tbuckley/cabot-search huggingface dataset:
Bendamustine Versus Chlorambucil in Treatment-Naive Patients with B-Cell Chronic Lymphocytic Leukemia (B-CLL): Results of an International Phase III Study.
Authors: Wolfgang Ulrich Knauf, Toshko Lissichkov, Ali Aldaoud, Raoul Herbrecht, Anna Marina Liberati, Javier Loscertales, Gunnar Juliusson, Christian Dittrich, Karlheinz Merkle
Journal: Blood (2007)
Pharmacokinetic and pharmacogenetic analysis in patients with advanced nasopharyngeal carcinoma (NPC) treated with 5-flurouracil (5-FU) and cisplatin.
Authors: Yuxiang Ma, Hongyun Zhao, Liping Zhao, Yunpeng Yang, Cong Xue, Xuan Wu, Wenhua Liang, YuanYuan Zhao, Wenfeng Fang, Tao Qin
Journal: Journal of Clinical Oncology (2014)

6063 Background: Many studies have demonstrated several pharmacokinetic and pharmacogenetic factors may affect the efficacy and toxicity of 5-FU. These factors include system drug exposure (area under the concentration-time curve, AUC), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). This study is to investigate correlation of these factors and efficacy and toxicity of 5-FU and Cisplatin in NPC patients. Methods: 122 NPC patients with measurable lesions were enrolled and received Cisplatin (80mg/m2, day1) and 5-FU (4g/m2, civ120h) regimen. The blood samples were collected at steady state of 5-FU infusion. AUC of 5-FU measurement was performed using an immune-based assay (MyCare). The 5-FU AUC target range was identified by Received Operating Characteristic Curve (ROC), based on 5-FU related mucositis and treatment response. Tumor tissues were also collected for evaluation the expression of TS, DPD by using immunohistochemistry (IHC). Results: 108 patients were analyzed (5 not assessable, 6 withdraw and 3 invalid sample). AUC of 5FU values ranged from 15 to 103mg·h/L. The optimal target range of 5-FU AUC was 31-37 mg·h/L. 20.4% of the patients were within the target range, while 39.8% was below and 39.8% was above. Within or above target range patients had better object response rate than those below target (75.4% vs 55.8%, P=0.033), within or below target range patients had lower toxicity rate (grade3/4) than those above target (6.2% vs 67.4%, P<0.001). A nomogram model based on AUC, DPD and TS expression for predicting treatment response shown that, all as independent variables, within the target AUC range, high-DPD or low-TS tumor had better response rate. Conclusions: The combination of pharmacokinetic and pharmacogenetic approach may be an innovative strategy for optimizing chemotherapy in patients with advanced NPC. These findings deserve confirmation in additional prospective studies.
A comparison of toxicity profiles between standard and lower dose capecitabine (CAP) in breast cancer (BC): a meta-analysis.
Authors: Tomohiro Funakoshi, Maya Suzuki, Hyman B. Muss
Journal: Journal of Clinical Oncology (2015)

1028 Background: CAP 1,250 mg/m2 BID x 14 days every 21 days (14/21) as monotherapy is the FDA approved dose and schedule for metastatic breast cancer (MBC). In trials of CAP 1,250 mg/m2 BID (14/21), 26%–65% of patients required a dose reduction due to toxicities. A more favorable toxicity profile has been reported in trials of CAP 1,000 mg/m2 BID (14/21). We performed a systematic review and meta-analysis to compare a safety profile between CAP starting dose of 1,250 and 1,000 mg/m2. Methods: Studies were identified using PubMed, and ASCO and San Antonio Breast Cancer Symposium abstract databases from 1966 to November 2014. Eligible studies included phase II and III trials of CAP monotherapy at 1,250 or 1,000 mg/m2 BID (14/21) for BC patients that reported adequate safety data for grade 1-4 or 3-4 adverse events (hand foot syndrome (HFS), diarrhea, fatigue, nausea, vomiting, stomatitis, neutropenia, thrombocytopenia, or anemia), dose reduction or treatment discontinuation. The summary incidence was calculated from CAP monotherapy arms of the included studies using random- effects models (comprehensive meta-analysis program Ver. 2, Englewood, NJ). Results: A total of 4,283 patients from 32 trials (12 phase III and 20 phase II) of CAP monotherapy were included. 29 trials were in the locally advanced or MBC setting, 2 trials were neoadjuvant, and 1 trial was adjuvant. 3,065 and 1,218 patients were treated with CAP 1,250 and 1,000 mg/m2, respectively. A significantly lower incidence of dose reductions, high grade HFS, diarrhea, neutropenia and anemia as well as all grade neutropenia was seen in CAP 1,000 mg/m2 compared to 1,250 mg/m2. (Table) Conclusions: CAP monotherapy at 1,000 mg/m2 BID (14/21) has a clinically meaningful and significantly better toxicity profile compared to 1,250 mg/m2 BID (14/21). CAP 1,250 mg/m2 Incidence % (95% CI) CAP 1,000 mg/m2 Incidence % (95% CI) P value Dose reduction 39.0 (32.4-45.9) 15.9 (7.5-30.5) 0.0007 HFS (G3-4) 18.6 (14.9-22.9) 12.0 (9.0-15.7) 0.0122 Diarrhea (G3-4) 10.0 (7.4-13.2) 5.3 (3.9-7.0) 0.0050 Neutropenia (G3-4) 7.0 (5.4-9.1) 1.8 (1.1-2.9) 0.0001 Anemia (G3-4) 3.4 (2.7-4.2) 1.9 (1.0-3.5) 0.0465 Neutropenia (G1-4) 25.4 (17.3-35.7) 5.8 (1.8-17.5) 0.0015
Colonic Metastasis From Esophageal Squamous Cell Carcinoma Demonstrated With 18F-FDG PET/CT
Authors: Na Fang, Yan-Li Wang, Lei Zeng, Zeng-Jie Wu, Li-Li Liu
Journal: Clinical Nuclear Medicine (2017)

Metastatic involvement of the colon is extremely rare. We report a 63-year-old man with colonic metastasis from esophageal squamous cell carcinoma. Whole-body F-FDG PET/CT showed abnormal tracer uptakes in the sigmoid colon, which was subsequently confirmed as metastatic from esophageal squamous cell carcinoma.
Effect of arsenic trioxide on epithelial-mesenchymal transition via induction of SH2?containing protein tyrosine phosphatase 1.
Authors: Jong-Jae Park, Moon Kyung Joo, Hyo Soon Yoo, Beom Jae Lee, Taehyun Kim, Ji ae Lee, Yu-ra Sim, Wonjae Choi, Hoon Jai Chun, Sang Woo Lee, Young-Tae Bak
Journal: Journal of Clinical Oncology (2017)

76 Background: Arsenic trioxide (ATO) is known to inhibit epithelial-mesenchymal transition (EMT) in hepatolocellular carcinoma and breast cancer cells, however, little has been reported in gastric cancer cells. In this study, we aimed to investigate the mechanism of ATO to inhibit signal transducer and activator of transcription 3 (STAT3) activity and EMT in gastric cancer cells. Methods: We performed wound closure assay and Matrigel invasion assay for functional studies of EMT, and western blot for measurement of protein markers using AGS gastric cancer cells. Results: Compared with control, 5 and 10 μM of ATO significantly inhibited cellular migration and inhibition in a dose-dependent manner. Furthermore, ATO significantly downregulated snail expression, a mesenchymal marker, and upregulated E-cadherin expression, an epithelial marker. We could observe that ATO induced SH2-containing protein tyrosine phosphatase 1 (SHP1), a non-receptor type protein tyrosine phosphatase, and subsequently downregulated phospho-STAT3 in a dose-dependent manner. To validate the molecular link between ATO and SHP1 to inhibit EMT in gastric cancer cell, we pre-treated 50 μM of pervanadate, a phosphatase inhibitor, before treatment of 10 μM ATO, and this significantly abolished anti-invasive effect by ATO in AGS cells. In xenograft tumor model, intraperitoneal injection of ATO significantly reduced the tumor volume and upregulated SHP-1 expression by immunohistochemistry stain compared with vehicle, which were reversed by ATO with pervanadate injection. Conclusions: Our findings suggest that ATO may show anti-EMT effects via induction of SHP1 and inhibition of STAT3 activity in gastric cancer cells.
Function of Growth Factor Independence 1 (GFI1) in the Polarization AML -Associated Stroma
Authors: Lacramioara Botezatu, Yahya S. A. Al-Matary, Bertram Opalka, Jan Dürig, Thomas Schroeder, Rainer Haas, Ulrich Dührsen, Cyrus Khandanpour
Journal: Blood (2014)
Density of immunogenic antigens and presence or absence of the T cell-inflamed tumor microenvironment in metastatic melanoma.
Authors: Thomas Gajewski, Yuanyuan Zha, Kyle Hernandez, Yan Li, Riyue Bao, Peter Alexieff, Jorge Andrade, Jason John Luke, Stefani Spranger
Journal: Journal of Clinical Oncology (2015)

3002 Background: Patients with melanoma can be categorized based on the presence or absence of a T cell-inflamed tumor microenvironment. The presence of baseline CD8+T cells is associated with clinical benefit to immunotherapies, including anti-PD1 and anti-CTLA4. The molecular mechanism explaining lack of a T-cell infiltrate in a major subset are poorly understood, but differential expression of immunogenic antigens has been proposed as one explanation. Methods: Using the TCGA data set for malignant melanoma, the T cell-inflamed gene expression signature was used to segregate patients by immune phenotype. Three categories of antigens were examined: cancer-testis (CT) antigens, differentiation antigens, and somatic mutational antigens. Results: By transcriptional profiling, no difference was observed in levels of CT antigens or differentiation antigens. Using exome sequencing of tumor versus germline, a range of 18 to 3001 of non-synonymous mutations was observed in both cohorts. Using the syfpeithi algorithm for HLA-A*0201 patients, a median of 123 mutations having a high immunogenicity score were found in the T cell-inflamed cohort versus 176 in the non-T cell inflamed. To confirm actual immunogenicity, several synthesized peptides show positive HLA-A*0201 binding and can be recognized by human CD8+T cells in vitro. Conclusions: Both the T cell-inflamed and non-T cell-inflamed subsets of melanoma show comparable expression of CT, differentiation, and mutational antigens. Lack of spontaneous immune infiltration in a major subset of tumors is unlikely to be due to lack of antigens. Strategies that improve spontaneous T-cell infiltration into tumors therefore could, in principle, render these patients response to immunotherapies once these antigens become recognized.
Relationship between depression and frailty in older adults: A systematic review and meta-analysis
Authors: Pinar Soysal, Nicola Veronese, Trevor Thompson, Kai G. Kahl, Brisa S. Fernandes, A. Matthew Prina, Marco Solmi, Patricia Schofield, Ai Koyanagi, Ping-Tao Tseng, Pao-Yao Lin, Che-Sheng Chu, Theodore D. Cosco, Matteo Cesari, Andre F. Carvalho, Brendon Stubbs
Journal: Ageing Research Reviews (2017)
Widespread use of complementary and alternative medicine (CAM) among non-Hodgkin lymphoma (NHL) survivors.
Authors: Alexis D. Leal, Cristine Allmer, Matthew J. Maurer, James R. Cerhan, Grzegorz S. Nowakowski, David James Inwards, William R Macon, Shawna L. Ehlers, Brian K. Link, Thomas Matthew Habermann, Carrie A. Thompson
Journal: Journal of Clinical Oncology (2012)

9057 Background: The incidence of CAM use among patients with cancer is higher when compared to the general population. However, there are few studies examining CAM use in NHL survivors, and limited data are available regarding beliefs in CAM. This study was conducted to examine the prevalence of CAM use in NHL, define CAM beliefs among NHL survivors, and explore differences between patients with indolent and aggressive lymphoma. Methods: Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource from 2002-2008. NHL patients who completed the 3-year post diagnosis questionnaire, which includes questions regarding CAM use and beliefs, were included in this study. Chi-squared tests and Wilcoxon rank-sum tests were used to assess the association of CAM use with prognostic and demographic factors. Results: 719 patients were included with a median age of 63 years (range 22-92). 53% were male. Overall, 636 (89%) reported ever using CAM. 78% of patients used vitamins and 54% alternative therapies (chiropractic (36%) and massage therapy (24%)). Among CAM users, 141 (22%) believe CAM can assist the body to heal, 123 (19%) believe CAM can relieve cancer symptoms, 115 (18%) believe CAM use gives a feeling of control, 106 (17%) believe CAM can boost immunity, 24 (4%) believe CAM can cure cancer, and 35 (6%) believe CAM can prevent the spread of cancer. Female gender was associated with increased overall CAM use (p&lt;0.0001) as well as use of vitamins (p&lt;0.0001), herbal supplements (p=0.006) and alternative therapy (p=0.0002) specifically for cancer. Older age was also associated with increased vitamin use (p=0.005) and decreased herbal supplements use (p=0.008). There was no significant difference in overall CAM use between those with follicular lymphoma grades I-II (n=195, 91%) and non-relapsed diffuse large B-cell lymphoma (n=151, 87%), although massage therapy was utilized more often by FL survivors (29% versus 18%, p=0.005). Conclusions: CAM modalities are used by the majority of NHL survivors (89%). The assessment of CAM use and education regarding potential harms is imperative for the NHL survivor.
Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized Trial on Imatinib at Two Dose Levels
Authors: Paolo G. Casali, John Zalcberg, Axel Le Cesne, Peter Reichardt, Jean-Yves Blay, Lars H. Lindner, Ian R. Judson, Patrick Schöffski, Serge Leyvraz, Antoine Italiano, Viktor Grünwald, Antonio Lopez Pousa, Dusan Kotasek, Stefan Sleijfer, Jan M. Kerst, Piotr Rutkowski, Elena Fumagalli, Pancras Hogendoorn, Saskia Litière, Sandrine Marreaud, Winette van der Graaf, Alessandro Gronchi, Jaap Verweij
Journal: Journal of Clinical Oncology (2017)

Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued. Median age was 60 years (range, 18 to 91 years). Median follow-up time was 10.9 years. Median progression-free survival times were 1.7 and 2.0 years in the 400- and 800-mg arms, respectively (hazard ratio, 0.91; P = .18), and median overall survival time was 3.9 years in both treatment arms. The estimated 10-year progression-free survival rates were 9.5% and 9.2% for the 400- and 800-mg arms, respectively, and the estimated 10-year overall survival rates were 19.4% and 21.5%, respectively. At multivariable analysis, age (< 60 years), performance status (0 v ≥ 1), size of the largest lesion (smaller), and KIT mutation (exon 11) were significant prognostic factors for the probability of surviving beyond 10 years. Conclusion This trial was carried out on a worldwide intergroup basis, at the beginning of the learning curve of the use of imatinib, in a large population of patients with advanced GIST. With a long follow-up, 6% of patients are long-term progression free and 13% are survivors. Among clinical prognostic factors, only performance status, KIT mutation, and size of largest lesion predicted long-term outcome, likely pointing to a lower burden of disease. Genomic and/or immune profiling could help understand long-term survivorship. Addressing secondary resistance remains a therapeutic challenge.
Molecular markers in malignant melanoma: Experience at an NCI-designated cancer center.
Authors: Matthew R. Zibelman, Nandini Kulkarni, Miriam Lango, Margaret von Mehren, Sujana Movva, Karen S. Gustafson, Sanjay S. Reddy, Hong Wu, Jeffrey M. Farma, Anthony J. Olszanski
Journal: Journal of Clinical Oncology (2015)

e20082 Background: As knowledge of the molecular make-up of malignant melanoma (MM) evolves, multi-gene panel testing by next generation sequencing (NGS) is an increasingly important tool to uncover actionable mutations and provide prognostic information. Given the plethora of FDA-approved and investigational drugs which target specific pathways, NGS may enhance potential treatment options. Methods: Archived tumor samples from patients with high-risk and recurrent MM were analyzed for mutations in targeted regions of 50 cancer-related genes using a NGS platform. The mutational profiles of MM samples were summarized for all patients and correlated with notable clinicopathologic features. Results: MM samples from 60 patients were included. Median age was 71 years (range 28-90) and 66.7% were male (n = 40). A total of 101 mutations affecting 25 unique genes were found. Two or more mutations were found in 43.3% (n = 26) of MM while 13.3% (n = 8) of MM had no genetic alterations identified. The most common mutations included: NRAS (33.3%, n = 20), BRAF (30.0%, n = 18), p53 (23.3%, n = 14), and CDKN2A (11.7%, n = 7). BRAFV600 accounted for 88.9% (16/18) of all BRAF mutations, of which 87.5% were BRAFV600E(14/16). Potentially actionable mutations with commercially available drugs (BRAF, KIT, NRAS) were found in 68.3% of patients (n = 41), while another 21 genes could be targetable on a clinical trial. Twelve patients had either an acral (n = 7) or mucosal (n = 5) MM, of which 58.3% (n = 7) had no identifiable mutation. Of the 48 remaining patients, only one had no mutations (2.1%). One patient with metastatic cutaneous melanoma had a GNAS mutation discovered but did not have a history of ocular melanoma. Conclusions: Multi-gene targeted panel testing by NGS reveals a significant number of actionable mutations in patients with MM. Patients with non-cutaneous MM were less likely to have identifiable mutations. Gene mutation MM Samples with mutations (n) Percentage of total MM samples (n=60) NRAS 20 33.3 BRAFV600 16 26.7 TP53 14 23.3 CDKN2A 7 11.7 PTEN 5 8.3 CTNNB1 4 6.7 KRAS 4 6.7 KIT 3 5.0 EGFR 3 5.0 FLT3 3 5.0 BRAFNon-V600 2 3.3 RB1 2 3.3 ERBB4 2 3.3 FGFR3 2 3.3 ATM 2 3.3 KDR 2 3.3 Others (HRAS, SMAD4, FBXW7, PIK3CA, FGFR2, HNF1A, CSF1R, GNAS, PDGFR, APC) 10 16.7
Hepatitis C, LC : A case of irreversible metronidazole-induced encephalopathy under treatment of Lung abscess in alcoholic Liver cirrhosis (초)
Authors: Young Woo Lee, Hyeon Woong Yang, Jae Woong Jeon, Sae Hee Kim, Hyang Ie Lee, Yun Jung Lee, Sung Hee Jung, An Na Kim, Sang Woo Cha
Journal: Clinical and Molecular Hepatology (2011)
Increasing evidence of tick-borne encephalitis (TBE) virus transmission, the Netherlands, June 2016
Authors: Adriaan CG Weststrate, Daan Knapen, Gozewijn D Laverman, Bart Schot, Jan JW Prick, Silke A Spit, Johan Reimerink, Barry Rockx, Felix Geeraedts
Journal: Eurosurveillance (2017)

We present a case of endemic tick-borne encephalitis (TBE) occurring in June 2016 in the eastern part of the Netherlands in an area where a strain of TBE virus, genetically different from the common TBE virus strains in Europe, was reported in ticks in 2016. With the start of the tick season in spring, this second autochthonous Dutch TBE case should remind physicians to consider the possibility of endemic TBE in patients with respective symptoms.
Erratum: A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2
Authors: S Hadano, C Hand, H Osuga, Y Yanagisawa, A Otomo, R Devon, N Miyamoto, J Showguchi-Miyata, Y Okada, R Singaraja, D Figlewicz, T Kwiatkowski, B Hosler, T Sagie, J Skaug, J Nasir, R Brown, S Scherer, G Rouleau, M Hayden, J-E Ikeda, Y Yang, A Hentati, H-X Deng, O Dabbagh, T Sasaki, M Hirano, W-Y Hung, K Ouahchi, J Yan, A Azim, N Cole, G Gascon, A Yagmour, M Ben-Hamida, M Pericak-Vance, T Siddique, P Avner, T Bruls, I Poras, L Eley, S Gas, Patricia Ruiz, V Wiles, R Sousa-Nunes, R Kettleborough, J Morrisette, L Bentley, M Goldsworthy, A Haynes, E Herbert, L Southam, H Lehrach, J Weissenbach, G Manenti, P Rodriguez-Tome, R Beddington, R Cox
Journal: Nature Genetics (2001)
Lapatinib or trastuzumab with taxane therapy as first-line treatment in metastatic breast cancer (MBC): A biomarker analysis in NCIC CTG MA.31.
Authors: Wendy R. Parulekar, Samuel Aparicio, Judy-Anne W. Chapman, Dongxia Gao, Lois E. Shepherd, Frances M. Boyle, Bella Kaufman, Louise Yelle, Theodore A. Vandenberg, Muhammad Salim, Julie Lorette, Rocco J. Crescenzo, Liting Zhu, Yvonne Murray, David Huntsman, Karen A. Gelmon
Journal: Journal of Clinical Oncology (2014)

601 Background: Lapatinib (L) was associated with shorter progression-free survival (PFS) than trastuzumab (T) when combined with a taxane (Tax) as first line therapy for HER2+ MBC. We report the effects of 6 centrally reviewed biomarkers on efficacy. Methods: MA.31 accrued 652 patients with locally assessed HER2+ tumors of which 537 (82%) were HER2+ by central review. Protocol-mandated immunohistochemistry was conducted centrally for ER, PR, Ki67, EGFR, and CK5. The primary endpoint was progression free survival (PFS) defined as time from randomization to progression or death in the intention to treat (ITT) population. Stratified step-wise forward Cox models examined the multivariate (mv) effects of baseline characteristics and continuous biomarkers (% positive) on PFS in the ITT and centrally confirmed HER2+ populations. Predictive effects were investigated with cutpoints of >0% of any staining intensity for ER, PR, EGFR, CK5, and >geometric mean for Ki67 for both populations. Results: Assessments were completed for > 80% of patients. Median follow-up was 21.5 months. LTax/L demonstrated inferior PFS to TTax/T (ITT, p<0.001). Centrally confirmed HER2+ status conferred a positive prognostic effect on PFS (p=0.005). Patients whose tumors had higher % positive ER had longer PFS [stratified HR=0.996 (95% CI 0.993-0.999); ITT, p=0.01, HER2+, p=0.003]. In ITT, lower % positive CK5 had improved PFS [stratified HR=1.008 (95% CI 1.001-1.014); p=0.03]. However, treatment interactions with each of HER2, ER, and CK5 were not significant (p>0.05). EGFR had a quantitative interaction with treatment favoring TTax/T: ITT, p=0.05; HER2+, p=0.06. Conclusions: LTax/L therapy was associated with shorter PFS compared to TTax/T as first line therapy for HER2+ MBC. Centrally confirmed HER2+ and higher % positive ER were prognostic for longer PFS. Higher EGFR positivity indicated a better response to TTax/T. Clinical trial information: NCT00667251.