tbuckley/cabot-search huggingface dataset:
Abstract 2639: A Randomized Comparison of Paclitaxel-Eluting Stents vs. Intra-coronary Brachytherapy in the Treatment of In-stent Restenosis: Intravascular Ultrasound Results from the TAXUS-V ISR Trial
Authors: Tomomi Koizumi, Peter J Fitzgerald, Yasuhiro Honda, Stephen G Ellis, Kenneth Kent, Steven L Martin, Charles L Brown, A. R. Zaki Masud, John B Patterson, Joel Greenberg, Joerg Koglin, Gregg W Stone
Journal: Circulation (2006)

Background: The TAXUS-V in-stent restenosis (ISR) trial demonstrated that the polymer-based, paclitaxel-eluting TAXUS stent (PES) is effective for the treatment of bare metal stent restenosis. The ...
Evaluation of data collection using internet-based electronic case report forms (eCRFs) for a non-small-cell lung cancer (NSCLC) clinical trial
Authors: D. M. Jaunakais, J. Crowley, T. Stewart, C. Marion, J. Chang, N. Campbell, J. James, R. Ghalie
Journal: Journal of Clinical Oncology (2005)

7221 Background: Internet-based eCRFs offer many advantages for monitoring and real-time access to clinical trial data. The acceptability of eCRFs by study coordinators is critical to obtaining timely, complete and accurate data. Methods: Cancer Research And Biostatistics (Seattle, WA) developed an internet-based, password-protected eCRF for a 150-patient multicenter NSCLC clinical trial sponsored by Ligand Pharmaceuticals (San Diego, CA). Study coordinators were provided an eCRF instruction manual and training via monthly teleconferences. The sponsor assessed study coordinators’ evaluations of the eCRF in a 7-item questionnaire sent to all sites that enrolled ≥ one patient. Results: Responses were submitted by 27 of 30 centers (90%) and 36 of 58 study coordinators (62%). Community oncology practices represented 83% of participating sites. This was the first experience with an eCRF for 28% of respondents. Most respondents (80%) preferred electronic rather than a paper-based CRF. All respondents preferred registering patients on-line. All but two respondents (94%) indicated that the eCRFs were easy to complete and that the eCRF instruction manual assisted in learning the process quickly. Most respondents (91%) liked using the on-line NCI CTC dictionary to select and record adverse events. For those respondents who had used another eCRF, 80% preferred this study’s eCRF. Conclusions: Study coordinators overwhelmingly preferred registering clinical trial patients on-line. Training tools such as an instruction manual and teleconferences assist study coordinators in using internet-based eCRFs. The use of an electronic adverse events coding system was readily accepted. Although this was the first use of an eCRF for 28% of respondents, most preferred electronic vs. paper-based CRFs. For the sponsor, the advantages of using eCRFs include real-time access to data for auditing a site’s performance, more efficient study monitoring, elimination of storing paper-based CRFs, and access to community oncology practices to rapidly accrue patients in large-scale oncology clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Ligand Ligand
Towards HIV-1 remission: potential roles for broadly neutralizing antibodies
Authors: Ariel Halper-Stromberg, Michel C. Nussenzweig
Journal: Journal of Clinical Investigation (2016)

Current antiretroviral drug therapies do not cure HIV-1 because they do not eliminate a pool of long-lived cells harboring immunologically silent but replication-competent proviruses - termed the latent reservoir. Eliminating this reservoir and stimulating the immune response to control infection in the absence of therapy remain important but unsolved goals of HIV-1 cure research. Recently discovered broadly neutralizing antibodies (bNAbs) exhibit remarkable breadth and potency in their ability to neutralize HIV-1 in vitro, and recent studies have demonstrated new therapeutic applications for passively administered bNAbs in vivo. This Review discusses the roles bNAbs might play in HIV-1 treatment regimens, including prevention, therapy, and cure.
Cytokine-STATs Signalings Upregulate C/EBPβ In BCR-ABL+ Leukemic Cells Independently From BCR-ABL/JAK-STAT Pathway
Authors: Asumi Yokota, Hideyo Hirai, Yoshihiro Hayashi, Akihiro Tamura, Atsushi Sato, Hisayuki Yao, Satoshi Yoshioka, Masaki Iwasa, Eishi Ashihara, Yasuo Miura, Taira Maekawa
Journal: Blood (2013)
Infectious (?) Myasthenia
Authors: Syamal K. Datta, Robert S. Schwartz
Journal: New England Journal of Medicine (1974)

Students of autoimmune diseases are witnessing a revolutionary movement that can be summarized by the difference between etiology and pathogenesis. Before the revolution, hazy images of "forbidden clones" and a faulty understanding of immunologic tolerance led to the assumption that autoimmunization was the etiology — the cause — of certain diseases. Now, however, the process of immunologic self-destruction seems better understood as a pathogenesis — i.e., as a mechanism that produces a lesion. The distinction that we draw is more than semantic. For example, there is abundant evidence from animal models that clinically silent, chronic viral infections can lead to . . .
A phase II trial of intraperitoneal cisplatin and etoposide as salvage treatment for minimal residual ovarian carcinoma.
Authors: S Kirmani, W E Lucas, S Kim, R Goel, L McVey, J Morris, S B Howell
Journal: Journal of Clinical Oncology (1991)

We conducted a phase II study of intraperitoneal (IP) cisplatin (CDDP) and etoposide (VP-16) as salvage therapy in patients with ovarian cancer who had persistent disease or who had relapsed after primary systemic chemotherapy and had residual disease of less than 2 cm. Two hundred eleven courses of IP chemotherapy consisting of CDDP 200 mg/m2 and VP-16 350 mg/m2 were administered. All patients received intravenous (IV) thiosulfate protection. Treatment was given once every 4 weeks for a median of six cycles. Twenty-four of 37 assessable patients were clinically free of disease at the end of treatment (normal physical exam, computed tomographic [CT] scan, CA-125 and peritoneal cytology); one patient had a partial response. Ten of these 24 patients consented to reexploration at the end of treatment, and nine were in pathologic complete remission, while one patient had positive peritoneal washings as her only evidence of persistent disease. The median survival of the 37 patients was 26 months from the first day of IP treatment and 51 months from diagnosis. The major toxicity was myelosuppression, with median nadir WBC, granulocyte, and platelet counts of 2,400, 684, and 134,000/mm3, respectively. There was no cumulative renal damage, hypomagnesemia, or chemical peritonitis. We conclude that IP CDDP and VP-16 can produce pathologic complete remissions when used as a second-line regimen for patients with ovarian cancer who have received systemic cisplatin-based therapy and have less than 2 cm disease.
Pharmacokinetics of gefitinib predicts the antitumor activity for advanced non-small cell lung cancer (NSCLC)
Authors: Y. Nakamura, K. Sano, M. Fukuda, H. Takatani, S. Nagashima, A. Kinoshita, M. Fukuda, H. Soda, M. Oka, S. Kohno
Journal: Journal of Clinical Oncology (2006)

2009 Background: Little is known about the relationship between the pharmacokinetics and efficacy of gefitinib. Methods: Plasma trough levels of gefitinib were measured on days 0, 3 (D3), and 8 (D8) by HPLC in advanced NSCLC patients treated with gefitinib 250 mg daily. Eligibility criteria included: performance status (PS) ≤ 3, age ≤ 80, stage IIIB-IV, and written informed consent. Results: Fifty patients were enrolled, and 44 patients were assessable. The median [25%-75%] values of D3 and D8 was 662 [440–937] and 1064 [782–1405] ng/ml, respectively. D8/D3 rate was categorized by 1.587 of the median value. In 44 patients, the median time to progression (TTP) was 83 days, and the median overall survival (OS) was 224 days. The differences in TTP were compared by Kaplan-Meier method and log-rank test: D8/D3 (high D8/D3, median 209 days vs. low D8/D3, 43 days; P = 0.0299), smoking (never-smokers, 224 days vs. smokers, 32 days; P = 0.0467), and histology (adenocarcinoma, 97 days vs. non-adenocarcinoma, 27 days; P = 0.0096). Sex, age, PS, previous treatments, and the use of antacids were not significant. Multivariate analysis showed that TTP was associated with D8/D3 (hazard rate, 95%CI; 0.458, 0.234–0.898) and smoking (2.005, 1.030–3.903). Never-smokers with high D8/D3 showed the best TTP, and smokers with low D8/D3 showed the worst TTP. Never-smokers with low D8/D3 and smokers with high D8/D3 showed similar TTP curves. In contrast, OS was associated with smoking (hazard rate, 95%CI; 3.182, 1.506–6.724), but not D8/D3. Conclusions: High D8/D3 was independently associated with better TTP in gefitinib-treated NSCLC patients. Our findings suggest that pharmacokinetics of gefitinib may be involved in its anti-tumor activity. No significant financial relationships to disclose.
The novel RAGE interactor PRAK is associated with autophagy signaling in Alzheimer’s disease pathogenesis
Authors: Yoonhee Kim, Chaeyoung Kim, Sung Min Son, Hyundong Song, Hyun Seok Hong, Sun-ho Han, Inhee Mook-Jung
Journal: Molecular Neurodegeneration (2016)

The receptor for advanced glycation end products (RAGE) has been found to interact with amyloid β (Aβ). Although RAGE does not have any kinase motifs in its cytosolic domain, the interaction between RAGE and Aβ triggers multiple cellular signaling involved in Alzheimer’s disease (AD). However, the mechanism of signal transduction by RAGE remains still unknown. Therefore, identifying binding proteins of RAGE may provide novel therapeutic targets for AD. In this study, we identified p38-regulated/activated protein kinase (PRAK) as a novel RAGE interacting molecule. To investigate the effect of Aβ on PRAK mediated RAGE signaling pathway, we treated SH-SY5Y cells with monomeric form of Aβ. We demonstrated that Aβ significantly increased the phosphorylation of PRAK as well as the interaction between PRAK and RAGE. We showed that knockdown of PRAK rescued mTORC1 inactivation induced by Aβ treatment and decreased the formation of Aβ-induced autophagosome. We provide evidence that PRAK plays a critical role in AD pathology as a key interactor of RAGE. Thus, our data suggest that PRAK might be a potential therapeutic target of AD involved in RAGE-mediated cell signaling induced by Aβ.
Long-term results of breast-conservation therapy for Japanese women classified according to intrinsic subtype
Authors: K. Shiraishi, K. Nakagawa, H. Yamashita, A. Terahara, K. Ohtomo, T. Yamaguchi
Journal: Journal of Clinical Oncology (2009)

e11578 Background: Microarray analysis has identified breast cancer subtypes with distinct gene expression profiles according to the estrogen receptor (ER) and the human epidermal growth factor 2 (HER2) expression. The luminal subtypes (ER-positive) appear to be associated with the better prognosis, whereas the basal and HER2 subgroups tend to have worse recurrence rates. The impact of intrinsic subtype for Japanese women with early-stage invasive breast cancer on prognosis is unknown. The purpose of this study is to address whether breast cancer subtype is associated with recurrence among Japanese women who receive breast-conservation therapy (BCT). Methods: The study cohort included 770 consecutive women with invasive breast cancer who received BCT at University of Tokyo Hospital from 1994 through 2007. Among them, 285 women had complete information on the ER and HER2 status of their primary tumors. The number of patients according to luminal A (ER+HER2- ), luminal B (ER+ HER2+), basal (ER-HER2-) and HER2 (ER-HER2+) subtype was 162, 66, 40 and 17, respectively. All patients received external-beam radiation therapy to the whole breast. The most common doses were 50 Gy in 25 fractions to the whole breast plus a tumor-bed boost to 60 Gy. Results: Median follow-up time was 55 months (range, 6 to 144 months). No significant difference was observed between 5-year disease control and four major subtypes. The 5-year relapse free survival rate of HER2-positive and -negative patients was 77% vs. 95%, which was of statistically significance (p = 0.001). Multivariate analysis showed that T stage, N stage, HER2 status and lymphatic vessel invasion correlated significantly with shorter relapse free survival. Multivariate analysis showed that only N stage was associated with decreased overall survival (p = 0.017). Conclusions: Overall, the 5-year relapse free survival rate after BCT was high, and no significant difference was found in four major subtypes as approximated using ER and HER2 status in Japanese women who receive BCT. Only HER2 status was a statistically significant risk factor after BCT. Although further follow-up is needed, BCT may still be optimal option in Japanese women with early-stage invasive breast cancer to whichever intrinsic subtype their tumors belong. No significant financial relationships to disclose.
Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate
Authors: Sara J. Bonvini, Mark A. Birrell, Megan S. Grace, Sarah A. Maher, John J. Adcock, Michael A. Wortley, Eric Dubuis, Yee-Man Ching, Anthony P. Ford, Fisnik Shala, Montserrat Miralpeix, Gema Tarrason, Jaclyn A. Smith, Maria G. Belvisi
Journal: Journal of Allergy and Clinical Immunology (2016)

BackgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored.ObjectiveWe hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung.MethodsWe used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues.ResultsHere we show TRPV4-induced activation of guinea pig airway–specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough.ConclusionThis study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP–mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough.
Bone marrow transplantation for hematologic malignancies in patients aged 30 years or older.
Authors: K G Blume, S J Forman, A P Nademanee, M R O'Donnell, D S Snyder, J L Fahey, I J Sniecinski, D O Findley, J A Lipsett, J A Zaia
Journal: Journal of Clinical Oncology (1986)

During the past 10 years, 86 patients 30 to 54 years of age with hematologic malignancies were prepared with high-dose radiochemotherapy and received histocompatible bone marrow grafts. Thirty-four of these patients are surviving for 4 months to 9 years (median, 26 months) following marrow transplantation and 32 of them are in continuing complete remission (CR). Disease-free survival is 44% for 37 patients who were in first remission of acute leukemia or in the chronic phase of chronic granulocytic leukemia (CGL), 23% for 39 patients whose leukemia had relapsed at least once before transplantation or who had advanced stages of CGL, and 60% for ten patients who had hematologic malignancies other than leukemia. The median age of the surviving 34 patients is 36 years (range, 30 to 43 years). The incidence of moderate to severe acute graft-v-host disease (GVHD) was 48% and of chronic GVHD, 26%. The major causes of failure were interstitial pneumonia in 31 patients (24 of whom had antecedent acute GVHD) and recurrent leukemia in 12 patients (11 of whom had either never entered a CR or had relapsed at least once with acute leukemia or had progressive CGL before transplantation). Our data warrant further prospective studies in patients with hematologic malignancies who are older than 30 years.
Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography
Authors: Carmen Kut, Kaisorn L. Chaichana, Jiefeng Xi, Shaan M. Raza, Xiaobu Ye, Elliot R. McVeigh, Fausto J. Rodriguez, Alfredo Quiñones-Hinojosa, Xingde Li
Journal: Science Translational Medicine (2015)

More complete brain cancer resection can prolong survival and delay recurrence. However, it is challenging to distinguish cancer from noncancer tissues intraoperatively, especially at the transitional, infiltrative zones. This is especially critical in eloquent regions (for example, speech and motor areas). This study tested the feasibility of label-free, quantitative optical coherence tomography (OCT) for differentiating cancer from noncancer in human brain tissues. Fresh ex vivo human brain tissues were obtained from 32 patients with grade II to IV brain cancer and 5 patients with noncancer brain pathologies. On the basis of volumetric OCT imaging data, pathologically confirmed brain cancer tissues (both high- and low-grade) had significantly lower optical attenuation values at both cancer core and infiltrated zones when compared with noncancer white matter, and OCT achieved high sensitivity and specificity at an attenuation threshold of 5.5 mm(-1) for brain cancer patients. We also used this attenuation threshold to confirm the intraoperative feasibility of performing in vivo OCT-guided surgery using a murine model harboring human brain cancer. Our OCT system was capable of processing and displaying a color-coded optical property map in real time at a rate of 110 to 215 frames per second, or 1.2 to 2.4 s for an 8- to 16-mm(3) tissue volume, thus providing direct visual cues for cancer versus noncancer areas. Our study demonstrates the translational and practical potential of OCT in differentiating cancer from noncancer tissue. Its intraoperative use may facilitate safe and extensive resection of infiltrative brain cancers and consequently lead to improved outcomes when compared with current clinical standards.
Integration of mRNA and microRNA profiles as prognostic and predictive markers in lung adenocarcinoma
Authors: J. H. Strickler, W. Mostertz, W. Kim, K. Walters, M. Stevenson, C. Acharya, M. Onaitis, J. Nevins, A. Potti
Journal: Journal of Clinical Oncology (2009)

7522 Background: Lung adenocarcinoma (ADC) is a distinct biologic entity with unique gene amplifications (Weir B, Nature 2008). Yet, comprehensive transcriptomic analysis, including microRNAs, specific to lung ADC are lacking. Methods: Using mRNA expression data from a discovery cohort of 154 patients with histologically proven early stage (I and II) lung ADC, signatures of oncogenic pathway and tumor microenvironment status were applied and further organized by hierarchical clustering to develop a metagene model. Further, using in vitro assays in a large cohort of lung ADC cell lines (n = 42) with corresponding mRNA and microRNA data, novel microRNAs associated with a poor prognosis and their relationship to cisplatin resistance was elucidated. Results: In the discovery cohort of 154 patients with early stage disease, activation of oncogenic pathways associated with wound healing (angiogenesis), chromosomal instability, and STAT signaling were associated with an increased risk of recurrence (p&lt;0.001). Utilizing the extremes of survival to identify cohorts of patients as high and low risk phenotypes, using bayesian regression, a 100 gene signature (‘metagene') that captured the diversity of signaling pathways unique to patients at increased risk of recurrence was identified and validated in an independent cohort (n = 364) of lung ADC samples with 78.3% accuracy. Kaplan Meier survival analysis and multivariate analysis further confirmed the independent prognostic value of the 100 gene signature (p= 0.007). Using in vitro cell proliferation assays, predicted high risk lung ADC cell lines were identified as being more resistant to cisplatin therapy than those predicted to be low risk (p=0.001). In a novel manner, we also identified several microRNAs (miR-215, miR-98, miR- 643, let-7b, miR-665, miR-629) associated with a high risk of recurrence and more importantly cisplatin resistance. Conclusions: mRNA and microRNA profiles reflect unique aspects of individual tumors and may characterize histology-specific tumor heterogeneity in lung ADC, providing an opportunity to better characterize the oncogenic process and refine therapeutic options. No significant financial relationships to disclose.
Tetrahydroisoquinolines as novel histone deacetylase inhibitors for treatment of cancer
Authors: Danqi Chen, Aijun Shen, Guanghua Fang, Hongchun Liu, Minmin Zhang, Shuai Tang, Bing Xiong, Lanping Ma, Meiyu Geng, Jingkang Shen
Journal: Acta Pharmaceutica Sinica B (2016)

Histone acetylation is a critical process in the regulation of chromatin structure and gene expression. Histone deacetylases (HDACs) remove the acetyl group, leading to chromatin condensation and transcriptional repression. HDAC inhibitors are considered a new class of anticancer agents and have been shown to alter gene transcription and exert antitumor effects. This paper describes our work on the structural determination and structure-activity relationship (SAR) optimization of tetrahydroisoquinoline compounds as HDAC inhibitors. These compounds were tested for their ability to inhibit HDAC 1, 3, 6 and for their ability to inhibit the proliferation of a panel of cancer cell lines. Among these, compound 82 showed the greatest inhibitory activity toward HDAC 1, 3, 6 and strongly inhibited growth of the cancer cell lines, with results clearly superior to those of the reference compound, vorinostat (SAHA). Compound 82 increased the acetylation of histones H3, H4 and tubulin in a concentration-dependent manner, suggesting that it is a broad inhibitor of HDACs.
Association of Google Search Volume Index Peaks for Skin Cancer With Skin Cancer Awareness Month
Authors: Jonathan Kantor
Journal: JAMA Dermatology (2016)

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