tbuckley/cabot-search huggingface dataset:
A single center, retrospective analysis evaluating aberrant drug behavior stratification utilizing the opioid risk tool in patients with cancer.
Authors: Joseph D. Ma, John M. Horton, Michael Hwang, Rabia S. Atayee, Eric Roeland
Journal: Journal of Clinical Oncology (2013)

167 Background: Historically, it was believed that cancer patients could not have aberrant drug behaviors. However, clinical experience suggests otherwise. The prevalence of aberrant drug behaviors of cancer patients is unknown as screening is uncommon. Consequently, the UCSD Moores Cancer Center outpatient palliative care clinic initiated screening of aberrant drug behaviors utilizing the opioid risk tool (ORT) on new consultations. The purpose of this retrospective analysis was to identify key risk factors of aberrant behaviors of cancer patients and formulate a routine approach to follow-up and medications quantities. Methods: The treating oncologist referred new consultations to the outpatient palliative care clinic. A cohort of 93 cancer patients was evaluated from July 2012 to February 2013. Patients completed a 10-item, provider-administered, ORT during the consultation visit. Based on the ORT, patients were stratified into high-, moderate-, or low-risk for abarrent drug behavior and follow-up appointments and opioid quantities were adjusted accordingly. Results: Of the 93 patients, 48% were men and 52% women. Most patients had metastatic cancer (n=50; 54%) of gastrointestinal primary (n=27; 29%). Fifty-six (60%) patients were stratified as low-, 15 (16%) moderate-, and 22 (24%) high-risk based on ORT score. The most common risk factors for aberrant behaviors were a history of depression (women=25; men=17) and family history of alcohol abuse (women=22; men=18). There was no difference in the prevalence of depression (p=0.17) or family history of alcohol abuse (p=0.57). The least common risk factor was a personal history of prescription drug abuse (n=1) in women and history of preadolescent sexual abuse in men (n=0). Conclusions: Screening of cancer patients suggests risk factors for aberrant drug behavior exist. Stratifying patients based on a standard, routine tool can help identify cancer patients at risk for aberrant drug behaviors. Moderate and high-risk patients can then be followed closely with limited quantities of opioids until trust is established.
A phase II trial of temsirolimus in metastatic neuroendocrine carcinomas (NECs)
Authors: I. Duran, L. Le, D. Saltman, J. Kortmansky, W. Kocha, D. Singh, G. R. Pond, J. M. Peralba, J. Dancey, L. L. Siu
Journal: Journal of Clinical Oncology (2005)

3096 Background: NECs are a varied group of endocrine neoplasms characterized by neurosecretory granules and cell surface markers. Except for islet cell carcinomas, NECs are resistant to conventional cytotoxics. Hormonal therapy such as somatostatin analogs or local therapies such as hepatic resection or arterial embolization are generally delivered to palliate symptoms. Temsirolimus is a novel mTOR inhibitor that downregulates cascades activated by loss of the tumor suppressor protein PTEN, a defect reported in moderately differentiated NECs. Due to the lack of effective systemic therapy for NECs, loss of PTEN detected in some cases, and a report of a partial response in this tumor type from phase I trials, a multi-centre 2-stage phase II trial in NECs was conducted. Methods: Patients were eligible if they demonstrated 25% increase in tumor volume, clinical deterioration or new tumor focus in the last 6 months. Temsirolimus 25 mg was administered intravenously over 30 minutes on a weekly basis. Results: To date, 23 patients (pts) with progressive NECs have been enrolled with the following demographics from 18 pts with baseline data: median age=55, range=36–68, M:F=9:9, ECOG 0:1:2= 8:9:1, and 11 pts had prior chemotherapy. Toxicity information is available from 15 pts in 50 four weekly cycles. The most frequently encountered grade 3–4 toxicities expressed as % of treatment cycles are: hypophosphatemia (14%), hyperglycemia (10%), cough (10%), hypokalemia (8%), hypercholesterolemia (8%), and hypertension (8%). The most frequent toxicities considering all grades are: fatigue (86%), anemia (76%) and lymphopenia (70%). Among 15 pts evaluable for response thus far, 10 have achieved prolonged stable disease (range: 3–11 cycles), including 1 pt with a 24% tumor shrinkage by RECIST criteria after 4 cycles, and 2 pts who have experienced significant clinical benefit and are on cycles 9 and 11, respectively. Levels of p70S6kinase in peripheral blood mononuclear cells at 24 hours post treatment have not shown correlation with clinical outcome in the majority of pts. Markers of cell cycle inhibition and apoptosis in paired tumor biopsies will be reported. Conclusions: Temsirolimus appears to have antitumor activity in NECs, study accrual is ongoing. No significant financial relationships to disclose.
Open-label, dose confirmation study of interstitial <sup>131</sup>I-chTNT-1/b mab for the treatment of glioblastoma multiforme (GBM) at first relapse: Interim results.
Authors: W. R. Shapiro, D. Gupta, A. K. Mahapatra, S. Gopal, K. Judy, S. J. Patel, J. Shan
Journal: Journal of Clinical Oncology (2011)

2035 Background: GBM is the most common and clinically aggressive primary brain tumor. For recurrent GBM, treatment by surgical resection, radiation therapy, and chemotherapy remains palliative, and prolonged survival has not been convincingly demonstrated with any treatment strategy. 131I-chTNT-1/B MAb (Cotara) is a radioiodinated chimeric monoclonal antibody specific for DNA and histone H1 complex exposed in necrotic core of malignant gliomas. Prior studies suggested improved survival with interstitial 131I-chTNT-1/B MAb in recurrent GBM patients. Methods: Phase II, open-label, dose confirmatory study of patients aged 18 to 75 yrs with histologically confirmed GBM at first relapse, a clinical target volume (CTV) of 5 to 60 cc, and KPS ≥70%. 131I-chTNT-1/B MAb was administered by convection enhanced delivery via 2 catheters placed under stereotactic guidance, at 0.18 mL/h for approximately 25 hours at a dose of 2.5 mCi/cc of CTV. Forty patients were planned to assess safety and tolerability. Additional endpoints included overall survival (OS), progression free survival (PFS), and proportion of patients alive at 6 months. Results: Forty-one patients (26 males) were enrolled and received study drug. Median age was 52 years (24-74). Median CTV was 28.3 cc (1.6-65.8) and median KPS was 80 (70-100). The median administered therapeutic dose was 66.9 mCi (3.5-148) with most patients receiving >90%; one received only 3% due to an infusion pump malfunction. The most common overall adverse events (AEs) (> 10%) were: brain edema (32%), headache (22%), convulsions (20%) and amnesia (12%). The most common drug-related AEs were brain edema (27%) and convulsions (15%) and most were managed with corticosteroids. Grade 3-4 drug-related AEs (all neurologic) were reported in 22% of patients. Interim median OS is currently at 38 weeks and median PFS at 23 weeks. Conclusions: Single interstitial administration of 131I-chTNT-1/B MAb at 2.5 mCi/cc was generally tolerated in this study of patients with recurrent GBM. Though follow-up is continuing, the current median survival of 38 weeks is encouraging and further clinical development is warranted.
Single nucleotide polymorphisms (SNPs) and circulating endothelial cells (CECs) as outcome predictors in patients (pts) with recurrent glioblastoma (rGBM) treated with bevacizumab (BEV) and sorafenib (SOR).
Authors: S. K. Anderson, J. M. Lafky, X. W. Carrero, T. K. Kimlinger, T. M. Halling, S. Kumar, P. J. Flynn, H. M. Gross, K. A. Jaeckle, J. C. Buckner, E. Galanis
Journal: Journal of Clinical Oncology (2011)

2019 Background: There is a lack of biomarkers to predict outcome or monitor antiangiogenetic therapies. We investigated whether SNPs or CECs could predict treatment efficacy/toxicity in rGBM pts treated with BEV/SOR. Methods: Blood was obtained for SNP and CEC analyses from rGBM pts enrolled in the Phase II trial N0776 (Galanis et al., ASCO. 2010). VEGF, VEGFR2, and HIF-1alpha SNPs were analyzed by Taqman or direct sequencing. Blood for CECs was collected at baseline, cycle 1 day 3, prior to treatment cycles 2, 3, 5, 7, 9, 11, 13, and at the time pt went off study. CECs were enumerated by flow cytometry. Unequal variance two-sample and paired t-tests were performed to compare values between pt outcome groups and serial measurements within a pt, respectively. Results: All 53 eligible pts had DNA available for SNP analyses. Significant differences (Chi-square or Fisher’s exact, p<0.05) were observed between genotypes and either progression free survival at 6 months (PFS6) (VEGF rs1005230, rs1570360, rs699947, rs833061, VEGFR2 rs2071559) or grade 3+ adverse events (AEs) fatigue (VEGF rs10434, rs1005230, rs699947, rs833061) or hypertension (rs1005230, rs699947, rs833061). After correcting for multiple comparisons (method of Benjamini & Hochberg), none of the p-values remained significant (p>0.05). CEC analysis was performed on 49 of 53 pts. Median baseline CECs (bCEC) were 83.3 (mean: 136; range: 6.5-594) cells/mL; there was no correlation between bCEC values and PFS6 (p=0.19). Absolute differences between bCECs and other time points were not significant; yet, the CEC log2-fold change (FC) from bCECs decreased during treatment and reached significance at cycles 2, 7, 9, and 11 (0.03, 0.047, 0.005, and 0.005, respectively). Differences in log2-FC from bCECs to off study CECs (≤ 14 days) for pts off study for progression was higher compared to pts off study for other reasons (p=0.02, t-test). Conclusions: Based upon this 53 pt cohort, further biomarker studies examining the utility of SNPs for predicting PFS and AEs and use of CEC monitoring for predicting pt progression in rGBM pts treated with BEV appear warranted.
Prognostic Significance of Molecular-Cytogenetic Abnormalities in Pediatric T-ALL Is Not Explained by Immunophenotypic Differences.
Authors: Martine van Grotel, Anton W. Langerak, H. Berna Beverloo, Jessica G.C.A.M. Buijs-Gladdines, Nicole B. Burger, Max M. van Noesel, Rob Pieters, Jules P.P. Meijerink
Journal: Blood (2007)
Allergenome characterization of the mosquito <i>Aedes aegypti</i>
Authors: J. F. Cantillo, L. Puerta, P. Puchalska, S. Lafosse‐Marin, J. L. Subiza, E. Fernández‐Caldas
Journal: Allergy (2017)

Saliva and muscle-derived mosquito allergens have been purified and characterized. However, the complete set of allergens remains to be elucidated. In this study, we identified and characterized IgE-binding proteins from the mosquito species Aedes aegypti.Serum was obtained from 15 allergic individuals with asthma and/or rhinitis and sensitized to mosquito. IgE binding was determined by ELISA. Total proteins from freeze-dried bodies of A. aegypti were extracted and IgE-reactive proteins were identified by 2D gel electrophoresis, followed by Western blot with pooled or individual sera. IgE-reactive spots were further characterized by mass spectrometry.Twenty-five IgE-reactive spots were identified, corresponding to 10 different proteins, some of which appeared as different variants or isoforms. Heat-shock cognate 70 (HSC-70) and tropomyosin showed IgE reactivity with 60% of the sera, lysosomal aspartic protease, and "AAEL006070-PA" (Uniprot: Q177P3) with 40% and the other proteins with <33.3% of the sera. Different variants or isoforms of tropomyosin, arginine or creatine kinase, glyceraldehyde-3-phosphate dehydrogenase (GPDH), calcium-binding protein, and phosphoglycerate mutase were also identified. The mixture of three allergens (Aed a 6, Aed a 8, and Aed a 10) seems to identify more than 80% of A. aegypti-sensitized individuals, indicating that these allergens should be considered when designing of improved mosquito allergy diagnostic tools.The newly identified allergens may play a role in the pathophysiology of mosquito allergy in the tropics, and some of them might be important arthropod-related proteins involved in cross-reactivity between A. aegypti and other allergenic arthropods.
Correlation of Wilms' tumor 1 (WT1) expression with infiltration by regulatory T cells (Tregs) in epithelial ovarian cancer
Authors: N. E. Tchabo, A. F. Beck, A. J. Miliotto, E. Sato, C. Andrews, S. Lele, K. Odunsi
Journal: Journal of Clinical Oncology (2008)

5578 Background: The Wilms' tumor 1 (WT1) gene is an important regulatory molecule involved in cell growth and development and has a dual effect depending upon the cell type in which it is expressed. The objectives of this study were to examine the significance of various subtypes of tumor-infiltrating lymphocytes (TILs) in patients with epithelial ovarian cancer (EOC) and to determine the relationship between TILs and WT1 expression. Methods: Formalin-fixed paraffin-embedded archival ovarian tumor specimens were obtained from 90 patients undergoing debulking surgery for EOC between 1995 and 2002. Immunohistochemistry (IHC) with anti-WT1 and anti-human CD4, CD8, CD20, CD25 were performed. The Kendall's rank correlation was used to determine the relationship between tumor infiltrating lymphocytes (TILs) and WT1 expression. Disease free (DFS) and overall survival (OS) estimates were conducted using Kaplan Meier method. Results: The median duration of follow-up was 30.6 months. Seventy-three tumor specimens (81%) expressed WT1 reactivity (focal - >75% of cells stained). The DFS was 55.3 months in WT1 negative patients compared to 26.6 months in WT1 positive patients (p = 0.49). OS was similar between the WT1 negative 44.6 months and WT1 positive 44.5 months. However, tumor positivity for WT1 correlated with higher frequencies of intraepithelial CD 8 TILs (tau = 0.197, p = 0.014) and CD4 TILs (tau = 0.233, p = 0.0039). In addition, WT1 expression also was significantly correlated with higher levels of intraepithelial Tregs (tau = 0.260, p = 0.0015). Conclusions: Although WT1 expressing tumors have higher frequencies of intraepithelial CD8 and CD4 T cells, there is also a higher frequency of Tregs that may abrogate beneficial effects of effector cells. Therefore, strategies to promote WT1 specific immunity and decrease regulatory T cell frequency and function in ovarian tumors are likely to be of benefit. No significant financial relationships to disclose.
Phase II study of sunitinib in patients with relapsed or refractory small cell lung cancer (SCLC).
Authors: J. Han, K. Y. Lim, H. Y. Kim, J. H. Han, S. H. Oh, T. Yun, H. T. Kim, J. S. Lee
Journal: Journal of Clinical Oncology (2011)

7084 Background: Sunitinib is a multitargeted tyrosine kinase inhibitor with direct antitumor and antiangiogenesis activity through targeting PDGFR, VEGFR, KIT, and FLT3 receptors. In preclinical models, sunitinib inhibits the growth of SCLC via direct antitumor activity mediated via KIT as well as tumor angiogenesis. This study was conducted to evaluate the efficacy and safety of sunitinib in patients (pts) with relapsed/refractory SCLC. Methods: Pts with SCLC, ECOG PS of 0 to 2, and progression after one or two prior chemotherapy or chemo/radiotherapy (CRT) were enrolled. Pts received sunitinib 50 mg/day for 4 weeks on and 2 weeks off in a 6-week cycle. The primary end point was objective response rate (ORR); secondary end points included progression-free survival (PFS), overall survival (OS), and safety. To continue into stage 2, 4 responders out of 23 pts were required. Results: From Mar 2008 to Oct 2010, 25 pts were enrolled and 24 received treatment. Median follow-up was 16.7 (range, 2.8-32.9) months; median age was 64.5 years; 22 pts (92%) were male; 8 pts (33%) had sensitive relapse; 7 pt (29%) received CRT, 15 pt (63%) received one prior platinum-based chemotherapy; 23 pts were evaluable for response. A median of one (range 1-4) cycle was administered. Two pts with sensitive relapse had partial response and 7 pts had stable disease. ORR was 9% (95% CI, 1% to 28%). At the time of final analysis (January 18, 2011), 3 pts (12.5%) were alive. The median PFS and OS were 1.4 (95% CI, 0.7-2.1) and 5.6 (95% CI, 3.2-8.0) months, respectively. Response criteria to proceed to full accrual were not met. Grade 3-4 toxicity for sunitinib included thrombocytopenia 63%, neutropenia 25%, asthenia 8%, and anorexia 8%. Grade 2 hypothyroidism and hypertension were developed in 42% and 17%, respectively. 46% of pts required 1 or 2 dose reductions. Conclusions: This study did not meet the primary endpoint. Although response was noted in 2 pts with sensitive relapse, median PFS was short and most pts were intolerable. Thus this approach does not appear to warrant further clinical study. Supported in part by NCC, Korea and Pfizer, Inc.
Inhibition of cMET in an experimental model of pancreatic cancer.
Authors: Sven A. Lang, Franziska Brandes, Edward K. Geissler
Journal: Journal of Clinical Oncology (2013)

185 Background: In human pancreatic cancer, expression of cMET is associated with poor survival. So far, activation/expression of cMET by hepatocyte growth factor (HGF) has been shown to induce proliferation and motility in cancer cells. Therefore, we hypothesized that inhibition of cMET in human pancreatic cancer cell lines impairs oncogenic signaling and tumor growth. Methods: Pancreatic cancer cell lines (HPAF-II, MiaPaCa2, L3.6pl, BxPC3, Panc02) and the cMET inhibitor INC280 (Novartis Oncology, Basel) were used. MiaPaCa2 and L3.6pl pancreatic cancer cells were grown with gemcitabine up to 500 and 250 nM, respectively (then called MiaPaCa2(G500) and L3.6pl(G250)). MTT and Boyden Chamber assays were used to determine effects of INC280 on growth and motility of cells in vitro. Expression of growth factor receptors, activation of signaling intermediates and expression of transcription factors were assessed by Western blotting. Finally, in vitro results were validated in an orthotopic tumor model using L3.6pl pancreatic cancer cell line. Results: All pancreatic cancer cell lines showed expression of cMET. In vitro treatment of cancer cells with INC280 led to a minor, dose-dependent inhibition of growth even when cells were supplemented with HGF. In contrast, migration assays showed a significant reduction of cancer cell motility upon INC280 when cells were stimulated with HGF (P&lt;0.05). Regarding oncogenic signaling, INC280 led to inhibition of HGF-induced phosphorylation of AKT, ERK and FAK. In addition, c-Myc expression was diminished in cancer cells. Interestingly, gemcitabine resistant cell line MiaPaCa2(G500) showed higher cMET expression levels compared to the normal MiaPaCa2. Stimulation of MiaPaCa2(G500) with HGF led to strong induction of oncogenic signaling and tumor cell motility, an effect that was significantly diminished by INC280. Moreover, results from in vivo experiments show that therapy with INC280 (10 mg/kg/d) significantly reduces tumor growth as determined by final tumor weight (P&lt;0.05). Conclusions: In pancreatic cancer cell lines, targeting cMET with INC280 abrogates oncogenic signaling in vitro and impairs tumor growth in vivo. Therefore, the concept of cMET inhibition warrants further preclinical evaluation.
Novel C3 Mutation Causing Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab
Authors: Joao Carlos Guerra, Claudio Galvao de Castro, Paulo Vidal Campregher, Tatiana Galvao, Oscar Pavao Santos, Bento Cardoso Santos, Luiz Vicente Rizzo, Flavia Munhoz Ferreira, Michelle P. Silveira, Nelson Hamerschlak, Helio Korkes
Journal: Blood (2014)
Dietary and pharmacological treatment of abdominal pain in IBS
Authors: Michael Camilleri, Guy Boeckxstaens
Journal: Gut (2017)

This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT<sub>3</sub> receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), μ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity. The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1 <h3>Classes of pharmacological agents for visceral pain</h3> Antidepressants (tricyclic agents, selective serotonin reuptake inhibitors) Peppermint oil 5-HT<sub>3</sub> receptor antagonists (alosetron, ondansetron, ramosetron) Non-absorbed antibiotic (rifaximin) Secretagogues (lubiprostone, linaclotide) μ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline) Histamine H1 receptor antagonist (ebastine) Neurokinin-2 receptor antagonist (ibodutant) GABAergic agents (gabapentin and pregabalin)
Pain score, analgesic utilization, and patient satisfaction among cancer patients at a community cancer center.
Authors: Dylan Michael Zylla, Jim Fulbright, Pamala A. Pawloski, Lisa Illig, Adina Peck, Sarah Van Peursem, Sara Richter, Amber Larson
Journal: Journal of Clinical Oncology (2014)

203 Background: Cancer-related pain is common, negatively impacts quality of life and survival, and often requires opioid analgesics. Patient level data describing the incidence and severity of pain, medication utilization, and patient satisfaction associated with care are lacking. An understanding of cancer pain prevalence and analgesic utilization is needed to initiate quality improvement (QI) interventions. Methods: We analyzed 2 months of outpatient oncology clinic encounters from the electronic medical record (EMR) and conducted a patient survey of 163 cancer patients to obtain baseline data on pain levels, opioid and non-opioid treatments, and patient satisfaction. Our survey incorporated questions from the Brief Pain Inventory to validate EMR reports and obtain patient satisfaction data. Results: Moderate to severe pain is reported in nearly 1 of every 9 cancer patient encounters (Table 1). On average, we achieved a personal pain goal (PPG) in 83.5 % of all patients (n=109). Among patients receiving opioids, a PPG was achieved in 16 of 29 patients (55.2%). Of the 13 opioid-consuming patients not achieving a PPG, 12 were not on a long-acting opioid, and 5 had never discussed a pain management plan with their physician. Oxycodone CR is the most commonly prescribed long-acting opioid (40.4% versus morphine SR (26.1%), methadone (23.0%), and fentanyl transdermal (10.6%)). Conclusions: Moderate to severe pain is commonly encountered among patients receiving cancer care in the clinic setting. Increasing the proportion of patients achieving a PPG is a critical quality and patient satisfaction goal, and may be improved by creating a pain plan incorporating a long-acting opioid. Our QI intervention aims to improve pain assessment documented in the EMR and educate both patients and staff regarding appropriate pain management. [Table: see text]