tbuckley/cabot-search huggingface dataset:
Whole-Exome Analysis Reveals Novel Somatic Genomic Alterations Associated with Cell of Origin in Diffuse Large B-Cell Lymphoma
Authors: Kerstin Wenzl, Bryce Manso, Yan W Asmann, Matthew J Maurer, Michelle Manske, Zhi-Zhang Yang, Susan L. Slager, Grzegorz S. Nowakowski, Stephen M Ansell, Thomas E. Witzig, Andrew L Feldman, Lisa Rimsza, Brian K Link, James R Cerhan, Anne J. Novak
Journal: Blood (2016)
Metastatic breast cancer in males: Impact of primary tumor resection.
Authors: Mahvish Muzaffar, Nasreen A. Vohra
Journal: Journal of Clinical Oncology (2015)

e12051 Background: Male Breast cancer is a rare disease but majority of the patients present with locally advanced or metastatic disease as opposed to female breast cancer. Primary Tumor Resection (PTR) is not routinely recommended for patients with metastatic breast cancer at diagnosis because of the incurable nature of disease. Impact of local surgery on survival is unclear. We undertook analysis to assess impact of PTR on survival of males with metastatic breast cancer at diagnosis using a national database. Methods: All Male patients with Stage IV breast cancer between the years 1988-2011 in the SEER database were identified. Uni and multivariate descriptive and survival analyses were performed. Results: 439 male Stage IV breast cancer patients’ were identified in SEER database. Median age of patients was 65yrs. More than 30% of patients had T3/T4 primary lesions, 65% of patients had estrogen receptor positive tumor, and 68% had invasive ductal carcinoma. Around 51% of males with metastatic breast cancer at presentation underwent PTR. Univariate analysis between surgery versus no surgery arm showed race (p = 0.04), T stage ( < 0.0001), ER positivity (0.0002), nodal status ( < 0.0001), treatment with radiation therapy (0.003) and year of diagnosis (0.006) as statistically significant. Multivariate analysis revealed race (0.08) T stage ( < 0.05), favorable histology as significant factors between the two groups. Surgery was associated with improved disease-specific median survival 36 vs. 21 months on univariate analysis and on multivariate analysis, not undergoing PTR was independently associated with increased mortality (HR 1.91, p < 0.05) Conclusions: Primary tumor resection among men with metastatic breast cancer was associated with improved survival. Men with breast cancer present with locally advanced cancer with significant local symptoms and may benefit from PTR.
A phase II study of biweekly oxaliplatin and S-1(SOX) as first-line combination therapy in patients with advanced gastric cancer.
Authors: Jing Deng, Genming Shi, Yulong Zheng, Jiong Qian, Haiping Jiang, Chenyu Mao, Xiaochen Zhang, Yao Wang, Nong Xu
Journal: Journal of Clinical Oncology (2015)

e15094 Background: Oxaliplatin and S-1 are both effective anti-tumor agents in advanced gastric cancer. However, the continuous administration of S-1 for three weeks or more can result in unacceptable toxicities, particularly hematological toxicities. Therefore, an alternative treatment schedule (one-week administration followed by a one-week rest) is warranted for testing in order to allow continuation of the therapy. We evaluated the efficacy and safety of biweekly oxaliplatin and S-1(SOX) as first-line combination therapy in patients with advanced gastric cancer. Methods: We enrolled untreated patient ( ≥ 18 years) with locally advanced or metastatic gastric cancer. Patients were administered intravenously oxaliplatin at a dose of 85 mg/m2 on day 1 and oral S-1 twice daily (BSA < 1.25 m2, 80 mg/day; 1.25 < or = BSA < 1.50 m2, 100 mg/day; 1.50 m2 < or = BSA, 120 mg/day) on days 1-7 followed by a drug-free interval of 1 week every 14-day a cycle. Results: Forty-six Chinese patients were included. Thirty-three were male and thirteen were female. Median age was 59 years (29-78). Seven patients (15.2%) had locally advanced disease and 39 (84.8%) had metastatic disease. Of the 46 eligible patients, the objective response rate (ORR) was 30.4% with partial response (PR)in 14 patients. Twenty-one patients had stable disease (SD) and 11 patients had progressive disease (PD). The median PFS and OS were 4.4 months (95% CI: 3.37-5.36 months) and 10.3 months (95% CI: 8.88-11.3 months), respectively. Thirty-five patients (76.1%) received second-line chemotherapy. The major hematological toxicities consisted of grade 3 neutropenia in 6 patients (13.1%) and grade 4 neutropenia in 1 patient (2.1%). No patient suffered febrile neutropenia. All grades of nausea, vomiting, diarrhea, fatigue and neurological toxicity occurred in 39.1%, 32.6%, 17.3%, 32.6% and 26.1% patients. Grade 3/4 non-hematological toxicities were seldom. Conclusions: Biweekly oxaliplatin and S-1(SOX regimen) combination therapy was effective and well tolerated for advanced gastric cancer patients. A well-designed randomized phase III study was expected to compare this regimen with other S-1-based combination treatments. Clinical trial information: ISRCTN85705844.
Short-term acenocumarine (A) or dalteparine (D) for the prevention of central venous catheter-related thrombosis (CVCrT) in cancer patients. A randomized controlled study based on serial venographies
Authors: M. De Cicco, M. Matovic, R. Pacenzia, D. Fantin, M. Caserta, R. Bortolussi, F. Fabiani, C. Santantonio, P. Nigri, A. Veronesi
Journal: Journal of Clinical Oncology (2006)

8549 Background: Timing and frequency of non occlusive (nO) or occlusive (O) CVCrT in cancer patients (pts) remain unclear. In this randomized controlled trial we studied these points and evaluated the efficacy and safety of short-term prophylaxis with A or D in the prevention of CVCrT. Methods: Consecutive cancer pts without contraindications to short-term anticoagulation, scheduled for chemotherapy via CVC, were randomly assigned to receive: A 1 mg/day for 3 days before and 8 days after CVC insertion; D 5,000 IU 2 hours before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All pts underwent venography (V) at day 8 and 30 after CVC insertion and then every two months until CVC removal . The primary endpoint was V detected CVCrT, evaluated as nO or O when it was partially or completely occlusive of the vein lumen, respectively. Bleeding episodes were recorded. Proportions were compared using chi-square test together with odds ratio (OR). Results: 450 pts were randomized, 348 of whom (120/150 A, 114/150 D, and 114/150 NT) underwent V (median number of procedures 4, range 2–8). Both A and D reduced the frequency of V detected CVCrT (21.9% A vs 55.3% NT, OR= 4.35 (95% CI 2.43–7.69), p&lt;0.001; 40% D vs 55.3% NT, OR= 1.85 (95% CI 1.10–3.13), p=0.02). A was more effective than D (OR= 2.37 (CI 1.34–4.22), p= 0.003). The frequency of O CVCrT was not different in the 3 groups (0.9% A, 5.0% D, 4.4% NT; p= 0.18). Overall, 5.1% of pts with CVCrT were symptomatic, all presenting O CVCrT (42% of pts with O CVCrT were not symptomatic). Most CVCrTs (95.6%) were observed at day 8 after CVC insertion. No major bleeding or pulmonary embolism occurred. Conclusions: In this study, acenocumarine was more effective than dalteparine in reducing V detected CVCrT. The doses of prophylactic agents used in this study proved to be safe. Symptomatic CVCrT evaluation alone underestimates the actual CVCrT frequency. The first days following CVC insertion are at highest risk for CVCrT. Short term thrombosis prophylaxis appears to be superior to no treatment without the expenses and inconveniences inherent in long-term prophylaxis. No significant financial relationships to disclose.
NF-κb / STAT3 Signaling Pathway Collaboration in Diffuse Large B-Cell Lymphoma (DLBCL) Cell-of-Origin (COO) Subtypes: Resolution of Myeloid Subversion By Standard Induction Chemotherapy
Authors: David Foureau, Qing Zhang, Lawrence J. Druhan, Nury M. Steuerwald, Fei Guo, Elizabeth Jandrisevits, Belinda R. Avalos, Danyu Sun, Ryan Jacobs, Nilanjan Ghosh
Journal: Blood (2016)
Abstract 181: Human Heart Valve-derived Scaffold Improves Cardiac Repair in a Murine Model of Myocardial Infarction
Authors: Jun Li, Long Wan, Yao Chen, Zhenhua Wang, Wentian Zhang, Sebastian Schmull, Weijun Wang, Weiqiang Gao, Jun Dong, Song Xue
Journal: Circulation Research (2015)

Cardiac tissue engineering using biomaterials with or without a combination of cardiac stem cell therapy offers a new therapeutic option for repairing infarcted heart. So far, cardiac tissue scaffold is designed mainly based on natural and synthetic biomaterials, which do not mimic human myocardial extracellular matrix. This raises a fundamental issue about the biocompatibility of currently used biomaterials with myocardial tissue. Here we hypothesized that human heart valve-derived scaffold (hHVS) may provide a clinically relevant novel biomaterial for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function, as shown by transthoracic echocardiography as well as by hemodynamic measurements via a Millar catheter, and by reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first evidence for translating the hHVS-based cardiac tissue engineering into clinical strategies to treat myocardial infarction.
DCC promoter hypermethylation in esophageal squamous cell carcinoma
Authors: Hannah Lui Park, Keishi Yamashita, Myoung Sook Kim, William H. Westra, Andre Lopes Carvalho, Jin Hyen Baek, Wei Wen Jiang, Jun-Wei Liu, Motonobu Osada, Joseph A. Califano, Masaki Mori, David Sidransky
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

35 

Deleted in Colorectal Cancer ( DCC ) is a putative tumor suppressor gene whose loss has been implicated in colorectal tumorigenesis. Decreased or loss of DCC expression has been demonstrated in a number of human cancers, including esophageal squamous cell carcinoma (ESCC). In this study, we analyzed ESCC cell lines and primary ESCCs as well as their corresponding normal tissues for DCC methylation by bisulfite sequencing and/or quantitative methylation-specific PCR (qMSP). When a qMSP cut-off value for positivity was set to 1.0, DCC methylation was detected in 10 of 12 ESCC cell lines tested, 74% of primary ESCCs (n=70), and 0% of corresponding normal esophageal tissues (n=20). DCC expression was undetectable in the majority of ESCC cell lines, and treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine reactivated gene expression. DCC overexpression suppressed colony formation in ESCC cell lines, suggesting that DCC may function as a tumor suppressor gene in the esophagus. We have demonstrated that DCC methylation is a frequent and cancer-specific event in primary ESCCs with 74% sensitivity and 100% specificity, suggesting that DCC and associated pathways may represent a new therapeutic target. Moreover, detection of DCC promoter methylation may potentially be used as a biomarker in the early detection of human ESCC.
Response to Metabolically Supported Chemotherapy (MSCT) with weekly carboplatin/paclitaxel in advanced stage/metastatic (Stage IV) non-small cell lung cancer: A survival, efficacy and tolerability analysis
Authors: M.S. Iyikesici, A. Slocum, A.K. Slocum, E. Turkmen, F.B. Berkarda
Journal: Annals of Oncology (2017)
Sofosbuvir-based therapy in patients with chronic hepatitis C virus infection and malignancies – A prospective observational study of 136 patients
Authors: H.A. Torres, M.P. Economides, A. Kyvernitakis, P. Mahale, J. Hosry, Y. Jiang, A. Kaseb, I. Raad, B.P. Granwehr
Journal: Journal of Hepatology (2017)
Sprint interval exercise training reduces intrahepatic, visceral and subcutaneous abdominal fat despite no change in body weight, but has variable effects on whole-body insulin sensitivity
Authors: J.A. Sargeant, S. Bawden, E.J. Simpson, M. Kaviani, P. Gowland, J.L. Dorling, M.A. Nimmo, I. MacDonald, G.P. Aithal, J.A. King
Journal: Journal of Hepatology (2017)
Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark
Authors: S. Hallager, S. Ladelund, M.S. Kjaer, L.G. Madsen, E. Belard, A.L. Laursen, J. Gerstoft, B.T. Roege, K.E. Groenbael, H.B. Krarup, P.B. Christensen, N. Weis
Journal: Journal of Hepatology (2017)
Carcinogenic Etheno DNA -adducts in alcohol liver disease: correlation with cytochrome P-4502E1 and fibrosis
Authors: H.K. Seitz, T. Pecerella, C. Flechtenmacher, B.K. Straub, F. Stickel, T. Bruckner, H. Bartsch, H.K. Seitz, S. Mueller, T. Peccerella, C. Flechtenmacher, B.K. Straub, F. Stickel, T. Bruckner, H. Bartsch, H.K. Seitz
Journal: Journal of Hepatology (2017)
Abstract 194: Increasing Expression of Connexin43 in Bone Marrow Stem Cells Enhances Their Protective Effects on the Infarcted Heart
Authors: Jason M Duran, Thomas E Sharp, Sharven Taghavi, Remus M Berretta, John Gaughan, Joseph E Rabinowitz, Hajime Kubo, Steven R Houser
Journal: Circulation Research (2012)

Introduction: Coupling of stem cells (SCs) injected into the infarcted heart to endogenous cells that survived injury may enhance SC survival and engraftment and improve their protective effects. Connexin43 (Cx43) gap junctions are some of the first proteins expressed by differentiating SCs transplanted into the heart after myocardial infarction (MI), suggesting that cell coupling is critical for SC survival and differentiation. Hypothesis: Overexpression of Cx43 in SCs will enhance their ability to engraft, differentiate, and improve cardiac function and survival after transplant into the infarcted heart. Methods: Adult mouse SCs isolated from compact bone were sorted for c-kit surface marker using magnetic beads. SCs were transduced with PLL3.7 lentivirus encoding the Cx43 gene (GJA1) at MOI=300 to produce overexpression, which was confirmed by Western analysis on SC lysates. MI was induced in 12-week-old male C57BL/6 mice by ligating the left anterior descending coronary artery, and 40,000 SCs in 20 uL saline were administered immediately after MI via intramyocardial injection. A total of 69 animals were used: 18 received Cx43 SCs, 30 received non-transduced SCs (NTSC), 11 received only saline, and 10 underwent sham surgery. Echocardiography was performed 1 and 2 weeks post-MI. Results: Animals receiving Cx43 SCs had improved survival (90.0%) versus NTSC (76.7%) and saline controls (70.0%). The Cx43 SC group displayed improved ejection fraction versus NTSC and saline controls at 1 week (48.7% v. 43.3%, p=0.04; 30.1%, p&lt;0.0001) and 2 weeks post-MI (45.7% v. 40.4%, p=0.08; 26.8%, p=0.0004). Similar improvements in fractional shortening, stroke volume, and cardiac output were observed. Administration of Cx43 SC and NTSC attenuated remodeling with no difference between the two groups. Both decreased end-diastolic and systolic volumes, increased thickness of the infarct-related anterior wall, and decreased heart weight (HW), HW/body weight and HW/tibia length ratios at 1 and 2 weeks post-MI. Conclusion: All SCs improved survival and cardiac function, and attenuated remodeling. Transplantation of Cx43 SCs improved survival and cardiac function even more than NTSCs, suggesting that Cx43 may play a crucial role in engraftment and differentiation.
Prognostic factors in crizotinib (CRZ)-resistant anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC) patients (Pts)
Authors: K.L. Reckamp, J. Lee, J. Huang, I. Proskorovsky, W. Reichmann, M. Krotneva, D. Kerstein, H. Huang
Journal: Annals of Oncology (2017)
Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy
Authors: Sacha Gnjatic, Vincenzo Bronte, Laura Rosa Brunet, Marcus O. Butler, Mary L. Disis, Jérôme Galon, Leif G. Hakansson, Brent A. Hanks, Vaios Karanikas, Samir N. Khleif, John M. Kirkwood, Lance D. Miller, Dolores J. Schendel, Isabelle Tanneau, Jon M. Wigginton, Lisa H. Butterfield
Journal: Journal for ImmunoTherapy of Cancer (2017)

As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy. A broad understanding of baseline immunity, both in the periphery and in the tumor microenvironment, is needed in order to fully realize the potential of cancer immunotherapy. Such interrogation of the tumor, blood, and host immune parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. To approach these opportunities for progress, the Society for Immunotherapy of Cancer (SITC) reconvened the Immune Biomarkers Task Force. Comprised of an international multidisciplinary panel of experts, Working Group 4 sought to make recommendations that focus on the complexity of the tumor microenvironment, with its diversity of immune genes, proteins, cells, and pathways naturally present at baseline and in circulation, and novel tools to aid in such broad analyses.
Abstract 267: High glucose-induced mitophagy limits Cardiomyocyte Injury
Authors: Qiangrong Liang, Satoru Kobayashi, Yuan Huang
Journal: Circulation Research (2014)

Cardiovascular complications are the major cause of death among diabetic patients. Mitochondrial dysfunction has been suggested to play an important role in the pathogenesis of diabetic cardiomyopathy. Therefore, timely elimination of dysfunctional mitochondria is essential for maintaining a healthy mitochondrial network and limiting diabetic cardiac injury. This function is performed by mitophagy, a process that selectively degrades mitochondria through the autophagy-lysosome pathway. In the present study, we investigated the functional role of mitophagy in cardiomyocytes treated with high glucose, an independent risk factor for heart failure in diabetic patients. We found that mitophagy in neonatal rat ventricular myocytes was increased by high glucose (30 mM) as indicated by a novel dual fluorescent reporter as well as the co-localization of mitochondrial protein Tom20 and lysosome-associated membrane protein 1 (LAMP1). Parkin is an E3-ubiquitin ligase that positively regulates mitophagy. Parkin overexpression enhanced high glucose-induced mitophagy and attenuated cardiomyocyte injury as measured by the levels of oxidative injury, mitochondrial damage, ROS generation and cardiomyocyte death. Conversely, Parkin knockdown potentiated the toxic effects of high glucose, suggesting that mitophagy is cardioprotective under hyperglycemic conditions. In addition, high glucose increased mitochondrial fragmentation. By overexpressing or knocking down Drp1, a key regulator of mitochondrial fission, we showed that mitochondrial fragmentation was coupled with mitophagy and negatively related to the toxic effects of high glucose. Together, these findings demonstrate that high glucose induces mitochondrial fragmentation and mitophagy, which are adaptive responses that protect cardiomyocytes against high glucose toxicity. Future studies are warranted to determine if mitophagy plays a similar role in diabetic cardiac damage in vivo.
Identification of factors associated with treatment refractoriness of oral lesions in pemphigus vulgaris
Authors: S. Kumar, D. De, S. Handa, R.K. Ratho, S. Bhandari, A. Pal, P. Kamboj, S. Sarkar
Journal: British Journal of Dermatology (2017)

The oral mucosal lesions of patients with pemphigus vulgaris are known to show more treatment refractoriness than skin lesions.To identify which clinical and laboratory parameters may indicate treatment refractoriness of oral lesions in pemphigus vulgaris.This was a prospective study of 50 adults with pemphigus vulgaris and oral lesions; patients were given treatment appropriate for overall disease severity. Treatment refractoriness was defined arbitrarily as less than 75% reduction in oral objective Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) after treatment for 6 months.Of 46 patients who completed the study, 17 (37%) were treatment refractory whereas 29 (63%) were treatment responsive. At baseline, the treatment refractory group had a significantly longer mean duration of disease (P = 0·02) and mean duration of oral lesions (P = 0·01), a higher percentage of lesions in the retromolar trigone (P = 0·05) and on the occlusion line along the buccal mucosa (P = 0·04), a higher percentage of deep/crateriform ulcers (P < 0·001) and erosions with a lichenoid hue (P < 0·001). Herpes simplex virus (HSV) DNA positivity, assessed by polymerase chain reaction in oral tissue scrapings (P = 0·02), was also significantly higher in the treatment refractory group. No other factors we tested for were statistically significant.Treatment refractoriness of oral lesions was significantly associated with duration of disease/oral lesions; specific morphology and location of oral lesions; and the presence of HSV DNA in the oral cavity. These factors may forewarn the treating physician about a refractory course of oral lesions that may help with counselling patients.
Liver microRNA hsa-miR-125a-5p may exert an oncosuppressor effect on HCC
Authors: N. Coppola, G. De Stefano, M. Panella, L. Onorato, V. Iodice, C. Minichini, N. Mosca, L. Desiato, N. Farella, M. Starace, G. Liorre, N. Potenza, E. Sagnelli, A. Russo
Journal: Journal of Hepatology (2017)
Evaluation of photochemistry reaction kinetics to pattern bioactive proteins on hydrogels for biological applications
Authors: Taylor B. Dorsey, Alexander Grath, Annling Wang, Cancan Xu, Yi Hong, Guohao Dai
Journal: Bioactive Materials (2017)

Bioactive signals play many important roles on cell function and behavior. In most biological studies, soluble biochemical cues such as growth factors or cytokines are added directly into the media to maintain and/or manipulate cell activities in vitro. However, these methods cannot accurately mimic certain in vivo biological signaling motifs, which are often immobilized to extracellular matrix and also display spatial gradients that are critical for tissue morphology. Besides biochemical cues, biophysical properties such as substrate stiffness can influence cell behavior but is not easy to manipulate under conventional cell culturing practices. Recent development in photocrosslinkable hydrogels provides new tools that allow precise control of spatial biochemical and biophysical cues for biological applications, but doing so requires a comprehensive study on various hydrogel photochemistry kinetics to allow thorough photocrosslink reaction while maintain protein bioactivities at the same time. In this paper, we studied several photochemistry reactions and evaluate key photochemical parameters, such as photoinitiators and ultra-violet (UV) exposure times, to understand their unique contributions to undesired protein damage and cell death. Our data illustrates the retention of protein function and minimize of cell health during photoreactions requires careful selection of photoinitiator type and concentration, and UV exposure times. We also developed a robust method based on thiol-norbornene chemistry for independent control of hydrogel stiffness and spatial bioactive patterns. Overall, we highlight a class of bioactive hydrogels to stiffness control and site specific immobilized bioactive proteins/peptides for the study of cellular behavior such as cellular attraction, repulsion and stem cell fate.