tbuckley/cabot-search huggingface dataset:
Dose escalation by high-dose 3D-conformal radiotherapy (HD-3D-CRT) or low-dose 3D-conformal radiotherapy plus HDR brachytherapy (LD-3D-CRT+HDR-B) for intermediate- or high-risk prostate cancer: Early results of a prospective comparative trial
Authors: B. Guix, J. Bartrina, J. Tello, L. Quinzanos, T. Lacorte
Journal: Journal of Clinical Oncology (2009)

5118 Background: To report early and late toxicity and preliminary biochemical outcome in 445 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-3D-CRT or with LD-3D-CRT+HDR-B. Methods: Between December 1999 and October 2005, 445 patients (pts) with PSA'10, Gleason score'6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were assigned to one of the two treatment groups: 76 Gy HD-3D-CRT to the prostate in 38 fractions (group 1; 223 patients) or 46 Gy LD-3D-CRT+ 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 222 patients). Both groups were well balanced taking into account patient's as well as tumors’ characteristics. Toxicities were scored by the EORTC /RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. Results: All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 rectal toxicity. 28 pts of group 1 (12.5%) and 6 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 15 pts in group 1 (6.7%) and 3 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). In group 1 and 2, 81.8%and 95,9% of pts were free from rectal reactions respectively (p &lt; 0.005). 19 pts in each group developed acute Grade 2 urinary symptoms (mainly dysuria), and none experienced urinary retention. No pts (0%) developed Grade 3 or 4 rectal or urinary complications. With a mean follow-up of 55 months, the 5-year actuarial PSA relapse-free survival rates for intermediate- and high-risk group 1 pts were 92 and 91 % respectively and 97 and 96 % for group 2 pts (p &lt; 0.06). Conclusions: High-dose 3D-EBRT +HDR brachytherapy is a safe and effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute and late rectal and urinary complications were significantly reduced with the combined treatment, compared with what was observed with high-dose conventional, 3D-CRT. Short-term PSA control rates tends to be better with in the HDR-boosted patients as spected by higher effective-dose. No significant financial relationships to disclose.
Abstract 14856: Serum Phosphate Level is a Predictive Marker for Aortic Calcification in Patients Without End-stage Renal Disease
Authors: Mitsuo Kinugasa, Tomofumi Takaya, Shumpei Mori, Akira Kasamatsu, Kazuhiro Kashio, Tatsuro Ito, Sachiko Takamine, Seimi Satomi-Kobayashi, Sei Fujiwara, Tatsuya Nishii, Atsushi K Kono, Ken-ichi Hirata
Journal: Circulation (2014)

Introduction:  Vascular calcification (VC), commonly related to renal failure, diabetes, hypertension, and aging, is closely associated with cardiovascular events and mortality. High serum calcium and phosphate levels are well-known risk factors for VC in hemodialysis patients with end-stage renal disease (ESRD). However, their association with VC in those without ESRD is unclear. We aimed to assess the ability of serum calcium and phosphate levels to predict the aortic calcification severity in patients without ESRD.   Methods:  Between January 2011 and December 2013, thoracoabdominal non-contrast-enhanced computed tomography was performed for 134 patients who were scheduled to undergo cardiac surgery as a general preoperative evaluation. Three patients receiving hemodialysis and 5 patients with a history of aortic surgery were excluded. The total aortic calcium volume (TAC-V) was quantified using the volume rendering method, by extracting the area with attenuation values of >130 HU within the aorta from just above the left main trunk to the aortic bifurcation. The TAC-V divided by body surface area was defined as the TAC-V index. Dense TAC-V (area with attenuation values of >400 HU) in the TAC-V was also quantified.   Results:  In the 126 patients (age, 65.0 ± 12.8 years; 37% female), the median TAC-V index was 1.29 mL/m2 (range, 0-34.42 mL/m2). The mean estimated glomerular filtration rate, serum calcium, and serum phosphate levels were 63.9 ± 19.8 mL/min/1.73 m2, 9.1 ± 0.5 mg/dL, and 3.5 ± 0.6 mg/dL respectively. The mean serum phosphate level was significantly higher in high TAC-V (>3.34 mL/m2) than in low TAC-V (   Conclusion:  Serum phosphate level was significantly associated with aortic calcification even in patients without ESRD, and may be a new predictor of VC progression.
Non-Hodgkin's Lymphoma Involving the Heart
Authors: Raymond Liang, C.M. Yu, W.Y. Au, C.K. W. Choy, Y.L. Kwong
Journal: Journal of Clinical Oncology (2000)

Article Tools Non-Hodgkin's Lymphoma Involving the Heart Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.9.1998 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10784642 Non-Hodgkin's Lymphoma Involving the Heart Raymond LiangxRaymond LiangSearch for articles by this author , C.M. YuxC.M. YuSearch for articles by this author , W.Y. AuxW.Y. AuSearch for articles by this author , C.K. W. ChoyxC.K. W. ChoySearch for articles by this author , Y.L. KwongxY.L. KwongSearch for articles by this author Show More Queen Mary Hospital, University of Hong Kong, Hong Kong https://doi.org/10.1200/JCO.2000.18.9.1998 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Phase II study of 2-methoxyestradiol NanoCrystal dispersion (2ME2) alone and in combination with sunitinib (SU) in patients with metastatic renal cell carcinoma (mRCC) progressing on SU
Authors: M. R. Harrison, R. Pili, T. Logan, G. Wilding, J. Eickhoff, C. Sidor, M. Staab, J. Arnott, G. Liu
Journal: Journal of Clinical Oncology (2009)

e16116 Background: Panzem NCD (2ME2) is a non-estrogenic derivative of estradiol with antiproliferative and antiangiogenic activity that downregulates HIF-1α. One mechanism of VEGFR TKI failure may be upregulation of HIF-1α. We hypothesized that 2ME2 may have single-agent activity in pts who previously progressed on SU and that addition of 2ME2 may restore response in pts progressing on SU. Methods: Pts with clear cell mRCC who had previously received or were currently receiving SU with disease progression were eligible. Pts who had previously received SU were treated with 2ME2 alone (arm A). Pts currently on SU continued on the 4:2 schedule, with the addition of 2ME2 (arm B). All pts received 2ME2 at 1,500 mg PO TID, repeated in 6 wk cycles. The primary endpoint was objective response (OR) rate by RECIST. An exploratory endpoint was metabolic response on FDG-PET. Simon optimal 2-stage design was used with plans to enroll 21 pts/arm, and if activity was seen to continue enrollment for a total of 41 pts/arm. Results: 17 pts were enrolled (A: 10; B: 7). Median number of cycles on study was 1 (range &lt;1 to 5). A pt remains on study in cycle 8. Adverse events (AE) of grade 3 or greater occurred in 4 pts (29%). Most frequent AE were: fatigue (71%), diarrhea (50%), dysgeusia (29%), anemia or decreased hemoglobin (29%), and anorexia (21%). Reasons for treatment discontinuation include: disease progression (7), pt/doctor discretion (3), AE (3), and noncompliance (1). No ORs by RECIST were seen. Conclusions: 2ME2 appears to have some single-agent activity, with an MR in a pt removed from study due to AE and a metabolic PR (ΔSUVmax -84%) in a pt with SD by RECIST. With 6/17 pts discontinuing therapy before meeting any OR endpoint, 2ME2 was not tolerable in this population. The study was closed to accrual knowing that a more promising 2ME2 analog is currently under development for oncologic use. The rationale to target HIF-1α after (and during) SU therapy remains of interest. This study design provides a unique way to assess both single-agent and rational combination strategies in pts with mRCC and should be utilized with other agents to seek evidence for clinical activity. [Table: see text]
Abstract 656: Discovery of MAbs against difficult GPCRs, ion channels, and transporters using the MPS Discovery Engine®
Authors: Sharon H. Willis, Kimberly Mattia, Riley Payne, Moniquetta Hall, Manu Mabila, Christine Rettew, Joseph Couto, Rohan Keshwara, Cheryl Paes, Benjamin J. Doranz, Joseph Rucker
Journal: Cancer Research (2015)

Abstract Integral membrane proteins are important drug targets and monoclonal antibodies (MAbs) directed against them are highly sought for therapeutic purposes. However, the complex structure of membrane protein targets makes the discovery of these MAbs especially challenging. To address this need, we have developed the MPS Discovery Engine® to enable the isolation, characterization, and engineering of monoclonal antibodies for challenging membrane protein targets, including GPCRs, ion channels, and transporters. MPS harnesses the strength of Integral's 10+ years of expertise in membrane protein expression and analysis, as well as proprietary technologies including Lipoparticles for high concentration membrane protein presentation and Shotgun Mutagenesis for comprehensive epitope mapping and MAb optimization. Integral Molecular currently has a pipeline of several dozen MAbs against complex membrane proteins that are involved in a variety of diseases, including cancer, inflammation, pain, and infectious diseases. There are currently no FDA-approved MAbs that target GPCRs, ion channels, or transporters, and MPS provides a pathway to these new and previously intractable targets. Citation Format: Sharon H. Willis, Kimberly Mattia, Riley Payne, Moniquetta Hall, Manu Mabila, Christine Rettew, Joseph Couto, Rohan Keshwara, Cheryl Paes, Benjamin J. Doranz, Joseph Rucker. Discovery of MAbs against difficult GPCRs, ion channels, and transporters using the MPS Discovery Engine®. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 656. doi:10.1158/1538-7445.AM2015-656
Text-Book of Embryology. For Students of Medicine.
Journal: JAMA (1907)

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
Mechanism of chemoresistance to 5-fluorouracil mediated by miR-192/miR-215 in colon cancer cell lines: Cell-cycle effects and post-transcriptional thymidilate synthase regulation.
Authors: V. Boni, N. Bitarte, I. Cristobal, R. Zarate, J. Rodriguez, E. Maiello, J. Garcia-Foncillas, E. Bandres
Journal: Journal of Clinical Oncology (2010)

e21007 Background: Thymidylate synthase (TYMS) is the target of fluoropyrimidines, one of the most widely used chemotherapeutic agents against gastrointestinal malignancies. TYMS expression levels have been considered as predictive biomarkers for 5-fluorouracil (5-FU) efficacy, although results to date remain controversial. We hypothesized that microRNAs (miRNAs) might play a role to modulate TYMS expression and 5-FU sensitivity. Methods: An in silico analysis coupled with experimental validation was carried out in order to identify miRNAs targeting TYMS gene. Transient transfections of miR-192/215 were performed to evaluate the impact of these miRNAs on cell proliferation, cell cycle control, downstream targets and sensitivity to 5-FU in colorectal cancer (CRC) cell lines. Results: We demonstrate that TYMS expression is regulated by miR-192/215. However, miR-192/215-mediated TYMS downregulation did not translate into an increased sensitivity of CRC cell lines to 5-FU treatment. On the contrary, transfection with pre-miR-192 for 96 hours increased cell resistance to 5-FU. Our data suggest that pleiotropic miRNA effects modulate response to 5-FU treatment mainly through targeting cell cycle. Overexpression of miR-192/215 significantly reduced cell proliferation, induced p21 and p27 expression and target G0/G1 cell cycle progression in wild-type p53 CRC cell lines. Interestingly, this effect was partially independent of p53 status, since reduction of cell proliferation and cell cycle arrest in G2/M was also detected in DLD1-p53-mutated cell line. The reduction of cells in S-phase by these miRNAs mitigates the efficacy of S phase-specific drugs, suggesting that the ectopic expression of miR- 192/215 may be an important determinant of 5-FU sensitivity. Conclusions: MiR-192/miR-215 may be new potential predictive biomarkers in colon cancer and novel therapeutic targets to overcome 5-FU resistance. Prospective clinical studies to elucidate the role of these miRNAs and their predictive value in vivo are warranted. No significant financial relationships to disclose.
Abstract 18364: Impact of Obesity on Left Atrial Enlargement: Does LV Geometry and Hypertrophy Matter?
Authors: Dharmendrakumar A Patel, Carl J Lavie, Richard V Milani, Yvonne Gilliland, Sangeeta B Shah, Hector O Ventura
Journal: Circulation (2010)

Obesity has been identified as a strong independent determinant of left atrial (LA) enlargement (LAE). However, studies examining the independent association of obesity with LAE in relation to LV mass and LV geometric patterns are lacking. We evaluated 47,749 patients [29,181 non-obese (BMI <30; age: 63.4 ± 16.2 yrs) and 18,568 obese (BMI ≥ 30; age: 58.6 ± 13.7 yrs)] with preserved EF to determine the significance of LV mass and geometric patterns in assessing the impact of obesity on the LAE, determined using mean + 2SD of LA volume indexed to height (LAVi). Obese patients had significantly higher LAVi (36.9 ± 13.9 vs. 31.4 ± 13.6, p<0.0001), LAE (6% vs. 4%, p<0.0001), LVMi (45.3 ± 15.0 vs. 37.1 ± 13.1, p<0.0001), and LV hypertrophy (28% vs. 11%, p<0.0001) than non-obese. Patients with LAE had higher BMI (31.5 ± 7.9 vs. 29.3 ± 6.9, p<0.0001), obesity (51% vs. 38%, p<0.0001), LVMi (53.6 ± 18.9 vs. 39.6 ± 13.8, p<0.0001), and LV hypertrophy (51% vs. 16%, p<0.0001). Patients with LV hypertrophy had higher LAVi compared to patients without LV hypertrophy but showed no difference in LAVi by obesity status (Figure 1). In multivariate analysis, to remove this potential confounding impact of LVMi (obesity status*LVMi interaction, p=0.001), the association of obese vs. non-obese with LAE was assessed separately in patients with normal or increased LVMi as well as by different LV geometric patterns (Figure 2). A significant independent association of obesity with LAE was present only in patients without LV hypertrophy. In conclusion, although obesity, LAE, and LV geometry are closely linked, LV geometry significantly impacts the association between obesity and LAE.

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A randomized phase III trial of irinotecan plus carboplatin versus etoposide plus carboplatin in patients with small cell lung cancer, extensive disease (SCLC-ED): IRIS-Study
Authors: A. Hermes, B. Bergman, R. Bremnes, L. Ek, S. Fluge, C. Sederholm, S. Sundstrøm, L. Thaning, J. Vilsvik, U. Aasebø, S. Sörenson
Journal: Journal of Clinical Oncology (2007)

7523 Background: A Japanese randomized trial has shown superior survival for SCLC-ED patients receiving irinotecan+cisplatin as compared to etoposide+cisplatin. Our trial was performed to evaluate the effect of irinotecan+carboplatin compared to oral etoposide+carboplatin. Patients and Methods: In a phase III trial, patients with SCLC-ED were randomly assigned to receive carboplatin, AUC=4 (Chatelut formula) and irinotecan, 175 mg/m 2 , both on day 1 (IC) or carboplatin (Chatelut AUC=4) on day 1 and etoposide 120 mg/m 2 /day, orally, on days 1–5 (EC). In both arms, courses were repeated on day 21 with 4 cycles planned. Primary endpoint was overall survival (OS), secondary endpoints were quality of life, evaluated by EORTC-QLQ-C30 and QLQ-LC 13, and complete response rate. There were neither upper limits for age or performance status. Results: Between November, 2001 and July, 2005, 220 patients were randomized. 210 patients were eligible for analysis (other type of cancer, 8 pts., limited disease, 1 pt., elevated liver function tests, 1 pt.). Performance status (PS) 0: 20 patients, PS 1: 91, PS 2: 62, PS 3: 29, PS 4: 8. Median age IC was 67 years (46–81), EC 67 years (39–82). OS was 255 days (IC) versus 214 days (EC) (P=0.04, log rank test). HR for overall survival was 1.34, 95% CI: 1.01–1.79. 1-year survival was 35% vs 28%. CR was observed in 18 patients in the IC arm and 7 patients in the EC arm (P=0.02, chi-square test). There were no statistically significant differences with respect to haematological grade III-IV toxicity. No severe diarrhea was observed in the IC group. There were no significant differences regarding quality of life. Conclusion: Irinotecan + carboplatin is superior to oral etoposide + carboplatin with respect to overall survival in SCLC-ED. No significant financial relationships to disclose.
Snake bite: a global failure to act costs thousands of lives each year
Authors: David J Williams
Journal: BMJ (2015)

Vulnerable populations need urgent access to effective and affordable treatments

For many years snake bite experts have sought to raise the profile of this forgotten problem with public health authorities and donors. Lamentably, however, it has taken news of the departure of antivenom manufacturer Sanofi-Pasteur from the sub-Saharan African market to focus the spotlight on the calamity of snake bite among the world’s poorest people.

Nevertheless, beyond this successful media storm,1 2 the reality is that for the majority of people bitten by snakes in Africa the loss of Sanofi’s FAV-Afrique polyvalent antivenom will mean little, if anything at all. This is because the product simply never reached them in the first place. In a region where median gross domestic product per capita is $550 (£360; €490), Sanofi’s product was simply too expensive (a four vial treatment cost about $540) and produced in insufficient quantities to meet the needs of more than a small part of the African continent.3 4

The harsh fact is that the continent is largely devoid of safe, effective, and affordable treatments for something that is eminently treatable. For decades there have …
The Genetic Landscape Of FPD/AML Revealed CDC25C Mutation As a Driver That Promotes Malignant Transformation
Authors: Akihide Yoshimi, Takashi Toya, Masahiro Nakagawa, Masahito Kawazu, Yasuhito Nannya, Motoshi Ichikawa, Shunya Arai, Hironori Harada, Kensuke Usuki, Yasuhide Hayashi, Etsuro Ito, Keita Kirito, Hideaki Nakajima, Hiroyuki Mano, Mineo Kurokawa
Journal: Blood (2013)
A phase I study of ABT 510 and concurrent temozolamide and radiotherapy for patients with newly diagnosed glioblastoma multiforme
Authors: M. Kekan, J. Fiveash, J. M. Markert, G. Y. Gillespie, H. Kuo, S. Meleth, C. L. Gladson, L. B. Nabors
Journal: Journal of Clinical Oncology (2009)

2023 Background: ABT-510 (Abbott Laboratories, Abbott Park, IL, USA) is a Thrombospondin-1 (TSP-1) mimetic drug with anti-angiogenic properties. This phase I dose escalation trial was designed to study the maximum tolerated dose (MTD) of ABT 510 when used concurrently with temozolomide (TMZ) and radiotherapy (RT) in patients with newly diagnosed glioblastoma multiforme (GBM). Methods: A total of 23 patients with newly diagnosed, histologically verified GBM were enrolled between April 2005 and January 2007, after obtaining written consent. The study was approved by the University of Alabama at Birmingham (UAB) Institutional Review Board. Four cohorts with three patients in each, receiving subcutaneous ABT 510 injection at doses of 20, 50, 100, and 200 mg/day were studied. The starting dose was primarily based on preclinical findings from animal studies and phase I studies on healthy subjects and cancer patients. Treatment plan included 10 weeks of induction phase (TMZ and RT with ABT 510) followed by a maintenance phase (ABT 510 and TMZ) of 14 cycles each consisting of 28 days. Patients were monitored with brain MRI along with laboratory values for dose limiting toxicities (DLT) defined as grades 3–4 non-hematological toxicities and grade 4 hematological toxicities (neutropenia or thrombocytopenia). In the absence of a DLT in at least two of the three patients, the dose was increased by 50% in the next cohort of patients. Therapy was discontinued if 14 maintenance cycles were completed, disease progression occurred, or if the patient requested withdrawal. Disease progression and survival statistics were analyzed. Results: During this trial, grade 3/4 DLT were not observed even after the dose was increased to 200 mg/day, hence, the last cohort was expanded to include 14 patients. A MTD was not defined. The median time to tumor progression (TTP) was 220 days and the median overall survival was 422 days. Gene expression analysis of the tumor pathology will be performed to evaluate the relationship between the expression of TSP-1, TSP-2, and patient response to the drug. Conclusions: ABT 510, at subcutaneous doses up to 200 mg/day, is tolerated well with concurrent TMZ and RT in patients with newly diagnosed GBM. No significant financial relationships to disclose.
National and State Medical Expenditures and Lost Earnings Attributable to Arthritis and Other Rheumatic Conditions—United States, 2003
Journal: JAMA (2007)

lina, South Dakota, Tennessee, Texas, Utah, Virginia, West Virginia, Wisconsin, and Wyoming.‡Includes only persons living with HIV that had not progressed to AIDS.These data were reported by the 33 U.S. states with confidential, name-based HIV reporting since at least 2001.Because HIV can be diagnosed at any time in the disease spectrum, the time between HIV and AIDS diagnoses varies.§Includes only persons living with AIDS.Cases were from the 50 U.S. states and the District of Columbia (DC).Because DC is not a state, caution should be exercised when comparing DC AIDS rates with those of the states.Reporting delays (i.e., time between diagnosis and report) can differ by geographic location, age, sex, transmission category, and racial/ethnic population.Adjustments for reporting time were calculated for HIV and AIDS cases using a maximum likelihood statistical procedure that accounts for differences in reporting time for the preceding characteristics while assuming the reporting delay has remained constant over time.Adjustments also were made for cases initially reported without transmission category information.Adjustments for adults and adolescents were based on the redistribution of cases across transmission categories by sex, race/ethnicity, and geographic region for cases diagnosed 3-10 years earlier and initially classified as reported without risk factor information but later reclassified.