tbuckley/cabot-search huggingface dataset:
Common variants at<i>PRSS1–PRSS2</i>and<i>CLDN2–MORC4</i>loci associate with chronic pancreatitis in Japan
Authors: Atsushi Masamune, Eriko Nakano, Shin Hamada, Yoichi Kakuta, Kiyoshi Kume, Tooru Shimosegawa
Journal: Gut (2015)

To the Editor,

We read with great interest the article by Derikx et al 1 reporting a replication study of the association between common variants at the PRSS1 – PRSS2 and CLDN2 – MORC4 loci and chronic pancreatitis (CP). In agreement with the results originally reported by Whitcomb et al ,2 they showed that the rs10273639 T allele at the PRSS1–PRSS2 locus protected against CP, whereas the rs7057398 C allele in RIPPLY1 and rs12688220 T allele in MORC4 at the CLDN2–MORC4 locus increased disease susceptibility.1 It has been recognised that geographical differences exist in the genetics of pancreatitis.3 Because the previous studies1 ,2 employed subjects of European ancestry only, we aimed to refine the association in Japanese patients with CP.

The three variants were genotyped by direct sequencing in 272 patients (men, n=245) with alcoholic CP (ACP), 197 patients …
Late-breaking abstract: Association between serum surfactant protein D (SP-D) and lung function measurements in self-reported healthy twins
Authors: Sofie Lock Johansson, Quiha Tan, Anders Schlosser, Ingrid Titlestad, Uffe Holmskov, Kirsten Kyvik, Grith Sørensen
Journal: European Respiratory Journal (2011)

Introduction:  Serum SP-D is suggested to serve as a biomarker in various pulmonary diseases, and has been showed negatively correlated to FEV1 in COPD.   Aim:  The objective of the present study was to investigate the association between serum SP-D and lung function in normal Danes.   Material and methods:  Data of serum SP-D originates from 1,476 self-reported healthy adult twins.  Association between variables were analyzed by using a multiple linear regression model using SP-D as response variable and pre-bronchodilatator FEV1 and FVC as explanatory variables. Intra-pair dependency was taken into account, and data was adjusted for sex, age and BMI.   Results:  There was a significant difference in mean serum SP-D levels in smokers with and without obstruction. (p  The association for SP-D with FEV1 and FVC was found to be negative in smokers (p   Conclusion and perspectives:  Findings indicate opposite phenotypic correlation between SP-D and FEV1 in smoking and non-smoking individuals. Further analysis of available data will include multivariate twin modelling to investigate whether there is a genetic correlation between the traits and genetic association analysis to find out whether such a genetic correlation could be explained by single nucleotide polymorphisms within candidate genes such as the SFTPD gene.
Phase III trial of docetaxel (D), estramustine (E), and prednisone versus docetaxel plus prednisone in patients with metastatic hormone-refractory prostate cancer (HRPC)
Authors: J. H. Machiels, F. Mazzeo, M. Clausse, B. Filleul, L. Marcelis, B. Honhon, L. D’Hondt, C. Dopchie, M. Bonny, J. Kerger
Journal: Journal of Clinical Oncology (2007)

5067 Background: D alone or in combination with E improves survival of pts with metastatic HRPC. Whether E is necessary in combination with D is controversial. Preclinical data suggest a synergistic activity between D and E. Phase II as well as small randomized trials support this hypothesis, although indirect comparisons between the large phase III studies are not in favor of D/E combination. We conducted a randomized, prospective, multicentric study to compare D versus D/E. Methods: 150 metastatic HRPC were randomized (minimisation, stratification parameters: PSA level, ECOG, previous E use (38 pts), and center) between D (35 mg/m 2 on day 2 and 9, every 3 wks) and D in combination with E (280 mg PO tid on days 1 to 5 and 8 to 12, coumadin 1mg/d). E was the only difference between the two treatment arms. All the pts received prednisone (10 mg/d). The primary endpoint was PSA response rate (decrease in PSA &gt; 50% from baseline) and the study was powered to detect a 25% difference in PSA response rate. Results: No significant difference was found for PSA response (D/E: 50/68 (73%); D: 48/69 (69%)), time to PSA progression (median 205 days for D/E and 210 days for D), duration of PSA response (median 185 days for D/E and 220 days for D), progression-free survival (median 186 days for D/E and 195 days for D), response rate according to RECIST, and overall survival (median 617 days for D/E and 629 days for D). PSA &lt; 4 ngr/mL occurred in 28/68 pts (41%) in D/E and in 17/69 (25%) in D (p=0.04). More pts had at least one grade 3/4 NCI-CTC toxicity in D/E (33/75 pts; 45%) compared to D (16/75 pts; 21%) (p=0.003). The main difference was grade 3/4 digestive toxicity (D/E:15% and D:4%; p=0.017). Serious adverse events were reported more frequently in D/E than D: 20 vs 9 (p=0.03). In D/E, the most frequent grade 3/4 toxicities were digestive (15%) and venous thrombosis (12%). In D, the most frequent grade 3/4 toxicity was anemia (9%) and venous thrombosis (8%). Conclusions: Our study did not show any clinically relevant advantage in term of efficacy for the addition of E to D. Both regimens were well-tolerated although the toxicity profile was in favor of D without E. Our study does not support the addition of E to D to treat pts with HPRC. [Table: see text]
Phase II evaluation of tremelimumab (Treme) combined with high-dose interferon alpha-2b (HDI) for metastatic melanoma.
Authors: A. A. Tarhini, S. J. Moschos, H. Tawbi, Y. Shuai, W. E. Gooding, C. Sander, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2010)

8524 Background: Anti-CTLA4 antibodies and HDI have significant immunomodulatory and antitumor activity in advanced melanoma. We hypothesized that the combination might abrogate immunologic tolerance and induce more significant and durable clinical responses. Methods: Treme was given at 15 mg/kg IV/course q12 wks. HDI was given concurrently including IV induction at 20 MU/m2 IV, 5 d/wk × 4 wks followed by maintenance at 10 MU/m2 SC TIW, for 8 wks/course. From course 2 onward, HDI maintenance was given SC. Dose delays were allowed for Treme, and if HDI was tolerable with dose modification pts continued HDI even if Treme was discontinued. Results: Thirty-six pts (23 M, 13 F), age 28-76 were enrolled. All had AJCC stage IV (9 M1a, 6 M1b, 21 M1c) and most had previously received therapy (0-5 regimens). Two pts had prior treated brain metastases. Seventy courses of Treme have been administered to date (average 2/pt; 5 pts continue on therapy). Grade 3/4 toxicities include neutropenia (6 pts; 17%), diarrhea/colitis (5; 14%), liver enzyme elevation (4; 11%), rash (4; 11%), fatigue (12; 33%), anxiety/depression (5; 14%). Autoimmune toxicities due to Treme were successfully managed with steroids. Response data are available for 33 pts. Two pts included in survival analysis and one responder who developed a second malignancy are not evaluable. Best OR rate (33 evaluable pts) is 30% (3 CR and 7 PR lasting 3, 9, 2+, 3+, 5+, 7+, 10+, 14+, 24+, 27+ months), including M1a (4), M1b (2), and M1c (4; one ocular). Twelve pts (36%) had SD (3 ongoing at 1+ to 7+ month and 9 progressed after 1.5 to 21 months). Disease control rate is 0.67, 95% CI (0.51, 0.83). Six mos PFS rate is 53%, 95% CI (0.34, 0.68) and median PFS is 6.4 mos, 95% CI (3.2, 16.3). One year OS rate is 57.8%, 95% CI (0.370, 0.739) and median OS is 15.9 mos, 95% CI (9.34, −). Baseline CRP ≤ 2.5ULN (p = 0.049) and the induction of autoimmunity (autoantibodies or AE) (p = 0.0059) are significantly associated with therapeutic benefit. Conclusions: HDI and Treme can be administered with acceptable toxicity, and exhibit promising durable antitumor efficacy. Baseline CRP is a predictive biomarker of response. Autoimmunity induced by therapy is significantly correlated with therapeutic benefit. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Racial variation in positive prostate needle biopsy templates, which include the transition zone.
Authors: Allison H. Feibus, Justin Levy, Krishnarao Moparty, Ian R. McCaslin, Michael M. Maddox, Oliver Sartor, Jonathan L. Silberstein
Journal: Journal of Clinical Oncology (2015)

125 Background: Reports have suggested that African Americans (AA) with prostate cancer (PCa) have both increased incidence and increased aggressiveness of tumors located in the transition zone (TZ). Our goal was to evaluate the utility of TZ−directed prostate biopsies in a predominantly AA population at a Veterans Affairs Hospital. Methods: After obtaining IRB approval, we retrospectively reviewed all patients with PCa found on a 14 core biopsy in which 12 needle biopsies were directed at the peripheral zone (PZ) and 2 at the TZ, between January 2010 and June 2014. Location of disease was determined by the results of the biopsy, either PZ alone, TZ alone or both. Aggressiveness of disease was defined by Gleason grade, percent involvement of PCa in any core and NCCN risk-stratification. Self−identified race was recorded for all patients. A series of Mann Whitney U and Chi−square tests were used to compare variables. Results: The total patient cohort consisted of 398 men, in which 277 (70%) were AA. When compared with Caucasian Americans (CA), AA patients had more NCCN intermediate or high risk (50% vs 39%, p = 0.25) PCa. Most patients had PCa limited to the PZ only (n=190) or in both the PZ and TZ (n=191). For 17 patients (4%) PCa was limited to TZ core(s) only, 14 (5%) AA vs 3 (2%) CA (p = 0.24). Of these 17 patients, 14 (82%) had Gleason 6 only disease. Patients with PCa in both the PZ and TZ had higher PSA and PSA density, greater volume of disease, higher-grade lesions and worse NCCN category (all values p &lt;0.01) compared with patients in which the positive biopsy was limited to the PZ. Of these 191 TZ and PZ positive patients, a greater proportion were AA (n=135, 49%) compared to CA (n=56, 46%) (p = 0.48). For patients with PZ and TZ disease, the TZ had the highest-grade in 21 (11%) men, 10% AA and 13% CA (p = 0.67). For most patients (89%), PZ tumor grade was equal to or greater than TZ. Conclusions: TZ−directed prostate needle biopsy cores were rarely the sole location of PCa and when found were usually low grade without clear racial variation. Patients with PCa in both the PZ and TZ had aggressive disease regardless of race although the TZ core resulted in upgrading in a minority of patients. TZ-directed biopsies do not appear to be of greater benefit to AA than CA.
Plasma amine oxidase and clinical features of schizophrenia
Authors: R Gruen, M Baron, M Levitt, J Kane
Journal: American Journal of Psychiatry (1985)

Among 76 chronic schizophrenic patients, plasma amine oxidase activity was unrelated to paranoid/nonparanoid subtype, narrow/broad diagnostic criteria, prognosis, or age at onset. These clinical indices do not identify biological subtypes of schizophrenia with deviant plasma amine oxidase activity.
Development of 3D Microvascular Networks Within Gelatin Hydrogels Using Thermoresponsive Sacrificial Microfibers
Authors: Jung Bok Lee, Xintong Wang, Shannon Faley, Bradly Baer, Daniel A. Balikov, Hak‐Joon Sung, Leon M. Bellan
Journal: Advanced Healthcare Materials (2016)

A 3D microvascularized gelatin hydrogel is produced using thermoresponsive sacrificial poly(N-isopropylacrylamide) microfibers. The capillary-like microvascular network allows constant perfusion of media throughout the thick hydrogel, and significantly improves the viability of human neonatal dermal fibroblasts encapsulated within the gel at a high density.
Recommendations for use of zoledronic acid (Z) for prevention and treatment of osteoporosis in men on androgen deprivation therapy (ADT) for prostate cancer (PC)
Authors: M. B. Pandya, W. Broderick, S. C. Campbell, H. Garewal, N. Friedman, T. Moritz, D. Reda, N. Bhoopalam
Journal: Journal of Clinical Oncology (2008)

16060 Background: Prolonged ADT for men with PC increases risk of osteoporosis and fracture. Z is a potent IV bisphosphonate that can improve the bone mineral density (BMD) in patients on ADT. There are no established treatment guidelines for such patients. We propose treatment recommendations based on two recent VA studies - our main study evaluating Z for prevention of osteoporosis due to ADT, and its companion study evaluating Z for treatment of patients with pre-existing osteoporosis. Methods: The main double blind, placebo (P) controlled trial randomized 93 patients to receive Z or P q3 mos. Preplanned strata (St) included 50 patients on ADT < 1 year (St 1) and 43 patients on ADT > 1 year (St 2). Baseline BMD T score was ≥ -2.0. The companion trial enrolled 27 patients with pre-existing osteoporosis (baseline BMD score < -2.0) on an open label, single arm trial to receive Z q3 mos. for 1 year. All patients in both trials received calcium, vitamin D, & counseling on lifestyle modification. BMD was measured by DEXA scan at enrollment, 6 and 12 mos. The primary endpoint was the % change in BMD at the lumbar spine at 12 mos. Results: In the main trial, patients were matched within the St across the treatment arms with respect to age, race, BMI, and osteoporosis risk factors. In St 1, spine BMD increased 5.95% in the Z arm and decreased 3.23% in the P arm (p=0.0044). In St 2, spine BMD increased 6.08% in the Z arm and increased only 1.57% in the P arm (p=0.0005). In the companion trial, lumbar spine BMD increased an average of 5.11% (p<0.0001) compared to baseline. In both trials, Z infusion was well tolerated with few side effects. Conclusions: Zoledronic acid improves BMD in men with PC on ADT. Benefit can be seen even in patients on prolonged ADT or those with pre-existing osteoporosis. We propose the following: patients initiating ADT should be evaluated for osteoporosis risk factors and counseled on preventive lifestyle modifications. DEXA scans should be obtained at baseline and repeated annually if normal. Treatment with Z should be considered for prevention and/or treatment of osteopenia/osteoporosis in men with PC who are on ADT. Supported by a grant from Novartis Pharmaceuticals Corporation Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
Cocarcinogenic Activity of Cholesterol Oxidation Products and Sesame Oil&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Fritz Bischoff
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Cocarcinogenic Activity of Cholesterol Oxidation Products and Sesame Oil Get access Fritz Bischoff Fritz Bischoff Chemical Laboratory, Santa Barbara Cottage Hospital Research Institute, Santa Barbara, California Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 5, November 1957, Pages 977–987, https://doi.org/10.1093/jnci/19.5.977 Published: 01 November 1957 Article history Received: 14 June 1957 Published: 01 November 1957
Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase II study.
Authors: R D Issels, S W Prenninger, A Nagele, E Boehm, H Sauer, K W Jauch, H Denecke, H Berger, K Peter, W Wilmanns
Journal: Journal of Clinical Oncology (1990)

From July 1986 to July 1989, 40 patients (92% pretreated) with deep-seated, advanced soft tissue sarcomas (STS, 25 patients), Ewing's sarcomas (ES, eight patients), osteosarcomas (OS, three patients) and chondrosarcomas (ChS, four patients) were treated at the University of Munich in a protocol involving regional hyperthermia (RHT) combined with ifosfamide plus etoposide. A total of 265 RHT treatments (mean, 6.6 RHT per patient) were applied including 33 pelvic, four extremity, and three abdominal sites. The mean tumor volume was 537 cc (range, 50 to 2,980 cc). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1 to 5), etoposide (100 mg/m2, days 1, 3, and 5), and mesna (300 mg/m2 x 4, days 1 to 5) with RHT given only on days 1 and 5 in repeated cycles every 4 weeks. Acute toxicity consisted primarily of pain (57%) combined with local discomfort within the annular phased array applicator (AA) of the BSD hyperthermia system (BSD Medical Corp, Salt Lake City, UT). The average maximum systemic temperature was 37.4 +/- 0.5 degrees C, and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. Detailed thermal mapping by invasive thermometry was performed in all patients. In 38 assessable patients, the overall objective response rate was 37%: six complete responses (CRs), four partial responses (PRs), and four favorable histologic responses (FHRs) (95% confidence limits, 22% to 54%). Complete responders are alive and disease-free at 40, 35, 23, 19, 19, and 8 months. Of patients with PR and FHR, two died from metastatic disease after 4 and 17 months and one died from other disease after 27 months. The remaining five patients are stable at 37, 25, 21, 13, and 8 months. Eleven patients showed no change (NC), and 13 patients showed local tumor progression (PD). The mean observation time for all patients was 11.6 months. The time-averaged temperatures (Ts) of all RHT treatments calculated as 20% (T20), 50% (T50), or 90% (T90) of measured tumor sites differed significantly between responders and nonresponders (T20, P = .003; T50, P = .006; and T90, P = .004; respectively). These data support activity for ifosfamide-etoposide combined with RHT in pretreated patients with advanced sarcomas.
Is there hope of improving the prognosis of pulmonary tumour thrombotic microangiopathy?
Authors: Mansouria Merad, Laurent Savale, Sami Antoun, François Vincent
Journal: European Respiratory Journal (2016)

We read with interest the letter by Kumar et al. [1] reporting two new cases of fatal pulmonary tumour thrombotic microangiopathy (PTTM). As discussed by the authors, ante mortem diagnosis of PTTM is difficult to confirm because of a rapid progression of the disease. The disease is characterised histopathologically by microscopic tumour emboli and remodelling of the pulmonary vasculature, leading to right heart failure, severe hypoxaemia and, ultimately, death in the very short term, within a few hours or days following admission. Better pathophysiological understanding of PTTM could result in specific targeted therapies and improve prognosis <http://ow.ly/U93wg>
Treatment evolution in localized Ewing tumors of the pelvis and femur
Authors: H. Juergens, A. Ranft, U. Dirksen, T. Boelling, M. Paulussen, W. Winkelmann
Journal: Journal of Clinical Oncology (2008)

10513 Background: The most common primary sites of Ewing tumors, with 45–50% of all cases, are the pelvis and the femur. Treatment in localized disease consists of systemic chemotherapy combined with surgery and/or radiation for local control. This approach achieves long-term survival rates of 60–70%. Both the choice of local therapy modality and outcome numbers vary widely depending, among other factors, on the primary site. Methods: Event-free survival (EFS) and overall survival (OS) of 344 patients with histologically proven localized osseous Ewing tumor of the pelvis (59.3%) and the femur (40.7%) were analyzed according to local therapy and related risk factors. All patients had received adjuvant chemotherapy and were recruited from consecutive Phase III trials of the German Society of Pediatric Oncology and Hematology (GPOH) between 1991 and 2006. The median follow-up was 3.96 years. Results: Survival was superior in patients with femoral tumors who showed a 3y EFS (OS) of 0.75 (0.88) as compared to 0.51 (0.62) for pelvic sites (p<0.001). The choice of local therapy modality varied significantly (p<0.001) according to site: Femoral tumors were more often treated by surgery alone (49.3% vs. 13.9%), pelvic tumors, more often by radiotherapy alone (31.4% vs. 5.7%); regarding combined therapy the difference was only small (pelvis: 54.6%; femur: 45%). 63.4% of pelvic tumors compared to 48.3% of femoral tumors were larger than 200ml (p<0.05). Multivariate analysis including site, tumor volume and local therapy modality, identified pelvic site (Hazard Ratios; EFS: 1.82; OS: 2.05; p<0.01) and the interaction factor large tumor volume (>200ml) as major risk factors. Conclusions: Patients with femoral Ewing tumor have reached a high level of survival probability. With today’s standard treatment 8–9 out of 10 patients are still alive 3 years after diagnosis. The unfavorable prognosis in pelvic tumors can be partially attributed to a higher proportion of large pelvic tumors treated with radiotherapy alone. New and innovative radiotherapy techniques may help to improve the outcome for inoperable large tumors in pelvic and other sites. No significant financial relationships to disclose.
Chemotherapy-free intervals (CFI) in patients with metastatic colorectal cancer (MRC)
Authors: A. Plantade, P. Afchain, C. Tournigand, F. Maindrault-Goebel, B. Chibaudel, O. Bourges, N. Perez-Staub, A. Larsen, C. Louvet, A. De Gramont
Journal: Journal of Clinical Oncology (2006)

3581 Background: Median survival in patients (pts) with MRC can reach 20 months with chemotherapy and should further improve with combined targeted therapies. CFI should be considered in order to improve quality of life of long survivors. Methods: 197 pts responders or stable with chemotherapy in a single institution benefited from CFI of at least 3 months, for any reason, in a 12 year period (1992–2005). Therapy was rechallenged in case of disease progression. Duration of CFI and overall survival (OS) were analyzed according to therapy and prognostic factors. Results: In 146 pts who had a CFI after a first-line, chemotherapy was 5FU-based in 32 pts, oxaliplatin-based in 103 pts (FOLFOX alone in 64 pts, FOLFOX followed by 5FU in 39 pts), irinotecan-based in 11 pts. In 51 pts who had a CFI after a second-line, chemotherapy was 5FU-based in 6 pts, oxaliplatin-based in 30 pts, irinotecan-based in 15 pts. There was no correlation between therapy duration before CFI and CFI duration, p=.66. Median CFI duration was 29 weeks (wks) in first line and 21 wks in second line, p=.0005. Median therapy duration and CFI were 42 and 26 wks after 5FU-based chemotherapy, 12 and 27 wks after FOLFOX and 36 and 37 wks after FOLFOX followed by 5FU, p=.001 and p=.12, respectively. In first-line, CFI lasted a median of 39 wks in 15 pts in complete response, 29 wks in 61 partial responders and 27 wks in 70 stable pts, p=.33. Among patients who had a CFI after a first-line therapy, those with good prognostic factors (PS 0, normal LDH and alkaline phosphatases &lt;3UNV) experienced a longer CFI and a longer OS than others, median 27 vs 25 wks (p=.025) and 139 vs 108 wks (p=.007), respectively. Conclusions: CFI should be considered especially in good prognosis patients and in first-line therapy. The Optimox 2 study which compares 5FU maintenance therapy and CFI after FOLFOX should further evaluate CFI. [Table: see text]
TCT-262 Thrombus aspiration does not reduce mortality in STEMI patients: a meta-analysis of 20,192 patients, with implications for future trial design
Authors: Yousif Ahmad, Sayan Sen, Daniel Keene, Christopher Cook, Sukhjinder S. Nijjer, Ricardo Petraco, Judith Finegold, Matthew Shun-Shin, Graham Cole, Iqbal S. Malik, Christopher S. Baker, Michael Bellamy, Raffi R. Kaprielian, Ghada Mikhail, Justin E. Davies, Jamil Mayet, Darrel P. Francis
Journal: Journal of the American College of Cardiology (2015)