tbuckley/cabot-search huggingface dataset:
Active Surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement
Authors: Ronald C. Chen, R. Bryan Rumble, D. Andrew Loblaw, Antonio Finelli, Behfar Ehdaie, Matthew R. Cooperberg, Scott C. Morgan, Scott Tyldesley, John J. Haluschak, Winston Tan, Stewart Justman, Suneil Jain
Journal: Journal of Clinical Oncology (2016)

Purpose To endorse Cancer Care Ontario’s guideline on Active Surveillance for the Management of Localized Prostate Cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations. Methods The Active Surveillance for the Management of Localized Prostate Cancer guideline was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and the recommendations. Results The ASCO Endorsement Panel determined that the recommendations from the Active Surveillance for the Management of Localized Prostate Cancer guideline, published in May 2015, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the Active Surveillance for the Management of Localized Prostate Cancer guideline with added qualifying statements. The Cancer Care Ontario recommendation regarding 5-alpha reductase inhibitors was not endorsed by the ASCO panel. Recommendations For most patients with low-risk (Gleason score ≤ 6) localized prostate cancer, active surveillance is the recommended disease management strategy. Factors including younger age, prostate cancer volume, patient preference, and ethnicity should be taken into account when making management decisions. Select patients with low-volume, intermediate-risk (Gleason 3 + 4 = 7) prostate cancer may be offered active surveillance. Active surveillance protocols should include prostate-specific antigen testing, digital rectal examinations, and serial prostate biopsies. Ancillary radiologic and genomic tests are investigational but may have a role in patients with discordant clinical and/or pathologic findings. Patients who are reclassified to a higher-risk category (Gleason score ≥ 7) or who have significant increases in tumor volume on subsequent biopsies should be offered active therapy.
Population pharmacokinetics of sunitinib in Japanese and Western healthy volunteers, solid tumor, metastatic renal cell carcinoma (MRCC) and imatinib-resistant or -intolerant gastrointestinal stromal tumors (GIST) patients
Authors: M. A. Amantea, B. E. Houk, C. Bello
Journal: Journal of Clinical Oncology (2008)

2522 Background: Sunitinib, an oral multi-targeted tyrosine kinase inhibitor, is approved internationally to treat advanced MRCC and imatinib-resistant or -intolerant GIST. Sunitinib is metabolized via CYP3A4 to an active metabolite, SU012662 (SU). Methods: Merged data from 12 Western and 2 Japanese studies in healthy volunteers (HV; n=73), GIST (n=241), MRCC (n=153), solid tumors (ST, n=95) and acute myelogenous leukemia (AML; n=29) patients were analyzed. The impact of tumor type, gender, performance status, creatinine clearance (CrCL), body weight (BW) and race on sunitinib and SU012662 clearance (CL/F) and volume of distribution (Vd/F) were assessed by nonlinear mixed effects modeling at p<0.01. Simulations with final parameter calculations estimated the impact of demographic and clinical factors on steady-state area under the curve (AUC) and maximum plasma concentrations (Cmax) of SU and total drug (SU + SU012662). Results: The terminal half-lives of sunitinib and SU012662 in HV were estimated to be 69 and 80 h, respectively. Inter- individual variability was estimated to be 38 % for CL/F and 43 % for Vd/F. Although tumor presence had the greatest impact on CL/F for SU and SU012662 vs HV, the magnitude of the decrease (26–29%) was similar across tumor types, except AML. Performance status and CrCL did not affect sunitinib or SU012662 CL/F. In Asians vs other races, CL/F decreased 13 % for sunitinib and 12 % for SU012662. CL/F was lower in females relative to males for sunitinib by 9 % and SU012662 by 26 %. BW correlated to sunitinib Vd/F, and to SU012662 CL/F and Vd/F. The lower CL/F in Asians predicted a 15% increase in AUC and Cmax for SU and total drug. In females, a 9–10% increase in AUC and a 17% increase in Cmax was predicted. Changes in total-drug AUC and Cmax were all <5% in low (40 kg) and high (100 kg) BW subjects. Conclusions: ST contributed the largest PK effect on sunitinib and SU012662. Asian race, gender, BW (metabolite only) and ECOG score had less impact. Predicted change are relatively small vs inter-individual variability. No dose adjustments are recommended for sunitinib based on the magnitude of predicted changes due to any covariate studied. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Inc Pfizer Inc
A prospective study of predictive factors for chemotherapy-induced nausea and vomiting.
Authors: J. A. Renkosik, D. J. Adelstein, L. A. Rybicki, C. P. Rodriguez, D. I. Ives
Journal: Journal of Clinical Oncology (2011)

e19720 Background: Despite effective antiemetics, patients (pts) still develop nausea and vomiting after chemotherapy. While the emetogenic potential of different chemotherapy drugs has been established, the contributing patient and disease factors are less understood, and are the subject of this prospective study. Methods: Cleveland Clinic (CC), pts with locoregionally advanced, non-metastatic cancer of the head and neck (HN), esophagus, and gastro-esophageal junction (E/GEJ) are frequently treated in the hospital with concurrent chemoradiation using 96 hour infusions of cisplatin (20 mg/m2/day) and 5FU (1000 mg/m2/day). Between 7/09 and 9/10, all pts receiving their first course of chemotherapy with this regimen were entered in this study. A standard antiemetic prophylactic and therapeutic algorithm was utilized. Demographics, disease characteristics, potential risk factors, and maximum CTCAE v3.0 grade nausea and vomiting were recorded. Logistic regression analysis was used to identify predictors for the primary endpoint of > grade 1 chemotherapy induced nausea and/or vomiting (CINV). Results: The study enrolled 120 consecutive pts; 87% were male, 90% white, 61 had HN cancer, and the median age was 57 (range 26-76) years. Alcohol use was moderate or heavy in 33% and pts lived a median 39 (range 4-3000) miles from the CC. Univariable predictors for CINV included limited (vs. moderate or heavy) alcohol use, greater distance from the CC, history of psychiatric disorder, and E/GEJ (vs. HN) cancer. Although a body mass index (BMI) <25 predicted for greater CINV than BMI >32, this was felt to reflect the chemotherapy dose reductions sometimes used in obese pts. On multivariable analysis, only limited alcohol intake (OR 2.64, 95% CI 1.12-6.22, P=0.026) and an E/GEJ primary (OR 3.53, 95% CI 1.50-8.31, P=0.004) proved predictive for CINV. Pts with HN cancer and moderate or heavy alcohol use had a 41% chance of CINV in contrast to an 86% chance of CINV in pts with E/GEJ cancer and limited alcohol. Conclusions: The importance of disease site in predicting for CINV in our series likely reflects the radiation therapy port used in this concurrent treatment. The only prospectively identified patient predictor for CINV was a limited alcohol intake.
A phase I study of a DNA plasmid based vaccine encoding the HER2/neu (HER2) intracellular domain (ICD) in subjects with HER2+ breast cancer
Authors: L. G. Salazar, M. Slota, D. Wallace, D. Higgins, A. L. Coveler, Y. Dang, J. Childs, N. Bates, J. Waisman, M. L. Disis
Journal: Journal of Clinical Oncology (2009)

3054 Background: HER2 is overexpressed in 25% of breast cancers and plays a role in the malignant transformation of cells. Vaccine-induced immunity against the HER2 ICD correlates with antitumor responses in animal models. DNA-based vaccines offer a strategy to immunize against multiple tumor antigens and are able to elicit both CTL and T helper immune responses. Plasmid DNA can also remain at the vaccine site, providing a constant source of antigen. However, DNA vaccines have been poorly immunogenic due in part to inefficient APC transfection. Intradermal (i.d.) delivery of DNA vaccines with GM-CSF as adjuvant may enhance immunogenicity due to local influx of dermal Langerhans cells. A phase I study was conducted to evaluate the safety and immunogenicity of a DNA-based vaccine encoding the HER2 ICD. Methods: 44 subjects with stage III and IV HER2+ breast cancer in complete remission were enrolled sequentially into 2 vaccine arms (22 subjects/arm) and received 10μg pNGVL3-hICD (Arm 1) or 100μg pNGVL3-hICD (Arm 2). All vaccines were admixed with 100μg GM-CSF and given i.d. monthly for a total of 3 vaccines. Toxicity was assessed at baseline, during vaccination, and at follow-up. Immune responses were assessed with IFN-γ ELISPOT at baseline and post-vaccination. Vaccine site biopsies were analyzed for plasmid persistence via RT-PCR, 1 and 6 months after vaccination. Results: 43 subjects (21 in Arm 1; 22 in Arm 2) completed 3 vaccines. Vaccine-related toxicity in both arms was primarily grade I/II; no cardiac or grade IV toxicity was observed. 13/21 (62%) subjects in Arm 1 developed T-cell immunity, defined as HER2-specific T cell precursors:PBMC, to the HER2 protein (median 1:5,972, range 1:717–1:3,000,000) and to p776, a HER2 pan DR binding epitope (median 1:3,150, range 1:543–1:108,696). 13/19 (68%) subjects in Arm 1 had persistent plasmid DNA at the vaccine site. ELISPOT and RT-PCR analysis for Arm 2 are on-going. Conclusions: Immunization with a DNA plasmid-based HER2 vaccine is safe and immunogenic. Moreover, plasmid DNA persists at the vaccine site post-immunization and HER2+ cancer patients are able to develop immunity to the HER2 ICD. No significant financial relationships to disclose.
Can GRADE2 Neutropenia Predict the Risk of Grade3 Neutropenia in Colorectal Cancer Patients Treated with Chemotherapy?
Authors: Y. Yoshida, S. Hoshino, M. Naito, N. Aisu, S. Tanimura, T. Sasaki, S. Takeno, Y. Yamashita
Journal: Annals of Oncology (2013)
Toward the Definition of a Bipolar Prodrome: Dimensional Predictors of Bipolar Spectrum Disorders in At-Risk Youths
Authors: Danella M. Hafeman, John Merranko, David Axelson, Benjamin I. Goldstein, Tina Goldstein, Kelly Monk, Mary Beth Hickey, Dara Sakolsky, Rasim Diler, Satish Iyengar, David Brent, David Kupfer, Boris Birmaher
Journal: American Journal of Psychiatry (2016)

The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths).Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders.Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<0.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed a bipolar spectrum disorder, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factors had a 49% predicted chance of conversion.Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.
Contribution of constitutive activation of Akt to the pathogenesis of mantle cell lymphoma (MCL) independent of PTEN protein expression
Authors: C. Economopoulou, A. Psyrri, E. Liakata, S. Papageorgiou, P. Economopoulou, F. Kontsioti, V. Pappa, T. Economopoulos
Journal: Journal of Clinical Oncology (2007)

8101 Background: To determine whether the PI3K/Akt signaling pathway is involved in the pathogenesis of mantle cell lymphoma (MCL), we investigated the phosphorylation status of Akt in primary MCL cases and cell lines. We also sought to determine whether loss of the phosphatase PTEN is the mechanism of Akt activation in MCL. Methods: We evaluated the protein levels of Akt, phosphorylated Akt and PTEN in 15 primary MCL cases and 2 cell lines by immunoblotting Results: Akt was phosphorylated in 3 of 15 MCL cases and in 2 of 2 mantle cell lymphoma cell lines. PTEN protein was expressed in 15 of 15 primary mantle cell lymphoma cases and in 2 of 2 MCL cell lines. Conclusions: We conclude that constitutive activation of the PI3K/Akt pathway contributes to the pathogenesis of MCL. Loss of PTEN protein expression is not the responsible mechanism for Akt activation. Alternative mechanisms of Akt activation are being evaluated to identify markers predictive for response to PI3K/Akt inhibitors in MCL. No significant financial relationships to disclose.
Comparison of the major outer-membrane protein (MOMP) gene of mouse pneumonitis (MoPn) and hamster SFPD strains of Chlamydia trachomatis with other Chlamydia strains.
Authors: Y X Zhang, J G Fox, Y Ho, L Zhang, H F Stills, T F Smith
Journal: Molecular Biology and Evolution (1993)

Restriction fragments containing the major outer-membrane protein (MOMP) gene from two nonhuman (rodent) strains of Chlamydia trachomatis, the mouse pneumonitis (MoPn) strain and the SFPD strain isolated from hamsters with transmissible proliferative ileitis, were cloned and sequenced. The MOMP genes of both MoPn and SFPD encode an identical 22-amino acid leader peptide and mature polypeptides of 365 and 382 amino acids, respectively. Alignment of the MOMP genes of the two rodent strains revealed 91% identity. By comparison with other known chlamydial MOMP gene sequences, there was 80%-83% identity with human biovars strains of C. trachomatis, and there was 69%-70% identity with C. psittaci and C. pneumoniae strains. The main differences in these sequences were clustered into four variable domains. A minimum-length evolutionary tree was constructed on the basis of the MOMP gene variable positions by using PIMA package software. The minimum mutation distances indicated that (i) the MOMP genes of all chlamydial strains may have evolved from a common ancestor; (ii) all the strains of C. trachomatis compose one of the subtrees, and strains of C. psittaci and C. pneumoniae compose the other subtree; and (iii) in the C. trachomatis subtree, the human and the rodent strains are divided into two clusters. The branching pattern of this evolutionary tree is generally consistent with current classification based on serological, morphological, and other biological characteristics.
Abstract 9762: Brain Tumor Necrosis Factor-α Augments Sympathoexcitation and Left Ventricular Remodeling of Ischemia-induced Heart Failure via Dysfunction of Keap1/Nrf2-mediated Antioxidant in Brain Astrocyte
Authors: Takuya Kishi, Yoshitaka Hirooka, Kenji Sunagawa
Journal: Circulation (2012)

[Backgrounds] We have demonstrated, in ischemic heart failure (HF), angiotensin II increases oxidative stress and induces apoptosis of brain astrocyte, sympathoexcitation and left ventricular (LV) remodeling. In astrocyte, the oxidant-sensing Keap1/NF-E2-related factor 2 (Nrf2) pathway mediates antioxidant function. Recent studies have indicated that brain proinflammatory cytokines also contribute to sympathoexcitation. The aim of the present study was to determine whether brain tumor necrosis factor (TNF)-α augments sympathoexcitation and LV remodeling caused by apoptosis of brain astrocyte in ischemia-induced HF, and if so, whether TNF-α impairs Keap1/Nrf2-mediated antioxidant function of brain astrocyte. [Methods and Results] We treated, for 4 weeks, Sprague-Dawley rats with HF (by coronary ligation) with a continuous intracerebroventricular infusion of angiotensin II type 1 receptor blocker (ARB), ARB+etanercept (ETN; TNF-a receptor blocker), vehicle (Veh) or sham. Urinary norepinephrine excretion (UNE; an index of sympathoexcitation), brain oxidative stress, and glial fibrillary acidic protein expression (GFAP; marker of astrocyte apoptosis) in the brain were significantly higher and LV end-systolic dimension (LVESD) were significantly larger in Veh than in sham (UNE; 2.3±0.3 μg/day vs. 1.1±0.2 μg/day, n=5 for each, p&lt;0.05). Brain Nrf2 expression was significantly lower in Veh than in Sham (0.3±0.1 U vs. 1.0 U, value is expressed relative to that in sham, n=5 for each, p&lt;0.05). In comparison to Veh, ARB lowered UNE (1.8±0.1 μg/day vs. 2.3±0.3 μg/day, n=5 for each, p&lt;0.05), brain oxidative stress, GFAP expression, and LVESD. Furthermore, all of these beneficial effects were augmented in ARB+ETN to the similar levels in sham (UNE; 1.4±0.2 μg/day, n=5). Brain Nrf2 expression was significantly higher in ARB+ETN than in Veh (0.7±0.1 U vs. 0.3±0.1 U, value is expressed relative to that in sham, n=5 for each, p&lt;0.05), although it was not different between in ARB and Veh. [Conclusion] Brain TNF-α augments angiotensin II-induced sympathoexcitation and LV remodeling of ischemia-induced HF via dysfunction of Keap1/Nrf2-mediated antioxidant in brain astrocyte.
PTU-083 Proteomic analysis of bile in benign and malignant pancreatobiliary disease
Authors: A A Zabron, V M Horneffer-Van der Sluis, M Geirula, C A Wadsworth, F Laird, A V Thillainayagam, P Vlavianos, D Westaby, S D Taylor-Robinson, R J Edwards, S A Khan
Journal: Gut (2010)

<h3>Introduction</h3> Obstruction of the biliary tree has a variety of aetiologies. The correct diagnosis is crucial for appropriate definitive therapy. A major differential diagnosis of biliary obstruction is pancreatic adenocarcinoma (PA). PA is the 10th most common cancer in the UK with mortality similar to incidence. Diagnosis of PA relies on a combination of cross-sectional imaging and serum biomarkers, but only a minority of cases are diagnosed correctly and early enough for curative resection. Earlier diagnostic certainty would be likely to improve outcome and guide therapeutic strategy. Proteomic profiling is a promising technique for new biomarker discovery, but has rarely been successfully carried out in human bile. This project (1) analyses and compares the proteomes of bile from PA patients vs. bile from patients with benign biliary disease and (2) seeks to identify potential protein biomarkers that can differentiate PA from benign biliary disease. <h3>Methods</h3> Bile was aspirated at ERCP from patients with benign or malignant biliary obstruction. Particulate matter was removed by centrifugation and equal volumes subjected to SDS-PAGE. In-gel trypsin digestion was performed and the resulting peptides analysed by tandem mass spectrometry. Proteins were identified using SEQUEST to search the human RefSeq protein sequence database. Progenesis software was used to compare relative levels of proteins between patient groups. <h3>Results</h3> Proteomic analysis of bile from four patients with PA and four with benign biliary obstruction was performed. Over 100 different proteins were identified, including pancreatic gastric triacylglycerol lipase, carboxypeptidase B and bile salt-activated lipase, confirming that the profile of proteins represents the biliary proteome. Several differentially expressed proteins were identified including upregulation of carcinoembryonic antigen–related cell adhesion molecule 6 (CEACAM6) in the malignant group. <h3>Conclusion</h3> This work confirms that bile is amenable to proteomic analysis and that differences in the biliary proteome can be detected in malignant and non-malignant cases. We confirmed earlier reports of CEACAM6 overexpression in PA. We are currently analysing the data further to identify additional candidate biomarker proteins. Future work will extend this approach to the study of bile in other diseases, such as cholangiocarcinoma.
History of the condom [letter]
Authors: Dooley Mm
Journal: Journal of the Royal Society of Medicine (1994)

Your article by Youssef (April 1993 JRSM p 226) was a most interesting review of the history of the condom.  However the different uses of the condom were not fully described.  Condoms are used routinely by many physiotherapy departments to cover the had of ultrasound machines used for bruised perineum.  Physiotherapists also fill condoms with ice which are then placed onto a swollen perineum in order to decrease the inflammation.  During the Gulf War shares in Okamotos Industries Japans largest condom manufacturers rose 10% on the strength of market talk that allied soldiers in the Gulf were using condoms to keep sand out of their gun barrels.  Durex Fold is an inch longer than most other products and marked extra large but generally speaking one size fits all men.  Rumor has it that Sir Winston Churchill was once asked by Stalin to help combat the Soviet condom shortage.  He persuaded a British manufacturers to have a special batch made twice as large as normal.  These were shipped to the USSR marked Made in Britain-Medium. They are also used to cover microphones during underwater filming.  The same idea is used to protect Sonicaids for underwater births. Smugglers to avoid customs have been known to swallow diamonds and even cocaine protected by condoms sometimes with disastrous results if the condom burst.  Emergency uses of the condom include acting as a temporary fanbelt for cars washing machines and vacuum cleaners.  Novel methods of storing condoms have also been developed.  An earring in which a condom can be stored is taking the fashion world by storm.  This limited review of the lay press has clearly demonstrated that there are many uses for the condom apart for the conventional family planning use. (full text)
Subpopulations of Human T-Lymphocytes. XIX. T-Cells and T-Cells With Receptors for IgMFc (Tμ), IgGFc (Tγ), or IgAFc (Tα) in the Peripheral Blood and Regional Lymph Nodes of Patients With Untreated Breast Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S Gupta, S Cunningham-Rundles
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Subpopulations of Human T-Lymphocytes. XIX. T-Cells and T-Cells With Receptors for IgMFc (Tμ), IgGFc (Tγ), or IgAFc (Tα) in the Peripheral Blood and Regional Lymph Nodes of Patients With Untreated Breast Cancer Get access Sudhir Gupta, Sudhir Gupta Address reprint requests to Dr. Gupta Search for other works by this author on: Oxford Academic PubMed Google Scholar Susanna Cunningham-Rundles Susanna Cunningham-Rundles Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 69, Issue 6, December 1982, Pages 1261–1264, https://doi.org/10.1093/jnci/69.6.1261 Published: 01 December 1982 Article history Received: 09 March 1982 Accepted: 30 June 1982 Published: 01 December 1982