tbuckley/cabot-search huggingface dataset:
The use of Internet as an information resource among cancer patients at a Canadian cancer centre
Authors: S. Verma, J. Fralick, J. Sue, M. Wu, G. Dranitsaris, M. Clemons, G. Piliotis
Journal: Journal of Clinical Oncology (2006)

18561 Background: Understanding the nature of Internet use among cancer patients is important to facilitate patient-education interventions and for providing optimal patient care. This questionnaire study is designed to evaluate Internet use by cancer patients at a cancer centre. Methods: Cancer patients attending ambulatory clinics at a single Canadian cancer centre were approached by their health care staff. Participants filled out self-administered questionnaire collecting information on demographics, frequency of Internet usage, timing of Internet use during treatment course, type of information sought, and information on patient’s comfort level and satisfaction with Internet use. Results: Of the total 250 participants, 174 (70%) had used the Internet before and 76 (30%) had never used the Internet. Users were more likely to be younger, female, have English as their first language, and be of Caucasian descent. Individuals with breast cancer were also more likely to have used the Internet than pts with other malignancies. Of the Internet users (n = 174), the majority (87%, n = 152) accessed the Internet once per week or more, and felt strongly confident (44%, n=76) in navigating the Internet. 29 users (17%) felt that the information on the Internet was not trustworthy. Of the users, 136 (78%) used the Internet to access information on cancer, and reportedly more often before visiting the cancer centre (50%, n = 70) and before starting initiating cancer treatment (78%, n = 106). The users seeking information on cancer were most likely to look for information on cancer treatment (87%, n = 118) and side effects (74%, n = 100). The top three visited sites were those for Canadian cancer society, Google, and American cancer society. Conclusions: Despite wide availability and accessibility of Internet, it is still not being used as a cancer information tool by many of our patients. By ensuring that accurate and comprehensive information is available on the Internet, perhaps even more patients will use this medium as their information resource, to better understand their diagnosis and make optimal treatment decisions. No significant financial relationships to disclose.
Clinical relevance of circulating CK-19mRNA-positive tumor cells at first diagnosis in patients with metastatic breast cancer.
Authors: N. E. M. Androulakis, M. Perraki, S. Apostolaki, V. Bozionelou, A. G. Pallis, K. Kalbakis, S. Agelaki, A. Xyrafas, D. Mavroudis, V. Georgoulias
Journal: Journal of Clinical Oncology (2011)

10553 Background: To investigate the clinical relevance of CK-19mRNA-positive CTCs detected before the initiation of front-line treatment in patients with metastatic breast cancer (MBC). Methods: A total of 300 patients with MBC (training set: 200 patients; validation set: 100 patients) at first diagnosis were enrolled. The presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction before any systemic treatment. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated. Results: CK-19 mRNA-positive cells were detected in 139 (69.5%) and 62 (62%) patients of the training and validation set, respectively. There was no association between the detection of CK-19 mRNA-positive CTCs and other clinico-pathological parameters, the tumor burden or the achievement of objective response in either set. The median PFS was significantly lower in patients with detectable CK-19 mRNA-positive CTCs compared to patients without detectable CTCs both in the training (9.0mo vs 12.0mo, respectively; p=0.018) and the validation (10.0mo vs 12.5mo, respectively; p=0.010) set. Similarly, the median OS was significantly higher in patients without detectable CK-19 mRNA-positive CTCs compared to patients with detectable CTCs both sets (training set: 41.4mo vs 29.9mo, respectively, p=0.014; validation set: 46.0mo vs 29.9mo, respectively, p=0.022). Multivariate analysis including all patients (n=300) demonstrated that ER status (HR=1.483; 95% CI: 1.140-1.928) and detection of CTCs (HR=1.440; 95% CI: 1.440-1.913) were independently associated with a decreased PFS and OS (ER status: HR=1.510, 95% CI: 1.085-2.113; detection of CTCs: HR=1.656, 95% CI: 1.148-2.390). Conclusions: These data indicate that the detection of CK-19 mRNA-positive CTCs in patients with MBC at first diagnosis defines a subgroup of patients with dismal clinical outcome.
Encouraging survival with erlotinib in advanced papillary renal cell carcinoma (pRCC): Final results from Southwest Oncology Group study 0317
Authors: C. Pan, M. Hussey, P. N. Lara, P. C. Mack, R. Nagle, J. P. Dutcher, W. E. Samlowski, J. Clark, M. S. Gordon, E. D. Crawford
Journal: Journal of Clinical Oncology (2008)

5051 Background: Historically, patients (pts) with advanced or metastatic pRCC have a median survival time of 7 to 17 months following systemic therapy (Motzer, et al. JCO 2002; Patard et al. JCO 2005). Pre-clinical studies showed greater activity for epidermal growth factor receptor (EGFR) inhibition in clear cell RCC with wild type von Hippel-Lindau (vHL) gene. In this trial, we evaluated the efficacy of erlotinib, an oral EGFR tyrosine kinase inhibitor in pts with advanced pRCC (usually associated with wild-type vHL). Methods: Pts with histologically confirmed locally advanced or metastatic pRCC were treated with erlotinib 150 mg PO QD until disease progression, patient refusal, unacceptable toxicity, or a treatment delay > 3 wks. The primary endpoint was RECIST response rate (RR). A RR of ≥ 20% was to be considered a promising outcome. Secondary endpoints included overall survival & 6-month probability of treatment failure. EGFR expression by IHC and vHL mutation status by PCR were assessed in tumor specimens. Results: Of 52 pts registered, 7 were ineligible due to insufficient pathology material submission. Of 45 evaluable pts, there were 33M/12F with a median age of 63.4 y (range 27.9 to 82.8). Median follow-up was 17.1 months (range 1.5 to 41.6). Overall RR was 11% (5/45, 95% CI: 3 - 24%). The disease control rate (DCR) was 64% (5 PR + 24 Stable). Median overall survival time was 27 months (95% CI: 13 to 36). Probability of freedom from treatment failure at 6 months was 29% (95% CI: 17–42%). There was one Grade 5 adverse event (AE) of pneumonitis, one Grade 4 thrombotic AE, and eight other Grade 3 AEs. There were two vHL mutations detected. The correlative study between EGFR expression and treatment outcomes will be presented at the meeting. Conclusions: Although the RECIST RR of 11% did not exceed pre-specified estimates for further study, single agent erlotinib yielded encouraging DCR and OS results in pts with pRCC with an expected toxicity profile. Further evaluation of the EGFR axis in pRCC should be considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech
Continuous interleukin-2 and lymphokine-activated killer cells for advanced cancer: a National Biotherapy Study Group trial.
Authors: R O Dillman, R K Oldham, K W Tauer, D W Orr, N M Barth, G Blumenschein, J Arnold, R Birch, W H West
Journal: Journal of Clinical Oncology (1991)

We conducted a multicenter, phase II trial of continuous-infusion recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells. Patients had advanced cancer, measurable disease, and a good performance level. Treatment included a 5-day continuous infusion of 18 x 10(6) IU/m2/d of rIL-2 followed by 1 day of rest, 4 days of leukapheresis to collect cells for in vitro augmentation of cellular cytotoxicity, and 5 more days of rIL-2 infusion with reinfusion of LAK cells for 3 successive days. Therapy was repeated after 2 weeks. There were 117 patients enrolled: 63% were males, with a median age of 51 years. Eighty-two percent were managed in oncology units, and 18% were in intensive care units. Six patients died within 1 month of initiating therapy. In renal cell carcinoma, the response rate was one of 31 patients (3%), with a median survival of 10.7 months. In melanoma, the response rate was four of 33 patients (12%), with a median survival of 6.1 months. For all other histologies, response rate was three of 53 patients (5%), with a median survival of 7.4 months. All responders were asymptomatic when therapy was initiated. This trial confirms the feasibility of administering continuous rIL-2 and LAK cells outside the intensive care unit environment. Antitumor activity in melanoma was similar to that seen in multicenter trials of bolus rIL-2 and LAK cells. Activity in renal cell cancer was disappointing.
Paclitaxel and Gemcitabine Chemotherapy for Advanced Transitional-Cell Carcinoma of the Urothelial Tract: A Phase II Trial of the Minnie Pearl Cancer Research Network
Authors: Anthony A. Meluch, F. Anthony Greco, Howard A. Burris, Timothy O’Rourke, Gregory Ortega, Ronald G. Steis, Lisa H. Morrissey, Valerie Johnson, John D. Hainsworth
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma of the urothelial tract. PATIENTS AND METHODS: Fifty-four patients with advanced unresectable urothelial carcinoma entered this multi-centered, community-based, phase II trial between May 1997 and December 1999. All patients were treated with paclitaxel 200 mg/m 2 by 1-hour intravenous (IV) infusion on day 1 and gemcitabine 1,000 mg/m 2 IV on days 1, 8, and 15; courses were repeated every 21 days. Patients who had objective response or stable disease continued treatment for six courses. RESULTS: Twenty-nine of 54 patients (54%; 95% confidence interval, 40% to 67%) had major responses to treatment, including 7% complete responses. With a median follow-up of 24 months, 16 patients (30%) remain alive and nine (17%) are progression-free. The median survival for the entire group was 14.4 months; 1- and 2-year actuarial survival rates were 57% and 25%, respectively. Seven (47%) of 15 patients previously treated with platinum-based chemotherapy responded to paclitaxel/gemcitabine. Grade 3/4 toxicity was primarily hematologic, including leukopenia (46%), thrombocytopenia (13%), and anemia (28%). Ten patients (19%) required hospitalization for neutropenia and fever, and one patient had treatment-related septic death. CONCLUSION: The combination of paclitaxel and gemcitabine is active and well tolerated in the first- or second-line treatment of patients with advanced transitional-cell carcinoma of the urothelial tract. Response rate and duration compare favorably with those produced by other active, first-line regimens. This regimen should be further evaluated in phase II and III studies, as well as in patients with compromised renal function.
Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function
Authors: Brandy Reid, Pierre-Olivier Girodet, Jonathan S. Boomer, Azza Abdel-Gadir, Kathy Zheng, Michael E. Wechsler, Leonard B. Bacharier, Susan J. Kunselman, Tonya S. King, Elliot Israel, Mario Castro, Manuela Cernadas, Jonathan M. Green
Journal: Journal of Allergy and Clinical Immunology (2016)
Role of an EpCAM auto-antibody in ovarian cancer patients with special regard to disseminated tumor cells in bone marrow
Authors: M. Heubner, S. Kasimir-Bauer, D. Errico, D. Herlyn, R. Kimmig, P. Wimberger
Journal: Journal of Clinical Oncology (2009)

e16557 Background: EpCAM is a tumor associated antigen which is frequently expressed in ovarian cancer. Recently, an autoantibody (AAB) against EpCAM has been identified in ovarian cancer patients. Autoantibodies are immunogene factors and might be of prognostic importance. We showed that disseminated tumor cells (DTC) in bone marrow carry the EpCAM antigen on their surface and correlate with poorer progression free survival (PFS). Here, we evaluated whether EpCAM-AABs have an impact on clinical parameters or the presence of DTC in ovarian cancer patients. Methods: EpCAM-AABs were determined in sera of 28 healthy voluntary age matched females and 62 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-epitope for antibody- detection by ELISA technique. Mean follow up time was 13 months. DTC in BM were detected by immunocytochemistry applying the pan cytokeratin antibody A45-B/B3. All samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. Results: The antibody titer of healthy controls was 0.061 + 0.015. Using a cut-off value of 0.091, we found 9/62 (15%) ovarian cancer patients to be positive for EpCAM-AABs after first-line treatment. Interestingly, no positive AAB-titers were seen before therapy. Using the paired T-Test, we noted a significant posttherapeutic increase of AABs (CI 0.95, p &lt; 0.0001). Analysis of PFS, FIGO stage, resection status, grading, age, sensitivity to platinum based chemotherapy and DTC did not reveal significant associations with positive EpCAM-AAB titers. Conclusions: The clinical course of ovarian cancer patients and the prevalence of DTC were not altered by EpCAM-AABs. Interestingly, we observed an increase of antibody-levels after first-line treatment. For further validation, we intend to extend our patient collective. In future, it might also be interesting to investigate the impact of AABs on response to targeted therapies against EpCAM. No significant financial relationships to disclose.
Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports
Authors: Tarang Sharma, Louise Schow Guski, Nanna Freund, Peter C Gøtzsche
Journal: BMJ (2016)

<b>Objective </b>To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors. <b>Design</b> Systematic review and meta-analysis. <b>Main outcome measures</b> Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. <b>Data sources</b> Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website. <b>Eligibility criteria for study selection</b> Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. <b>Data extraction and analysis</b> Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model). <b>Results</b> We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete. <b>Conclusions</b> Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.
Increased efficacy and toxicity with combination anti-VEGF therapy using sorafenib and bevacizumab
Authors: N. S. Azad, E. M. Posadas, V. E. Kwitkowski, C. M. Annunziata, T. Barrett, A. Premkumar, H. L. Kotz, G. A. Sarosy, L. M. Minasian, E. C. Kohn
Journal: Journal of Clinical Oncology (2006)

3004 Background: The multikinase inhibitor, sorafenib (sor), targets raf-kinase and vascular endothelial growth factor receptor 2 (VEGFR2). Bevacizumab (bev) is a monoclonal antibody against VEGF. We theorized that combining the two agents would have synergistic therapeutic effects. Methods: Eligible pts had advanced solid tumors, good end organ function, and PS ≤ 1. A phase I dose-escalation study (cohort 1) used sor 200 mg po BID, and bev 5 mg/kg q2 wks IV (dose level, DL1) or 10 mg/kg (DL2). After DLT was reached, DL4 was added to cohort 1 which tested sor 200 mg po BID on days 1–5 q wk with bev IV 5 mg/kg q 2 wks in an attempt to minimize toxicity. Cohort 2 is an expansion phase at MTD (DL1: sor 200 mg po BID daily with bev IV 5 mg/kg), randomized to start with single drug for 4 wks. Cohort 2 has extensive translational endpoints, including imaging. Results: 34 pts have enrolled, 16 in cohort 1 and 18 in cohort 2. Tumor types include ovarian cancer (13), melanoma (4), and renal cell carcinoma (3). The median age was 58 yrs (30–76); pts received a median of 6.5 (1–15) prior regimens. In cohort 1, 3/16 pts had PR (19%; duration 4, 5+, 12+ mos), all with ovarian cancer, and 11/16 had stable disease (SD; 69%; 3+ - 13+ mos). 10/13 assessable cohort 2 pts had SD (77%; 3+ - 6.5+ mos). The most common DL1 AEs Gr ≥ 2 were hypertension (HTN; 6/6) and hand-foot syndrome (4/6). Other Gr 3 AEs in DL1 were leukopenia and infection (2; 2). DLT was reached at DL2 when 2/6 patients developed Gr 3 proteinuria (4, 5 gm/24 hr) and 3/6 developed uncontrolled Gr 3 HTN. Dose reduction on daily sor (DL1 and DL2) occurred for 11/12 pts at a median of 2 cycles, but is delayed on the intermittent schedule (DL4). In all pts, common Gr 1–2 AEs were elevated AST/ALT (18), rhinorrhea (12), fatigue (10), and anorexia (4). 4 pts developed Gr 2–3 diarrhea and 4 Gr 2–3 nausea/vomiting. Gastrointestinal fistulae occurred in two pts with PR, occurring within 4 wk of initiation of therapy, both in areas of tumor regression. Serial PET and DCE-MRI results and proteomic signal pathway analysis will be reported. Conclusions: The combination of sorafenib and bevacizumab appeared to increase both clinical effect and toxicity at below recognized single agent doses. Sor 200 mg po BID d1–5 qwk and bev of 5 mg/kg q2 wks is suggested for further study, pending further dose escalation. No significant financial relationships to disclose.
Regulation of the renal Na
Authors: S K Mujais, N A Nora, Y Chen
Journal: Journal of the American Society of Nephrology (1993)

In male Sprague-Dawley rats, the effects of exogenous high physiologic levels of progesterone simulating those observed in pregnancy (5 mg/day) on Na:K pump activity (picomoles per millimeter per hour) in microdissected nephron segments were evaluated. In adrenal-intact rats, progesterone led to a generalized decrease in Na:K pump activity in proximal convoluted tubule from 2,524 +/- 61 to 741 +/- 41 (71% reduction; P < 0.01), medullary thick ascending limb (MAL) from 4,793 +/- 217 to 2,000 +/- 133 (59% reduction; P < 0.01), and cortical collecting tubule (CCT) from 1,141 +/- 69 to 591 +/- 133 (49% reduction; P < 0.01). This effect was similar in magnitude to the decline observed with adrenalectomy alone. In adrenalectomized rats, progesterone had no further inhibitory effect on the pump in MAL (2,172 +/- 66 versus 2,312 +/- 71) or CCT (493 +/- 58 versus 530 +/- 31) but led to a modest decline in Na:K pump activity in the proximal convoluted tubule (from 1,136 +/- 88 to 528 +/- 31; P < 0.01). In adrenal-intact rats, a high K diet for 7 days led to an increase in CCT Na:K pump activity from 1,141 +/- 69 on a normal potassium diet to 2,224 +/- 33 pmol/mm per h (P < 0.001). Progesterone treatment reduced basal Na:K pump activity in CCT, and concurrent progesterone treatment blunted the stimulatory effect of K adaptation on the pump (973 +/- 68 pmol/mm per h; P < 0.001 versus untreated).(ABSTRACT TRUNCATED AT 250 WORDS)
Blocking c-Met–mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors
Authors: Yi Du, Hirohito Yamaguchi, Yongkun Wei, Jennifer L Hsu, Hung-Ling Wang, Yi-Hsin Hsu, Wan-Chi Lin, Wen-Hsuan Yu, Paul G Leonard, Gilbert R Lee, Mei-Kuang Chen, Katsuya Nakai, Ming-Chuan Hsu, Chun-Te Chen, Ye Sun, Yun Wu, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Chung-Hsuan Chen, Morag Park, Philip Jones, Gabriel N Hortobagyi, Mien-Chie Hung
Journal: Nature Medicine (2016)
Abstract 17900: Coronary Artery Plaque Burden and Stenosis by Cardiovascular CT Correlate with Peripheral Gene Expression in 614 Patients: Results from the PREDICT and COMPASS Studies
Authors: Szilard Voros, William Kraus, Matthew J Budoff, Michael Elashoff, James Wingrove, Gregory Thomas, Steven Rosenberg
Journal: Circulation (2012)

Background. We previously validated a composite peripheral blood gene expression score (GES) based on age, sex and 23 genes measured by real-time PCR to detect obstructive coronary artery disease (...
Distribution of the molossinus allele of Sry, the testis-determining gene, in wild mice.
Authors: C M Nagamine, T Shiroishi, N Miyashita, K Tsuchiya, H Ikeda, N Takao, X L Wu, M L Jin, F S Wang, A P Kryukov
Journal: Molecular Biology and Evolution (1994)

When the Y chromosome of the laboratory inbred mouse strain C57BL/6 (B6) is replaced by the Y of certain strains of Mus musculus domesticus, testis determination fails and all XY fetuses develop either as hermaphrodites or XY females (XY sex reversal). This suggests the presence of at least two alleles of Sry, the male-determining gene on the Y:M. m. domesticus and B6. The B6 Y chromosome is derived from the Japanese house mouse, M. m. molossinus and therefore carries a molossinus Sry allele. As a first step to determine how the molossinus Sry allele evolved, its distribution pattern was determined in wild mice. The cumulative data of 96 M. musculus samples obtained from 58 geographical locations in Europe, North Africa, and Asia show the molossinus Sry allele is restricted to Japan and the neighboring Asian mainland and confirm that Japanese M. m. molossinus mice were derived in part from a race of M. m. musculus from Korea or Manchuria. Sry polymorphisms, as illustrated by the molossinus Sry allele, can serve as molecular markers for studies on the evolution of wild M. musculus populations and can help determine the role sex determination plays in speciation.
Association of Occupation as a Physician With Likelihood of Dying in a Hospital
Authors: Saul Blecker, Norman J. Johnson, Sean Altekruse, Leora I. Horwitz
Journal: JAMA (2016)

Although most people report a preference to die at home vs at a medical facility, most deaths occur in a hospital or nursing home. Some articles have proposed that physicians die after receiving less intensive medical care and in a manner more consistent with end-of-life preferences than the general population, although studies on this topic are lacking. This study compared location of death for physicians with that of other clinicians, non–health care professionals with similar education levels, and the general population.