tbuckley/cabot-search huggingface dataset:
Evaluation of topotecan in resistant and relapsing multiple myeloma: a Southwest Oncology Group study.
Authors: E H Kraut, J J Crowley, J L Wade, L R Laufman, M Alsina, S A Taylor, S E Salmon
Journal: Journal of Clinical Oncology (1998)

PURPOSE Topotecan is a topoisomerase I inhibitor with antitumor activity against hematologic and solid tumor malignancies. We evaluated its activity in refractory and relapsing multiple myeloma patients who had received one prior chemotherapeutic regimen. PATIENTS AND METHODS Toptecan 1.25 mg/m2/d was administered as a 30-minute infusion for 5 days repeated every 3 weeks. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d subcutaneously was administered after the first course of treatment if neutropenia was dose-limiting. RESULTS Forty-six patients entered the study, with 43 patients eligible. The major toxicity was granulocytopenia with grade 3 or better occurring in 40 of 43 patients treated; 21 of 43 patients developed grade 3 or greater thrombocytopenia. Other significant toxicity included mild nausea in 23 patients and mild vomiting in 13 patients. The overall response rate (partial response or better) was 16% (95% confidence interval, 7% to 31%), with responses occurring in both relapsed and refractory patients. Responses have lasted 70 to 477+ days, with a median progression-free survival duration of 13 months and median survival time of 28 months. CONCLUSION Topotecan has activity in refractory and relapsing multiple myeloma. Future investigation of topotecan in multiple myeloma including combination therapy and the study of other topoismerase I inhibitors is warranted.
Current Approaches in Hereditary Nonpolyposis Colorectal Cancer
Authors: Patrick M Lynch
Journal: Journal of the National Comprehensive Cancer Network (2012)

This article emphasizes the central role of tumor-based testing for microsatellite instability followed by performance of genetic counselor-driven germline mutation testing in hereditary nonpolyposis colorectal cancer (HNPCC). Suitably aggressive colorectal neoplasm surveillance is shown to be critical. Limitations of the evidentiary base for extracolonic screening are conceded, with some cautious suggestions for possible strategies notwithstanding the lack of data. Advances in chemoprevention have been made in both familial adenomatous polyposis (clinical trial data favoring eicosapentaenoic acid) and HNPCC (controversial aspirin data). For various reasons, however, no agent or combination of agents has yet come into routine use in either condition, with further trials underway or being designed for both conditions.
Correlation of survival with tumor histology, age, and prognostic risk group for previously untreated patients with advanced renal cell carcinoma (adv RCC) receiving temsirolimus (TEMSR) or interferon-alpha (IFN)
Authors: J. P. Dutcher, C. Szczylik, N. Tannir, P. Benedetto, P. Ruff, A. Hsu, A. Berkenblit, A. Thiele, A. Strahs, J. Feingold
Journal: Journal of Clinical Oncology (2007)

5033 Background: Temsirolimus is a novel mTOR inhibitor and has demonstrated significantly longer overall survival (OS, P=0.0069) and progression-free survival (PFS, P=0.0001) vs IFN for patients (pts) with previously untreated adv RCC with poor-risk features (Hudes et al. ASCO 2006). Planned and post-hoc analyses were performed to assess the influence of tumor histology (clear- cell vs other), age (&lt;65 y vs =65 y), and prognostic-risk groups (intermediate vs poor; Motzer et al. JCO 20:289) on survival in pts treated with TEMSR or IFN. Methods: Pts received IFN 3 million units [MU] subcutaneously 3x weekly, escalating to 18 MU; TEMSR 25-mg intravenous infusion weekly; or TEMSR 15-mg infusion plus IFN 6 MU. Kaplan-Meier analysis and a Cox proportional hazards model were used to analyze OS and PFS for pt subsets. Histologies were reported by investigators. Results: The proportion of pts with different histologies was balanced across the 2 arms (81% clear-cell; 13% indeterminate, 6% non-clear-cell). Of those with additional subtype data, 75% were papillary. For pts with clear-cell tumors, median OS and PFS were longer for TEMSR vs IFN with hazard ratios (HR) of 0.82 and 0.76, respectively ( Table ). For pts with other tumor histologies, median OS and PFS also were longer for TEMSR vs IFN with HR of 0.49 and 0.38, respectively. Among pts &lt;65 y, median OS and PFS were longer for TEMSR than for IFN (OS: TEMSR [n=145] 12.0 mo; IFN [n=142] 6.9 mo; HR=0.62 [95% CI, 0.47, 0.82]; PFS: TEMSR 5.6 mo; IFN 3.1 mo; HR=0.61 [0.47, 0.79]). There was no difference in OS or PFS for pts =65 y treated with TEMSR or IFN but TEMSR had a better side effect profile than IFN. OS and PFS for pts with intermediate- or poor-risk features will be reported. Conclusions: TEMSR benefits pts with clear-cell RCC and other histologies as well as younger and older pts. [Table: see text] No significant financial relationships to disclose.
P-037 Advanced Pancreatic Cancer Patients' Characteristics, Treatment and Outcome Based on Three Age Groups: ≤ 39, 39-74 and ≥ 75, a Report from Single Cancer Institution
Authors: M. Gilabert, R.Y. Soo, T. Kavan, A. Mamo, J. Mc Lean, P. Viens, J.L. Raoul, G. Batist, P. Kavan
Journal: Annals of Oncology (2015)
A preliminary retrospective analysis of weekly topotecan in recurrent small-cell lung cancer
Authors: V. K. Kasturi, J. R. Eckardt, F. A. Greco
Journal: Journal of Clinical Oncology (2004)

7359 Background: Topotecan 1.5 mg/m2 administered IV on days 1 - 5 of a 21-day cycle is a standard regimen in recurrent small-cell lung cancer (SCLC). Topotecan administered weekly may offer improved tolerability in this patient (pt) population. Methods: We are performing a retrospective study to investigate the tolerability and potential treatment benefit of weekly topotecan in pts with recurrent SCLC. Records from pts treated with weekly topotecan after failure of first-line therapy with platinum/etoposide were reviewed. All pts who received topotecan were evaluated for toxicity, and tumor response was determined for pts who had completed ≥ 8 weeks of topotecan therapy. Results: Eleven eligible pts were identified (median age, 55 years; all but 1 had extensive disease SCLC; previous best response (CR:PR:SD:PD; 1:8:1:1); median response duration to first-line therapy of 24 weeks; and chemosensitivity (sensitive: resistant; 8:3). Median starting dose and cycles (3 weeks on, 1 week off) of topotecan were 4 mg/m2/wk (range, 2.5 - 4 mg/m2/wk) and 4 cycles (range, 1 - 16 cycles), respectively. Weekly topotecan was generally well tolerated; the most common hematologic toxicity was grade 3 leukopenia and anemia in 6 and 4 pts, respectively. Erythropoietin and G-CSF were used in 10 and 2 pts, respectively. One case of grade 4 neutropenia was observed. Hematologic toxicity was managed with dose reductions (n = 3) and/or delays (n = 6). Nonhematologic toxicity was generally limited to grade 3 fatigue in 4 pts. Of 9 pts who received ≥ 2 cycles of weekly topotecan, there were 5 PRs, 2 SD, and 2 PD. Two of the PRs were achieved in platinum resistant pts. Median response duration for PR was 26 weeks, and for the 2 pts with SD as best response were 20 and 25 weeks. Conclusions: Topotecan 4 mg/m2 administered in a weekly regimen was well tolerated and appeared to exhibit improved tolerability over historical data with the standard daily × 5 schedule. Our preliminary results suggest that future prospective investigations of weekly topotecan as single-agent therapy and in novel combinations are warranted in this pt population. An updated analysis will be provided. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Abstract 01: The Role of Renin-Angiotensin-Aldosterone System Genes in the Progression of Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Tanika N Kelly, Dominic Raj, Mahboob Rahman, Matthias Kretzler, Radhakrishna R Kallem, Ana C Ricardo, Sylvia E Rosas, Kaixiang Tao, Daiwei Xie, L. Lee Hamm, Jiang He
Journal: Circulation (2015)

Background: We conducted single-marker, gene-based and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort (CRIC) study participants. Methods: A total of 1,523 white and 1,490 black subjects were genotyped for 490 SNPs in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Results: Among white and black participants, eGFR declined an average of 1.2 and 2.3 ml/min/1.73m 2 per year, respectively, while renal events occurred in a respective 11.5% and 24.9% of participants. We identified strong gene and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (all P &lt;1.00х10 -6 ). Driven by the significant gene-based findings, the entire RAAS pathway was also associated with renal events in both groups (both P &lt;1.00х10 -6 ). No single-marker associations with CKD progression were observed. Conclusions: The current study provides strong evidence for a role of the RAAS in CKD progression.
The pharmacokinetics and pharmacodynamics of IMGN242 (huC242-DM4) in patients with CanAg-expressing solid tumors
Authors: A. Qin, J. Watermill, R. A. Mastico, R. J. Lutz, J. O'Keeffe, S. Zildjian, A. C. Mita, A. T. Phan, A. W. Tolcher
Journal: Journal of Clinical Oncology (2008)

3066 Background: IMGN242 is a targeted anticancer agent in development for treating CanAg-expressing tumors. In a Phase I clinical study, patients with CanAg-expressing solid tumors were treated with IMGN242 at doses ranging from 18 to 297 mg/m2. A Phase II study was initiated to evaluate IMGN242 for treating CanAg-expressing gastric cancer at the dose of 168 mg/m2. Methods: The pharmacokinetics and safety are being evaluated in on-going Phase I and II studies of IMGN242 given as a single infusion every three weeks. Blood plasma samples were collected throughout the treatment period to determine the pharmacokinetic properties of IMGN242, to evaluate the levels of circulating CanAg and to assess the formation of human anti-IMGN242 antibodies. Assessment of CanAg expression by immunohistochemical staining was performed on tumor biopsies for all patients in the studies. Results: Forty-five patients have been treated with IMGN242 in two clinical trials. Dose limiting toxicities included decreased visual acuity, corneal deposits and keratitis, which appeared to improve in patients where follow-up data is available. A two-phase pharmacokinetic profile was observed for IMGN242 in plasma from patients with low circulating CanAg levels (<1,000 U/mL), with an initial rapid distribution phase that lasted about 48 hours, followed by a slower terminal elimination phase. Eleven patients were noted to have circulating CanAg levels greater than 1,000 U/mL, although there appeared to be no correlation between high plasma CanAg and the pattern of tumor CanAg expression. High plasma CanAg levels appeared to have a marked impact on the pharmacokinetics of IMGN242 with clearance increased 3 to 5-fold in patients with high CanAg (>1,000 U/mL) compared to patients with low levels (<1,000 U/mL). It appeared that patients who developed study drug-related ocular toxicities had low plasma CanAg levels which may correlate with higher IMGN242 exposure in these patients. Conclusions: There appears to be no correlation between the circulating CanAg level and the tumor CanAg antigen expression in patients. Analysis is being performed to further examine the relationship of pharmacokinetics and pharmacodynamics with regards to dose, plasma CanAg level, and tumor CanAg antigen expression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration ImmunoGen ImmunoGen ImmunoGen
Brief Communication: Graft Versus Leukemia. VI. Adoptive Immunotherapy in Combination With Chemoradiotherapy for Spontaneous Leukemia-Lymphoma in AKR Mice23
Authors: Mortimer M. Bortin, William C. Rose, Robert L. Truitt, Alfred A. Rimm, Edward C. Saltzstein, Glenn E. Rodey
Journal: JNCI Journal of the National Cancer Institute (1975)

A three-step treatment plan incorporating adoptive immunotherapy and chemoradiotherapy was used to treat AKR (H-2k) mice bearing spontaneous leukemia-lymphoma (SLL). 1) Leukemic mice were treated with chemoradiotherapy for immunosuppression and leukemia cytoreduction. 2) To introduce a graft-versus-leukemia reaction against residual malignant cells, the immunosuppressed AKR mice were given immunocompetent cells from H-2 mismatched DBA/2 (H-2d) donors. 3) To “rescue” the AKR hosts from incipient graft-versus-host disease, the mismatched DBA/2 cells were killed with combination chemotherapy, and cells from allogeneic H-2 matched RF (H-2k) donors were administered to restore hematopoiesis. Leukemic AKR mice thus treated had significant prelongation of their median survival time and a higher 6O-day survival rate post treatment than did untreated controls, chemoradiotherapy controls, or control mice that received chemoradiotherapy plus cells from syngeneic donors. Therefore, adoptive immunotherapy may be useful as an adjunct to conventional therapy for treatment of SLL in AKR mice.
Abstract 11518: Stent Edge Dissection and Tiny Reference Vessel Area are Related to Target Lesion Revascularization After Self-expanding Nitinol Stent Implantation in the Superficial Femoral Artery
Authors: Kojiro Miki, Kenichi Fujii, Daizo Kawasaki, Masashi Fukunaga, Masahiko Shibuya, Takahiro Imanaka, Hiroto Tamaru, Motomaru Masutani, Mitsumasa Ohyanagi, Tohru Masuyama
Journal: Circulation (2012)

Background: Previous intravascular ultrasound (IVUS) studies reported that tiny reference vessel cross-sectional area (CSA), stent under-expansion, stent asymmetry, edge dissection, and tissue prot...
Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells
Authors: Fanny Oliveira Arcolino, Silvia Zia, Katharina Held, Elli Papadimitriou, Koen Theunis, Benedetta Bussolati, Anke Raaijmakers, Karel Allegaert, Thierry Voet, Jan Deprest, Joris Vriens, Jaan Toelen, Lambertus van den Heuvel, Elena Levtchenko
Journal: Journal of the American Society of Nephrology (2016)

In humans, nephrogenesis is completed prenatally, with nephrons formed until 34 weeks of gestational age. We hypothesized that urine of preterm neonates born before the completion of nephrogenesis is a noninvasive source of highly potent stem/progenitor cells. To test this hypothesis, we collected freshly voided urine at day 1 after birth from neonates born at 31–36 weeks of gestational age and characterized isolated cells using a single–cell RT-PCR strategy for gene expression analysis and flow cytometry and immunofluorescence for protein expression analysis. Neonatal stem/progenitor cells expressed markers of nephron progenitors but also, stromal progenitors, with many single cells coexpressing these markers. Furthermore, these cells presented mesenchymal stem cell features and protected cocultured tubule cells from cisplatin-induced apoptosis. Podocytes differentiated from the neonatal stem/progenitor cells showed upregulation of podocyte-specific genes and proteins, albumin endocytosis, and calcium influx via podocyte–specific transient receptor potential cation channel, subfamily C, member 6. Differentiated proximal tubule cells showed upregulation of specific genes and significantly elevated p -glycoprotein activity. We conclude that urine of preterm neonates is a novel noninvasive source of kidney progenitors that are capable of differentiation into mature kidney cells and have high potential for regenerative kidney repair.
Rate and Predisposing Factors for Sacroiliac Joint Radiographic Progression After a Two‐Year Follow‐up Period in Recent‐Onset Spondyloarthritis
Authors: Maxime Dougados, Christophe Demattei, Rosaline van den Berg, Viet Vo Hoang, Fabrice Thevenin, Monique Reijnierse, Damien Loeuille, Antoine Feydy, Pascal Claudepierre, Désirée van der Heijde
Journal: Arthritis & Rheumatology (2016)

Objective To evaluate the rate of radiographic structural progression in the sacroiliac (SI) joints in patients with radiographic or nonradiographic axial spondyloarthritis (SpA), and to determine factors predisposing to such progression, over 2 years. Methods Patients with recent‐onset axial SpA (from the Devenir des Spondyloarthropathies Indifferérenciées Récentes cohort) were assigned a radiographic SI joint score according to the modified New York criteria. Demographic characteristics, smoking status, HLA–B27 positivity, inflammation on magnetic resonance imaging (MRI) of the SI joints, disease activity, and treatment were investigated as potential predisposing factors. The main analysis consisted of the evaluation of the switch from nonradiographic to radiographic axial SpA, but other definitions of radiographic progression were also evaluated. Results Of the 708 patients enrolled, 449 had baseline and 2‐year pelvic radiographs. Of these patients, 47% were men. Their mean ± SD age was 34 ± 9 years, 61% were B27 positive, and 37% had inflammation of the SI joints on MRI. The percentages of patients who switched from nonradiographic to radiographic axial SpA (4.9% [16 of 326]) and from radiographic to nonradiographic axial SpA (5.7% [7 of 123]) were low. The mean ± SD change in the total SI joint score (range 0–8) was small (0.1 ± 0.8) but highly significant ( P &lt; 0.001). The potential baseline predisposing factors for meeting the modified New York criteria in the multivariate analysis were current smoking, HLA–B27 positivity, and inflammation of the SI joints on MRI, with odds ratios of 3.3 (95% confidence interval [95% CI] 1.0–11.5], 12.6 (95% CI 2.3–274), and 48.8 (95% CI 9.3–904), respectively. Conclusion Our findings suggest that structural progression does exist in early SpA, but it is quite small and observed in a small number of patients, and that environmental (smoking status), genetic (HLA–B27 positivity), and inflammation (inflammation of the SI joints on MRI) markers might be independent predisposing factors for progression.
Optimization of Conformational Dynamics in an Epistatic Evolutionary Trajectory
Authors: Mariano M. González, Luciano A. Abriata, Pablo E. Tomatis, Alejandro J. Vila
Journal: Molecular Biology and Evolution (2016)

The understanding of protein evolution depends on the ability to relate the impact of mutations on molecular traits to organismal fitness. Biological activity and robustness have been regarded as important features in shaping protein evolutionary landscapes. Conformational dynamics, which is essential for protein function, has received little attention in the context of evolutionary analyses. Here we employ NMR spectroscopy, the chief experimental tool to describe protein dynamics at atomic level in solution at room temperature, to study the intrinsic dynamic features of a metallo-β-lactamase enzyme and three variants identified during a directed evolution experiment that led to an expanded substrate profile. We show that conformational dynamics in the catalytically relevant microsecond to millisecond timescale is optimized along the favored evolutionary trajectory. In addition, we observe that the effects of mutations on dynamics are epistatic. Mutation Gly262Ser introduces slow dynamics on several residues that surround the active site when introduced in the wild-type enzyme. Mutation Asn70Ser removes the slow dynamics observed for few residues of the wild-type enzyme, but increases the number of residues that undergo slow dynamics when introduced in the Gly262Ser mutant. These effects on dynamics correlate with the epistatic interaction between these two mutations on the bacterial phenotype. These findings indicate that conformational dynamics is an evolvable trait, and that proteins endowed with more dynamic active sites also display a larger potential for promoting evolution.
Extranodal Follicular Dendritic Cell Tumor of the Abdominal Wall
Authors: Roderich E. Schwarz, Peiguo Chu, Daniel A. Arber
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.7.2290 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561286 Extranodal Follicular Dendritic Cell Tumor of the Abdominal Wall Roderich E. SchwarzxRoderich E. SchwarzSearch for articles by this author , Peiguo ChuxPeiguo ChuSearch for articles by this author , Daniel A. ArberxDaniel A. ArberSearch for articles by this author Show More City of Hope National Medical Center, Departments of General Oncologic Surgery and Anatomic Pathology, Duarte, CA https://doi.org/10.1200/JCO.1999.17.7.2290 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Progesterone supplements do not reduce risk of recurrent miscarriage, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Progesterone supplements in the first trimester of pregnancy do not improve the rate of live births in women who have unexplained recurrent miscarriages, shows a large study published in the New England Journal of Medicine .1

The study selected 826 women who were trying to conceive naturally after three or more recurrent losses of pregnancy in the first trimester and randomised them to twice daily treatment with vaginal suppositories containing 400 mg of micronised progesterone or matched placebo. They …
Corrigendum to “Profiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: Implications for antiviral therapy” [J Hepatol 2011;54:195–200]
Authors: James Fung, Wai-Kay Seto, Ching-Lung Lai, John Yuen, Danny Ka-Ho Wong, Man-Fung Yuen
Journal: Journal of Hepatology (2016)