tbuckley/cabot-search huggingface dataset:
A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer
Authors: J.A. Ajani, M. Abramov, I. Bondarenko, Y. Shparyk, V. Gorbunova, A. Hontsa, N. Otchenash, M. Alsina, S. Lazarev, J. Feliu, A. Elme, V. Esko, K. Abdalla, U. Verma, F. Benedetti, T. Aoyama, H. Mizuguchi, L. Makris, G. Rosati
Journal: Annals of Oncology (2017)
Hepatitis C virus seropositivity and head and neck cancers: A new trio.
Authors: Parag Mahale, Erich M. Sturgis, Harrys A. Torres
Journal: Journal of Clinical Oncology (2015)

6041 Background: Hepatitis C virus (HCV) infection is associated with hepatocellular carcinoma [odds ratio (OR), 17] and non-Hodgkin lymphomas (NHL) (OR, 2). In 2009, we established the first clinic in US devoted to managing HCV-infected cancer patients (pts) where we observed a large number of pts with head and neck cancers (HNC). We aimed to test the association between HCV seropositivity (HCV-Ab+) and HNCs. Methods: Medical records of cancer pts who were tested for HCV antibodies at MD Anderson between 6/2004 – 5/2014 were identified. Cases had first primary oropharyngeal cancers (OPCs) and non OPCs (cancers of oral cavity, nasopharynx, hypopharynx, and larynx). Lymphomas of OP/non OP region were excluded. Controls had smoking-associated cancers of lung, esophagus, and urinary bladder. Biopsy reports of OPCs tested for HPV by in-situ hybridization were obtained. Multivariable logistic regression models were constructed. Results: Of 34,545 cancer pts tested for HCV antibodies, 409 cases [OPC, 164 (40%); non OPC, 245 (60%)] and 694 controls [lung, 378 (55%); esophagus, 168 (24%); urinary bladder, 148 (21%)] were identified. OPC pts were mostly males (82% vs 68%; p = .001), with cancer diagnosed at younger age [median (yrs), 59 vs 63; p < .0001], better educated [ ≥ bachelor’s degree, 57% vs 38%; p < .0001], smoked fewer cigarettes [median pack-years (py), 24 vs 36; p = .0001] but more alcohol intake [drinks/week > 28, 23% vs 13%; p = .002] than controls. Non OPC pts were mostly males (77% vs 68%; p = .01), with cancer diagnosed at younger age [median (yrs), 59 vs 63; p < .0001], smoked fewer cigarettes [median py, 30 vs 36; p = .2], more alcohol intake [drinks/week > 28, 29% vs 13%; p = .002], and more HIV co-infected (4% vs 1%; p = .05) than controls. Adjusted models showed significant association of HCV-Ab+ with OPCs (OR 2.1; 95% CI 1.1 – 4.2; p = .02) and non OPCs (OR 2.8; 95% CI 1.4, 5.7; p = .005). However, it was significant with only HPV+ OPCs (OR 4.4; 95% CI 1.9 – 10.5; p = .001) but not HPV–OPCs (OR 1.1; 95% CI 0.4 – 3.1; p = .82). Conclusions: HCV-Ab+ may be associated with non-liver cancers such as HNCs, particularly HPV+ OPCs. The strength of this association is as high as the one reported for NHLs. Further studies are warranted to explore this association and interaction of HPV with HCV.
Discovery of ovarian cancer tumor vascular markers using immuno-LCM and transcriptional profiling.
Authors: D. James Morre, Kenneth L. Pennington, Heather Hignite, Helen Orvis, Douglas J. Schwartzentruber, Xiaoyu Tang, Dorothy M. Morre
Journal: Cancer Research (2006)

5684   The use of reverse transcription-PCR (RT-PCR) to detect cells in the blood of cancer patients based on levels of mRNA expressed in tumor cells has implications for monitoring tumor progression and therapy in cancer patients. This study has utilized splice variant-specific probes to detect a cancer-specific mRNA variant responsible for cell surface expression of pancancer isoforms of a growth related, NADH oxidase protein with protein disulfide-thiol interchange designated tNOX specific for cancer (Morre′ and Morre′. 2003 Free Radical Res. 37:795–808). tNOX is also shed into the serum as a useful pancancer marker for clinical metastatic disease. Using RT-PCR and exon-specific primers, an RT-PCR 150 bp product indicative of tNOX splice variant mRNA was measured in the blood of cancer patients and healthy volunteers. Venous blood samples were collected into 7 ml vacutainers containing potassium EDTA. The specimens were snap frozen and stored at -80° C until RNA extraction. Total RNA from whole peripheral blood was extracted using Fast Lane Cell cDNA kit (Qiagen). Cancer fraction, purity and amounts of total RNA were assessed by electrophoresis in Tris-Acetate-EDTA buffer on 1% agarose gels, with the DNA bands visualized by ethidium bromide staining. We evaluated 32 patients with histologic diagnosis of breast, lung, or ovarian cancer and 22 healthy volunteers. The specificity and sensitivity of the nested RT-PCR procedure was established initially using human cancer cell lines in culture (HeLa cervical carcinoma, BT-20 mammary carcinoma, MCF-10 mammary non-cancer.) Splice variant-specific tNOX primers were designated according to published sequence information (Available from GenBank under Accession No. AF 207881). Each RT-PCR run included a positive control (tNOX-positive cell line or blood donor and blood from a negative donor). Under the assay conditions developed, 100% of patients with cancer were positive for tNOX splice variant mRNA. Samples from individuals free of disease or with disorders other than cancer were negative within the limits of detection of the assay. In conclusion, this assay is a promising tool for detecting circulating cancer cells. Larger cohorts will be required in future studies to define the impact, if any, of this technology to detect splice variant-tNOX mRNA in blood borne cells and it9s utility in cancer management.
Endovascular treatment for locally advanced head and neck tumors.
Authors: Irina V. Aedinova, M. N. Chernyak, Yulia Ulianova, Viktoriya L. Volkova, Natalia A. Chertova, Mamuka Bauzhadze
Journal: Journal of Clinical Oncology (2017)

e17554 Background: Treatment of locally advanced head and neck tumors is an extremely difficult task. Preoperative polychemotherapy allows improving the efficiency of combined treatment in most cases. We performed 6 chemoembolization procedures for locally advanced head and neck cancer in order to increase the effectiveness of chemotherapy with minimal systemic side effects and to reach cytostatic concentrations in tumors higher than at their intravenous administration. Methods: We performed the standard puncture femoral approach and selective catheterization of the external carotid artery followed by angiography. Superselective catheterization of targeted vessels using 2.6 F microcatheter was performed after evaluation of blood supply to the affected area. Chemoembolization was performed with platinum drugs (cisplatin at a mean dose of 50 mg/m 2 ) in an oil emulsion with Lipiodol (4 patients) and saturable microspheres (2 patients). Results: All patients showed a severe pain syndrome during embolization with its increase by the evening of the day and its regression on the third day after surgery; general toxic symptoms were not observed. Significant perioperative complications were not registered. A marked necrosis of the tongue base tumor was observed in one patient after 10 days. All patients showed a partial positive response to the therapy which allowed radical surgical treatment. Conclusions: Chemoembolization with polymeric microspheres provides a longer (up to one month) contact between malignant cells and antitumor agents; chemoembolization is not accompanied by the development of adverse reactions and complications or immunosuppressive effect which allows its use in the most serious cases.
Bosutinib (BOS) versus imatinib (IM) for newly diagnosed chronic myeloid leukemia (CML): Initial results from the BFORE trial.
Authors: Jorge E. Cortes, Carlo Gambacorti-Passerini, Michael W.N. Deininger, Michael J. Mauro, Charles Chuah, Dong-Wook Kim, Laurence Reilly, Allison Marianne Jeynes-Ellis, Eric Leip, Nathalie Bardy-Bouxin, Andreas Hochhaus, Tim H. Brümmendorf
Journal: Journal of Clinical Oncology (2017)

7002 Background: BOS is a potent, dual SRC/ABL tyrosine kinase inhibitor approved for treatment (tx) of adults with Ph+ CML resistant/intolerant to prior therapy. We assessed the efficacy and safety of BOS vs IM for first-line tx of chronic phase (CP) CML. Methods: In this ongoing, multinational, phase 3, open-label study, 536 patients (pts) with newly diagnosed CP CML were randomized 1:1 to BOS 400 mg QD (n = 268) or IM 400 mg QD (n = 268 [3 not treated]). Per protocol, efficacy was assessed in a modified intent-to-treat (ITT) population of 487 Ph+ pts (BOS, n = 246; IM, n = 241) with e13a2/e14a2 transcripts; results in full ITT will also be presented. Results: After≥12 mo of follow-up, 78% of BOS and 73.2% of IM pts remain on tx with median tx durations of 14.1 and 13.8 mo, respectively. Major molecular response (MMR) rate at 12 mo (primary endpoint) was significantly higher with BOS vs IM (47.2% vs 36.9%; P= 0.02). Time to MMR was shorter for BOS (hazard ratio [HR] 1.34; P&lt; 0.02). Rate of complete cytogenetic response (CCyR) by 12 mo was also significantly higher with BOS vs IM (77.2% vs 66.4%; P&lt; 0.008), with time to CCyR shorter for BOS (HR 1.38; P≤0.001). Rates of BCR-ABL transcripts≤10% (Intl Scale) at 3 mo (75.2% vs 57.3%), MR 4 at 12 mo (20.7% vs 12%) and MR 4.5 at 12 mo (8.1% vs 3.3%) were higher with BOS vs IM, respectively (all P&lt; 0.025). 1 BOS pt and 4 IM pts discontinued tx due to progression to accelerated or blast phase. There were no deaths within 28 d of last dose of BOS and 4 with IM. Safety data were consistent with known safety profiles of BOS and IM. 12.7% of BOS and 8.7% of IM pts discontinued due to drug-related toxicity. Gr≥3 diarrhea (7.8% vs 0.8%) and increased alanine (19% vs 1.5%) and aspartate (9.7% vs 1.9%) aminotransferase levels were more common with BOS. Cardio-, peripheral- and cerebrovascular events were infrequent (3%, 1.5% and 0% BOS vs 0.4%, 1.1% and 0.4% IM; gr≥3: 1.5%, 0% and 0% vs 0%, 0% and 0.4%). Conclusions: Pts on BOS had significantly higher rates of 12-mo MMR and CCyR and achieved responses faster than those on IM, but had higher incidence of gastrointestinal events and transaminase elevations. Results suggest BOS may be an important tx option for pts with newly diagnosed CP CML. Funding. Avillion, Pfizer. Clinical trial information: NCT02130557 .
Somatic Loss of HLA Class I Alleles Is a Common Genetic Alteration in Acquired Aplastic Anemia and Reveals Aplastic Anemia Risk Alleles
Authors: Daria V. Babushok, Jamie Duke, Hongbo M. Xie, Deborah Ferriola, Natasha Stanley, Jamie Atienza, Hugh Huang, Jaclyn A Biegel, Monica Bessler, Dimitri S. Monos, Timothy S. Olson
Journal: Blood (2016)
PS01.55: IMpower010: Phase III Study of Atezolizumab vs BSC After Adjuvant Chemotherapy in Patients with Completely Resected NSCLC
Authors: Eric Vallieres, Enriqueta Felip, Nasser Altorki, Caicun Zhou, Yunxia Zuo, Michael Howland, Fan Xia, Tien Hoang, Alan Sandler, Heather Wakelee
Journal: Journal of Thoracic Oncology (2016)
Outcomes of Mismatched Related Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia: A Retrospective Study on Behalf of the Chronic Malignancies Working Party of the EBMT
Authors: Gwendolyn van Gorkom, Michel van Gelder, Dimitris Ziagkos, Henric-Jan Blok, Maria Teresa van Lint, Yener Koc, Fabio Ciceri, Dietrich W. Beelen, Patrice Chevallier, Dominik Selleslag, Didier Blaise, Roberto Foà, Paolo Corradini, Luca Castagna, Carol Moreno, Carlos Solano, Lutz P. Müller, Johanna Tischer, Inken Hilgendorf, Michael Hallek, Joerg Thomas Bittenbring, Matthias Theobald, Johannes Schetelig, Nicolaus Kröger
Journal: Blood (2016)
ビオチン化脂質自己挿入細胞膜の利用による量子ドットを用いたウイルスエンベロープ脂質の標識【Powered by NICT】
Authors: Lv Cheng, Lin Yi, Liu An-An, Hong Zheng-Yuan, Wen Li, Zhang Zhenfeng, Zhang Zhi-Ling, Wang Hanzhong, Pang Dai-Wen
Journal: Biomaterials (2016)
Caveolin-1 as a target for colon cancer inhibition by lovastatin and celecoxib
Authors: Suresh Guruswamy, swamy malisetty, Levy Kopelovich, Vernon Steele, Chinthalapally Rao
Journal: Cancer Research (2007)

3360  Colon cancer is the most common type of cancer among men and women in the United States. Previously, we have shown that combination of low doses of celecoxib (COX-2 inhibitor) and lovastatin (HMG-R inhibitor) synergistically suppress colon cancers in preclinical models. However, the molecular mechanism by which combinations of celecoxib and lovastatin provides synergistic chemopreventive effects has not yet been fully understood. In this study we report key molecular changes associated with the synergistic action of celecoxib and lovastatin. Experiments were designed to test effect of lovastatin and celecoxib or their combination on cell growth, apoptosis, Caveolin-1, Cyclin A, Cyclin D1 and lipid body formation in human colon cancer HCT-116 cell line. Using MTT assay, the IC50 values were found to be 25 μM and 50 μM for lovastatin and celecoxib respectively. HCT-116 cells were treated with 25μM lovastatin or 50 μM celecoxib or a combination of both and analyzed for apoptosis (EB-AO and DAPI methods), caveolin-1 expression and cellular distribution (by immunoblot and immunofluorescence methods), cyclin A, cyclin D1 expression (immunoblot) and lipid body formation (oil-red staining). Our results found that an combination of lovastatin and celecoxib significantly increases apoptosis in colon cancer cells compared to individual treatments (p
P2.03: Treatment of Malignant Pleural Mesothelioma Beyond First-Line Among Hispanics (MeSO-CLICaP)
Authors: Luis Corrales-Rodriguez, Andrés F. Cardona, Oscar Arrieta, George Oblitas, Leonardo Rojas, Ludwing Bacon, Claudio Martin, Beatriz Wills, Mauricio Cuello, Luis Mass, Carlos Vargas, Hernán Carranza, Jorge Otero, María Angelina Pérez, Lisde González, Luis Chirinos, Rafael Rosell
Journal: Journal of Thoracic Oncology (2016)
mTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy
Authors: Rosa Bartolomeo, Laura Cinque, Chiara De Leonibus, Alison Forrester, Anna Chiara Salzano, Jlenia Monfregola, Emanuela De Gennaro, Edoardo Nusco, Isabella Azario, Carmela Lanzara, Marta Serafini, Beth Levine, Andrea Ballabio, Carmine Settembre
Journal: Journal of Clinical Investigation (2017)

The mammalian target of rapamycin complex 1 (mTORC1) kinase promotes cell growth by activating biosynthetic pathways and suppressing catabolic pathways, particularly that of macroautophagy. A prerequisite for mTORC1 activation is its translocation to the lysosomal surface. Deregulation of mTORC1 has been associated with the pathogenesis of several diseases, but its role in skeletal disorders is largely unknown. Here, we show that enhanced mTORC1 signaling arrests bone growth in lysosomal storage disorders (LSDs). We found that lysosomal dysfunction induces a constitutive lysosomal association and consequent activation of mTORC1 in chondrocytes, the cells devoted to bone elongation. mTORC1 hyperphosphorylates the protein UV radiation resistance-associated gene (UVRAG), reducing the activity of the associated Beclin 1-Vps34 complex and thereby inhibiting phosphoinositide production. Limiting phosphoinositide production leads to a blockage of the autophagy flux in LSD chondrocytes. As a consequence, LSD chondrocytes fail to properly secrete collagens, the main components of the cartilage extracellular matrix. In mouse models of LSD, normalization of mTORC1 signaling or stimulation of the Beclin 1-Vps34-UVRAG complex rescued the autophagy flux, restored collagen levels in cartilage, and ameliorated the bone phenotype. Taken together, these data unveil a role for mTORC1 and autophagy in the pathogenesis of skeletal disorders and suggest potential therapeutic approaches for the treatment of LSDs.
薬剤耐性感染の治療のための相乗的抗菌剤としての抗生物質負荷,銀コアに埋め込まれたメソ多孔性シリカナノ媒体【Powered by NICT】
Authors: Wang Yao, Ding Xiali, Chen Yuan, Guo Mingquan, Zhang Yan, Guo Xiaokui, Gu Hongchen
Journal: Biomaterials (2016)
Early presence of anti-angiogenesis-related adverse events as a potential biomarker of antitumor efficacy in metastatic gastric cancer patients treated with apatinib: a cohort study
Authors: Xinyang Liu, Shukui Qin, Zhichao Wang, Jianming Xu, Jianping Xiong, Yuxian Bai, Zhehai Wang, Yan Yang, Guoping Sun, Liwei Wang, Leizhen Zheng, Nong Xu, Ying Cheng, Weijian Guo, Hao Yu, Tianshu Liu, Pagona Lagiou, Jin Li
Journal: Journal of Hematology & Oncology (2017)

Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients. We conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria, or hand and foot syndrome (HFS) in the first 4 weeks. Time-to-event variables were assessed using Kaplan–Meier methods and Cox proportional hazard regression models. Binary endpoints were assessed using logistic regression models. Landmark analyses were performed as sensitivity analyses. Predictive model was analyzed, and risk scores were calculated to predict overall survival. Presence of AEs in the first 4 weeks was associated with prolonged median overall survival (169 vs. 103 days, log-rank p = 0.0039; adjusted hazard ratio (HR) 0.64, 95% confidence interval [CI] 0.64–0.84, p = 0.001), prolonged median progression-free survival (86.5 vs. 62 days, log-rank p = 0.0309; adjusted HR 0.69, 95% CI 0.53–0.91, p = 0.007), and increased disease control rate (54.67 vs. 32.77%; adjusted odds ratio 2.67, p < 0.001). Results remained significant in landmark analyses. The onset of any single AE or any combinations of the AEs were all statistically significantly associated with prolonged OS, except for the presence of proteinuria. An AE-based prediction model and subsequently derived scoring system showed high calibration and discrimination in predicting overall survival. Presence of HTN, proteinuria, or HFS during the first cycle of apatinib treatment was a viable biomarker of antitumor efficacy in metastatic GC patients.
Antibiotic residues in the environment of South East Asia
Authors: Cecilia Stålsby Lundborg, Ashok J Tamhankar
Journal: BMJ (2017)

<b>Cecilia Stålsby Lundborg</b> and <b>Ashok Tamhankar</b> discuss how antibiotic residues in the environment contribute to antibiotic resistance in South East Asia and propose actions to mitigate the problem
Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study
Authors: Nico van Zandwijk, Nick Pavlakis, Steven C Kao, Anthony Linton, Michael J Boyer, Stephen Clarke, Yennie Huynh, Agata Chrzanowska, Michael J Fulham, Dale L Bailey, Wendy A Cooper, Leonard Kritharides, Lloyd Ridley, Scott T Pattison, Jennifer MacDiarmid, Himanshu Brahmbhatt, Glen Reid
Journal: The Lancet Oncology (2017)
A subset of conserved mammalian long non-coding RNAs are fossils of ancestral protein-coding genes
Authors: Hadas Hezroni, Rotem Ben-Tov Perry, Zohar Meir, Gali Housman, Yoav Lubelsky, Igor Ulitsky
Journal: Genome biology (2017)

Only a small portion of human long non-coding RNAs (lncRNAs) appear to be conserved outside of mammals, but the events underlying the birth of new lncRNAs in mammals remain largely unknown. One potential source is remnants of protein-coding genes that transitioned into lncRNAs. We systematically compare lncRNA and protein-coding loci across vertebrates, and estimate that up to 5% of conserved mammalian lncRNAs are derived from lost protein-coding genes. These lncRNAs have specific characteristics, such as broader expression domains, that set them apart from other lncRNAs. Fourteen lncRNAs have sequence similarity with the loci of the contemporary homologs of the lost protein-coding genes. We propose that selection acting on enhancer sequences is mostly responsible for retention of these regions. As an example of an RNA element from a protein-coding ancestor that was retained in the lncRNA, we describe in detail a short translated ORF in the JPX lncRNA that was derived from an upstream ORF in a protein-coding gene and retains some of its functionality. We estimate that ~ 55 annotated conserved human lncRNAs are derived from parts of ancestral protein-coding genes, and loss of coding potential is thus a non-negligible source of new lncRNAs. Some lncRNAs inherited regulatory elements influencing transcription and translation from their protein-coding ancestors and those elements can influence the expression breadth and functionality of these lncRNAs.
Impaired intranuclear trafficking of AML1 causes transformation-coupled arrest of myeloid maturation
Authors: Diana Vradii, Sayyed K. Zaidi, Xiangen Li, Jane B. Lian, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein
Journal: Cancer Research (2005)

6117   The t(8;21) chromosomal translocation in acute myeloid leukemias disrupts the  Runx1  ( AML1)  gene that is essential for definitive hematopoiesis. The resulting AML-ETO fusion protein, which contains the amino terminal DNA binding domain and nuclear import signal of AML1 but lacks the subnuclear targeting signal (NMTS), functions as a dominant repressor of AML1 function  in vivo . Loss of the obligatory AML1 subnuclear targeting signal results in misdirection of this leukemia fusion protein to nuclear microenvironments distinct from AML1 sites. In this study, we directly addressed the contribution of AML1 subnuclear targeting to myeloid differentiation. A single amino acid substitution in the AML1 NMTS that abrogates intranuclear trafficking was introduced. The mutant protein retains the ability to enter the nucleus, binds to DNA and forms nuclear complexes with co-regulatory and signaling proteins. However, the mutant is incapable of association with architecturally organized subnuclear domains. Expression of the mutant AML1 protein blocks differentiation of myeloid progenitor cells to granulocytes. These cells continue to proliferate, maintain an immature blast-like morphology, and exhibit transformed properties that are hallmarks of leukemogenesis. Changes in cell growth and phenotype were reflected by altered gene expression profiles. These findings functionally link fidelity of AML1 subnuclear organization with competency for myeloid differentiation and expression of the transformed/leukemia phenotype.
Quality of life in patients with vitiligo using the Short Form-36
Authors: Y. Yang, L. Zapata, C. Rodgers, K. Hernandez, M. Iyer, G. Jia, L. S. Hynan, A.G. Pandya
Journal: British Journal of Dermatology (2017)

Vitiligo is an acquired pigmentary disorder affecting 0.5-1% of the world's population. Affected individuals often have low self-esteem, and poor quality of life (QOL) due to the disfigurement caused by the disease [1]. Vitiligo's impact on QOL compared to other diseases using general health questionnaires like the Short Form 36 (SF-36) is not well understood. We performed a cross-sectional study of patients with vitiligo and controls using the SF-36 and compared our scores to studies of patients with depression, chronic lung disease, psoriasis, atopic dermatitis, arthritis, cancer, congestive heart failure, myocardial infarction, type 2 diabetes, hypertension, and healthy adults.

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Haploidentical Stem Cell Transplantation for Rare Pediatric Diseases at Peking University People's Hospital
Authors: Yao Chen, Huan Chen, Lan-Ping Xu, Yu-Hong Chen, Jing-Zhi Wang, Feng-Rong Wang, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Jun Huang
Journal: Blood (2016)