tbuckley/cabot-search huggingface dataset:
A phase I dose-escalation study of weekly multiple dose intravenously administered SR271425 in patients with refractory solid tumors
Authors: E. Calvo, A. C. Lockhart, A. W. Tolcher, E. K. Rowinsky, G. Shackleton, J.-G. Morrison, R. Rafi, M. L. Rothenberg
Journal: Journal of Clinical Oncology (2005)

3095 Background: The thioxanthone analog, SR271425, is a novel cytotoxic DNA-interacting agent with a broad spectrum of antitumor activity in preclinical murine tumor models. This clinical trial aims to determine tolerability and toxicities of SR271425 as a 1-hour single intravenous dose repeated weekly for 2 weeks followed by 1 week rest, to determine the maximum tolerated dose (MTD), recommended phase II dose (RPIID), and to assess its pharmacokinetic profile. Methods: A modified Fibonacci dose escalation design is being used. A single intravenous dose of SR271425 is administered over 1-hour weekly for 2 weeks, followed by 1 week rest, in a variety of refractory solid tumors. Of note, in the rabbit model, QTc prolongation, related to Cmax, has been reported at doses >660mg/m2. Therefore, all patients are undergoing cardiology assessment with serial ECGs, which are assessed by a central reviewer. Results: To date, 17 patients have been treated at 5 dose levels (ranges, 64–675 mg/m2/week). The mean age is 53 (range 24 -74 years) and ECOG performance status is 0–2. Grade 1–2 toxicities including QTc prolongation, nausea/vomiting/ constipation, and fatigue have been observed. The pharmacokinetics of SR271425 following weekly dosing were consistent with that observed previously in a single dose ascending study with SR271425. Both Cmax and AUC (day 1) increased in a dose dependent manner. As would be predicted from the drugs short half-life (6.7 h), no systemic accumulation was observed as assessed by Cmax and C6h values on Day 1 versus Day 8. Stable disease has been observed in 3 patients. Conclusions: Preliminary data on this ongoing study suggests that SR271425 administered at split, weekly doses will likely allow greater cumulative exposure without significant toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Research
Discovery of a Gene Expression Profile on Primary Tumour Able to Detect Characteristics of Nodal Invasion in Advanced Squamocellular Oral Cavity Cancer
Authors: P. Bossi, L. De Cecco, F. Perrone, B. Cortelazzi, L. Locati, M. Giannoccaro, S. Pilotti, S. Canevari, L. Licitra
Journal: Annals of Oncology (2014)
Methotrexate pharmacokinetics following administration of recombinant carboxypeptidase-G2 in rhesus monkeys.
Authors: P C Adamson, F M Balis, C L McCully, K S Godwin, D G Poplack
Journal: Journal of Clinical Oncology (1992)

PURPOSE Carboxypeptidase-G2 (CPDG2) is a bacterial enzyme that rapidly hydrolyzes methotrexate (MTX) into inactive metabolites. As an alternative form of rescue after high-dose MTX (HDMTX), CPDG2 has more potential advantages than standard leucovorin (LV) rescue. In this study, the plasma pharmacokinetics of MTX with and without CPDG2 were evaluated in adult rhesus monkeys. MATERIALS AND METHODS The plasma pharmacokinetics of MTX were determined in groups of animals that had received a 300-mg/m2 loading dose of MTX followed by a 60-mg/m2/h infusion during an 18-hour period. One group received CPDG2 at the end of the infusion, and the other group served as a control. Two additional animals with high titers of anti-CPDG2 antibody also were studied. RESULTS During infusion, the steady-state MTX plasma concentration was 11.3 +/- 4.8 mumol/L. Without CPDG2, the postinfusion plasma MTX concentration remained above 0.1 mumol/L for more than 6 hours. After the administration of 50 U/kg of CPDG2, plasma MTX concentrations decreased to nontoxic levels (less than 0.05 mumol/L) within 30 minutes. The initial half-life (t1/2 alpha) of MTX decreased from 5.8 +/- 2.1 minutes to 0.7 +/- 0.02 minutes after enzyme administration. The postinfusion area under the plasma concentration time curve of MTX was 301 +/- 171 mumol/L/min without CPDG2 compared with 19.6 +/- 6.1 mumol/L/min with CPDG2. The immunogenicity studies performed indicated that although animals developed anti-CPDG2 antibodies, none of them manifested allergic symptoms. The effectiveness of CPDG2 was diminished but not eliminated in animals with high titers of anti-CPDG2 antibody. CONCLUSIONS CPDG2 is capable of rapidly decreasing plasma MTX concentrations to nontoxic levels. The administration of CPDG2 seems safe, well tolerated, and it may be useful as an alternative to LV rescue.
Evidence for effect of random genetic drift on G+C content after lateral transfer of fucose pathway genes to Escherichia coli K-12.
Authors: K Aoyama, A M Haase, P R Reeves
Journal: Molecular Biology and Evolution (1994)

The cps cluster of Escherichia coli K-12 comprises genes involved in synthesis of capsular polysaccharide colanic acid. Part of the E. coli K-12 cps region has been cloned and sequenced and compared to its Salmonella enterica LT2 counterpart. The cps genes from the two organisms are homologous; in the case of the LT2 genes, with G+C content of 0.61 and codons characteristic of high G+C species, it seems clear that they have been acquired relatively recently by lateral transfer from a high G+C species. The K-12 form of these cps genes is closely related to those of LT2 so must derive from the same high G+C species, but it appears to have transferred much earlier such that random genetic drift has brought P3 (the corrected G+C content of codon base 3) down from 0.77 to 0.64, more than halfway to the E. coli average of 0.57. We estimate, using an equation developed by Sueoka, that the lateral transfer to E. coli took place approximately 45 million years ago. This is the first report we are aware of demonstrating the expected adjustment of P3 after lateral transfer between species with different G+C content DNA.
Sexual Health in America
Authors: David Satcher, Edward W. Hook, Eli Coleman
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Accommodated MCAT Time and Performance Measurements—Reply
Authors: Cynthia A. Searcy
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Novel swine model of transfusion-related acute lung injury (TRALI)
Authors: Hitoshi Okazaki, Osamu Ishikawa, Takehiko Iijima, Takahiro Kohira, Mai Teranishi, Shin Kawasaki, Akira Saito, Yu Mikami, Ayumi Horikawa, Asuka Sugiura, Shiho Hashimoto, Eiko Shimada, Makoto Uchikawa, Mika Matsuhashi, Nelson Tsuno, Minoru Tanaka, Nobutaka Kiyokawa, Junichiro Fujimoto, Takahide Nagase, Kenji Tadokoro, Koki Takahashi
Journal: European Respiratory Journal (2012)

Background: TRALI is a life-threatening complication of blood transfusion. Antibodies against human leukocyte antigens in donors9 serum are major causes of TRALI. Several animal models of TRALI have been developed, and the mechanism underlying TRALI development has been extensively investigated using rodent models. Although sheep models of nonimmune TRALI have been developed, large-animal models of immune TRALI have not yet been developed. Because the incidence of TRALI is low and prospective human studies are difficult to conduct, large-animal models mimicking TRALI might be useful for developing treatment options.  Aim: To determine whether a swine model of TRALI can be developed using a monoclonal antibody (mAb) to swine leukocyte antigens (SLAs).  Materials and methods: Male Clawn strain miniature pigs (9-10 months) were used. A mAb against SLA class I (4G8: 0.3 or 1.0 mg/kg body weight (BW)) and a control antibody (1.0 mg/kg BW) were prepared and injected into the peripheral vein after priming with or without 1 μg/kg BW of lipopolysaccharide (LPS) (n=3; each arm). Lung injury was assessed using the PaO 2 /FiO 2  (P/F) ratio and by chest X-ray monitoring. Histopathological analysis was also performed.  Results: Lung injury was induced only when the 4G8 mAb with a concentration of 1.0 mg/kg BW was injected after LPS priming. The P/F ratio 90 min after the administration of the antibody had significantly decreased (p
Pre-operative breast magnetic resonance imaging (MRI) influences patient selection for partial breast irradiation
Authors: L. A. Vallow, S. Packianathan, E. R. Deperi, M. D. McDonough, J. D. Earle, E. A. Perez
Journal: Journal of Clinical Oncology (2006)

604 Background: Many patients with localized breast cancer undergo breast conservation therapy. Partial breast irradiation (PBI) is a technique that reduces irradiated tissue volume and decreases treatment time. Appropriate patient selection for this technique is critical. We studied the influence of pre-operative breast MRI on patient selection for PBI. Methods: Between 05/04 and 05/05, 231 women with newly diagnosed breast cancer underwent pre-operative bilateral breast MRI (median age = 64, range 34 to 89). Following initial clinico-pathologic review, patients were deemed to be eligible for PBI based on the NSABP B39 protocol if they satisfied its inclusion criteria (tumor size ≤3 cm, ≤3 positive nodes, negative surgical margins, lack of multicentric disease), derived through physical examination, mammography and/or ultrasonography. Breast MRI scans of all patients deemed eligible for PBI by these criteria were then reviewed to determine the impact of the MRI findings on their eligibility for PBI. Only patients who had pathological assessment to correlate with the MRI findings were included in the analysis. Results: Based on the NSABP B39 inclusion criteria, 186 patients (81%) were considered to be appropriate candidates for PBI without influence from MRI findings. Of these 186 women, MRI findings led to pathologically proven additional disease that altered the recommendations for PBI in 26 patients (14%). Mammographically occult, biopsy proven multicentic disease was detected in the ipsilateral breast in 13 patients (7%), whereas 5 women (2.7%) had mammographically occult, biopsy proven multicentric disease in the contralateral breast. In 8 patients (4.3%), pathological assessment confirmed more extensive local disease than was detected by breast MRI. Conclusions: Up to 14% of patients initially deemed eligible for PBI were later found to be ineligible because of breast MRI findings. Ipsilateral multicentric disease was identified in 7%, contralateral disease was discovered in 2.7%, and more extensive local disease was noted in 4.3%. Bilateral breast MRI complements other imaging modalities in determining eligibility for PBI by identifying mammographically occult disease in patients for whom PBI may be inappropriate. No significant financial relationships to disclose.
Abused to abuser: antecedents of socially deviant behaviors
Authors: A W Burgess, C R Hartman, A McCormack
Journal: American Journal of Psychiatry (1987)

The authors interviewed 34 young people who had been sexually abused as children 6 or 8 years after the abuse had occurred and compared them with 34 control subjects who had not been abused. They also compared subjects who had been abused for less than 1 year with those who had been abused for more than 1 year. The findings suggest a link between childhood sexual abuse and later drug abuse, juvenile delinquency, and criminal behavior. The authors explore the effects of pretrauma factors of previous childhood physical abuse and parental modeling of aggression and the postdisclosure factors of social and family blaming.
Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft of class I major-histocompatibility-complex molecules.
Authors: A L Hughes, T Ota, M Nei
Journal: Molecular Biology and Evolution (1990)

Certain major-histocompatibility-complex (MHC) loci are highly polymorphic, and the mechanism of maintenance of this polymorphism remains controversial. Recent studies of the pattern of nucleotide substitution at MHC loci have produced strong evidence that this polymorphism is maintained mainly by positive Darwinian selection that operates on the antigen recognition site (ARS) of the MHC molecule. The ARS of the class I MHC consists of three subregions: (1) the binding cleft, (2) T-cell-receptor-directed residues, and (3) outward-directed residues. Here we report that the rate of nonsynonymous nucleotide substitution is much higher in the binding cleft than in the other ARS subregions. Furthermore, nonsynonymous nucleotide substitutions that result in a change of residue side-chain charge occur significantly more frequently than expected by chance. We conclude that the main target of positive selection on the class I MHC molecules is the binding cleft of the ARS and that this selection acts primarily to promote diversity among alleles with respect to the pattern of residue side-chain charges (charge profile) in the binding cleft. These results provide additional support for the hypothesis that MHC polymorphism is maintained by overdominant selection relating to antigen-binding capacity and thus to disease resistance.
Statement of the 3rd International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015
Authors: Tamara Hew-Butler, Mitchell H Rosner, Sandra Fowkes-Godek, Jonathan P Dugas, Martin D Hoffman, Douglas P Lewis, Ronald J Maughan, Kevin C Miller, Scott J Montain, Nancy J Rehrer, William O Roberts, Ian R Rogers, Arthur J Siegel, Kristin J Stuempfle, James M Winger, Joseph G Verbalis
Journal: British Journal of Sports Medicine (2015)

The 3rd International Exercise-Associated Hyponatremia (EAH) Consensus Development Conference convened in Carlsbad, California, in February 2015, with a panel of 17 international experts. The delegates represented four countries and nine medical and scientific subspecialties pertaining to athletic training, exercise physiology, sports medicine, water/sodium metabolism and body fluid homoeostasis. The primary goal of the panel was to review the existing data on EAH and update the 2008 Consensus Statement.1 This document serves to replace the 2nd International EAH Consensus Development Conference Statement and launch an educational campaign designed to address the morbidity and mortality associated with a preventable and treatable fluid imbalance .

The following statement is a summary of the data synthesised by the 2015 EAH Consensus Panel and represents an evolution of the most current knowledge on EAH. This document will summarise the most current information on the prevalence, aetiology, diagnosis, treatment and prevention of EAH for medical personnel, athletes, athletic trainers and the greater public. The EAH Consensus Panel strove to clearly articulate what we agreed on, did not agree on and did not know, including minority viewpoints that were supported by clinical experience and experimental data. Further updates will be necessary to: (1) remain current with our understanding and (2) critically assess the effectiveness of our present recommendations. Suggestions for future research and educational strategies to reduce the incidence and prevalence of EAH are provided at the end of the document; areas of controversy that remain in this topic have also been outlined.

The 3rd International EAH Consensus Development Conference utilised National Institutes of Health guidelines, amended for a more holistic approach to fit the needs of both the group and the topic. Twenty-two individuals (17 accepted) were invited to participate in the consensus conference who: (1) have made scientific and/or clinical contributions to the topic …
After a treatment breakthrough: a comparison of trial and population-based data for advanced testicular cancer.
Authors: E J Feuer, C M Frey, O W Brawley, S G Nayfield, J B Cunningham, N L Geller, G J Bosl, B S Kramer
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine to what extent the benefits of cisplatin-based combination chemotherapy have been disseminated to all American men diagnosed with advanced testicular cancer. PATIENTS AND METHODS One hundred seventy-two advanced testicular cancer cases from five population-based registries of the Surveillance, Epidemiology, and End Results (SEER) Program diagnosed from 1978 to 1984 were compared with 133 diagnostically comparable cases from the Memorial Sloan-Kettering Cancer Center (MSKCC) vinblastine, dactinomycin, and bleomycin (VAB) regimens 7 through 9. Exclusions were made in both series for cases with elevated markers only, abdominal disease only, or extragonadal tumors. Ratings of extent of disease using the Indiana University system (minimal/moderate or advanced) were available for the MSKCC cases, and were determined retrospectively on the SEER cases based on information abstracted from medical records. RESULTS Among the SEER cases, 89% reported receiving chemotherapy, and 95% of these received cisplatin-containing regimens. Survival among the MSKCC patients was significantly better than for the SEER cases in the minimal/moderate extent of disease category (95% and 73% 3-year survival rate, respectively); however, the difference for advanced cases was only marginally significant (52% and 40% 3-year survival rates, respectively). Survival did not vary significantly by year of diagnosis in either series. CONCLUSION Although most of the patients in the SEER series received cisplatin-based chemotherapy, this alone did not produce results equivalent to that in the MSKCC series. Since the patients were selected to be as diagnostically comparable as possible at baseline, remaining differences in survival may be due to adherence to a fixed regimen and level of dose-intensity, adequacy of diagnostic work-up, implementation of salvage therapies and debulking surgery, and unknown factors related to who is willing and able to travel to a tertiary care center for treatment. Whatever the reason for not achieving optimal results in the SEER series, the very modest survival improvements over the time period 1978 to 1984 indicates that the differences in outcome between the two series were basically stable over the study period.
Epiregulin contributes to breast tumorigenesis through regulating matrix metalloproteinase 1 and promoting cell survival
Authors: Mariya Farooqui, Laura R. Bohrer, Nicholas J. Brady, Pavlina Chuntova, Sarah E. Kemp, C. Taylor Wardwell, Andrew C. Nelson, Kathryn L. Schwertfeger
Journal: Molecular Cancer (2015)

The epidermal growth factor (EGF) family of ligands has been implicated in promoting breast cancer initiation, growth and progression. The contributions of EGF family ligands and their receptors to breast cancer are complex, and the specific mechanisms through which different ligands regulate breast tumor initiation and growth are not well-defined. These studies focus on the EGF family member epiregulin (EREG) as a mediator of early stage breast tumorigenesis.EREG expression levels were assessed in both cell lines and human samples of ductal carcinoma in situ (DCIS) using quantitative RT-PCR, ELISA and immunohistochemistry. Gene knock-down approaches using shRNA-based strategies were used to determine the requirement of EREG for growth of MCF10DCIS cells in vivo, and for identifying mechanisms through which EREG promotes tumor cell survival. Experiments were performed using a combination of two-dimensional culture, three-dimensional culture and tumor growth in vivo.In comparison with other EGF family members, EREG was induced in MCF10DCIS cells compared with MCF10A and MCF10AT cells and its expression was partially regulated by fibroblast growth factor receptor (FGFR) activity. Reduced EREG expression in MCF10DCIS cells led to decreased tumor growth in vivo, which was associated with reduced cell survival. Furthermore, treatment of MCF10A cells with exogenous EREG enhanced cell survival both in three-dimensional culture and in response to chemotherapeutic agents. Examination of EREG-induced signaling pathways demonstrated that EREG promoted survival of MCF10A cells through regulating expression of matrix metalloproteinase-1 (MMP-1). To determine the relevance of these findings in human tumors, samples of DCIS were analyzed for EREG and MMP-1 expression. EREG was induced in DCIS lesions compared to normal breast epithelium, and EREG and MMP-1 were correlated in a subset of DCIS samples.Together, these studies lead to identification of a novel pathway involving EREG and MMP-1 that contributes to the formation of early stage breast cancer. Understanding these complex pathways could ultimately lead to the development of novel biomarkers of neoplastic progression and/or new therapeutic strategies for patients with early stage cancer.