tbuckley/cabot-search huggingface dataset:
Predicting prostate cancer specific mortality following biochemical recurrence after radical prostatectomy
Authors: S. J. Freedland, E. B. Humphreys, L. A. Mangold, M. Eisenberger, P. C. Walsh, A. W. Partin
Journal: Journal of Clinical Oncology (2005)

4546 Background: The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) can be long, but variable. Better predictive models are needed to identify men early who are at high-risk for CaP death for aggressive salvage treatment as well as to identify men who are at low-risk for CaP death and can be safely observed. We sought to define risk factors for CaP specific mortality following RP and develop tables to risk stratify for CaP specific survival. Methods: We retrospectively studied 5,096 patients treated with RP between 1982 and 2000 of which 379 experienced a BCR and had at least 2 PSA values available after BCR separated by at least 3 months in order to calculate a PSA doubling time (PSADT). Multivariable Cox proportional hazards analysis was used to determine the significant predictors of CaP specific mortality. Results: With a median follow-up of 10.3 yrs after BCR (range 1–16 yrs) the CaP specific survival was 55%. On multivariable analysis, pathological Gleason sum (p=0.002), time from RP to BCR (p=0.02), and PSADT as a continuous variable (p<0.001) were all significant independent predictors of time to CaP death. Using these three variables, the 5-, 10-, and 15-year risk of CaP specific survival can be estimated. The 15-year risk of CaP specific survival is shown in the table. Conclusions: Clinical parameters (PSADT, pathological Gleason sum, and time from RP to BCR) can help risk stratify patients for CaP death following BCR after RP. No significant financial relationships to disclose.
Abstract 19209: Ectonucleoside Triphosphate Diphosphohydrolase-1 (cd39) Attenuates Expression f of P-Selectin Glycoprotein Ligand-1 in Hypoxic Raw Cells via Hif-1{alpha}
Authors: Hui Liao, Amy E Baek, David J Pinsky
Journal: Circulation (2012)

CD39 is a transmembrane enzyme that phosphohydrolyzes ATP and ADP to AMP. CD39 inhibits platelet reactivity and inflammation and thus limits platelet accumulation and leukocyte transmigration to si...
Efficacy of breast MRI in elderly women
Authors: J. Yu, E. Morris, A. Park, H. Cody, M. L. Gemignani
Journal: Journal of Clinical Oncology (2007)

608 Background: Breast MRI is useful in evaluating extent of disease and screening of high risk patients, especially younger patients with dense breasts. The utility of MRI in the elderly population is currently unknown. The purpose of this study was to review the use of breast MRI and MRI findings in elderly women. Methods: Retrospective review identified women over the age of 70 who underwent breast MRI at our institution between 11/2000 and 12/2005. Clinicopathologic features, MRI results and mammograms (MMG) were reviewed. Results: 228 patients were identified. The mean age was 73.5 years (range 70–91). Forty-three patients (19%) had no history of breast cancer, 99 (43%) had a history of breast cancer, and 86 (38%) had a current diagnosis of breast cancer at the time of MRI. Ninety-two patients (40%) underwent MRI for screening, 49 (21%) as further workup for an abnormal MMG or physical finding, and 78 (34%) for extent of disease assessment. MRI found 49 additional sites of abnormality and 15 additional cancers (14% false positive). Five cancers were detected in women with no current diagnosis of cancer. In patients with a diagnosis of cancer at the time of MRI, 10 additional cancers were found: 7 in the contralateral breast and 3 additional ipsilateral sites. Conclusions: MRI detected an additional 15 mammographically occult breast cancers in this population of women over the age of 70. MRI was efficacious in screening as well as evaluating extent of disease, with a relatively low false-positive rate of 14%. Breast MRI is a useful tool in the evaluation of elderly patients; further study in the use of MRI for screening in this population is needed. [Table: see text] No significant financial relationships to disclose.
A 13-Gene Panel Targeted To Investigate CLL By Next-Generation Amplicon Deep-Sequencing Can Be Successfully Implemented In Routine Diagnostics
Authors: Alexander Kohlmann, Andreas Roller, Andreia Albuquerque, Sabrina Kuznia, Sandra Weissmann, Sabine Jeromin, Wolfgang Kern, Claudia Haferlach, Susanne Schnittger, Torsten Haferlach
Journal: Blood (2013)
Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial
Authors: Ludwig Kappos, Giancarlo Comi, Hillel Panitch, Joel Oger, Jack Antel, Paul Conlon, Lawrence Steinman, Giancarlo Comi, Ludwig Kappos, Joel Oger, Hillel Panitch, Alexander Rae-Grant, John Castaldo, Nancy Eckert, Joseph B. Guarnaccia, Pamela Mills, Gary Johnson, Peter A. Calabresi, Carlo Pozzilli, Stefano Bastianello, Elisabetta Giugni, Tatiana Witjas, Patrick Cozzone, Jean Pelletier, Dieter Pöhlau, Horst Przuntek, Volker Hoffmann, Christopher Bever, Eleanor Katz, Michel Clanet, Isabelle Berry, David Brassat, Irene Brunet, Gilles Edan, Pierre Duquette, Ernst-Wilhelm Radue, Dagmar Schött, Carmen Lienert, Alice Taksaoui, M. Rodegher, M. Filippi, Alan Evans, Pierre Bourgouin, Alex Zijdenbos, Shawki Salem, Nicholas Ling, David Alleva, Eric Johnson, Amitabh Gaur, Paul Crowe, Xin-Jun Liu
Journal: Nature Medicine (2000)
Abstract 17001: Is There Cytomegalovirus Disease After Prophylaxis?
Authors: Helen C Huang, Jignesh Patel, David H Chang, Zhe Yu, Frank Liou, Jamie Yabuno, Michelle Kittleson, Babak Azarbal, Lawrence Czer, Phillip Zakowski, Jon Kobashigawa
Journal: Circulation (2014)

Purpose: Cytomegalovirus (CMV) disease (specific organ involvement) is a significant cause of morbidity and mortality in orthotopic heart transplantation (OHT). CMV disease is reported to increase the development of cardiac allograft vasculopathy (CAV). The duration of CMV prophylaxis in recipients is dependent on their CMV serostatus in relation to the donors. However, the effective duration of CMV prophylaxis post-transplant remains unclear. Methods: Between 2007 and 2012, 267 OHT patients were divided into four groups based on the CMV serostatus of the donors (D) and recipients (R): D+/R-, D+/R+, D-/R+, D-/R-. CMV prophylaxis was given for up to one year in D+/R- patients, up to six months in D+/R+ and D-/R+ patients, and three months in D-/R-. Endpoints included two-year overall survival and freedom from development of CMV disease, CAV, and NF-MACE (defined as myocardial infarction¼..) after the end of CMV prophylaxis in the four study groups, respectively. Results: After the end of respective CMV prophylaxis in the four study groups, there was no significant difference in two-year overall survival and freedom from development of CMV disease, CAV, and NF-MACE among the four groups. Of the D+/R- group, one patient developed CMV gastritis, one patient CMV pneumonia, and one patient CMV colitis. Two patients developed CMV colitis in the D+/R+ group. Conclusions: The current recommendations for the duration of CMV prophylaxis appear to be satisfactory in preventing CMV disease and complications after the end of prophylaxis.
A phase Ia study of MPDL3280A (anti-PDL1): Updated response and survival data in urothelial bladder cancer (UBC).
Authors: Daniel Peter Petrylak, Thomas Powles, Joaquim Bellmunt, Fadi S. Braiteh, Yohann Loriot, Cristina Cruz Zambrano, Howard A. Burris, Joseph W. Kim, Siew-leng Melinda Teng, Jean-Marie Bruey, Priti Hegde, Oyewale O. Abidoye, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2015)

4501 Background: PD-L1 may contribute to immune escape in UBC, a disease of high mutational complexity and immunogenicity. MPDL3280A was designed to restore T cell–mediated antitumor activity by blocking PD-L1 binding to PD-1 and B7.1 receptors. Methods: Previously treated, metastatic UBC pts were enrolled in an expansion cohort and received 15 mg/kg or 1200 mg IV MPDL3280A q3w. Efficacy-evaluable pts had ≥ 12 wk of follow-up (dosed by Jun 9, 2014; Sep 2, 2014 cutoff). ORR was assessed by RECIST v1.1 (unconfirmed), and archival biopsies were centrally evaluated for PD-L1 tumor-infiltrating immune cell (IC) expression by IHC. In-tumor gene expression and peripheral biomarkers were assessed as exploratory analyses in a subset of pts. Results: Updated analyses include 85 efficacy-evaluable, selectively enrolled UBC pts; 46 were PD-L1 IHC 2/3, 38 were IHC 0/1 and 1 had unknown IHC status. Median age was 66 y (36-89 y), and 75% were male. Baseline visceral mets were present in 77% of pts; 98% received ≥ 1 prior therapy (eg platinum in 93%). The ORR for IHC 2/3 pts was 46% (95% CI 31-61%; 6 CRs, 15 PRs), and for IHC 0/1 pts was 16% (95% CI 6-31%; 6 PRs) with median response durations not yet reached (IHC 2/3 pts, 0+ to 54+ wk; IHC 0/1 pts, 4+ to 33+ wk). Median PFS was 24 wk (95% CI 12-NE) for IHC 2/3 pts and 8 wk (95% CI 6-12 wk) for IHC 0/1 pts. 24-wk OS rates for IHC 2/3 and 0/1 pts were 85% (95% CI 74-96%) and 71% (95% CI 54-88%), respectively, with the medians not yet reached (3 to 72+ wk and 2+ to 51+ wk, respectively). Pts with visceral mets had ORRs of 32% (IHC 2/3: 3 CRs, 7 PRs; n = 31) and 12% (IHC 0/1: 4 PRs; n = 33). Median safety follow-up was 16 wk (3-73 wk). Drug-related AEs occurred in 64% of 87 safety-evaluable pts (most often fatigue, asthenia, nausea); 8% had a related G3-4 AE. 12% of pts had an immune-related AE. No related deaths were seen. Responders had lower myeloid gene expression at baseline (eg Cox-2, IL8; IL1B) and decreased circulating inflammatory and tumor markers (eg CRP; HCG, CA 19-9, CA-125) by cycle 2. Conclusions: MPDL3280A was well tolerated and had durable activity in UBC pts. Response, PFS and OS data are promising for IHC 2/3 and IHC 0/1 UBC pts vs historic controls. Response also correlated with in-tumor and blood-based biomarkers. Clinical trial information: NCT01375842.
Recommendations for HIV Testing Services for Inpatients and Outpatients in Acute-Care Hospital Settings
Journal: JAMA (1993)

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Role of interferon-γ in tumor necrosis factor-α-mediated increase of lung microvascular endothelial cells
Authors: Yoshio Nakajima, Yutaka Nakamura, Naomi Suzuki, Yu Utsumi, Nobuhito Sasaki, Kohei Yamauchi
Journal: European Respiratory Journal (2012)

Background : Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease in which tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) are overexpressed and have been suggested to play pathogenic roles. The effect of these agents on angiogenesis in the lung tissues of COPD is unknown.  Objective : To examine the effects of these mediators on lung endothelial cells (ECs).  Methods :  Nrf2  knockout mice were exposed to cigarette smoke (CS) for 4 weeks, and the down-regulated genes referring to vascularity in the whole lung were identified by microarray analysis. To confirm the protein levels, which were indicated in the microarray data, co-cultivation of lung fibroblasts with ECs in the presence of TNF-α and IFN-γ was performed, thereafter ECs were submitted to an examination of protein levels expression using immunoblotting or immunocytochemistry.  Results : Microarray analysis data have shown that the mRNA expression of angiomotin-like protein 1 (AmotL1) decreased in response to CS when compared to no exposure to CS. TNF-α enhanced vascular endothelial growth factor (VEGF) production by cultured lung fibroblasts, however, vascularity was decreased when treated with IFN-γ. In addition, IFN-γ induced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors on ECs and attenuated the expression of AmotL1 localized to endothelial cell-cell junctions.  Conclusions : These results suggest that IFN-γ acts as anti-angiogenesis by regulating the expression of TRAIL receptors and AmotL1 on ECs, which were induced by the enhanced VEGF production by TNF-α-stimulated lung fibroblasts.
Spatial distribution of synchronous colorectal adenomas reflect field cancerization effect
Authors: Kevin Clarke, Mark Mattar, Paul Frankel, David Z. J. Chu, Yun Yen
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1601 

Extrarenal production of 1,25-dihydroxyvitamin D3 in human colonic epithelium has recently been suggested as a physiological defense mechanism against colorectal cancer. Since both vitamin D receptor as well as 1,25-dihydroxyvitamin D3 (CYP27 B1) protein demonstrate increased expression in early colorectal tumors compared to adjacent normal epithelium, an autocrine mode of growth control by elevated mucosal 1,25-dihydroxyvitamin D3 levels has been postulated. Estrogen administration also appears to reduce colorectal cancer risk although mechanisms of action have not been clarified. Estrogen increases the intestinal absorption of calcium, and our recent findings suggest it may enhance the activity of vitamin D3 in colorectal epithelium. In this study we evaluated the effects of estradiol administered to 10 post-menopausal women who were maintained on controlled nutritional intakes, with estradiol given in amounts sufficient to raise serum values to premenopausal levels for 4 weeks. Rectal biopsies were taken before and after administration of estradiol. Following estradiol administration, 1α-hydroxylase mRNA, determined by real-time-PCR increased significantly (p<0.01), without changes occurring in CYP24 or caspase 3 mRNA. Immunohistochemical measurements confirmed that CYP27 B1 was present in rectal epithelial cells. Trends toward correlations between CYP27 B1 and CYP24, as well as between CYP27 B1 and caspase 3 mRNA were seen. No significant changes were observed in ERα, ERβ and vitamin D receptor mRNA, nor in circulating 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3. We conclude that estrogen administration in protecting against colorectal neoplasia modifies the metabolism of vitamin D3 in colorectal epithelium, resulting in increased levels of 1,25-dihydroxyvitamin D3 the active intracellular form of vitamin D. Since vitamin D has been shown to decrease colorectal cancer risk estrogen may function at least in part by its ability to increase the activity of vitamin D and its protective effect against colon cancer.
Impact of extent of resection of glioblastoma multiforme (GBM) in the era of chemoradiation
Authors: B. J. Slotman, W. S. Eppinga, J. C. Reijneveld, D. P. Noske, J. Buter, L. M. Braam, F. J. Lagerwaard
Journal: Journal of Clinical Oncology (2009)

e13029 Background: Controversy remains regarding the impact of the extent of resection (EOR) on survival in patients with GBM (Sanai 2008). The main reason for this is the fact that most studies were based on the surgeon's estimate of the EOR, which is known to be unreliable, rather than early postoperative MRI scans (po-MRI). Data for the current standard of postoperative chemo-radiotherapy (CTRT) have recently been reported, but suffer from the same limitation (Gorlia 2008). We studied the prognostic impact of the EOR using early (&lt;72 hours) po-MRI scans in a cohort of GBM patients treated with CTRT in a single center. Methods: The results of 48 consecutive patients (35 male, 13 female; age 18–73 yrs) treated with surgery, followed by concurrent CTRT (60 Gy plus temozolomide) and adjuvant temozolomide were assessed with respect to survival and relapse patterns. EOR was determined by both the surgeon's estimation and early po-MRI scans that were available in all but two patients. EOR was categorized as biopsy (N = 3), partial resection (N = 24), major resection (N = 11; i.e., total resection according to the surgeon's report, but residual tumor on po-MRI), and total resection (N = 10; i.e. no residual tumor on po-MRI). Results: Median overall survival of the entire cohort was 18.9 months, and EOR was the only significant prognostic factor (p = 0.02) on multivariate analysis, which also included age, gender, performance, and radiotherapy target volume. 2-year survival rates improved significantly with increasing EOR, with 0%, 18.9%, 68.6%, and 100% for biopsy, partial-, major-, and total resection, respectively. In-field progression was the predominant pattern of failure in 27 out of 30 patients (90%) with a recurrence. Time to neurological progression (TNP) was significantly correlated with EOR (p &lt; 0.001). Median TNP was 3.0 months for biopsy, 7.0 months for partial resection, 20.5 months for major resection, and was not reached for total resection. Conclusions: With the use of more effective local therapy in the form of surgery and CTRT, the prognostic impact of the EOR on survival appears to be higher than previously reported. This should be accounted for in future trials. No significant financial relationships to disclose.
Final safety results from the post-marketing survey (PMS) of bevacizumab (BV) in Japanese colorectal cancer patients
Authors: T. Doi, K. Shirao, H. Uetake, K. Hatake, Y. Takahashi, S. Nihira
Journal: Journal of Clinical Oncology (2009)

e15035 Background: BV was approved in Apr. 2007 in Japan in patients (pts) with advanced colorectal cancer. The number of pts in Japanese clinical trials were extremely limited. Therefore, the Japanese MHLW (Ministry of Health Labor and Welfare) required Chugai to initiate a PMS in all pts after the launch as a post-approval commitment to evaluate the incidence of adverse drug reactions (ADRs) in Japanese pts. This is the first safety well controlled large cohort PMS in Asian pts. Objectives: To assess the use of BV in clinical practice and to evaluate the incidence of ADRs in Japanese pts. Methods: All pts who were treated by BV were registered before initial administration since the launch of BV in Jun. 2007. Follow-up period was 6 months. Results: Between Jun. and Nov. 2007, 2712 pts were registered from 574 institutions, and 2699 pts were eligible for the safety analysis. Pts characteristics were colon/rectum/colon and rectum cancer; 1580/1105/14, M/F; 1632/1067, median age; 61 (15–86), ECOG P.S.0/1/2/3; 2192/477/28/2, combination chemotherapy regimens with BV (FOLFOX / FOLFIRI /5-FU LV /IFL/Other); 1716/778/141/54/10, treatment lines (1st, 2nd, 3rd and more); 1238/1418/43. Of 2699 pts, ADRs were reported in 1589 pts (58.9%) with serious ADRs in 381 pts (14.1%). The common BV ADRs of interest were hypertension; 13.0%, hemorrhage; 11.3% (epitaxis;7.3%), proteinuria; 4.1%. Other ADRs were wound healing complications 1.2%, GI Perforation 0.9%, and thromboembolism (arterial/venous); 0.4 /1.3%. No Japanese-specific ADRs were observed. Conclusions: These safety results are consistent with those reported in International observational studies (BRiTE, Hedrick et al. JCO 2006;24(Jun 20 Suppl.):abstr 3536; First BEAT, Berry et al. JCO 2008;26(May 20 Suppl):abstr 4025). [Table: see text]
Open-label study of pemetrexed alone for chemonaive patients and pre-treated patients with malignant pleural mesothelioma: Outcomes of the International Expanded Access Program (EAP)
Authors: P. Taylor, J. von Pawel, B. Castagneto, G. Dark, M. Marangolo, R. van Klaveren, J. van Meerbeeck, S. Adachi, J. Blatter
Journal: Journal of Clinical Oncology (2007)

7709 Background: In a previous phase II study of chemonaive malignant pleural mesothelioma (MPM) patients (pts), single-agent pemetrexed (P) resulted in a 14.1% response rate (RR) and median survival of 10.7 mos (95% CI 7.7–14.5) (Scagliotti 2003). Likewise, the P arm in a phase III study of pre-treated MPM pts yielded an 18.7% RR (40.7% with stable disease, SD) and median survival of 8.4 mos (95% CI 6.2–10.5) (Jassem 2006). The EAP provided 3311 MPM pts with access to P alone, P plus cisplatin, or P plus carboplatin in 13 countries. In this abstract we report on the safety and efficacy data of those MPM pts treated with P alone. Methods: Eligible pts had histologic or cytologic diagnosis of MPM and were either chemonaïve or previously treated with =1 line(s) of chemotherapy. Pts pre-treated with P were allowed if they had experienced clinical benefit from the prior P. Treatment consisted of P (500 mg/m 2 ) once (day 1) every 21 days with standard pre-medication of vitamin B 12 , folic acid, and dexamethasone. Investigator-determined response (RR) and survival data (with censoring) were recorded at the end of study participation. Myelosuppression data (CTC) were also collected. Results: 812 MPM pts (319 chemonaïve; 493 pre-treated) received =1 dose of P and were evaluated for safety, and 643 pts (247 chemonaïve; 396 pre-treated) were evaluated for efficacy (RR and survival). In chemonaïve pts with MPM, the median age was 69 yrs (range: 39–87 yrs), 78.1% were male, and 71.6% had a KPS ≥80 (of the 93% who had PS evaluated). In pre-treated pts with MPM, the median age was 63 yrs (range: 31–85 yrs), 75.9% were male, and 74.5% had a KPS ≥80 (of the 95% who had PS evaluated). Both groups received a median of 4 cycles (chemonaive group range 1–18; pretreated group range 1–23). See the table for efficacy and safety data. Conclusions: Results of the EAP confirm earlier phase II and phase III studies. No significant financial relationships to disclose. [Table: see text]