tbuckley/cabot-search huggingface dataset:
Phase II trial of a 10-epitope CTL vaccine, EP-2101, in metastatic NSCLC patients
Authors: S. Brown, C. Cunningham, G. Mary, M. Morse, F. A. Greco, D. McCune, H. Khong, R. Steis, B. Mills, G. Ishioka, J. Bender
Journal: Journal of Clinical Oncology (2007)

3068 Background: The 10-peptide EP-2101 vaccine is designed to induce multi-specific CTL responses against epitopes in CEA, p53, HER-2/neu and MAGE 2/3. Seven epitopes are modified for enhanced MHC binding or heteroclitic T-cell activation including the previously described CAP1–6D heteroclitic analog and 2 epitopes are native wild-type (WT) sequences. Also included is the helper epitope PADRE. We report here immunogenicity results from a Phase II trial of the EP-2101 vaccine. Methods: 66 HLA-A2+ good performance patients with Stage IIIB/IV NSCLC were enrolled. Patients received 6 induction doses (0.5 mg/epitope) q3 wks followed by maintenance treatments at 2–3 month intervals. Endpoints included survival and induction of immune responses. CTL responses in peripheral blood MNC were measured after a 10 day in vitro stimulation with peptide followed by an IFNγ ELISPOT assay. Results: 33 patients completed induction and the first 11 patients were monitored for CTL against all vaccine epitopes. Seven of 11 patients generated responses against ≥ 4 epitopes after 3 and 6 vaccine doses and 8 patients generated CTL against ≥ 3 WT vaccine epitopes and WT sequences of vaccine analogs. Responses ranged between 10–50 spots/5x10e4 cells with stronger responses of &gt;100 spots observed. All 9 vaccine epitopes were immunogenic in at least 1 patient. CTL responses against epitopes were maintained at Wk 30 and/or Month 9 in 7 of 8 patients. At Month 12, 2 of 4 patients also had detectable CTL against the vaccine. The 22 remaining patients were monitored against 5 representative vaccine epitopes. 13 of these patients generated CTL responses to ≥ 2 epitopes and 7 patients generated responses to ≥ 3 epitopes. Th-cell responses against PADRE measured with a direct IFNγ ELISPOT assay were observed in 18 of the 33 patients tested. Toxicities attributable to vaccine were mild and consisted mostly of injection site reactions. Follow-up for survival is ongoing. Conclusions: The peptide vaccine EP-2101 is well-tolerated and induces broadly-specific CTL responses in metastatic NSCLC patients. [Table: see text]
P1064 RANDOMIZED TRIAL OF TENOFOVIR MONOTHERAPY VERSUS TENOFOVIR PLUS ENTECAVIR COMBINATION THERAPY IN CHRONIC HEPATITIS B PATIENTS WITH GENOTYPIC RESISTANCE MUTATIONS TO ADEFOVIR
Authors: Y.-S. Lim, B.C. Yoo, K.S. Byun, S.Y. Kwon, Y.J. Kim, J. An, H.C. Lee, Y.S. Lee
Journal: Journal of Hepatology (2014)
Severe colitis related to granulomatosis with polyangiitis (Wegener’s granulomatosis)
Authors: Fatih Karaahmet, Serta Kılıncalp, Yusuf Coskun, Sahin Coban, Ilhami Yuksel
Journal: Endoscopy (2014)

A 58-year-old man presented with weakness, cough, weight loss, and intermittent painless rectal bleeding for 2 weeks. He was on no medication and gave no history of smoking or alcohol use. His family history was unremarkable. On examination, his abdomen was soft and diffusely tender. Blood tests showed the following results: white cell count 13 × 109/L, hemoglobin 8.1 g/dL, alanine aminotransferase 31 U/L, albumin 2.9 g/dL, creatinine 0.5 mg/dL, erythrocyte sedimentation rate (ESR) 93 mm/h, CRP 160 mg/L, complement C3 0.63 g/L (normal range 0.8 – 1.52 g/L) with no hypergammaglobulinemia. Proteinase 3 antineutrophil cytoplasmic antibody (ANCA) and myeloperoxidase ANCA were negative.
Celebrate a Bad Day
Authors: Jacob Adashek
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Two Hundred Years of Hospital Costs and Mortality — MGH and Four Eras of Value in Medicine
Authors: Gregg S. Meyer, Akinluwa A. Demehin, Xiu Liu, Duncan Neuhauser
Journal: New England Journal of Medicine (2012)

An unusual window into health care value over the past two centuries is afforded by mortality and cost data from Massachusetts General Hospital, which celebrated its 200th anniversary in 2011. These data tell a story that reflects national trends in acute care.
AB0908 Evaluation of the Activity of Juvenile Idiopathic Arthritis by Jadas: Jadas ESR versus Jadas3
Authors: M.E.I. Fanata, A. Bouchra, R. Samira, E.B. Dalal, M. Nada, E. Majda, S. Siham, G. Sanae, W. Moudjibou, H.-H. Najia
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The Jadas (Juvenile arthritis Disease Activity Score) is a recently developed and validated for the assessment of the activity of juvenile idiopathic arthritis (JIA), including articular index composite score, physician global assessment, evaluation overall relatives of patients and erythrocyte sedimentation rate (ESR). However, it is not always measured systematically in consultation for this JADAS3 excluding the VS has been proposed [1]. <h3>Objectives</h3> – To Compare the activity of JIA by Jadas with and without VS – To Explore how the exclusion of the VS Jadas (JADAS3) influence the correlation with parameters of disease activity. <h3>Methods</h3> Cross-sectional study that included 47 patients aged under 18 years, suffering from juvenile idiopathic arthritis, defined according the ILAR 2001 classification. Sociodemographic parameters, clinical and para-clinical trials relating to patients were collected. The Jadas 10-VS and JADAS3-10 (Jadas10 without VS) were used to assess disease activity. The scores Jadas-10- VS and JADAS3 -10 were calculated as a simple linear sum of the different components, giving a total score of 0-40 for JADAS 10 –VS and to 0-30 for JADAS3-10, with highest scores corresponding to a severe disease activity. A descriptive and analytical statistical analysis was performed. <h3>Results</h3> 47 patients were included with a male predominance n=28 (59.6%). The mean age was 11.59 years ±3.35.The disease duration of JIA had a median of 4 years [2-6], with a predominance of persistent oligoarthritis n=12 (26.7%), the median overall EVA patient was 20 [10-40] with EVA welfare of the mother who averaged 62.06±26.84. The average of DAS28 was 3.1±1.5 with a median of JADAS10-VS =12 [10-13], the median of JADAS3 -10 was 9.5 [8-10] low compared to that of JADAS10 but with a strongly positive correlation between them (p&lt;0.001; r=0.76). Correlations between JADAS10 and JADAS3 -10 with different types of JIA were not statistically significant. Correlation between Jadas3 and clinical, biological, and evaluation of the disease was not statistically significant, but significantly with duration of evolution of the disease (p=0.04, r =0.04) the Jadas 10 was strongly correlated with DAS28 (p=0.003, r=0.48) and index limited joints (p=0.02, r=0.37). <h3>Conclusions</h3> In our study the modified JADAS10 excluding VS -3 is highly correlated with Jadas 10. A study on a larger scale would be desirable to show the ability of Jadas 3 to evaluate the activity of JIA. <h3>References</h3> Flora Mcerlane et al. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5262
Abstract 1737: Pharmacological inhibition of fatty acid synthase regulates BH3-only proteins and sensitizes breast cancer cells to a small molecule Bcl-2/Bcl-xL inhibitor to induce apoptosis.
Authors: Chandra Mohan Kurapaty Venkatapoorna, Ingrid Espinoza, Scott H Kaufmann, Ruth Lupu
Journal: Cancer Research (2013)

Abstract Fatty acid synthase (FASN), the key enzyme in de novo lipogenesis, is significantly upregulated and activated in many carcinomas, including breast cancer. Pharmacological inhibition of FASN induces apoptosis of FASN expressing cancer cells. However, the mechanism is still unclear. Inhibition of FASN in breast cancer cells induces a dose dependent increase in apoptotic cell death with a concomitant upregulation of the pro-apoptotic BH3-only proteins Noxa, Bim and Puma (mRNA and protein). Blockage of the BH3-only protein expression using specific small interfering ribonucleic acid (siRNA), significantly diminishes the apoptotic effect induced by the inhibition of FASN. Moreover, addition of palmitate, the end product of FASN, protects the cells from the proapoptotic effects of FASN inhibition by suppressing expression of Noxa, Bim and Puma. These data indicate that Noxa, Bim and Puma are essential for the apoptotic effect induced by the inhibition of FASN. Combination therapeutic regimens have received growing attention for the possibility of higher efficacy with reduced toxicity. Thus, we investigated the combinatorial effect of pharmacological inhibition of FASN and Bcl-2/Bcl-xL. While a small molecule Bcl-2/Bcl-xL inhibitor alone did not induce apoptosis, co-treatment of the small molecule Bcl-2/Bcl-xL inhibitor with a synthetic FASN inhibitor significantly surpassed the apoptotic effect of the synthetic FASN inhibitor alone. Accordingly, combined treatment of a FASN inhibitors and Bcl-2/Bcl-xL antagonists represents a new rational combination that merits further consideration in FASN overexpressing tumors. Citation Format: Chandra Mohan Kurapaty Venkatapoorna, Ingrid Espinoza, Scott H Kaufmann, Ruth Lupu. Pharmacological inhibition of fatty acid synthase regulates BH3-only proteins and sensitizes breast cancer cells to a small molecule Bcl-2/Bcl-xL inhibitor to induce apoptosis. [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 1737. doi:10.1158/1538-7445.AM2013-1737 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Genomic Profiling of Breast Cancer (BC) in Mali by Oligonucleotide Comparative Genomic Hybridization (CGH) Array.
Authors: M. Ly, G. Diallo, A. Valente, D. Diallo, K. Dumke, V. Marty, V. Scott, L. Pusztai, N. Berrada, V. Lazar, B. Job, P. Viehl, J. Bernaudin, F. André
Journal: Cancer Research (2009)

Abstract Background: Epidemiological studies suggest that BC in Africa exhibit specific biological characteristics as compared to BC from US/Europe. In order to identify therapeutic targets that would be specific from Africa, we analyzed 28 samples from Mali by high resolution CGH array, and compared gene gains/losses to the ones observed in USA [André F et al, Clin Cancer Res, 2009]Patients and methods: 71 paraffin-embedded samples of invasive BC from patients treated by surgery at Bamako were retrieved, 28 of them (from 2 pts stage 1; 13 pts stage 2; 11 pts stage 3 and 2 pts stage 4) were eligible for CGH array (1) (Agilent, 4*44K) (cancer cells&amp;gt;50%; undamaged DNA &amp;gt;1µg).Results were compared to 106 samples from MD Anderson, profiled in the sample genomic platform using the same array (1)Results: The median age was 49 year old. Twenty-one samples (75%) were ER-negative. No difference was observed regarding the frequency of gene gains in 17q12-21 (ERBB2) nor 8p11-12 (FGFR1). Six regions were more frequently gained in BC from Mali, as compared to those from US (FDR&amp;lt;5%). Two regions included targetable molecular abnormalities. 9p34 region was gained in 43% of samples and included Abl1, a tyrosine kinase involved in CML, and VAV2, a guanine exchange factor. 22q11-13.1 region was gained in 34% of samples and included bcr, ewsr1, pdgfb and MAF-E. These two regions were gained in less than 5% of BC from US. Finally, a region located in 6p21 was gained in 56% of BC from Mali. This region included a cluster of genes involved in immune response (lymphotoxin A, MICA/MICB).Conclusion: BC from Mali present some candidate specific targetable alterations as gains of Abl1, bcr and pdgf-B. FISH and IHC are being done in order to validate targets.Additional high throughput analyses will be performed to characterize such tumors, including virus arrays, exon arrays and hot spot mutations. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3059.
LONG-TERM CARDIAC AND NON-CARDIAC MORTALITY IN ST-ELEVATION ACUTE MYOCARDIAL INFARCTION PATIENTS WHO UNDERWENT PRIMARY PERCUTANEOUS CORONARY INTERVENTION: INSIGHT FROM THE CREDO-KYOTO AMI REGISTRY
Authors: Yugo Yamashita, Hiroki Shiomi, Takeshi Morimoto, Hidenori Yaku, Yutaka Furukawa, Yoshihisa Nakagawa, Kenji Ando, Kazushige Kadota, Mitsuru Abe, Satoshi Shizuta, Koh Ono, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2016)
Similarities and contrasts between cerebellar LTD and hippocampal LTP
Authors: Michel Baudry
Journal: Behavioral and Brain Sciences (1996)

In this commentary, I review the articles by Crépel et al., Linden, and Vincent to compare and contrast the similarities and differences between hippocampal LTP and cerebellar LTD. In particular, the role of glutamate receptors in the induction of plasticity, the participation of different second messenger pathways, and the mechanisms involved in expression/maintenance of these forms of synaptic plasticity are discussed. [CRÉPEL et al.; LINDEN; Vincent]
Abstract 4089: Identification of a DNA methylation marker to detect the presence of lymph node metastases of gastric cancers
Authors: Yasuyuki Shigematsu, Tohru Niwa, Satoshi Yamashita, Hirokazu Taniguchi, Ryoji Kushima, Hitoshi Katai, Masao Ichinose, Toshikazu Ushijima
Journal: Cancer Research (2012)

Abstract Accurate detection of the presence of lymph node metastases of gastric cancers (GCs) is clinically important. However, current methods to detect it are unsatisfactory. As a marker, DNA methylation is advantageous because it is biologically and chemically stable and the DNA methylation profile is not disturbed by a small population of cells. Therefore, we focused on aberrant DNA methylation in GCs as a possible marker to detect the presence of lymph node metastases. We first performed genome-wide methylation analyses by Illumina Infinium HumanMethylation450 BeadChip array using three metastatic lymph nodes (MLNs) and three primary GCs without MLNs, and isolated 31 differentially methylated CpG sites. Then, using primary GCs with and without MLNs (screening set; 28 GCs with MLNs and 10 GCs without MLNs), their methylation levels were analyzed by quantitative PCR-based methods. Among the 31 regions, 10 regions showed higher methylation levels in GCs with MLNs than in GCs without MLNs (P &amp;lt; 0.05). In further analysis of the 10 regions using another sample set (validation set; 129 GCs with MLNs and 20 GCs without MLNs), hypermethylation of a region (cg06436185) in GCs with MLNs was validated, and the presence of lymph node metastases was detected with sensitivity of 43% and specificity of 85%. These results indicated that the methylation status of the cg06436185 region is a good marker to detect the presence of lymph node metastases of GCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4089. doi:1538-7445.AM2012-4089
Federal Funding for Stem-Cell Research
Authors: Robert Matz
Journal: New England Journal of Medicine (2005)

tion with ALPS in the Italian population (odds ratio, 28.6; 95 percent confidence interval, 1.9 to 830.6).Third, the unpublished data on two additional perforin mutations in the patient described in the report that Rieux-Laucat et al. cite 2 do not rule out a role for N252S, since three causal mutations of a gene in the same patient have been reported in persons with other diseases. 3,4 Finally, the detection by Rieux-Laucat et al. of a Fas mutation and N252S in a patient with ALPS and his healthy father supports the possibility, suggested in our report, that other environmental or genetic factors may contribute to ALPS.
Sonazoid-enhanced EUS for pancreatic diseases
Authors: Iwano Hirotoshi
Journal: Endoscopy (2011)

Purpose: In this study, the usefulness of Sonazoid-enhancement in pancreatic diseases was evaluated by EUS. Subjects & Methods: Ninteen cases in which contrast-enhanced (CE)-EUS was performed from October, 2009 to April, 2010. Differences in the effect of Sonazoid-enhancement in different diseases were studied. Results: CE-EUS was performed in 9 cases of pancreatic carcinoma, 8 cases of IPMN, 1 case of pancreatic carcinoma & IPMN, 1 case of acinar cell carcinoma. In 8 cases out of 9 cases of pancreatic carcinoma, a mass with less blood flow compared to the surrounding pancreatic parenchyma was evident. In IPMN, there was no enhancement effect in cysts and debris. Nodular elevations were easily identifiable based on blood flow. In the 1 case of acinar cell carcinoma, the lesion was diagnosed as splenic vein thrombosis before enhancement, but was found upon enhancement to be a tumor extending into the vein. Conclusions: CE-EUS can be used to reliably and objectively detect subtle lesions based on comparison of blood flow between a lesion and its surroundings.
Secretion of Chromogranin A by Peptide-Producing Endocrine Neoplasms
Authors: Daniel T. O'Connor, Leonard J. Deftos
Journal: New England Journal of Medicine (1986)

Chromogranin A, the protein that is co-stored and co-released with catecholamines from the adrenal medulla, has recently been identified in a variety of human endocrine tissues, both normal and neoplastic. We investigated the secretion of chromogranin A by peptide hormone-producing human tumors in studies of patients with the following neoplastic disorders: pheochromocytoma, parathyroid adenoma, primary parathyroid hyperplasia, medullary thyroid carcinoma, thyroidal C-cell hyperplasia, carcinoid tumor, oat-cell lung carcinoma, pancreatic islet-cell tumor, and aortic-body tumor. All these patient groups had elevated concentrations of plasma chromogranin A. We distinguished different forms of immunoreactive plasma chromogranin A by size with the use of gel filtration. Plasma chromogranin A levels were not elevated in patients with diverse "control" conditions--both benign and malignant and both endocrine and nonendocrine--in which peptide hormones are not produced. The sensitivity and specificity of plasma chromogranin A elevations in the diagnosis of peptide-producing endocrine neoplasms were 81 and 100 percent, respectively. The elevation of plasma chromogranin A in our subjects suggests that their neoplasms co-release chromogranin A along with the usual resident hormone of the tumor, that these neoplasms could be characterized as "chromograninomas," and that measurement of plasma chromogranin A may be a useful diagnostic procedure in subjects with endocrine tumors, especially multiple endocrine neoplasia.
In B-CLL, time to first treatment is dependant on the IgV<sub>H</sub> gene mutations and expression of CD38 on leukemic cells
Authors: T. Wasil, K. R. Rai, E. Albesiano, R. N. Damle, S. L. Allen, J. Kolitz, N. Chiorazzi
Journal: Journal of Clinical Oncology (2005)

6555 Background: Clinical outcome in B-CLL is correlated IgVH gene mutations and CD38 expresion A recent study repoted that expression of ZAP-70 and IgVH gene mutations could be correlated with time from diagnosis to treatment which could be used as a reliable end point for progression. We report the time to first treatment based on IgVH mutation status and CD38 expression. Methods: Clinical histories were obtained from the patient charts. Analyses of IgVH gene mutations and CD38 expression were done on frozen blood samples from these patients as described elsewhere(Fais et al. J Clin Invest 102:1515,1998 and Damle et al. Blood 94:1840, 1999, respectively). A cut-off of 30% was used to define CD38- vs. CD38+ cases. Mutation was defined as 2% or higher change as compared with germline. Time-to-first treatment was analyzed using Kaplan-Meier curves, comparing these curves using the Log Rank test and Bonferroni-corrected pairwise comparisons performed as needed. Results: A total of 115 CLL patients were analyzed. Conclusions:B-CLL patients with either unmutated IgVH genes and/or CD38+ status (either 1 or both adverse factors) require chemotherapy significantly sooner than those with mutated IgVH genes and CD38- status. The patients in the worse group/s may be followed more closely and also may be enrolled to clinical trials studying early treatment vs. late treatment as the survivals of these patients is also significantly shorter. The following table 1 summarises the results: Table 2 shows the differences in treatment at 2 fixed time points of 2 and 5 years: No significant financial relationships to disclose.
Rate of Pregnancy-Related Relapse in Multiple Sclerosis
Authors: Christian Confavreux, Michael Hutchinson, Martine Marie Hours, Patricia Cortinovis-Tourniaire, Thibault Moreau
Journal: New England Journal of Medicine (1998)

Multiple sclerosis often occurs in young women, and the effect of pregnancy on the disease is poorly understood. We studied 254 women with multiple sclerosis during 269 pregnancies in 12 European countries. The women were followed during their pregnancies and for up to 12 months after delivery to determine the rate of relapse per trimester and the score on the Kurtzke Expanded Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability). The relapse rate in each trimester was compared with the rate during the year before the pregnancy. The effects of epidural analgesia and breast-feeding on the frequency of relapse during the first three months post partum and the disability score at 12 months post partum were also determined.