tbuckley/cabot-search huggingface dataset:
Abstract LB-153: Introduction of Th1 help by a novel cancer vaccine, helper/killer hybrid epitope long peptide (H/K-HELP): From basic to clinical study
Authors: Takashi Nishimura, Takayuki Ohkuri, Daiko Wakita, Hidemitsu Kitamura
Journal: Cancer Research (2011)

Abstract Using mouse tumor model, we have demonstrated that there are strong immunosuppressive tumor escape mechanisms in tumor-bearing hosts. Especially, we have emphasized the following three mechanisms; (i) CD133+ cancer-stem cells (CSC) produced high levels of active TGF-β and they are resistant to CD8+ T cell-mediated immunosurveillance via inducing regulatory T cells (Tregs); (ii) Immature myeloid cells (ImC), which are abnormally increased in tumor-bearing mice, are classified into three distinct populations and MΦ-ImC and NeutSeg-ImC, but not NeutStab-ImC act as myeloid-derived suppressor cells (MDSC); (iii) IL-17-producing γδ T cells act as protumor cells during carcinogenesis and tumor progression via promoting angiogenesis. We have proposed that Th1-dominant immunity played a critical role for overcoming such immunosuppressive tumor-escape mechanisms to induce tumor-specific memory and CTL, which are essential for the cure of tumor. In addition, we have reported rational strategies such as Th1 cell therapy and its combination with chemo or radiation therapy. To apply these basic findings to a clinical trial, we first identified a novel helper epitopes of MAGE-A4 and Survivin tumor antigens, which can activate tumor-specific Th1 cells by combination with Th1 adjuvant, OK-432. To induce an efficient Th1-dependent antitumor immunity, we further developed a novel cancer vaccine, artificial helper/killer hybrid epitope long peptide (H/K-HELP) of MAGE-A4 or Survivin. In phase I study, H/K-HELP consisted of both killer and helper epitopes was mixed with adjuvants (OK-432 and Oil adjuvant) and subcutaneously administered into cancer patients 4 times with 2 wks interval. Both MAGE-A4-H/K-HELP and Survivin-H/K-HELP induced tumor-specific Th1 and Tc1 immune responses and tumor-specific C-fixing antibody (IgG1 and IgG3) responses in cancer patients. H/K-HELP vaccination inhibited the growth of tumor in patients with melanoma and colon cancer. Moreover, H/K-HELP vaccination induced a complete regression of chemo and radio-resistant lateral deep cervical node recurrence of triple-negative breast cancer. Thus, our results propose that H/K-HELP vaccination or its combination with Th1 cells will become a promising tumor vaccine/cell therapy of human cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-153. doi:10.1158/1538-7445.AM2011-LB-153
Omeprazole Compared with Misoprostol for Ulcers Associated with Nonsteroidal Antiinflammatory Drugs
Authors: Christopher J. Hawkey, Jeffrey A. Karrasch, Leszek Szczepañski, Donald G. Walker, Alan Barkun, Anthony J. Swannell, Neville D. Yeomans
Journal: New England Journal of Medicine (1998)

Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs.
IMPROVED ASSESSMENT OF CAD IN OBESE SUBJECTS WITH FLURPIRIDAZ F18 PET MYOCARDIAL PERFUSION IMAGING: A SUBSET ANALYSIS OF THE FLURPIRIDAZ F18 301 PHASE 3 STUDY
Authors: Timothy M. Bateman, Jamshid Maddahi, James Udelson, Rob Beanlands, Juhani Knuuti, Gary Heller, Daniel Berman, Joel Lazewatsky, Cesare Orlandi
Journal: Journal of the American College of Cardiology (2016)
Abstract 1411: Pathogenesis and treatment of rhabdomyosarcoma in a susceptible murine model.
Authors: Samer Zaid-Kaylani, Joseph G. Pressey, David R. Kelly, Mohammad Athar
Journal: Cancer Research (2013)

Abstract Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. While the establishment of standard multi-modal therapy has led to improved survival, new therapeutic approaches are desperately needed to improve outcomes in patients with metastatic and recurrent disease. Our objective was to develop a highly penetrant mouse model of RMS to study the molecular pathways of the disease and to evaluate novel anticancer agents for the treatment of RMS. The hedgehog (Hh) pathway has been demonstrated to be activated in embryonal RMS. Communication between Hh and PI3K/AKT/mTOR pathways provides a rationale for the study of mTOR inhibitors such as rapamycin in RMS therapy. We developed a novel RMS mouse model by breeding Ptch6-7 knockouts onto a tumor susceptible SKH1 genetic background. We employed these animals (n=20/group) to study the effects of mTOR inhibitor, rapamycin, on the growth and progression of RMS tumors. We found that 42% of the Ptch1+/−SKH1 mice receiving no treatment developed RMS. These tumors were confirmed to have embryonal RMS morphology. These animals spontaneously develop RMS with embryonal histology predominantly in the hind limbs. The tumors developed at approximately 20 weeks of age; thereafter they grew very prolifically. Molecular studies demonstrated high expression of both Myogenin and Myf5. The tumors also manifested Hh pathway activation. The RMS bearing animals were divided into two groups with a third group of Ptch+/+ mice acting as a wild-type control group. Group-I animals receiving no treatment served as positive controls. The increase in tumor size in these animals was compared with the tumor growth of animals treated with rapamycin. The treatment resulted in a significant decrease in the rate of tumor growth as compared to the control group (p&amp;lt;0.05). This treatment also reduced the expression of AKT and Hh pathways, which was consistent with the tumor inhibitory response seen on a gross level. Decreases in markers of tumor invasiveness and VEGF expression were also noted. We conclude that the Ptch1+/− Skh1 mouse represents a novel murine model for aggressive embryonal RMS that recapitulates the pathobiology of human disease. Rapamycin effectively inhibits the growth of Ptch1+/− Skh1 RMS tumors providing insight into the mechanism underlying RMS tumorigenesis. mTOR inhibition with possible Hh pathway cross talk inhibition represents a promising target in the treatment of RMS in this murine model. Citation Format: Samer Zaid-Kaylani, Joseph G. Pressey, David R. Kelly, Mohammad Athar. Pathogenesis and treatment of rhabdomyosarcoma in a susceptible murine model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1411. doi:10.1158/1538-7445.AM2013-1411
THU0164 Tnf-Alpha Bioactivity: A New Biomarker of Aspa Activity in Patients with Tnf-Alpha Blockers
Authors: E. Constant, M. Rinaudo-Gaujous, A. Amouzougan, B. Pallot-Prades, P. Collet, T. Thomas, S. Paul, H. Marotte
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> Glomerular filtration rate (GFR) decreases without or prior to the development of albuminuria in many patients with diabetes. Therefore, albuminuria and/or a low GFR in patients with diabetes is referred to as diabetic kidney disease (DKD). A certain proportion of patients with diabetes show a rapid progressive decline in renal function in a unidirectional manner and are termed early decliners. This study aimed to elucidate the prevalence of DKD and early decliners and clarify their risk factors. <h3>Research design and methods</h3> This combination cross-sectional and cohort study included 2385 patients with diabetes from 15 hospitals. We defined DKD as a urinary albumin to creatinine ratio (ACR) ≥30 mg/gCr and/or estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m². We classified patients into four groups based on the presence or absence of albuminuria and a decrease in eGFR to reveal the risk factors for DKD. We also performed a trajectory analysis and specified the prevalence and risk factors of early decliners with sequential eGFR data of 1955 patients in five facilities. <h3>Results</h3> Of our cohort, 52% had DKD. Above all, 12% with a low eGFR but no albuminuria had no traditional risk factors, such as elevated glycated hemoglobin, elevated blood pressure, or diabetic retinopathy in contrast to patients with albuminuria but normal eGFR. Additionally, 14% of our patients were early decliners. Older age, higher basal eGFR, higher ACR, and higher systolic blood pressure were significantly associated with early decliners. <h3>Conclusions</h3> The prevalence of DKD in this cohort was larger than ever reported. By testing eGFR yearly and identifying risk factors in the early phase of diabetes, we can identify patients at high risk of developing end-stage renal disease.
Abstract 68: Increased H3K27 trimethylation is associated with decreased expression of miRNAs and bivalently modified genes in rhabdoid tumors
Authors: Samantha L. Gadd, Elizabeth J. Perlman
Journal: Cancer Research (2011)

Abstract Background: Rhabdoid tumors (RT) are aggressive tumors of infancy for which no effective treatment is currently available. These tumors are characterized by genetic loss of the SMARCB1 (SNF5, INI-1) component of the SWI/SNF chromatin remodeling complex. We previously reported an overall pattern of repression of genes associated with bivalent histone modification in embryonic stem cells within RT. We hypothesize that loss of SMARCB1 in RT results in an overall failure to release the repressive (H3K27) histone methylation in genes responsible for early differentiation. To test this hypothesis, we performed chromatin immunoprecipitation (ChIP) using antibodies specific for permissive (H3K4) and H3K27 trimethylation, comparing an RT cell line (G-410) with a human embryonic kidney cell line (HEK293). In addition, we report the global miRNA analysis of RT using the Illumina 96-sample Universal Matrix Array. Results: Those genes previously shown by others to be direct targets of SMARCB1 (PTN, CDK2NA, ATP1B1, HESR1, and FZD7) and genes previously shown to be down-regulated in RT (CDH2, SPON1, LEF1, SOX11, CDKN1B, SERPINE2, SPOCK1, DOCK4) all showed a significantly higher ratio of H3K27 methylation to H3K4 methylation (1.5-fold to 130-fold) in G410 cells compared with HEK293. In contrast, genes shown to have increased expression in RT (TFRC and DDX21) showed increased H3K4 methylation. Global miRNA analysis demonstrated striking downregulation of 156/158 (p&amp;lt;0.05) miRNAs compared with other pediatric renal tumors. ChIP analysis for H3K4 and H3K27 associated with miRNAs mir127, mir134, mir519e, mir99b, and mir152 likewise showed increased association with H3K27. Summary: Gene and miRNA expression strongly correlate with histone methylation patterns in the RT cell line. This suggests that loss of SMARCB1 in RTs results in striking repression of gene and miRNA expression which may be due to aberrant repressive (H3K27) histone methylation. The use of histone methylation inhibitors may therefore merit investigation for this pediatric tumor for which there is no effective therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 68. doi:10.1158/1538-7445.AM2011-68
Obesity and sexism: fact or fiction?
Authors: D. Debnath, R. K. Choudhary, S. Lari, J. G. Stephen
Journal: Gut (2011)

<h3>Introduction</h3> Male stoicism is often blamed for delay in seeking medical help.1–3 We aimed to address this issue by assessing correlation between sex and different factors related to obesity surgery. <h3>Methods</h3> All eligible patients between 1986 and 2006 were included. Analyses of age (year), diabetes, ASA status, smoking, mental health state, pre- and post-operative weights (kg), duration of operation (minutes), hospital stay (days), complication rates and follow-up (months) were performed. <h3>Results</h3> Out of a total of 48 patients, 13 were male. Mean age was comparable among males (42.2) and females (40.4) (p=0.54). Occurrence of smoking among males (n=3, 23.0% of 13) and females (n=11; 31.4% of 35) was similar (p=0.57). Incidence of diabetes was higher among males (n=5, 38.4% of 13), than females (n=4, 11.4% of 35) (p=0.01). Females had more mental health issues (n=6, 46.1% of 35), than males (n=0, 0% of 13) (p=0.043). ASA status were similar among both groups (p=0.43). Preoperative weight was more among males (154.9) than females (136.7) (p=0.019). Weight loss over a follow-up period of 52.6 months was significant (preoperative 141.67 vs postoperative 117.29) (p&lt;0.0000001). Weight loss was more among males (21.5), than females (15.24) (p=0.01). Operative time was higher among males (190.88) than females (172.06) (p=0.06). Stay in hospital was similar among males (10.7) and females (11.2) (p=0.62). Complication rates were not significantly different among males (n=4, 30.7% of 13) and females (n=6, 17.1% of 35) (p=0.30). Compliance with follow-up was higher among males (63.69) than females (48.6) (p=0.18). <h3>Conclusion</h3> Males enjoyed significantly more weight loss and complied better in follow-up, than females. Incidence of diabetes and mental health were higher among males and females, respectively. Age, smoking, ASA status, complication rates and stay in hospital were similar in both groups. These findings do not support the hypothesis of typical male stereotyping.
PRECLINICAL SAFETY ASSESSMENT OF A NEOINTIMAL SUPPRESSING CIGLITAZONE-COATED STENT: DATA FROM SCANNING ELECTRON AND CONFOCAL MICROSCOPY IN A RABBIT ILIACAL ARTERY MODEL
Authors: Sylvia Otto, Kristin Jaeger, Renu Virmani, Hans R. Figulla, Tudor Poerner
Journal: Journal of the American College of Cardiology (2015)
MS-10 * CLEAR CELL EPENDYMOMA: A RARE VARIANT FIRST TIME REPORTED BY A TERTIARY CARE HOSPITAL IN PAKISTAN
Authors: F. A. Hashmi, S. A. Khan, M. Waqas, M. E. Bari, A. Ahmed
Journal: Neuro-Oncology (2014)

OBJECTIVES: Clear Cell Ependymoma has never been reported from Pakistan. We aim to see the features and outcomes of this rare entity in Pakistan. METHODS: A retrospective case-series conducted at the Department of Neurosurgery, Aga Khan University. The medical record files of patients with Clear Cell Ependymoma from 2003 - 2012 were reviewed, MRI/C.T scans and Histopathological slides were reviewed. Patients lost to follow-up were contacted on telephone. Analysis was done on SPSS 20. RESULTS: Nine cases of CCE were found. The median age was 47 years. The symptoms included Headache 66.6%, seizures, hemiparesis, raised ICP 33.3% patients. Seven patients had supra-tentorial and 2 had infra-tentorial tumor. MRI showed hypo-intense signals on T1 and hyper-intense signals on T2 weighted images. Contrast enhancement was found in 7 patients (77.8%). Histopathology: Clear cells were found frequently in 5 cases. Immunohistochemistry showed GFAP and EMA positivity in all cases. Ki-67 showed high proliferative index in 5 patients. WHO class was II in 1 patient and III in 8 patients. Gross total resection was done in 5 (55.5%), Subtotal Resection in 4 patients (44.4%). 5 patients underwent radiotherapy, 3 patients underwent Radiotherapy + chemotherapy, post-surgery. Recurrence was there in 7 patients. Repeat surgery was done in 3 patients. Six patients died of the disease. Median Progression free survival was 8 months (range 5-28 months), the median overall survival was 15 months (range 6-52months). CONCLUSION: CCE is a significantly aggressive tumor in Pakistan with prognosis worse than other parts of the world.
1240 CHRONIC HEPATITIS E IN LUNG TRANSPLANT RECIPIENTS
Authors: S. Pischke, B. Bremer, A. Gisa, P. Lehmann, R. Raupach, M. Darnedde, T. Welte, M.P. Manns, A. Haverich, J. Gottlieb, H. Wedemeyer
Journal: Journal of Hepatology (2013)
AB0024 Genetic association of interleukin-1 beta (-511C/T), interleukin-1 receptor antagonist (IL-1RN) and osteopontin (9250 C/T) polymorphisms with bone mineral density and osteoporosis in russian postmenopausal women
Authors: M. Krylov, N. Tortoptsova, O. Nikitinskaya, E. Samarkina, T. Korotkova, V. Maykotkin, L. Benevolenskaya
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and objectives</h3> Osteoporosis (OP) is a common disease of elderly, in which the immune system plays a critical role in the pathophysiology of postmenopausal OP. Estrogen deficiency induces mild increase in production of proinflammatory cytokines which promotes osteoclastogenesis in the bone marrow. Intermittent PTH treatment increases cancellous bone mass in OP patients. Molecular mechanisms for anabolic PTH actions are largely unknown. Because it regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one targets of PTH in bone. <h3>Objectives</h3> We studied the genetic associations between bi-allelic polymorphism (-511C/T) of IL-1b, 86 bp VNTR polymorphism IL-1RN and (9250 C/T) polymorphism OPN and bone mineral (BMD) values in postmenopausal women. <h3>Methods</h3> OP was diagnosed by DXA method. The study included 175 women with a diagnosed BMD T-score lower than -2.5 SD (mean:-3.01±0.76) and 212 postmenopausal healthy controls (HC) with a BMD T-score greater -2.5 SD (mean: - 0.30±0.75). Gene polymorphisms were analyzed by PCR-RFLP. <h3>Results</h3> IL-1b (-511C/T) and OPN (9250 C/T) polymorphisms were significantly associated with OP. IL-1b (-511CT) and OPN (9250CC) were associated with high risk of OP [OR=1.62, CI (1.06-2.48), p=0,018 and OR=1.87, CI (1.10-3.18), p=0,014 Mantel-Haenzel, correspondingly]. Among the women with OP, the BMD values were significantly lower in the carriers of the IL-1b TT genotype compared with the CC genotype (0.679±0.048 vs.0.743±0.087 p=0.03) for the lumbar spine. The BMD values were significantly lower in the carriers of the OPN CT genotype compared with the TT genotype (0.703±0.069 vs. 0.740±0.088, p=0,04 Mantel-Haenzel). There were no statistically significant associations between the IL-1RN genotypes and BMD values in the OP women. <h3>Conclusions</h3> These results suggest that the pathogenesis of OP is associated with IL-1b (-511C/T) and OPN (9250C/T) polymorphisms in postmenopausal Russian women. <h3>Disclosure of Interest</h3> None Declared
PTU-120 A review of patients in a single centre with ileal pouch-anal anastomosis for ulcerative colitis and an assessment of those patients who require on going medical therapy
Authors: N Allen, E Garforth, R Heath, P Rooney
Journal: Gut (2012)

<h3>Introduction</h3> Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical therapy of choice for patients with chronic ulcerative colitis. However IPPA is frequently accompanied by early and late complications. A proportion of patients require ongoing medical management which this study assesses. <h3>Methods</h3> A prospectively collected hospital database of patients who were followed up after IPAA at a single centre was retrospectively reviewed. A review of all case notes was carried out to assess surgical intervention prior to IPAA. All post operative complications were recorded and an assessment was made of those patients recommenced on medical therapy. <h3>Results</h3> 102 patients9 case notes were reviewed, (60 male: 42 female mean age 42 years SD of ±12.01). The follow-up is ongoing and is currently between 2 and 193 months. The complications included anastomotic leak (n=4), incisional hernia (n=7), pouchitis (n=36), stenosis (n=15), pre pouch stricture (n=1), ileitis (n=2), enterocutaneous fistula (n=2), perianal fistula (n=6), pouch vaginal fistula (n=5), pouch ulceration (n=8). All patients prior to surgery had a histological diagnosis of ulcerative colitis, 4 patients were reclassified as having Crohn9s or indeterminate colitis at further follow-up. There were 13 (12.7%) patients whom were recommenced on medical therapy, including sulphasalazine, budesonide, azathioprine, 6-mercaptopurine and infliximab. Patients who were on antibiotics were not included in these numbers. All patients who were reclassified as having Crohn9s were recommenced on medical therapy and seen in a joint gastro/surgical clinic. <h3>Conclusion</h3> Long term anastomotic problems are common after IPPA. Most pouch patients do not require additional medical treatment other than antibiotics but 13% need continued complex medical therapy under the care of gastroenterologists and surgeons. Use of steroids is low. Diagnostic problems remain an issue. <h3>Competing interests</h3> None declared.
SEX DIFFERENCES IN UTILIZATION AND OUTCOMES OF CATHETER DIRECTED THROMBOLYSIS IN PATIENTS WITH PROXIMAL LOWER EXTREMITY DEEP VENOUS THROMBOSIS
Authors: Vladimir Lakhter, Chad Zack, Vikas Aggarwal, Yevgeniy Brailovsky, Harish Jarrett, Estefania Oliveros, Michael Lashner, Grayson Wheatley, Alfred Bove, Riyaz Bashir
Journal: Journal of the American College of Cardiology (2015)
A Molecular Marker for Chloroquine-Resistant Falciparum Malaria
Authors: A Djimdé, O K Doumbo, J F Cortese, K Kayentao, S Doumbo, Y Diourté, D Coulibaly, A Dicko, X Z Su, T Nomura, D A Fidock, T E Wellems, C V Plowe
Journal: New England Journal of Medicine (2001)

Chloroquine-resistant Plasmodium falciparum malaria is a major health problem, particularly in sub-Saharan Africa. Chloroquine resistance has been associated in vitro with point mutations in two genes, pfcrt and pfmdr 1, which encode the P. falciparum digestive-vacuole transmembrane proteins PfCRT and Pgh1, respectively.To assess the value of these mutations as markers for clinical chloroquine resistance, we measured the association between the mutations and the response to chloroquine treatment in patients with uncomplicated falciparum malaria in Mali. The frequencies of the mutations in patients before and after treatment were compared for evidence of selection of resistance factors as a result of exposure to chloroquine.The pfcrt mutation resulting in the substitution of threonine (T76) for lysine at position 76 was present in all 60 samples from patients with chloroquine-resistant infections (those that persisted or recurred after treatment), as compared with a base-line prevalence of 41 percent in samples obtained before treatment from 116 randomly selected patients (P<0.001), indicating absolute selection for this mutation. The pfmdr 1 mutation resulting in the substitution of tyrosine for asparagine at position 86 was also selected for, since it was present in 48 of 56 post-treatment samples from patients with chloroquine-resistant infections (86 percent), as compared with a base-line prevalence of 50 percent in 115 samples obtained before treatment (P<0.001). The presence of pfcrt T76 was more strongly associated with the development of chloroquine resistance (odds ratio, 18.8; 95 percent confidence interval, 6.5 to 58.3) than was the presence of pfmdr 1 Y86 (odds ratio, 3.2; 95 percent confidence interval, 1.5 to 6.8) or the presence of both mutations (odds ratio, 9.8; 95 percent confidence interval, 4.4 to 22.1).This study shows an association between the pfcrt T76 mutation in P. falciparum and the development of chloroquine resistance during the treatment of malaria. This mutation can be used as a marker in surveillance for chloroquine-resistant falciparum malaria.
Brain Tumor Incidence Rising; Researchers Ask Why
Authors: N. S. Larsen
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Brain Tumor Incidence Rising; Researchers Ask Why Get access Natalie S. Larsen Natalie S. Larsen Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 13, 7 July 1993, Pages 1024–1025, https://doi.org/10.1093/jnci/85.13.1024 Published: 07 July 1993
637 AGREEMENT AND PREDICTIVE VALIDITY OF NEUROPHYSIOLOGICAL, PSYCHOMETRIC AND PSYCHOPHYSICAL INDICES OF HEPATIC ENCEPHALOPATHY (HE)
Authors: S. Montagnese, S. Schiff, M. De Rui, I.D. Raduazzo, A. Gatta, P. Angeli, M. Bolognesi, D. Sacerdoti, C. Merkel, P. Amodio
Journal: Journal of Hepatology (2012)