tbuckley/cabot-search huggingface dataset:
Comparison of tenofovir plus lamivudine versus tenofovir monotherapy in patients with lamivudine-resistant chronic hepatitis B
Authors: Chan Ho Park, Seok Won Jung, Jung Woo Shin, Mi Ae Bae, Yoon Im Lee, Yong Tae Park, Hwa Sik Chung, Neung Hwa Park
Journal: Clinical and Molecular Hepatology (2016)

Background/Aims: Tenofovir disoproxil fumarate (TDF) exhibits similar antiviral efficacy against treatment-naïve and lamivudine (LAM)-resistant chronic hepatitis B (CHB). However, there are few clinical reports on the antiviral effects of TDF–LAM combination therapy compared to TDF monotherapy in patients with LAM-resistant CHB. Methods: We investigated the antiviral efficacy of TDF monotherapy vs. TDF–LAM combination therapy in 103 patients with LAM-resistant CHB. Results: The study subjects were treated with TDF alone (n=40) or TDF–LAM combination therapy (n=63) for ≥6 months. The patients had previously been treated with TDF-based rescue therapy for a median of 30.0 months (range, 8–36 months). A virologic response (VR) was achieved in 99 patients (96.1%): 95.0% (38/40) of patients in the TDF monotherapy group and 96.8% (61/63) of patients in the TDF–LAM combination therapy group. The VR rates were not significantly different between the TDF monotherapy and TDF–LAM combination therapy groups (88.9 vs. 87.3% at month 12, and 94.4 vs. 93.7% at month 24, log-rank p=0.652). Univariate and multivariate analyses revealed that none of the pretreatment factors were significantly associated with VR. Conclusions: TDF monotherapy was as effective as TDF–LAM combination therapy for maintaining viral suppression in the vast majority of patients with LAM-resistant CHB, which suggests that TDF add-on therapy with LAM is unnecessary. Keywords: Tenofovir; Lamivudine; Resistance; Chronic hepatitis B
A new anti-CEA-SN-38 antibody-drug conjugate (ADC), IMMU-130, is active in controlling metastatic colorectal cancer (mCRC) in patients (pts) refractory or relapsing after irinotecan-containing chemotherapies: Initial results of a phase I/II study.
Authors: Efrat Dotan, Alexander Starodub, Jordan Berlin, Christopher Hanyoung Lieu, Michael J. Guarino, John Marshall, J. Randolph Hecht, Steven J. Cohen, Wells A. Messersmith, Pius P Maliakal, William A. Wegener, Robert M. Sharkey, David M. Goldenberg
Journal: Journal of Clinical Oncology (2015)

2505 Background: Combination chemotherapies with 5-FU, irinotecan, oxaliplatin, anti-VEGF, and anti-EGFR agents have improved the outcome of mCRC pts. However, there is still an urgent need for better therapies to control this disease. IMMU-130 (labetuzumab govitecan), a conjugate of a humanized anti-CEACAM5 antibody, coupled site-specifically to SN-38 (7.6 moles SN-38/IgG) using a proprietary linker, is an attractive therapeutic option for mCRC pts. Methods: A phase I/II clinical trial (NCT01605318) was initiated in irinotecan- refractory/relapsed mCRC pts with an elevated CEA ( > 5 ng/mL), treated with IMMU-130 once- or twice-weekly at escalating 4-10 mg/kg dosages on weeks 1 and 2 of 3-week cycles. The primary objective of the study was determination of MTD, with secondary objectives of efficacy (by RECIST 1.1), PK and immunogenicity. Treatment was continued until disease progression or intolerance. Results: Between Feb 2013 and Nov 2014, 66 patients were enrolled. Median age was 57 years [39-82]. Median prior therapies were 5 [1-9], with 76% and 36% pts receiving prior bevacizumab and an EGFR inhibitor, respectively. Median number of cycles per pt was 2 [1-15]. Fifty-eight patients were evaluable for toxicity, with 3 DLTs (G3 typhlitis, G4 neutropenia and G3 nausea/vomiting > 48h) in all pts. Grade 3/4 drug-related toxicities were found in 25% pts, including neutropenia (G3, 7%; G4, 3%), diarrhea (G3, 2%), anemia (G3, 3%) and lymphopenia (G3, 3%). The dose selected for further study was 10 mg/kg weekly or 6 mg/kg biw. No pt developed antibodies to the conjugate. Tumor reductions were seen in 23/66 (35%) pts, including one PR with 88% best tumor shrinkage still being treated for 52+ weeks, 6 pts with 20-30% tumor reductions, and 16 pts with 0-20% tumor reductions. Conclusions: Repeated cycles of IMMU-130 monotherapy had an acceptable toxicity profile. Tumor reductions were noted in 35% of patients despite prior relapse to irinotecan-containing therapies. These results encourage further evaluation of IMMU-130 in combination with other agents in mCRC. Clinical trial information: NCT01605318.
Impact of bevacizumab (BEV) on efficacy of second-line chemotherapy (CT) for triple-negative breast cancer (TNBC): Analysis of RIBBON-2.
Authors: A. Brufsky, V. Valero, B. Tiangco, S. R. Dakhil, A. Brize, N. Bousfoul, H. S. Rugo, D. A. Yardley
Journal: Journal of Clinical Oncology (2011)

1010 Background: The efficacy of first-line BEV-containing therapy for metastatic breast cancer (MBC) has been proven in three randomized trials. BEV combined with CT resulted in longer progression-free survival (PFS, primary endpoint) and higher objective response rates (RRs) than with CT alone. In the second-line MBC setting, the RIBBON-2 trial demonstrated significantly improved PFS in patients (pts) receiving BEV combined with CT vs CT alone. We present a prespecified analysis of subgroup data in pts with TNBC. Methods: RIBBON-2 enrolled pts with MBC that had progressed on first-line non-BEV-containing CT. After CT was selected from a prespecified list (taxane, gemcitabine, capecitabine, or vinorelbine), pts were randomized 2:1 to receive CT with either BEV (10 mg/kg q2w or 15 mg/kg q3w) or placebo. Crossover to BEV at progression was permitted. The primary endpoint was PFS. Results: Of 684 pts treated in RIBBON-2, 159 (23%) had TNBC. Baseline characteristics were reasonably balanced in the two treatment groups. Baseline characteristics and efficacy results are summarized below. Conclusions: Pts with TNBC derive significant RR and PFS benefit from the combination of BEV with second-line CT. Despite the small sample size, there was a trend (HR 0.624; p=0.0534) towards OS benefit. Larger prospective randomized trials of BEV in TNBC are ongoing. Characteristic BEV + CT (n=112) Placebo + CT (n=47) Median age, years (range) 55 (28–86) 49 (33–79) Metastatic sites, % ≥3 48 32 Visceral, % 74 62 CT partner, % Taxane 42 43 Gemcitabine 23 28 Capecitabine 16 21 Vinorelbine 19 9 PFS Events, n (%) 94 (84) 42 (89) Median, months 6.0 2.7 HR* (95% CI) P value (log-rank) 0.494 (0.33–0.74) p=0.0006 OS Events, n (%) 52 (46) 29 (62) Median, months 17.9 12.6 HR*(95% CI) P value (log-rank) 0.624 (0.39–1.007) p=0.0534 1-year OS, % (95% CI) 63 (52–72) 50 (34–64) Difference in rates, % (95% CI) 13 (–6 to 31) p=0.1758 Objective RR, % (95% CI)* 41 (31–51) 18 (8–34) Difference, % (95% CI) P value* 23 (7–39) p=0.0078 * Stratified analysis (CT regimen and disease-free interval). Abbreviations: HR, hazard ratio; OS, overall survival.
Pain relief is not a confounder in joint space narrowing assessment of full extension knee radiographs
Authors: K. Pavelka, Lucio C Rovati, J. Gatterova, Olivier Bruyère, Rita Deroisy, S. Machacek, Giampaolo Giacovelli, C. Gonzalez, Jean-Yves Reginster
Journal: Annals of the Rheumatic Diseases (2002)
Breast cancer surgery: Do all patients want to go to high-volume hospitals?
Authors: G. Bouche, V. Migeot, S. Mathoulin-Pélissier, R. Salamon, P. Ingrand
Journal: Journal of Clinical Oncology (2008)

6636 Background: Inequalities in access to high-volume hospitals have been found in many surgical procedures. We aimed to assess the association between patient's choice and the volume of the hospital where they underwent breast cancer surgery. Methods: Multivariate analysis of data from 932 women who underwent breast cancer surgery in low, moderate or high- volume hospitals in France. Results: One hundred and fifty-six (17%) patients had undergone surgery in low-volume, 414 (44%) in moderate-volume and 362 (39%) in high-volume hospitals. Patients in low-volume hospitals were more likely to be over 70 year old (adjusted OR, 2.2; 95% Confidence Limits, 1.2 to 3.4) and to have an elementary education level (adjusted OR, 7.1; 95% CL, 2.4 to 21.2). In areas where there was little provision of surgical care, patients were more likely to go to low-volume hospitals, with no effect of active (adjusted OR, 10.1; 95% CL, 3.3 to 31.0) or passive (adjusted OR, 11.6; 95% CL, 2.9 to 46.0) choice of the surgeon. In areas where there was higher provision of surgical care, patients involved in the choice of the surgeon were more likely to go to low-volume hospitals (adjusted OR, 4.4; 95% CL, 1.5 to 13.1). Conclusion: Some patients were involved in the choice of the surgeon to go to low-volume hospital, nearer from their place of residence. Even though a minimum threshold has been set up in France for breast cancer surgery, volume-based referral policies should anticipate their own consequences, which would concern older and more isolated patients and go against some patients' will. No significant financial relationships to disclose.
Abstract 65: Regulation of Cardiac Hypertrophy and Dilated Cardiomyopathy by CIP
Authors: Zhan-Peng Huang, Masaharu Kataoka, Jinghai Chen, Da-Zhi Wang
Journal: Circulation Research (2014)

Cardiac hypertrophy is one of the primary responses of the heart to pathophysiological stress. However, the mechanism of the transition from compensative hypertrophic growth to cardiac dilation is poor understood. Recently, we identified a cardiac-specific expressed gene CIP. The expression of CIP is unchanged in hypertrophic heart but significantly down-regulated in dilated hearts, suggesting CIP may play an important role in the transition from cardiac hypertrophy to dilated cardiomyopathy. We generated CIP knockout mice and found that CIP is dispensable for cardiac development. Interestingly, CIP-null mutant mice developed severe cardiac dilation 4 weeks after TAC (transverse aortic constriction) surgery, while control mice were still at the stage of compensative hypertrophic growth. Echocardiography and histological examinations showed that mutant hearts had enlarged chamber with thinner ventricle wall and decreased cardiac performance compared to controls. The expression of marker genes of cardiac disease, BNP and Myh7, was elevated. Consistently, deletion of CIP in Myh6-CnA transgenic mice result in premature death, displaying severe left ventricle dilation. Conversely, cardiac-specific CIP overexpression inhibited pressure overload-induced cardiac hypertrophy. CIP transgenic mice exhibit decreased ventricle weight/body weight ratio, decreased cardiomyocyte cross-section area and repressed expression of hypertrophic related marker genes. CIP overexpression also protected the heart from developing cardiac dilation and preserved the cardiac function after prolonged pressure overload. We performed unbiased microarray assay to document the transcriptome in CIP knockout and control mice which were subjected to pressure overload (TAC). The analysis of Gene Ontology term indicated the Negative Regulation of Apoptosis was down-regulated while the Collagen/Extracellular Structure Organization was up-regulated in CIP-null hearts under TAC condition. In summary, our studies established CIP as a key regulator of the transition from cardiac hypertrophy to dilated cardiomyopathy. The protective effect of CIP in cardiac remodeling indicates that CIP could become a therapeutic target for cardiac diseases.
A prospective randomised trial of adjuvant vinorelbine (VIN) and cisplatin (CIS) in completely resected stage 1B and II non small cell lung cancer (NSCLC) Intergroup JBR.10
Authors: T. L. Winton, R. Livingston, D. Johnson, J. Rigas, Y. Cormier, C. Butts, K. Ding, L. Seymour, N. Magoski, F. Shepherd
Journal: Journal of Clinical Oncology (2004)

7018 Background: In meta-analyses platinum based adjuvant chemotherapy using 2nd generation regimens increased cure rate by 5% in completely resected NSCLC. JBR.10 was undertaken to determine whether the 3rd generation regimen VIN/CIS prolonged survival in this clinical setting. Methods: Patients with completely resected stage 1 (T2N0) or stage 2 (excluding T3N0) NSCLC were stratified by nodal status (N0 vs. N1) and ras mutation status (present vs. absent vs. unknown) and randomised to receive 4 cycles of VIN (25mg/m2 weekly x 16 weeks) plus CIS (50mg/m2 days 1 and 8 q 4 weeks x 4) or follow up alone; VIN dose was reduced from 30mg/m2 shortly after the study started due to unacceptable toxicity. The endpoints of the study were survival (OS), recurrence-free survival (RFS), quality of life (QOL) and toxicity. Results: 482 patients were randomized between 1994 and 2001. Patients: age 61 years, 65% male, 51% PS 1, 53% N1, 24% ras mutation present. 45% of patients had T2N0, 40% T2N1 and 15% T1N1. 53% had adenocarcinoma. Grade 4 neutropenia, was common with febrile neutropenia in 7%, predominantly in patients receiving VIN 30mg/m2. The commonest non-hematologic toxicities for VIN/CIS patients were fatigue (77%), nausea (76%), anorexia (53%), vomiting (46%), sensory neuropathy (45%) and constipation (44%). Two patients died of drug-related toxicity [1 febrile neutropenia, 1 pulmonary fibrosis]. The most common cause of death was NSCLC (including 1 patient with 2nd primary NSCLC), while 3 patients died from toxicity related to later anti-cancer therapy, 9 patients died of other primary malignancies, and 21 from other causes. Overall survival was significantly prolonged for VIN/CIS patients (94 months vs. 73 months; HR 0.69, p=0.011), as was RFS (not reached vs. 46.7 months; HR 0.6, p 0.0003). 5-year survival for VIN/CIS patients was 69% compared to 54% for patients followed expectantly. 38 patients developed 2nd malignancies. Conclusions: This is the first randomized clinical trial demonstrating that a 3rd generation platinum-based doublet prolongs OS and RFS after surgery in early stage NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Adjuvant Chemotherapy for T3 Non–Small Cell Lung Cancer with Additional Tumor Nodules in the Same Lobe
Authors: Michelle C. Salazar, Joshua E. Rosen, Brian N. Arnold, Daniel C. Thomas, Anthony W. Kim, Frank C. Detterbeck, Justin D. Blasberg, Daniel J. Boffa
Journal: Journal of Thoracic Oncology (2016)
Ganglioside Patterns: New Biochemical Markers for Human Hematopoietic Cell Lines
Authors: G Rosenfelder, A Ziegler, P Wernet, D G Braun
Journal: JNCI Journal of the National Cancer Institute (1982)

The ganglioside patterns from a representative collection of 20 human B-cell, T-cell, null cell, myeloid cell, and early erythroid cell lines were determined. Radioactive sugar-labeled gangliosides from cultured cells were extracted, analyzed, and quantitated by high-performance thin-layer chromatography (HPTLC) and high-pressure liquid chromatography, essentially according to the polarity of the oligosaccharide chain. The ganglioside labeling patterns of the human cell lines were in some cases extremely complex, since more than 100 components could be separated upon two-dimensional HPTLC, e.g., in the case of a promyelocytic cell line. Each type of cell showed a characteristic pattern: Null cell lines were much less complex than T-cell lines, and myeloid and erythroid lines exhibited characteristic patterns as well. Although clearly distinguishable from all other cell lines, the B-cell lines showed a high degree of heterogeneity. Therefore, gangliosides can be expected to serve as additional markers to establish the origin, of a cell line or to classify pathologic cell populations.
Inhibition of &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide-Induced Mammary Tumorigenesis in Rats by Dietary Polybrominated Biphenyls&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: E L Schwartz, W M Kluwe, S D Sleight, J B Hook, J I Goodman
Journal: JNCI Journal of the National Cancer Institute (1980)

Female SD rats were maintained for approximately 1 year on diets containing 300 ppm N-2-fluorenylacetamide (2-FAA), 50 ppm polybrominated biphenyls (PBB), or a combination of these chemicals (PBB + 2-FAA). Ingestion of 2-FAA significantly reduced the average survival time of the rats; this effect was virtually blocked by the simultaneous ingestion of PBB. Simultaneous ingestion of PBB also significantly reduced the overall incidence of 2-FAA-induced tumors during the examination period. The lower incidence of tumorigenesis was accompanied by an increase in the latency time for tumor induction; tumors were found in 100% of the animals given 2-FAA after 29 weeks of carcinogen ingestion, whereas only 50% of the PBB + 2-FAA-fed animals had tumors at the end of the experiment (53 wk of carcinogen ingestion). PBB significantly reduced the incidence of 2-FAA-induced tumors at non hepatic locations (mammary gland and ear duct) but did not affect the incidence of hepatic tumors to a statistically significant extent. PBB ingestion did not significantly increase the incidence of tumors when compared with controls; 1 tumor was found in 1 of 12 rats fed 50 ppm PBB for 57 weeks, and no tumors were detected in 8 controls.
Adenomatous polyps in ulcerative colitis and colonic Crohn’s disease: less frequent, but does this change surveillance strategy?
Authors: Zsuzsanna Vegh, Zsuzsanna Kurti, Peter Lakatos
Journal: Endoscopy (2016)

The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been known for several decades, with CRC remaining one of the most feared complications. Early studies reported an excess risk of CRC in ulcerative colitis patients; however, in these reports, which were published from tertiary referral centers, patients with severe disease were over-represented. In the meta-analysis by Eaden et al. from 2001 [1], the cumulative probability of CRC in ulcerative colitis was 2 % by 10 years, 8 % by 20 years, and 18 % by 30 years. Chronic inflammation is thought to be one of the key factors in the pathogenesis, together with genetic predisposition [2].
Ifosfamide and paclitaxel salvage chemotherapy for advanced epithelial ovarian cancer
Authors: M.A. Dimopoulos, C. Papadimitriou, C. Gennatas, T. Akrivos, G. Vlahos, Z. Voulgaris, E. Diacomanolis, P. Athanassiades, S. Mihalas
Journal: Annals of Oncology (1997)
Fibroblast-Mediated Collagen Remodeling Within the Tumor Microenvironment Facilitates Progression of Thyroid Cancers Driven by BrafV600E and Pten Loss
Authors: Lee Ann Jolly, Sergey Novitskiy, Phillip Owens, Nicole Massoll, Nikki Cheng, Wei Fang, Harold L. Moses, Aime T. Franco
Journal: Cancer Research (2016)

Contributions of the tumor microenvironment (TME) to progression in thyroid cancer are largely unexplored and may illuminate a basis for understanding rarer aggressive cases of this disease. In this study, we investigated the relationship between the TME and thyroid cancer progression in a mouse model where thyroid-specific expression of oncogenic BRAF and loss of Pten (Braf(V600E)/Pten(-/-)/TPO-Cre) leads to papillary thyroid cancers (PTC) that rapidly progress to poorly differentiated thyroid cancer (PDTC). We found that fibroblasts were recruited to the TME of Braf(V600E)/Pten(-/-)/TPO-Cre thyroid tumors. Conditioned media from cell lines established from these tumors, but not tumors driven by mutant H-ras, induced fibroblast migration and proliferation in vitro Notably, the extracellular matrix of Braf(V600E)/Pten(-/-)/TPO-Cre tumors was enriched with stromal-derived fibrillar collagen, compared with wild-type or Hras-driven tumors. Further, type I collagen enhanced the motility of Braf(V600E)/Pten(-/-)/TPO-Cre tumor cells in vitro In clinical specimens, we found COL1A1 and LOX to be upregulated in PTC and expressed at highest levels in PDTC and anaplastic thyroid cancer. Additionally, increased expression levels of COL1A1 and LOX were associated with decreased survival in thyroid cancer patients. Overall, our results identified fibroblast recruitment and remodeling of the extracellular matrix as pivotal features of the TME in promoting thyroid cancer progression, illuminating candidate therapeutic targets and biomarkers in advanced forms of this malignancy. Cancer Res; 76(7); 1804-13. ©2016 AACR.
Portal biliopathy treated with endoscopic biliary stenting
Authors: Sung Jin Jeon, Jae Ki Min, So Young Kwon, Jun Hyun Kim, Sun Young Moon, Kang Hoon Lee, Jeong Han Kim, Won Hyeok Choe, Young Koog Cheon, Tae Hyung Kim, Hee Sun Park
Journal: Clinical and Molecular Hepatology (2016)

Portal biliopathy is defined as abnormalities in the extra- and intrahepatic ducts and gallbladder of patients with portal hypertension. This condition is associated with extrahepatic venous obstruction and dilatation of the venous plexus of the common bile duct, resulting in mural irregularities and compression of the biliary tree. Most patients with portal biliopathy remain asymptomatic, but approximately 10% of them advance to symptomatic abdominal pain, jaundice, and fever. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography are currently used as diagnostic tools because they are noninvasive and can be used to assess the regularity, length, and degree of bile duct narrowing. Management of portal biliopathy is aimed at biliary decompression and reducing the portal pressure. Portal biliopathy has rarely been reported in Korea. We present a symptomatic case of portal biliopathy that was complicated by cholangitis and successfully treated with biliary endoscopic procedures. Keywords: Bile duct obstruction; Portal hypertension; Endoscopic retrograde cholangiopancreatography; Biliary stent
21-Gene Recurrence Score Assay As a Predictor of Adjuvant Chemotherapy Administration for Early-Stage Breast Cancer: An Analysis of Use, Therapeutic Implications, and Disparity Profile
Authors: Jagar Jasem, Arya Amini, Rachel Rabinovitch, Virginia F. Borges, Anthony Elias, Christine M. Fisher, Peter Kabos
Journal: Journal of Clinical Oncology (2016)

The 21-gene Recurrence Score (RS) assay is used to predict disease recurrence and benefit of chemotherapy in estrogen receptor-positive, lymph node-negative early-stage breast cancer (EBC). Our study is the first analysis of trends and differences in the use of the RS assay and its impact on recommending chemotherapy in a population-based data set.Patients with EBC diagnosed from 2004 to 2012 and included in the National Cancer Data Base were analyzed. Multivariate logistic regression analysis was used to estimate the covariates associated with use of the test and its impact on chemotherapy decisions.The RS assay was ordered for 54.0% of the 143,032 identified patients. Of all the variables, RS assay had the strongest association with recommendation for chemotherapy, with an adjusted odds ratio (AOR) of 83 for high assay scores. When indicated, test use was significantly associated with younger age, white race, academic centers, private insurance, and pT2/pN0(i+) grade 2 to 3 disease. Black patients (AOR, 1.31; 95% CI, 1.20 to 1.43) and those treated in community facilities (AOR, 1.49; 95% CI, 1.35 to 1.63) were more likely to be tested outside the National Comprehensive Cancer Network guidelines. Black patients (AOR, 1.51; 95% CI, 1.31 to 1.69) and those with high tumor grade (AOR, 30.76; 95% CI, 26.48 to 35.73) had significantly higher assay scores. Younger black patients (AOR, 1.33; 95% CI, 1.16 to 1.54) were more likely to receive chemotherapy despite low assay scores.The RS assay significantly influences clinicians' recommendations for chemotherapy in patients with EBC. Black patients tended to have higher assay scores, which may reflect use patterns or less favorable tumor biology for estrogen receptor-positive disease. There are significant differences in use and clinical implications of the test on the basis of race, insurance, and type of facility.