer.
Authors: H. Lee, Y. Oh, H. Kim, S. Jin, H. Yun, D. Jo, S. F. Kim
Journal: Journal of Clinical Oncology (2010)

10630 Background: Chemokine SDF-1α and its receptor CXCR4 have been shown to impact cancer progression. Accumulating evidence suggests that CXCR4 and SDF-1α expression is useful for evaluating the risk of gastric cancer progression. CXCR4 expression is associated with lymph node metastasis and development of peritoneal carcinomatosis in patients with gastric cancer, and SDF-1α expression in the primary cancer is reported to be an independent prognostic factor in these patients. Thus, combined analysis of SDF-1α and CXCR4 would have strong prognostic potential as a molecular marker for gastric cancer. Here we investigated for the first time the effects of combined CXCR4 and SDF-1α expression on the prognosis of patients with gastric cancer. Methods: We studied SDF-1α and CXCR4 protein expression in 221 specimens of primary gastric cancer using immunohistochemistry, and analyzed the clinicopathological features and clinical outcomes. Results: Patients were categorized into three groups according to CXCR4 and SDF-1α expression: high CXCR4/high SDF-1α, low CXCR4/low SDF-1α, and high CXCR4/low SDF-1α–low CXCR4/high SDF-1α. No significant differences existed in age, gender, histology, tumor location, lymphovascular invasion, or proportion of tumor size < 5 cm among the three groups. However, high CXCR4/high SDF-1α expression in tumor cells was significantly associated with invasion depth of the tumor (T status; p = 0.001), lymph node involvement (N status; p = 0.029), and higher tumor stage (p = 0.001) compared to tumors with low CXCR4/low SDF-1α expression or high CXCR4/low SDF-1α–low CXCR4/high SDF-1α expression. Furthermore, patients with high CXCR4/high SDF-1α expression had the worst prognosis (5-year survival rate 26.7%; median, 2.2 years; range, 0.8 - 3.6 years), whereas patients who had low CXCR4/low SDF-1α expression showed the most favorable prognosis (5-year survival rate, 57%; median, not reached; log-rank test, p = 0.01). Conclusions: CXCR4 and SDF-1α are useful prognostic factors in gastric cancer, and the combination of high CXCR4 protein expression with high SDF-1α expression suggests a dismal prognosis. No significant financial relationships to disclose.
Residual tumor volume and change in tumor volume during adjuvant therapy to predict long-term survival in AVAglio: Phase 3 newly diagnosed glioblastoma patients treated with radiation, temozolomide, and bevacizumab or placebo.
Authors: Benjamin M. Ellingson, Josep Garcia, Cedric Revil, Olivier L. Chinot, Wolfgang Wick, Frank Saran, Ryo Nishikawa, Roger Henriksson, Warren P. Mason, Lauren E. Abrey, Timothy Francis Cloughesy
Journal: Journal of Clinical Oncology (2016)

2021 Background: Anti-angiogenic agents have raised doubts about the reliability of contrast enhancement as a surrogate of tumor burden in glioblastoma (GBM). Contrast-enhanced T1 subtraction maps increase lesion conspicuity in anti-angiogenic therapy. In the current study we used T1 subtraction maps to test whether post-surgical residual enhancing tumor volume and early changes in contrast enhancement during adjuvant therapy are prognostic of overall survival (OS) in patients with newly diagnosed GBM treated with radiation (RT) and temozolomide (TMZ) with or without bevacizumab (BV). Methods: A total of 798 patients (404 BV and 394 placebo) with newly diagnosed GBM enrolled in the AVAglio trial (Phase III; NCT00943826) had post-surgical, pre-RT MRI scans available. A total of 359 BV-treated and 333 placebo-treated patients had > 3 MRI scans for analyses. The volume of tumor with contrast enhancement plus central necrosis after T1 subtraction was quantified. Results: Patients with large (> 10cc) residual enhancing tumors after surgery have a significantly shorter OS regardless of chemotherapy (All patients, HR = 0.61, P < 0.0001; BV, HR = 0.62, P < 0.0001; Placebo, HR = 0.60, P < 0.0001). A decrease in enhancing tumor volume after RT and TMZ/TMZ+BV with respect to the pre-RT baseline predicted OS in the placebo arm (HR = 0.63, P < 0.0001) but not the BV arm (HR = 0.88, P = 0.49). If the post-RT/TMZ with or without BVscan is used as a new baseline for subsequent evaluation, change in enhancing tumor volume was a strong predictor of OS in both treatment arms (BV, HR = 0.74, P = 0.02; Placebo, HR = 0.66, P = 0.0003). Conclusions: Post-surgical residual enhancing tumor volume is prognostic for OS in newly diagnosed GBM patients. Change in enhancing tumor volume is useful as an early measure of response as indicated by correlation with OS in both treatment arms only after initial therapeutic changes have occurred. Thus, results suggest the first scan after radiation therapy should be used as the baseline for subsequent radiographic evaluation in both standard and anti-angiogenic treatment paradigms. Clinical trial information: NCT00943826.