tbuckley/cabot-search huggingface dataset:
Identification of ABCA5 as a tissue and urine diagnostic marker for prostatic intraepithelial epithelial or PIN
Authors: M. E. Stearns, Y. Hu, M. Wang, K. Veverka
Journal: Journal of Clinical Oncology (2006)

10089 Background: Bostwick and colleagues have suggested that prostatic intraepithelial neoplasia or PIN is the precursor of prostate cancer and that a significant percentage of men with PIN develop prostate cancer (Sakr, 1994; Bostwick, 1995b; Arakawa, 1995; Qian, 1995; Qian, 1997). Currently there are no diagnostic markers for PIN. Methods and Results: Recently, we have developed ‘DNA-protein’ binding assays for the identification of novel transcriptional regulatory proteins associated with PIN glands. Electrophoretic mobility assays (EMSAs) revealed that 1 (of 4096 sequences screened) DNA sequences specifically bound a 160 Kda protein over-expressed in PIN and not found in BPH, SV or PCA glands (n=11). The gene encoding for the 160 Kda protein was cloned from a lamda ZAP expression library by ‘in situ’ hybridization assays with the 32 P labeled DNA sequence. Sequencing revealed that the gene encoding for the 160 Kda protein was ABCA5, a member of the superfamily of ATP-binding cassette (ABC) transporters of multi-drug resistant genes. RT-PCR assays indicated the mRNA was over-expressed in primary PIN cell cultures and by PIN tissue, but it was not present in BPH, or SV tissue. Rabbit polyclonal antibodies were raised against a n-terminal peptide (20 b) plus a c-terminal peptide (20b) and found to specifically label the cell junctions of 3% glutaraldehyde fixed cultured cells and to label putative adult cancer stem cells in sections of PIN tissue. ‘Blinded’ ELISA studies with urine specimens from biopsed patients showed that ABCA5 was over-expressed urine from patients with PIN (n=∼20), faintly expressed in PIN + PCA patients (n=8), and not expressed in BPH (n=10) or normal patients (n=20). Conclusions: The data suggest that the expression of ABCA5 is over-expressed by PIN and is a urine diagnostic marker for detection of the disease (&gt;95% COI). Supported by NIH-NCI grant CA90397 to mes and by GTx. [Table: see text]
Role of Nonsteroidal Antiinflammatory Drugs in the Association Between Osteoarthritis and Cardiovascular Diseases: A Longitudinal Study
Authors: Mohammad Atiquzzaman, Mohammad E. Karim, Jacek Kopec, Hubert Wong, Aslam H. Anis
Journal: Arthritis & Rheumatology (2019)

Objective To elucidate the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the increased risk of cardiovascular disease (CVD) among osteoarthritis (OA) patients. Methods This longitudinal study was based on linked health administrative data from British Columbia, Canada. From a population‐based cohort of 720,055 British Columbians, we selected 7,743 OA patients and 23,229 age‐ and sex‐matched non‐OA controls. We used multivariable Cox proportional hazards models to estimate the risk of developing incident CVD (primary outcome) as well as ischemic heart disease, congestive heart failure, and stroke (secondary outcomes). To estimate the mediating effect of NSAIDs, defined as current use of an NSAID according to linked PharmaNet data, in the OA–CVD relationship, we implemented a marginal structural model. Results OA patients had a higher risk of developing CVD than controls without OA. After adjusting for socioeconomic status, body mass index, hypertension, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, and Romano comorbidity score, the adjusted hazard ratio (HR) was 1.23 (95% confidence interval [95% CI] 1.17–1.28). The adjusted HRs for congestive heart failure, ischemic heart disease, and stroke were 1.42 (95% CI 1.33–1.51), 1.17 (95% CI 1.10–1.26), and 1.14 (95% CI 1.07–1.22), respectively. Approximately 41% of the total effect of OA on increased CVD risk was mediated through NSAIDs. For the secondary outcomes, the proportion mediated through NSAIDs was 23%, 56%, and 64% for congestive heart failure, ischemic heart disease, and stroke, respectively. Conclusion The findings of this first study to evaluate the mediating role of NSAIDs in the relationship between OA and CVD suggest that NSAID use contributes substantially to the OA–CVD association.
CBT-1 in combination with doxorubicin in patients with metastatic, unresectable sarcomas who previously progressed on doxorubicin.
Authors: Gregory Michael Cote, Sant P. Chawla, Melissa Amber Burgess, Katherine Anne Thornton, Robert K. Oldham, Scott H. Okuno, Karla V. Ballman, Susan Matlow, Daryl Barnett, Steven Attia
Journal: Journal of Clinical Oncology (2019)

TPS11077 Background: The response rates of advanced soft tissue sarcomas (STS) to single-agent, first-line anthracycline are typically less than 25%. P-glycoprotein 1 (P-gp), a cell membrane drug efflux pump, is believed to be a resistance mechanism in STS. CBT-1 is a small molecule, orally administered, P-gp antagonist currently under clinical development. This is a multi-institutional open label phase I study of CBT-1 in combination with doxorubicin in patients with anthracycline-refractory sarcoma. The study is designed to determine a maximum tolerable dose (MTD), recommended phase II dose (RP2D), and the safety/tolerability of the combination of CBT-1 and doxorubicin. The study will evaluate anti-cancer activity as a secondary objective as measured by Disease Control Rate (DCR; complete response [CR] + partial response [PR] + stable disease [SD]) at 12 weeks. Objective Response Rate (ORR; CR+PR) and Progression Free Survival (PFS) will be monitored. Correlative studies include assessment of pharmacokinetic and pharmacodynamicendpoints. Methods: Patients 18 years or older with locally advanced metastatic, unresectable STS, prior progression on ≤ 150 mg/m 2 of doxorubicin (or another anthracycline equivalent), ECOG PS ≤ 1 and normal organ function, are eligible for this study. Dosing includes fixed doxorubicin (37.5 mg/m 2 IV day 5 and day 6) and escalation of oral CBT-1 on days 1-7 of a 21 day cycle. This study follows a standard 3+3 phase I design where dose escalation will occur if &lt; 0/3 or 1/6 patients experience a dose-limiting toxicity (DLT). Tumor assessments are conducted at Week 6 and Week 12. For patients with response or stable disease, treatment is allowed to continue for 4-5 cycles to a maximum of 450 mg/m 2 lifetime doxorubicin exposure. Once RP2D is defined, an additional 10 patients will be enrolled into the dose expansion phase. To date, Cohorts 1 (50 mg CBT-1) and 2 (100 mg CBT-1) have been completed with one DLT of grade 4 neutropenia lasting longer than 7 days in Cohort 1. Enrollment to Cohort 3 began December 2018. (References: Oldham, R. K., Reid, W. K., Preisler, H. D., and Barnett, D. (1998) Cancer Biother. Radiopharm. 13, 71-80; Kelly, R. J., Robey, R. W., Chen, C. C., Draper, D., Luchenko, V., Barnett, D., Oldham, R. K., Caluag, Z., Frye, R. A., Steinberg, S. M., Fojo, T., Bates, S. E. (2012) The Oncologist 17 (4) 512-e523; Robey, R. W., Shukla, S., Finely, E. M., Oldham, R. K., Barnett, D., Ambudkar, S. V., Fojo, T., Bates, S. E., (2008) Biochemical Pharmacology 75, 6, 1302-1312). Clinical trial information: NCT03002805.
Prognostic factors and nomogram for survival prediction in patients with primary pulmonary lymphoma: A SEER population-based study.
Authors: Soon Khai Low, Gehad Mohamed Tawfik, Ahmad Helmy Zayan, Obaida Istanbuly, Minh Duc Nguyen Tran, Amr Ebied, Shin Yin Lee, Nguyen Tien Huy
Journal: Journal of Clinical Oncology (2019)

e19069 Background: The prognostic factors influencing survival and optimal management of primary pulmonary lymphomas (PPLs) have not been clearly defined due to rarity of the disease. This study sought to characterize the significant prognostic factors of PPL and develop a prognostic nomogram for individualized prediction of survival outcomes in patients with PPL. Methods: Patients diagnosed with PPL between 1983 and 2010 were identified using the Surveillance, Epidemiology, and End Results (SEER) Program database. Kaplan-Meier survival analysis and Cox proportional hazards regression model were performed to identify significant independent prognostic factors for overall survival (OS) in patients with PPL. A nomogram was constructed for the prediction of 5-year OS probability based on these variables. Results: The study cohort of 2325 PPL patients has a 5-year OS rate of 52% and a median OS of 67 months. Older age at diagnosis (HR 1.031; 95% CI, 1.026-1.036; p&lt;0.001], males (HR 1.434; 95% CI, 1.267-1.622; p&lt;0.001), Hispanic race (HR 1.370; 95% CI, 1.113-1.687; p=0.003), non-marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT) histology (p&lt;0.001), primary site at main bronchus (HR 1.326; 95% CI, 1.014-1.735; p=0.039), Ann Arbor stage IV (HR 1.542; 95% CI, 1.324-1.795; p&lt;0.001) were significantly associated with worse OS. All treatment modalities, including chemotherapy (HR 0.615; 95% CI, 0.536-0.706; p&lt;0.001), surgery (HR 0.666;95% CI, 0.577-0.769; p&lt;0.001) and radiotherapy (HR 0.829; 95% CI, 0.693-0.992; p=0.041) were independent predictors of survival. The nomogram constructed using these variables has a higher concordance index of 0.716 (95% CI, 0.699-0.734) compared to that of Ann Arbor staging system [0.571 (95% CI,0.552-0.591); p&lt;0.001]. Conclusions: Older age, male sex, Hispanic race, non-MALT histology, primary site at main bronchus, advanced Ann Arbor stage, not receiving treatment were independent prognostic factors that are associated with worse OS in patients with PPL. The nomogram demonstrated good agreement between the predicted probabilities and actual observations on calibration plots.
Difficult conversations with terminal patients: Palliative care and death at home.
Authors: Eduardo L. Morgenfeld, Gaston Martin Reinas, Daniela Gercovich, Ernesto Gil Deza, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2012)

9038 Background: More than half the total number of oncological patients may die due to the disease’s progression, and at some point in time the oncologist must communicate that the disease is terminal. This is the hardest conversation (HC) of a clinical oncologist. The following paper’s objective is to determine whether or not the treatments applied to patients, and their evolution, are affected by having had the HC. Methods: All patients who died due to progression of the disease in 2011 were selected for this study. Both medical histories and applied treatments were evaluated. All doctors were interviewed to establish when the HC had taken place. The distribution of variables was analyzed and both populations compared. Results: Between January 2011 and December 2011, 110 patients who met the previous criteria were studied. Population characteristics: Sex (Female: 52 pts; Male: 58 pts). Median age at the time of death: 61 years (Range: 27-88). Patients were divided in two groups: A (terminal status of the disease had been discussed; 70 pts) and B (terminal status of the disease had not been discussed; 40 pts). Both groups were similar in diagnosis, age and previous treatments. During the post HC evolution, three elements were categorized according to the table below. Conclusions: 1 – The conviction, ethical sense and strength of will of the doctor are determining factors when related to his or her capacity to talk with the patient about the terminal aspect of the disease. 2 – The chemotherapy treatments applied during the last two months of life are similar in both groups. 3 – The percentage of patients that died at their homes under palliative care was remarkably higher amongst those who had been informed than those who had not been informed. [Table: see text]
A static diagnostic biopsy in patients with mutated EGFR lung adenocarcinom to guide therapeutic decisions.
Authors: Giuseppe Altavilla, Mariacarmela Santarpia, Carmela Arrigo, Chiara Tomasello, Sara Benecchi, Antonio Picone, Francesco Monaco, Vincenzo Pitini
Journal: Journal of Clinical Oncology (2012)

e18039 Background: Approximately 70% of the pts. whose lung cancers harbor EGFR mutations acquire drug resistence after a response to EGFR tyrosine kinase inhibitors (TKIs) treatment; this acquired resistance is mainly due to a secondary mutation in EGFR (T790 M) in about 50% of patients, amplification of MET in 15%, PIK3CA mutations in 5%, an unknown mechanism in almost 30%, and SCLC transformation in some patients. Furthermore, clinical experience revealed that cancers with acquired resistance can respond again to TKIs, after a drug-free interval. To aid in identification and treatment of these patients we examined a cohort of patients whose cancers were assessed with tumor biopsies at multiple times before and after their treatment with TKIs. Methods: 21 lung adenocarcinomas pts. (10 male, 11 female, median age 53 years) with EGFR mutations at 19 or 21 exons received TKIs, as first line of treatment. All showed a clinical response and all relapsed ( mTTP 10 months). At the time of relapse a new biopsy was performed, histologic samples were reviewed to re-confirm the diagnosis, EGFR and MET amplification were identified by FISH, while EGFR mutations have been tested by DNA sequencing. Results: At the time that drug resistence was acquired all pts. retained their original activating EGFR mutations, 9 pts. developed EGFR T790M resistance mutation with pronunced EGFR amplification in 3, 2 pts. developed MET amplification, 8 biopsies did not reveal any new mutations, two pts. were found to have a diagnosis of small cell lung cancer in their drug resistant tumor biopsies and responded well to conventional chemotherapy regimen.15 of 19 confirmed lung adenocarcinoma patient underwent to a cisplatin - pemetrexed chemotherapy regimen and at the time of progression 10 of them accepted to undergo a new biopsy. Three pts. ( after 4, 5 and 6 months break from treatment with TKIs ) lost T790M mutation and their disease responded to a second-line course of erlotinib. Conclusions: In our cohort of pts. with acquired EGFR resistence some patients lost acquired T790M mutation and become sensitive to EGFR inhibitor, in addition, two pts. underwent the histologic transformation from NSCLC to SCLC at the time of TKI resistence.
Endoscopic ultrasound-guided liver biopsy using a 22-G fine needle biopsy needle: a prospective study
Authors: Muhammad K. Hasan, Kambiz Kadkhodayan, Evgeny Idrisov, Saeed Ali, Ehsan Rafiq, Dana Ben-Ami Shor, Ala Abdel-Jalil, Uday Navaneethan, Ji Bang, Shyam Varadarajulu, Robert Hawes, Peter Pernicone
Journal: Endoscopy (2019)

Endoscopic ultrasound-guided liver biopsy (EUS-LB) using a 19-gauge (19-G) EUS needle is becoming increasingly popular. We evaluated the efficacy and safety of a 22-G EUS fine needle biopsy (FNB) needle for performing EUS-LB.Patients referred for evaluation of elevated liver enzymes and without obstructive disease requiring endoscopic retrograde cholangiopancreatography (ERCP) were included. Using a 22-G FNB needle, two passes were made from the left lobe and one from the right. The main outcome measure was adequacy of the specimen for histology interpretation, and the secondary outcome was the safety of EUS-guided liver biopsy with a 22-G FNB needle. Patients were followed for post-procedure complications for 30 days.40 patients (median age 61 years; 26 women) underwent EUS-LB. Analyzing by needle passes, the median longest core fragment was 12 mm (1st quartile - 3rd quartile 10 mm - 16.25 mm, interquartile range [IQR] 6.25 mm) from the left lobe and 11 mm (10 mm - 15.75 mm, IQR 5.75 mm) from the right lobe. The median cumulative core length per patient was 55 mm (44.5 mm - 68 mm, IQR 23.5 mm). The median cumulative number of complete portal triads (CPTs) per patient was 42 (28.5 - 53, IQR 24.5). The specimen was considered adequate in all 40 patients (100 %). Self-limiting abdominal pain was reported in 6 patients (15 %).EUS-LB using a 22-G FNB needle is a safe and viable alternative to the use of larger gauge needles, yielding adequate tissue for evaluation of parenchymal disease in 100 % of the patients.
Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis
Authors: Kenji Sakurai, Teruki Dainichi, Sandra Garcet, Soken Tsuchiya, Yosuke Yamamoto, Akihiko Kitoh, Tetsuya Honda, Takashi Nomura, Gyohei Egawa, Atsushi Otsuka, Saeko Nakajima, Reiko Matsumoto, Yuri Nakano, Masayuki Otsuka, Yoichiro Iwakura, Yenkel Grinberg-Bleyer, Sankar Ghosh, Yukihiko Sugimoto, Emma Guttman-Yassky, James G. Krueger, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2019)
Microarray study of gene expression profiles in peripheral blood samples from lung cancer patients before and after erlotinib treatment
Authors: A. Irigoyen, C. Olmedo, J. Valdivia, A. Comino, C. Cano, R. Luque, V. Conde, J. Delgado, A. Blanco, P. Bueno
Journal: Journal of Clinical Oncology (2009)

e19072 Background: The gene expression profile in peripheral blood samples from lung cancer patients is a potential predictor to treatment response. Methods: The study has been developed using 10 healthy volunteers as the control group and 10 lung cancer patients (stage IV). Written informed consent was obtained being the protocol approved by the local Clinical Research and Ethics Committee. Peripheral blood samples were obtained from lung cancer patients before (T0) and after treatment (T15d). RNA from peripheral blood samples was extracted and purified selecting 28S/18S ratios&gt;1.5 to obtain cDNA and cRNA for hybridization of the 20,000 genes included in Human 20K CodeLink. An array from each participant was obtained in duplicate. For each array, 2 μg of cRNA was compared to 2 μg of healthy cRNA.. Significant genes were found using Significance Analysis of Microarrays which uses repeated permutations of the data. Results: The selected genes were expressed &gt;3-fold with a false discovery rate =0.05. Before treatment (T0) when patients were compared to healthy volunteers there was an increase in the expression of: histone 1 H4c, transforming growth factor beta 2, endothelial cell growth factor 1 (platelet-derived), glucose-6-phosphatase catalytic 2, Relaxin 3 receptor 1, Insulin-like growth factor binding protein 2, RAS-like family 11 member B, and ELK4. After treatment (T15d), when each lung cancer patient's results were compared to their own before treatment results (T0), there was an increase in the expression of: Bcl2, myosin light polypeptide 4; interferon alpha-inducible protein 27; interferon gamma receptor 1; RASSF5, ARHGEF6, IGFBP5, tumor protein p53 inducible nuclear protein 1, peroxisome proliferative activated receptor gamma. Conclusions: The data presented identifies biologically relevant over-expressed genes in lung cancer. A validation of these results and the analysis of the genes that identify patients who will respond positively to erlotinib treatment is being carried out. No significant financial relationships to disclose.
Single center phase II trial analysing the role of imatinib/hydroxyurea in patients (pts) with pretreated non-progressive glioblastoma (GBM) as maintenance treatment
Authors: G. Dresemann, C. Hosius, Z. Nikolova, L. Letvak
Journal: Journal of Clinical Oncology (2007)

2055 Background: In GBM the highest malignant brain tumor with a median survival of about 15 months dysregulated signalling of platelet derived growth factor receptors (PDGF-Rs) is implicated in pathogenesis. I/HU showed impressive efficacy and tolerability in patients (pts) with recurrent progressing GBM. In 30 pilot pts with recurrent GBM the progression free survival (PFS) at 6 and 24 months (m) was 32% and 16% respectively. Disease stabilisation (SD) in 37% was an important result. SD for more than 2 years was possible. In GBM a short period of SD after primary or relapse treatment is typical. In this phase II study the efficacy of I/HU as maintenance treatment in pts with GBM in stage of SD was analysed. Methods: From December 2003 up to June 2005 30 GBM pts with documented SD for more than 6 weeks following prior treatment, including surgery, radiotherapy and at least one chemotherapeutic regimen were included,. No enzyme-inducing anticonvulsive drugs were allowed. I dose was 600 mg od, HU dose was 1000 mg (500 mg bid) as continuous oral treatment, pts were followed up by blood cell count weekly and magnetic resonance imaging every 6 weeks. Results: All 30 pts were eligible for safety and for 6, 12 and 18 m PFS and overall survival (OS); 25 pts were male, 5 pts female, median age was 44 years (32 to 71), 24 pts had primary (de novo) and 6 pts secondary GBM. All 30 pts had prior radiotherapy, 21 pts had prior temozolomide and 9 pts non- temozolomide containing regimens. 8 pts were free from relapse, 17 pts after first and 5 pts after second relapse. The median observation time is 28 m. 6, 12 and 18 m PFS was 60% (18/30), 40% (12/30) and 30% (9/30) respectively. 6, 12 and 18 m OS is 90% (27/30), 67% (20/30) and 53% (16/30) so far. PFS for more than 24 m occurred in 3/6 pts with secondary and in 2/24 pts with primary GBM. Toxicity was low (anemia grade 3: 2 pt; grade 2: 4 pts; leucocytopenia grade 3:2 pts; grade 2: 7 pts; thrombocytopenia grade 2: 4 pts), HU dose was reduced in 8 pts, I dose in 1 pt and G-CSF was given in 8 pts, no treatment related death occurred. Conclusion: I (600 mg/d)/ HU (1000 mg/d) was well tolerated in this study. Long-term disease stabilisation was possible - especially in pts with secondary GBM. Confirmation in further investigation is required. [Table: see text]
The Use of Random Forests to Classify Amyloid Brain PET
Authors: Katherine Zukotynski, Vincent Gaudet, Phillip H. Kuo, Sabrina Adamo, Maged Goubran, Christopher Scott, Christian Bocti, Michael Borrie, Howard Chertkow, Richard Frayne, Robin Hsiung, Robert Laforce, Michael D. Noseworthy, Frank S. Prato, Demetrios J. Sahlas, Eric E. Smith, Vesna Sossi, Alexander Thiel, Jean-Paul Soucy, Jean-Claude Tardif, Sandra E. Black
Journal: Clinical Nuclear Medicine (2019)

Purpose To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification. Methods The data set included 57 baseline 18 F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with severe white matter disease, presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter, and clinically read by 2 nuclear medicine physicians with interpretation based on consensus (35 negative, 22 positive). SUV ratio data and clinical reads were used for supervised training of an RF classifier programmed in MATLAB. Results A 10,000-tree RF, each tree using 15 randomly selected cases and 20 randomly selected features (SUV ratio per region of interest), with 37 cases for training and 20 cases for testing, had sensitivity = 86% (95% confidence interval [CI], 42%–100%), specificity = 92% (CI, 64%–100%), and classification accuracy = 90% (CI, 68%–99%). The most common features at the root node (key regions for stratification) were (1) left posterior cingulate (1039 trees), (2) left middle frontal gyrus (1038 trees), (3) left precuneus (857 trees), (4) right anterior cingulate gyrus (655 trees), and (5) right posterior cingulate (588 trees). Conclusions Random forests can classify brain PET as positive or negative for amyloid deposition and suggest key clinically relevant, regional features for classification.