tbuckley/cabot-search huggingface dataset:
Assessment of human papilloma virus in non-small cell lung cancer in never-smokers: A study from a prospective registry of never-smokers.
Authors: Tomoya Kawaguchi, Shigeki Shimizu, Norimasa Itoh, Akihito Kubo, Shunichi Isa, Tomoki Utsumi, Masahiro Sakaguchi, Hyungeun Yoon, Sai-Hong Ignatius Ou, Masanori Kitaichi, Akihide Matsumura
Journal: Journal of Clinical Oncology (2012)

e18126 Background: Driver mutations have been identified in most non-small cell lung cancers (NSCLC) from never-smokers. However, a small percentage of the tumors still have no its mutations detected. Human papillomavirus (HPV) has been hypothesized to contribute to lung carcinogenesis in East Asia. Methods: We started a prospective registry of never-smokers with NSCLC at the Kinki-chuo Chest Medical Center, Japan, in 2008. We consecutively enrolled all the never-smokers after obtaining written informed consent. Among these, we selected the 114 patients treated with surgery to obtain a large amount of DNA. After exclusion of samples with suboptimal quality, DNA was extracted from 93 formalin-fixed paraffin-embedded surgical tissues. HPV genotyping was performed using a PCR-based microarray system for detecting 23 HPV types, including high-risk (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk or risk-unknown types (HPV types 6, 11, 30, 34, 40, 42, 53, 54, 61, and 66). Epidermal growth factor receptor (EGFR) and KRAS mutations were examined with real time PCR (genotyping), and EML4-ALK rearrangements were detected using immunohistochemical staining and fluorescence in-situ hybridization. Results: There were 80 female (86.0%) and 13 male patients (14.0%), with a median age of 67 years (range 29-83). Almost all cases were of the adenocarcinoma histological subtype (92.5%). Molecular analysis of these 93 patients detected 59 EGFR mutations (63.4%), 5 K-ras mutations ( 5.4% ) and 4 EML4-ALK rearrangements (4.3%). These abnormalities were mutually exclusive except for one case who had both EGFR and KRAS mutations. HPV 6 was detected in only one case (1.1%), a 49-year-old female who had an EGFR mutation with wild type KRAS and ALK. No others examined were positive for any HPV type. Conclusions: The three driver mutations accounted for 72.0% of NSCLC in never-smokers. Although a low-risk HPV type was evident in one case, no high-risk HPV types were detected in the tumors with or without the mutations. Our results suggest that HPV does not play a major role as the driving oncogenic event in adenocarcinoma in never-smokers in Osaka, the central area of Japan.
Longitudinal evaluation of EGFR mutation in plasma for non-small cell lung cancer patients with front-line chemotherapy
Authors: B. Hua, J. Zhao, S. H. Wang, L. Yang, J. C. Duan, M. N. Wu, J. Wang
Journal: Journal of Clinical Oncology (2009)

8099 Background: To investigate longitudinally epidermal growth factor receptor (EGFR) mutation status in the plasma of pre- and post-chemotherapy for patients with advanced non-small cell lung cancer. Methods: Total of 153 advanced lung cancer patients were included in this study. Plasma samples in pre- and post-chemotherapy ( 2 cycles after) were collected. The DNA concentration was determined by real-time PCR. The EGFR exon 19 and 21 were amplified by mutant-enriched PCR and detected by denaturing high performance liquid chromatograph (DHPLC). The associations between EGFR mutation, DNA level and chemotherapeutic response were analyzed. Results: Among the 153 pts, EGFR mutation were detected 41.2% (63/153) and 27.4% (42/153) in plasma of pre-and post-chemotherapy, respectively. The objective response rate was 31.4% (48/153) and the circulating DNA level trend to decrease after chemotherapy in PR group but increase in PD group (p=0.012). 25 and 73 cases showed consistent EGFR mutation and wild-type status in pre-treatment and post-treatment plasma, respectively. Among 38 patients with change from pre-treatment EGFR mutant-type to post-treatment wild-type status, 11 gained PR, 12 SD and 15 PD. While for 17 patients with change from pre-treatment EGFR wild-type to post-treatment mutant-type, PR, SD and PD were 8, 7 and 2, respectively. The change to mutant-type in post-treatment plasma were found to be significantly higher in PR and disease control than PD(P=0.047, P=0.042). Conclusions: The data indicated that chemotherapy could not only affect the DNA concentration but also change the EGFR mutation detection in plasma for pts with advanced NSCLC. Reason for EGFR mutation change related with response of chemotherapy deserves further study. No significant financial relationships to disclose.
Efficacy of Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Myeloma Based on Prior Lines of Therapy: Updated Analysis of Castor
Authors: Maria-Victoria Mateos, Jane Estell, Wolney Barreto, Paolo Corradini, Chang-Ki Min, Eva Medvedova, Ming Qi, Jordan Schecter, Himal Amin, Xiang Qin, William Deraedt, Tineke Casneuf, Christopher Chiu, A. Kate Sasser, Ajay Nooka
Journal: Blood (2016)
ROUTINE INVASIVE VERSUS CONSERVATIVE STRATEGY FOR ELDERLY PATIENTS AGED&gt;75 YEARS WITH NON-ST ELEVATION ACUTE CORONARY SYNDROME (NSTE-ACS): A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Aakash Garg, Amit Rout, Sahil Agrawal, Tanush Gupta, Shivank Madan, Gautam Visveswaran, Lohit Garg, Parasuram Krishnamoorthy, Abhishek Sharma, John Kostis
Journal: Journal of the American College of Cardiology (2017)
Clinicopathologic and molecular factors associated with early progressive disease after front-line platinum-doublet chemotherapy (CT) for advanced non-small cell lung cancer (NSCLC).
Authors: Etienne Giroux Leprieur, Martine Antoine, Thibault Vieira, Michael Duruisseaux, Virginie Poulot, Nathalie Rabbe, Laure Belmont, Valérie Gounant, Armelle Lavole, Bernard Milleron, Roger Lacave, Jacques Cadranel, Marie Wislez
Journal: Journal of Clinical Oncology (2012)

e18075 Background: The majority of cases of NSCLC are diagnosed at an advanced stage and treated with a platinum-doublet CT. However, some patients are resistant to this treatment and develop early progressive disease. We investigated the clinicopathologic and molecular characteristics of such patients. Methods: All consecutive patients with NSCLC IIIB−IV treated with a platinum-doublet CT between 2003 and 2006 were included. Platinum resistance was defined as early progressive disease at the first tumor assessment according to WHO criteria. The clinical, histologic and molecular characteristics (EGFR:exon 19, 20, 21 and KRAS:exon 2 by PCR sequencing; ALK by IHC, confirmed by FISH) and survival of patients with early progression (P) and controlled disease (C) were compared by univariate analysis. Factors differing between the two groups with a p-value &lt;0.25 in univariate analysis were entered into multivariate analysis. Results: 178 patients were included (mean age 59.1 years, 66.3% male, 54.5% smokers). Platinum was associated with gemcitabine (52.2%), paclitaxel (32.6%) or docetaxel (11.8%). The first tumor assessment was carried out after a median of three cycles [range 1−4]. Forty-six (25.8%) patients had early progression. Overall survival of P-group was significantly shorter than that of C-group (median 5 months vs. 15.1 months, respectively; p &lt;0.0001). Clinical presentation was similar in the two groups. The sarcomatoid histologic subtype was more common among P-group than C-group (10.9% vs. 1.5%, respectively; p=0.057). The proportion of EGFR (5.2% vs. 9.6%, respectively; p=0.224) and KRAS mutations (11.1% vs. 5.7%, respectively; p=0.357), and expression of ALK (6.3% vs. 2.5%, respectively; p=0.327) did not differ significantly between the two groups. In multivariate analysis, sarcomatoid histologic subtype was the only factor associated with early progression [OR=7.50, 95%CI: 1.02−55.45; p=0.048]. Conclusions: Patients with early progression had a shorter survival than controlled patients. Sarcomatoid histologic subtype was the only independent factor associated with early progressive disease.
An intensive screening program detected high incidence of hepatocellular carcinoma (HCC) in hepatitis B virus carriers (HBVC) with abnormal alfa-fetoprotein (AFP) or abdominal ultrasongraphy (AUS)
Authors: T. Mok, B. Zee, J. Lau, W. M. Ho, P. Lai, A. Chan, W. Yeo, H. Chan, J. Koh, P. Johnson
Journal: Journal of Clinical Oncology (2004)

4002 Background: Screening holds the promise to early detection and treatment of HCC. However, the efficacy in terms of decreasing disease-specific mortality and its cost-effectiveness remain controversial. Intensity of screening and selection of target patient group contribute to the success of such program. In this study we subjected hepatitis B virus carriers (HBVC) with at least 1 abnormal AFP or AUS to an intensive screening program and determine their prevalence and incidence of HCC. Methods: Enrollment criteria: age 40–70 years, HBsAg positive, Child-Pugh Liver Classification A or B. All patients were screened by serum AFP and AUS at enrollment. Patients with either AFP>20ng/dl or abnormal AUS were enrolled to an intensive program that screened patient with one or more hepatic angiogram plus lipiodol CT scan, followed by AFP/AUS every 3 months for 2 years then every 6 months. Patients with normal AFP/AUS were followed with AFP every 6 months and AUS repeated at the end of 2 years. Histology is the gold standard for diagnosis of HCC. Results: Between 10/97 and 11/00 we screened 1018 patients (m:f 688:330; mean age 48.4) and enrolled 171 patients (AFP+/AUS- 126; AFP-/AUS+ 38; AFP+/AUS+ 7) to the intensive screening program. After a median follow-up of 4.4 years we detected 47 HCCs (15 at enrollment and 32 during follow-up), giving a prevalence of 1473/100,000 (95%CI 858 to 2477 per 100,000) and annual incidence of 794/100,000 (95% CI 562 to 1122 per 100,000). 9 HCC were detected from 847 pts with normal AFP/AUS over 2 years giving an incidence of 223/100,000 (95% CI 116 to 429 per 100,000). Surgical resection: 17 cases. Main reasons for inoperability: poor liver function and multi-centric disease. Conclusion: An intensive screening program detects a high prevalence and incidence of HCC in HBVC with at least one abnormal AFP or AUS. Incidence of HCC is significantly lower in the population with normal screening AFP and AUS for 2 years. Survival data will be available for presentation. We acknowledge the Hong Kong Cancer Fund for support towards this project. No significant financial relationships to disclose.
Interleukin-6 Enhances the Survival of Myeloma Cells by Regulating Bim Binding to Anti-Apoptotic Bcl-2 Proteins
Authors: Shannon M. Matulis, Jiangxia Liu, Vikas A. Gupta, Jason E. Conage-Pough, Ajay K. Nooka, Edmund K. Waller, Jonathan L. Kaufman, Sagar Lonial, Lawrence H. Boise
Journal: Blood (2012)
The Influence of HIV on the Evolution of Mycobacterium tuberculosis
Authors: Anastasia S. Koch, Daniela Brites, David Stucki, Joanna C. Evans, Ronnett Seldon, Alexa Heekes, Nicola Mulder, Mark Nicol, Tolu Oni, Valerie Mizrahi, Digby F. Warner, Julian Parkhill, Sebastien Gagneux, Darren P. Martin, Robert J. Wilkinson
Journal: Molecular Biology and Evolution (2017)

HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates.
RENAL NERVE DENERVATION SUPPRESS VENTRICULAR ARRHYTHMIA IN A PORCINE MODEL AFTER ACUTE MYOCARDIAL INFARCTION
Authors: Sungsoo Kim, Kim Hyun Kuk, Hyung Wook Park, Myung Ho Jeong, Dong Goo Kang, Seung Uk Lee, Sang Ki Cho, Cho Jae Young, Min Chul Kim, Ki Hong Lee, Namsik Yoon, Jeong-Gwan Cho
Journal: Journal of the American College of Cardiology (2017)
High-dose erlotinib for refractory leptomeningeal metastases (LM) after failure of standard dose EGFR-TKIs.
Authors: Takahisa Kawamura, Akito Hata, Takehiro Otoshi, Daichi Fujimoto, Koji Tamai, Jumpei Takeshita, Takeshi Matsumoto, Kazuya Monden, Kazuma Nagata, Kyoko Otsuka, Atsushi Nakagawa, Ryo Tachikawa, Kojiro Otsuka, Reiko Kaji, Shiro Fujita, Nobuyuki Katakami, Keisuke Tomii
Journal: Journal of Clinical Oncology (2013)

8098 Background: EGFR-TKIs, gefitinib and erlotinib can demonstrate dramatic and durable response in patients with EGFR-mutant non-small cell lung cancer. Approximately one-third of patients develop central nervous system (CNS) metastases, including leptomeningeal metastases (LM) after initial response to EGFR-TKIs. Pharmacokinetic failure due to insufficient penetration of EGFR-TKIs is suggested as a cause of CNS failure. Therefore, high-dose EGFR-TKIs are considered reasonable therapeutic options for refractory CNS metastases after failure of standard dose EGFR-TKIs, but there is little present evidence of high-dose EGFR-TKI’s efficacy and tolerability. Methods: Between 2007 and 2012, we screened 279 patients harboring EGFR sensitive mutations, and identified 31 patients with LM. Ten of 31 patients received high-dose erlotinib, and the other 21 underwent only standard dose EGFR-TKIs (gefitinib and/or erlotinib). In these 10 patients, erlotinib was administered at 200 mg on alternating days (n=2), 300 mg on alternating days (n=6), 300 mg every 3 days (n=1), or 600 mg every 4 days (n=1). We retrospectively investigated the efficacy and tolerability of high-dose erlotinib. Additionally, survivals from the diagnosis of LM to death were compared in patients with or without high-dose erlotinib. Results: Regarding high-dose erlotinib, five of 10 patients were radiologically evaluable, and partial response was observed in 60% (3/5), stable disease in 20% (1/5), and progressive diasease 20% (1/5). Median time to CNS progression was 3.4 months (range, 0.3-6.6 months). Improvement of neurological symptoms was observed in 9 (90%) of 10 patients. No severe adverse events (≥ grade 3) associated with high-dose erlotinib were confirmed. Median survival from the diagnosis of LM in patients with high-dose erlotinib was 6.5 months (95% CI: 2.5-12.3 months), and that in those without was 5.8 months (95% CI: 1.1-7.8 months) (p =0.51). Conclusions: The efficacy and tolerability of high-dose erlotinib were suggested for refractory LM. It can be a therapeutic option in patients after failure of standard dose erlotinib. Optimal dose and schedule are unclear, and further investigations are warranted.
CLINICAL, BIOCHEMICAL, NEUROHUMORAL, ECHOCARDIOGRAPHIC AND HEMODYNAMIC CHARACTERISTICS IN RELATION TO SURVIVAL IN PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH CONGENITAL HEART DISEASE: INSIGHTS FROM EUPHRATES STUDY
Authors: Fatih Yilmaz, Ozgur Akbal, Aykun Hakgor, Hacer Ceren Tokgoz Demirel, ibrahim Halil Tanboga, Canan Elif Yildiz, Sevim Turkday, Nertila Poci, Tugba Aktemur, Durmus Demir, Seda Tanyeri, Nihal Ozdemir, Cihangir Kaymaz
Journal: Journal of the American College of Cardiology (2017)
SIGNIFICANCE OF 123I-BMIPP-SCINTIGRAPHY IN THE RECOVERY OF LEFT VENTRICULAR SYSTOLIC DYSFUNCTION IN TAKOTSUBO CARDIOMYOPATHY: INSIGHT FROM THE NEW TAKOTSUBO BMIPP REGISTRY
Authors: Takayuki Warisawa, Katsumasa Sato, Tsuyoshi Kobayashi, Kensuke Takagi, Toru Naganuma, Nobuo Tomizawa, Takeo Horikoshi, Fujino Yusuke, Hisaaki Ishiguro, Satoko Tahara, Naoyuki Kurita, Itsuro Morishima, Seiichi Haruta, Takeshi Nojo, Sunao Nakamura
Journal: Journal of the American College of Cardiology (2017)
MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If
Authors: Barbara Schenk, Timo Imbach, Christian G. Frank, Claudia E. Grubenmann, Gerald V. Raymond, Haggit Hurvitz, Annick Raas-Rotschild, Anthony S. Luder, Jaak Jaeken, Eric G. Berger, Gert Matthijs, Thierry Hennet, Markus Aebi, Jaak Jaeken
Journal: Journal of Clinical Investigation (2003)

Mutation analysis of TNNI3 by direct sequencing identified a 87A→G nucleotide substitution of exon 8 resulting in an Asp190Gly amino acid substitution that segregated with the disease in the family (maximal two-point lode score: 4.8).Direct sequencing of TNNI3 identified a 93G→A nucleotide substitution of exon 8, which resulted in an Arg192His amino acid substitution.
PROGNOSTIC VALUE OF PLATELET-FIBRIN CLOT STRENGTH ON OCCURRENCE OF CARDIOVASCULAR EVENTS AFTER NON-CARDIAC SURGERY
Authors: Jong-Hwa Ahn, Min Gyu Kang, Jin-Sin Koh, Yongwhi Park, Jin-Yong Hwang, Jeong Rang Park, Young-Hoon Jeong
Journal: Journal of the American College of Cardiology (2017)
A BRIDGE OVER WATER: SUCCESSFUL IMPLEMENTATION OF A HEART FAILURE BRIDGE CLINIC (HFBC) TO REDUCE HEART FAILURE (HF) HOSPITALIZATIONS
Authors: Nisha Aggarwal Gilotra, Kimberly Cuomo, Abby Cummings, Bonnie Marino, Parker Rhodes, Johana Almansa, Julianne Chambers, Tasha B. Freitag, Tolulope Adesiyun, Stuart Russell
Journal: Journal of the American College of Cardiology (2017)
Second-line chemotherapy with combined docetaxel and cisplatin for patients with far advanced gastric carcinoma
Authors: C. Kunisaki, H. Akiyama, Y. Otsuka, G. Matsuda, M. Nomura, S. Hatori, T. Imada, S. Togo, H. Ike, H. Shimada
Journal: Journal of Clinical Oncology (2004)

4214 Background: Prognosis of patients with unresectable, palliatively resected, or metastatic gastric cancer is extremely poor. However, there have been few chemotherapeutic agents to provide satisfactory results for these populations. To evaluate the efficacy and safety of a docetaxel and cisplatin combination for such population, therapeutic results were investigated. Methods: Twenty six patients (unresectable;15, palliatively resected; 6, metastatic; 5) were registered into this study. All patients were administered prior chemotherapy with S-1 (80–100mg daily for 8 weeks or more: n=16), or low-dose fluorouracil and cisplatin combination therapy (fluorouracil; 500mg/m2, cisplatin; 5mg/m2, on day1–5, 8–12, 15–19, 22–26: n=10). S-1 was administered to patients who can take food orally. As second line, 60mg/m2 of docetacel and 60mg/m2 of cisplatin were administered every 3 weeks and treatment response was assessed after 3 courses. Results: The overall response rate of combined docetaxel and cisplatin therapy was 23.1% (6/26). The response rate with no change was 92.3% (24/26). The site-specific response rates were 33.3, 43.0, 33.3, and 11.8% for patients with stomach, hematogenous, peritoneal, and lymph node metastasis, respectively. At a median follow-up time of 11 months, 17 died of gastric cancer. Overall median survival time (MST) was 6 months and time to progresson was 5 months after second line. MST in patients with response was 7 months whereas 4 months without response. Furthermore, MST was 7 months in patients with response in addition to no change, whereas 3 months in patients with progressive disease. MST in patients with the third line (60mg/m2 of irinotecan, 60mg/m2 of cisplatin, every 3 weeks, 3 times) was 13 months whereas 5 months without the third line (p=0.0031).The adverse reactions in these populations were alopecia (96%), leucopenia (62%), neutropenia (62%), nausea and vomiting (38%), thrombocytopenia, anemia, and diarrhea. All cases recovered with adequate medication. Conclusions: Docetaxel with cisplatin may have the possibility to improve survival with advanced gastric cancer as second line regimen. No significant financial relationships to disclose.
Rituximab Plus CHOP Followed by Maintenance Rituximab as Initial Therapy for Aggressive Non-Hodgkin’s Lymphoma (NHL); Initial Results of Induction Therapy, Including Rituximab Pharmacokinetics, in a Phase II Study.
Authors: Jane E. Huang, Alfred Saleh, J. Thomas Lee, Virginia Langmuir, Fan Zhang, John Hainsworth
Journal: Blood (2004)
INCREMENTAL VALUE OF ESTIMATED GLOMERULAR FILTRATION RATE IN IMPROVING STROKE RISK STRATIFICATION IN PATIENTS WITH AND WITHOUT ATRIAL FIBRILLATION CONSIDERED TO BE LOW RISK BY CHA2DS2VASC SCORE
Authors: Geetanjali Dang, Susan Olet, Muhammad Shahreyar, Nasir Sulemanjee, Khwaja Ammar, Indrajit Choudhuri, Imran Niazi, Jasbir Sra, A. Jamil Tajik, Arshad Jahangir
Journal: Journal of the American College of Cardiology (2017)
Risk-adapted maintenance therapy (MaintRx) after ASCT in first-line therapy for multiple myeloma (MM).
Authors: Jonathan L. Kaufman, Joanne Willey, Michael E. Williams, Brynn Tiscione, Arden Buettner, Douglas Neely, Mark R. Green
Journal: Journal of Clinical Oncology (2013)

8607 Background: Maintenance lenalidomide improves survival in patients who have undergone induction therapy and then autologous stem cell transplant (ASCT) as first line management for MM. We studied how the extent of cytoreduction after induction therapy à ASCT (as measured by CR, VGPR, or PR as best response) influences MAINTRX prescribing preferences among American Hematology-Oncology physicians (AHOP). Methods: We studied 284 individual AHOPs using a proprietary, live, case-based market research tool to assess prescribing preferences. A core case scenario and variations based on extent of response to induction à ASCT was constructed. Preference data were acquired using blinded audience response technology. All responses for each scenario were obtained contemporaneously prior to any display of respondent selections. All sources of research support were double blinded. The core scenario involved a 59-year-old patient (42% plasma cells in BM, no cytogenetic abnormalities, CrCl 65ml/min, B2M 5.8, PS 1) treated with induction therapy of choice à ASCT. The same query was then posed in each of 3 settings: Following CR (or following VGPR or following PR) as best response, what, if any, further therapy would you recommend now? Results: See Table. Conclusions: Among patients with myeloma getting first-line therapy, MaintRx is almost uniformly preferred by AHOPs. Specific single or doublet therapy preferences are dependent upon best response to induction à ASCT treatment. Compared to the CR setting, preferences for 2 drug MaintRx are significantly increased in patients with VGPR (p &lt;.0.001) or with PR (p &lt; 0.001)] as best overall response. The potential for benefit from intensified MaintRx in these response subsets needs prospective phase III testing. [Table: see text]