tbuckley/cabot-search huggingface dataset:
Phase II study of the angiogenesis inhibitor AZD2171 in first line, progressive, unresectable, advanced metastatic renal cell carcinoma (RCC): A trial of the PMH Phase II Consortium
Authors: S. S. Sridhar, S. J. Hotte, M. J. Mackenzie, C. Kollmannsberger, M. A. Haider, G. R. Pond, E. X. Chen, R. Srinivasan, S. P. Ivy, M. J. Moore
Journal: Journal of Clinical Oncology (2007)

5093 Background: AZD2171 is an oral, highly potent inhibitor of VEGFR1, VEGFR2, with activity also against cKit, PDGFRβ and Flt-4. We conducted a two-stage, phase II trial of AZD 2171 in first line advanced RCC, with a planned sample size of 37 pts, and a primary endpoint of tumor control rate (PR+SD). Methods: Pts had progressive, unresectable, advanced RCC, measurable disease, a performance status of ≤ 2 and no prior cytokine or antiangiogenic therapy. Pts received AZD2171 45 mg orally, daily, continuously (1cycle = 4wks) as monotherapy. Disease was evaluated with cross-sectional imaging every 8 wks. Functional DCE-MRI imaging was performed at baseline, 24h and 28d after the first dose. Pharmacokinetic studies were performed on day 8, 15 and 28. Results: From January- November 2006, 24 pts median (range) age 62 (44–80), were entered on study. Sixteen pts evaluable for response, 7 too early; 23 pts evaluable for toxicity; 1 pt inevaluable due to withdrawal. There have been 6 confirmed PR (6/16=38%), 1 unconfirmed PR, 5 SD, 4 PD. Tumor control rate 12/16=75%. Seventeen patients remain on treatment, 6 now off due to PD and 1 off due to consent withdrawal. Eighteen patients had dose reductions due to toxicity. Most common toxicities (any grade) were fatigue (21pts), voice alteration (14pts), hypertension (12pts), diarrhea (15pts), and increased creatinine (10pts). Common (&gt;5% of cycles) grade 3+ adverse events were hypertension (5pts), joint pain (4pts), fatigue (7pts), dyspnea (2pts), increased ALT (2pts) and anorexia (3pts). Preliminary pK analysis is available on 6 patients: median (range) Tmax: 2hr (2- 6hr), Cmax: 107.8± 29.8 ng/ml, T 1/2 : 12.1 ± 2.2hr. Conclusion: AZD2171 is an active agent in first line, progressive, unresectable, advanced RCC with a partial response rate of 38% and tumor control rates of 75%. Accrual is ongoing with pharmacokinetics, functional imaging, and correlative studies. This agent warrants further investigation. No significant financial relationships to disclose.
Patient burden, resource utilization, and treatment outcomes of grade 3/4 chimeric or humanized monoclonal antibody-associated infusion reactions
Authors: B. V. Fortner, L. Zhu, W. Tsong, C. Burns, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2006)

18544 Background: Treatment with chimeric and humanized monoclonal antibodies (MAb) is associated with infusion reactions that may limit their usage. Despite growing use and importance of MAb regimens, there is a dearth of information describing MAb-associated infusion reactions (MAb-IRs) outside of clinical trials. The purpose of this study is to describe the patient burden, resource utilization, and treatment outcomes of grade 3 and 4 chimeric or humanized MAb-IRs in a community sample. Methods: We obtained a convenience sample of charts from 8 US outpatient oncology practices for patients who were treated between Feb 2004 to Dec 2005 with bevacizumab, cetuximab, or rituximab and experienced a grade 3 or 4 MAb-IR during their treatment. Results: Data were abstracted for 30 (n = 3 bevacizumab, 4 cetuximab, 23 rituximab) adult cancer patients who experienced a grade 3 (26, 87%) or grade 4 (4, 13%) MAb-IR. Of these, 63% (19) of patients were male; the mean age was 62 yrs. Twenty (67%) of these patients received premedication before experiencing their grade 3/4 MAb-IR. Twenty (67%) MAb-IRs occurred during the first cycle, 6 (20%) occurred at or beyond cycle 4. The most common MAb-IRs were rigors/chills (13, 43%), bronchospasms (5, 17%), and dyspnea (6, 20%). Grade 4 MAb-IRs were sinus bradycardia (2), severe pain (1), and apnea, seizure, ventricular arrhythmia (1). The consequences of MAb-IRs required increased utilization of resources as shown in the table . Additionally, 9 (30%) required antihistamines, 19 (63%) corticosteroids, 1 (3.3%) an H2 blocker, 3 (10%) an H3 blocker, 4 (13%) epinephrine, 14 (47%) intravenous fluids, 4 (13%) antiemetics, 10 (33%) narcotics, and 17 (57%) oxygen. Conclusions: Grade 3 and 4 chimeric or humanized MAb-IRs result in substantial patient symptom burden, numerous clinical interventions, and changes to subsequent MAb treatment. Further analyses will be required to estimate the direct medical costs and long term consequences of MAb-IRs, and the impact of less severe infusion reactions. [Table: see text] [Table: see text]
Role of the p16 tumor suppressor gene in cancer.
Authors: W H Liggett, D Sidransky
Journal: Journal of Clinical Oncology (1998)

Since its discovery as a CDKI (cyclin-dependent kinase inhibitor) in 1993, the tumor suppressor p16 (INK4A/MTS-1/CDKN2A) has gained widespread importance in cancer. The frequent mutations and deletions of p16 in human cancer cell lines first suggested an important role for p16 in carcinogenesis. This genetic evidence for a causal role was significantly strengthened by the observation that p16 was frequently inactivated in familial melanoma kindreds. Since then, a high frequency of p16 gene alterations were observed in many primary tumors. In human neoplasms, p16 is silenced in at least three ways: homozygous deletion, methylation of the promoter, and point mutation. The first two mechanisms comprise the majority of inactivation events in most primary tumors. Additionally, the loss of p16 may be an early event in cancer progression, because deletion of at least one copy is quite high in some premalignant lesions. p16 is a major target in carcinogenesis, rivaled in frequency only by the p53 tumor-suppressor gene. Its mechanism of action as a CDKI has been elegantly elucidated and involves binding to and inactivating the cyclin D-cyclin-dependent kinase 4 (or 6) complex, and thus renders the retinoblastoma protein inactive. This effect blocks the transcription of important cell-cycle regulatory proteins and results in cell-cycle arrest. Although p16 may be involved in cell senescence, the physiologic role of p16 is still unclear. Future work will focus on studies of the upstream events that lead to p16 expression and its mechanism of regulation, and perhaps lead to better therapeutic strategies that can improve the clinical course of many lethal cancers.
Temporal trends and variability of colonoscopy performance in a gastroenterology practice
Authors: Chantal le Clercq, Rick Mooi, Bjorn Winkens, Bouke Salden, C. Bakker, Annick van Nunen, Eric Keulen, Rogier de Ridder, Ad Masclee, Silvia Sanduleanu
Journal: Endoscopy (2016)

<b>Background and study aim</b>: Quality measures for colonoscopy are operator dependent and vary. It is unclear whether quality measures change over time. In this study, time-dependent variation in colonoscopy performance was examined in a gastroenterology practice. <b>Patients and methods: </b>Colonoscopy and histopathology records that were collected at three hospitals (one university and two non-university hospitals) over three time periods (2007, 2010, and 2013) were reviewed. Data from colonoscopists performing at least 100 procedures per year were analyzed. Inter-colonoscopist variation in performance (i. e. adjusted cecal intubation rate [aCIR], adenoma detection rate [ADR], advanced ADR, mean adenomas per procedure [MAP], proximal ADR, nonpolypoid ADR, and serrated polyp detection rate) were examined using coefficients of variation. Logistic regression analyses were also performed, adjusting for covariates. <b>Results: </b>A total of 23 colonoscopists performing 6400 procedures were included. Overall, the mean aCIR, ADR, MAP, and proximal ADR improved significantly over time, from 91.9 %, 22.5 %, 0.37, and 10.2 % in 2007 to 95.3 %, 25.8 %, 0.45, and 13.4 %, respectively, in 2013 (<i>P</i> < 0.05). The inter-colonoscopist variation in ADR decreased from 37 % in 2007 to 15 % in 2013 (<i>P</i> < 0.05). In the non-university hospitals, mean values for quality measures increased significantly over time, whereas they remained stable in the university hospital. <b>Conclusions: </b>Variability in performance among colonoscopists decreased significantly within the gastroenterology clinical practice. Core quality measures improved over time, mainly through improvement of the lower performers. Measurement of inter-colonoscopist variation in performance helps to identify factors that stimulate or hinder performance, and forms the basis for interventions. Trial registration: <ext-link href="http://http://www.trialregister.nl.">http://www.trialregister.nl.</ext-link>
Normale und Pathologische Anatomie der Haut II
Authors: Thomas P. Kugelman
Journal: JAMA (1965)

ABSTRACT Lehrbuch der Haut- und Geschlechtskrankheiten. By Walther Schonfeld, 9th ed. 553 pp, 392 illus. 48 marks. Thieme Verlag, West Germany (Intercontinental Medical Book Corp., 381 Park Ave S. New York 16), 1965An interesting contrast in the virtues of Germanic pedagogy is provided by these two new editions. The supplement volume to Jadassohn's monumental Handbuch of 30 years ago illustrates the continuing tradition and flair for encyclopedic scholarship. The vast scope, authority, and scrupulous attention to detail which characterized the original work are well preserved in this revision of the sections on gross anatomy, pigmentation, general cutaneous pathology, and lymph node pathology. Approximately 80% of the space is devoted to descriptions of the pathological responses of each tissue component and cell type in the epidermis, dermis, subcutis, and adnexa, respectively. This approach differs from that of the standard histopathology texts in that a disease entity is not discussed as such
Developmental Genetics of Neuroblastoma12
Authors: Alfred G. Knudson, Anna T. Meadows
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Developmental Genetics of Neuroblastoma Get access Alfred G. Knudson, Jr., M.D., Ph.D., Alfred G. Knudson, Jr., M.D., Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Anna T. Meadows, M.D. Anna T. Meadows, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 3, September 1976, Pages 675–682, https://doi.org/10.1093/jnci/57.3.675 Published: 01 September 1976
CAPG and GIPC1: Breast Cancer Biomarkers for Bone Metastasis Development and Treatment
Authors: Jules A. Westbrook, David A. Cairns, Jianhe Peng, Valerie Speirs, Andrew M. Hanby, Ingunn Holen, Steven L. Wood, Penelope D. Ottewell, Helen Marshall, Rosamonde E. Banks, Peter J. Selby, Robert E. Coleman, Janet E. Brown
Journal: JNCI Journal of the National Cancer Institute (2016)

Background:Bone is the predominant site of metastasis from breast cancer, and recent trials have demonstrated that adjuvant bisphosphonate therapy can reduce bone metastasis development and improve survival. There is an unmet need for prognostic and predictive biomarkers so that therapy can be appropriately targeted.
Optimal indications for palliative chemotherapy in elderly patients with metastatic or recurrent gastric cancer.
Authors: Hiroko Hasegawa, Kazumasa Fujitani, Aya Sugimoto, Shoichi Nakazuru, Motohiro Hirao, Toshimasa Tsujinaka, Eiji Mita
Journal: Journal of Clinical Oncology (2015)

207 Background: Gastric cancer is the second causes of cancer-related deaths in the world and its incidence of advanced gastric cancer (AGC) in the elderly is increasing as a result of increased life expectancy. However, elderly patients have been underrepresented in many kinds of chemotherapy clinical trials. Therefore it is difficult to evaluate the efficacy and safety of chemotherapy for elderly patients and select the appropriate patients aged 70 years or older who are likely to benefit from the chemotherapy. Methods: There were 265 patients with primary unresectable or recurrent gastric cancer treated at our institution between April 2007 and March 2014. Of all, 90 patients aged 70 years or older were retrospectively identified. We evaluated the efficacy of the chemotherapy and prognostic significance of clinico-pathologic factors to identify the optimal indications for chemotherapy. Univariate and multivariate analyses were perfomed on the base-line characteristics such as patient’s performance status (PS), gender, chemotherapy regimens, history of gastrectomy, presense of co-morbidity, serum LDH level, serum C reactive protein, and nutritional status, at the initiation of the first-line chemotherapy. Results: The median overall survival time (OS) was 343 days and the median TTF on first-line chemotherapy was 111 days. The toxicity was mild and tolerable. There were no significant difference in overall survival between patients receiving monotherapy and combination therapy. On multivariate analyses, PS 1 or 2 (hazard ratio (HR), 1.883; 95% confidence interval (CI), 1.047–3.390), presence of primary tumor (HR, 1.916; 95% CI, 1.063–3.448) at the initiation of the first- line chemotherapy were identified as significant independent poor prognostic factors for overall survival. Especially in patients aged 75 years or older, only PS was an independent prognostic factor for OS (HR, 3.703; 95% CI, 1.314–9.900). Conclusions: Analysis of our results shows that patients aged 70 years or older with good performance status and absence of primary tumor might achieve clinical benefit from chemotherapy.
Needs satisfaction for cancer patients in an ambulatory chemotherapy service (ACS). An exploratory study
Authors: S. Wbanet, A. Cayuela, L. Bernal, B. Valderrama, M. Valero, M. Ruiz, M. Iglesias, L. Iglesias, J. Moreno, A. M. Casas
Journal: Journal of Clinical Oncology (2006)

18607 Background: ACS are currently the main way for the delivery of Chemotherapy to cancer patients. Aproximately half of them require intravenous chemotherapy and many need two or three separate lines of treatment during their clinical career. How these treatments are delivered will affect their health and quality of life. Appraisal of needs along chemotherapy process enable to identify problems related to health satisfaction status and quality of health care provided. Methods: We have evaluated the perceived needs of patients receiving ambulatory chemotherapy through an “ad hoc” questionnaire of 49 items exploring the following areas: treatment related symptoms, information and communication/interpersonal interaction, psychological, social and spiritual support, economical needs and management of health service. Results: 141 consecutive patients attending the ACS one year after its set up were evaluated. Demographics (age, gender and income), diagnosis and types of Chemotherapy (Adjuvant vs. Palliative) were considered for interrelationships. The most frequent tumors were breast and colorectal carcinoma. More than 50% of the patients reported having controlled symptoms (pain, nausea and vomiting, mucositis etc.). Information needs related to their illness and treatment were satisfied to more than half of the sample, but reported a need for more information about diagnostic procedures and prognosis; 48% perceived shortcomings in communication with their clinicians and 50% believed they received little advice about how cancer affects their sexual behaviour. Most patients (53%) reported not to need pshycological support neither for their family (60%) nor themselves, 83% not needing spiritual support and 50% were satisfied with the economical support they received. With respect to the facilities’ structure, 50% perceived enough intimacy in doctor’s offices and Chemotherapy Room and 64% felt comfortable in the waiting room but 72% perceived waiting too long before being attended by doctor’s and nurses. Conclusions: younger patients and breast cancer diagnosis are among the people that express more unsatisfaction related to the accomplishment of their needs (p &lt; 0.05). No significant financial relationships to disclose.
Motexafin Gadolinium (MGd) induces apoptosis in lymphoma cell lines by redox mechanisms: Rationale for targeted radiation sensitization with <sup>90</sup>Yttrium-zevalin/MGd in relapsed lymphoma
Authors: A. M. Evens, L. Naumovski, R. Miller, L. I. Gordon
Journal: Journal of Clinical Oncology (2004)

3199 Background: MGd is a tumor-selective redox mediator that generates reactive oxygen species such as hydrogen peroxide. MGd enhances the efficacy of ionizing radiation in animal models and is in clinical trials combined with radiation for treatment of solid tumors. We now report the results of MGd activity in various lymphoma cell lines in vitro. These results provide the rationale for an ongoing phase I/II trial combining MGd with 90Yttrium-Zevalin for relapsed non-Hodgkin's lymphoma (NHL). Methods: B-cell lines (HF-1, DHL-4, Ramos), Jurkat and HL60 were cultured in vitro +/- MGd (0–50uM). Cell growth and apoptosis were measured using Annexin-V staining. A modified Fibonacci phase I/II trial is enrolling patients with relapsed NHL to receive combination 90Yttrium-Zevalin with increasing doses of MGd. Patients receive MGd daily days 1 to 4 (with 111Indium-Zevalin) and days 8 to 11 with standard 90Yttrium-Zevalin given day 8. Magnetic resonance imaging (MRI) is used to visualize selective uptake of MGd in tumors. Results: MGd inhibited growth of all cell lines by 60%–80% with an increase in apoptotic cells ranging from 20%–50%. Incubation of HF-1 cells with rituximab alone induced apoptosis in 40% of cells, which increased to over 80% with the addition of MGd. Combination 90Yttrium-Zevalin (0.4 mCi/kg) and MGd (2.5mg/kg) therapy has been well tolerated by the first cohort enrolled/treated. There is one evaluable patient who had a 60% decrease in a 6cm diffuse follicle-center scalp mass ten days following treatment. The mass completely resolved 4 weeks following therapy with associated 80% decrease in bulky follicular lymphoma abdominal disease. A day 4 noncontrast MRI of the scalp mass showed a 30% increase in MRI signal intensity (compared to a pre-MGd scan) indicating selective tumor uptake of MGd. Conclusions: MGd induces apoptosis in various lymphoma cell lines and is additive with rituximab. MGd can be given together with 90Yttrium-Zevalin to achieve targeted radiation sensitization. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pharmacyclics, Inc. Pharmacyclics, Inc. Pharmacyclics, Inc. Pharmacyclics, Inc. Pharmacyclics, Inc. Pharmacyclics, Inc. Pharmacyclics, Inc.
Surrogate endpoints for overall survival (OS) in head and neck squamous cell carcinoma (HNSCC): Evaluation using individual data of 23,737 patients
Authors: S. Michiels, A. Le Maître, M. Buyse, T. Burzykowski, J. Bogaerts, J. B. Vermorken, W. Budach, K. Ang, T. Pajak, J. P. Pignon
Journal: Journal of Clinical Oncology (2007)

6035 Background: The gold standard endpoint in randomized trials of HNSCC is OS. Our objective was to study if event-free survival (EFS) or loco-regional control (LRC) could be good surrogate endpoints to estimate the effect of radiotherapy (RT) and chemotherapy (CT) on OS. This would permit to decrease the duration and cost of the development of new treatments for HNSCC. Methods: EFS is the time from randomization to first event (loco-regional, distant recurrence or death), LRC the time from randomization to first loco-regional event. Individual patient data from two meta-analyses (MARCH; Bourhis, Lancet 2006, MACH-NC; Bourhis, ASCO 2004) were used. At the individual level, the rank correlation coefficient ρ between the surrogate endpoint (EFS or LRC) and OS was estimated from the bivariate distribution of these endpoints. At the trial level, the correlation coefficient R between treatment effects (estimated by log hazard ratios) on the surrogate endpoint and OS was estimated from a linear regression. EFS and LRC would be acceptable surrogates only if the correlation coefficients ρ and R were close to 1. Results: At the individual level, EFS was more strongly correlated with OS than LRC. For RT, treatment effects on both LRC and EFS were strongly correlated with those on OS. For CT, the correlation coefficients between treatment effects on EFS and OS were larger than those between LRC and OS. Conclusions: The preliminary analysis indicates that EFS can be used as a surrogate for OS to evaluate the treatment effect in randomized trials of patients with HNSCC. LRC is a possible alternative in RT alone trials. Unrestricted grants from ARC, LNCC, PHRC, Sanofi-Aventis. [Table: see text] [Table: see text]
Abstract 355: Autologous Cleavage of the GPIbalpha Receptor Promotes Platelet Dysfunction Following Trauma
Authors: Jessica Cardenas, Willa Wang, Lisa Baer, Nena Matijevic, Bryan Cotton, John Holcomb, Charles Wade
Journal: Circulation (2013)

Background: Trauma is the most common cause of death in individuals 0-50 years of age and is responsible for more year of life lost than cancer, heart disease, and stroke combined. One quarter of all trauma patients experience some degree of prolonged hemorrhage due to impaired blood clotting, or trauma-induced coagulopathy (TIC). Protein C activation and hyperfibrinolysis have been proposed as key drivers in developing TIC. While primary hemostasis is mediated by von Willebrand factor (vWF) binding to the GPIbα receptor on the platelet surface, tethering them to damaged endothelium. Whether this interaction is altered in TIC remains unexplored. Data from our laboratory has previously shown a significant reduction in platelet-vWF adhesion over time following injury as measured by platelet aggregation response to ristocetin. The aim of this study was to determine the mechanisms behind defective platelet-vWF adhesion in trauma patients. Methods and Results: We obtained samples from 25 transfused trauma patients on admission and at 3, 5, 12, 24, and 120 hours later. Expression of the GPIbα receptor on the platelet surface and circulating in the plasma was measured by flow cytometry and western blot, respectively. We observed a time-dependent decrease in platelet bound GPIbα receptor expression (p=0.01) which was accompanied by up to a 6-fold increase in GPIbα shed into the plasma. Due to its role in proteolytic regulation of platelet aggregation through cleavage of GPIbα, we then measured expression of tumor necrosis factor-α converting enzyme (TACE). Membrane-bound TACE was analyzed by flow cytometry on platelets and leukocytes. We found a significant increase in platelet-derived TACE compared to healthy controls (p&lt;0.01) and over time in trauma patients (p&lt;0.05). The highest expression of platelet TACE corresponded to the time at which we observed the lowest GPIbα expression and lowest platelet-vWF adhesion in these patients. Conclusions: These data suggest that upregulation of platelet-derived TACE results in increased proteolytic cleavage of the GPIbα receptor and reduced platelet-vWF adhesion. These results have important implications for the use of TACE inhibitors to promote effective primary hemostasis in severely injured patients.
Hepatitis E Virus Does Not Contribute to Hepatic Decompensation Among Patients With Advanced Chronic Hepatitis C
Authors: Niharika Samala, Elizabeth C. Wright, A. Gretchen Buckler, Vanessa Vargas, Kirti Shetty, K. Rajender Reddy, Michael R. Lucey, Harvey J. Alter, Jay H. Hoofnagle, Marc G. Ghany
Journal: Clinical Gastroenterology and Hepatology (2016)