tbuckley/cabot-search huggingface dataset:
Intracellular pH regulation in freshly isolated suspensions of rabbit inner medullary collecting duct cells
Authors: D Kikeri, M L Zeidel
Journal: Journal of the American Society of Nephrology (1990)

To define proton transport mechanisms involved in the regulation of intracellular pH (pHi) in cells of the inner medullary collecting duct (IMCD), pHi and cell membrane potential were estimated by using the fluorescent dyes 2,7-biscarboxyethyl-5(6)-carboxyfluorescein and 3,3'-dipropylthiadicarbocyanine iodide, respectively, in suspensions of freshly isolated rabbit IMCD cells. The resting pHi of IMCD cells in nonbicarbonate Ringer's solution (pH 7.4) was 7.21 +/- 0.03 (mean +/- SE). When cells were acidified by ammonium withdrawal, the initial pHi recovery rate was 0.33 +/- 0.02 pH unit/min; replacement of extracellular Na+ (130 mM) with N-methyl-D-glucamine+ reduced the pHi recovery rate to 0.08 +/- 0.02 pH unit/min, while addition of 0.1 mM amiloride in the presence of extracellular Na+ reduced the rate of pHi recovery to 0.02 +/- 0.02 pH unit/min. Similar results were obtained in cells acid loaded with HCl. Cells recovering from acidification exhibited 22Na+ uptake rates threefold higher than did nonacidified cells. The rate of Na(+)-dependent pHi recovery was independent of the cell membrane potential. In the absence of extracellular Na+, depolarizing cell membrane potential in a stepwise manner by increasing extracellular K+ concentrations from 1 to 130 mM resulted in graded increments in the rate of pHi recovery. In the presence of 130 mM K+, the pHi recovery rate in acidified cells was dependent on cellular ATP levels, sensitive to 1 mM N-ethylmaleimide, and insensitive to 0.01 mM oligomycin in the presence of glucose (control, 0.24 +/- 0.01; ATP-depleted, 0.13 +/- 0.02; addition of N-ethylmaleimide, 0.16 +/- 0.01; addition of oligomycin, 0.27 +/- 0.02 pH unit/min). ATP depletion markedly inhibited H+ extrusion from IMCD cells measured by using a pH stat. These results provide direct evidence in freshly isolated IMCD cells that both a Na+:H+ antiporter and a rheogenic H(+)-ATPase participate in pHi regulation.
Gene Expression Profile of the Clinically Aggressive Micropapillary Variant of Bladder Cancer
Authors: Charles Chuanhai Guo, Vipulkumar Dadhania, Li Zhang, Tadeusz Majewski, Jolanta Bondaruk, Maciej Sykulski, Weronika Wronowska, Anna Gambin, Yan Wang, Shizhen Zhang, Enrique Fuentes-Mattei, Ashish Madhav Kamat, Colin Dinney, Arlene Siefker-Radtke, Woonyoung Choi, Keith A. Baggerly, David McConkey, John N. Weinstein, Bogdan Czerniak
Journal: European Urology (2016)
Long-term results of a phase II trial of preoperative concurrent radiochemotherapy for breast cancers.
Authors: M. A. Bollet, L. Belin, V. Dieras, F. Thibault, F. Reyal, F. Campana, Y. M. Kirova, J. Pierga, B. Sigal-Zafrani, A. Fourquet
Journal: Journal of Clinical Oncology (2010)

651 Background: Concurrent radiotherapy (RT) and chemotherapy (CT), two effective treatments for breast cancers (BC), has seldom been reported in the preoperative setting. This phase II trial was designed to investigate its efficacy for operable, nonmetastatic BC not amenable to initial breast-conserving surgery (BCS). The primary endpoint, the in-breast pathological complete response, was 27% with acceptable acute toxicity (Bollet et al., Eur J Cancer, 2006). Methods: From 2001 to 2003, 60 women were included (planned sample size = 50), 1 withdrew her consent leaving 59 studied patients (pts). CT consisted of 4 cycles of 5-FU, 500 mg/m2/d, continuous infusion (d1–d5) and vinorelbine, 25 mg/m2 (d1; d6). Starting with the second cycle, RT delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular areas. Breast surgery and axillary lymph node dissection were then performed. Adjuvant treatment consisted of a 16 Gy boost to the tumour bed after BCS; FEC (4 cycles of fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2, d1;d21) in the case of axillary involvement and hormone-therapy in the case of positive hormone receptors. Median follow-up was 83 months (64-96). Late toxicity was scored according to CTCAE-V3. Results: BCS was performed in 41 (69%) pts, mastectomy in the remaining 18 (31%). Seven pts died of their cancer, 2 developed second non-breast cancers, 3 contralateral BC, 2 local and 7 regional recurrences and 13 distant metastases. Overall and distant- disease-free survivals at 5 years were respectively 88% (95%CI 80-98) and 83% (95%CI 74-93) whereas locoregional and local controls were 90% (95%CI 82-98) and 97% (95%CI 92-100). Late toxicity was assessable at last diagnosis in 51 pts (86%). Four (7%) experienced grade 3 toxicities (1 telangectasia, 3 fibroses), 16 (27%) developed grade 2 (11 fibroses, 10 telangectasia, 1 lymphoedema, 1 dyspnea). Cosmetic results, assessed in 35 of the 41 pts (85%) who retained their breasts, were poor in 4 pts (10%). Conclusions: Preoperative concurrent administration of RT and CT is an effective regimen. Long-term toxicity is moderate. This association should undergo further evaluations in prospective trials. No significant financial relationships to disclose.
The novel antiangiogenic, PTC299, as a treatment for women with metastatic breast cancer.
Authors: A. Tiersten, M. Volm, J. L. Speyer, Y. Novik, B. P. Schneider, M. N. Dickler, L. A. Callahan, C. H. Darby, L. L. Miller, H. H. Miao
Journal: Journal of Clinical Oncology (2010)

e13537 Background: PTC299 is a novel oral investigational drug designed to inhibit tumor expression of VEGF and other angiogenic cytokines. PTC299 also induces a parallel interruption of tumor cell division at the G1/S phase of the cell cycle. In preclinical models of breast cancer, PTC299 shows antitumor activity alone and in combination with aromatase inhibitors. Methods: In stage 1 of this phase Ib, open-label, dose-ranging, escalating-dose, safety, pharmacokinetic, and pharmacodynamic study, women with metastatic breast cancer received PTC299 at dose levels of 0.3 mg/kg, 0.6 mg/kg, or 1.2 mg/kg BID in repeated 6-week cycles (4 weeks on, 2 weeks off therapy). In stage 2, patients received PTC299 at 100 mg BID continuously in combination with letrozole, anastrozole, or exemestane. Final accrual will be completed by the time of the meeting. Results: Stage 1 enrolled 9 patients (3 per dose level) with median age [range] of 58 [32-76] years, ECOG PS of 0 (n=1) or 1 (n=8), and extensive prior treatment with hormonal (patient n=6), chemotherapy (n=9), and/or antiangiogenic agents (n=6). Stage 2 enrolled 13 patients with median age [range] of 56 [34-82] years, ECOG PS of 0 (n=7) or 1 (n=6), and ≥1 prior hormonal therapy (n=11) to receive PTC299 with letrozole (n=7), anastrozole (n=3), or exemestane (n=3). Across both stages, no dose-limiting toxicity was observed; adverse events were infrequent and not obviously PTC299-related. No hypertension, bleeding, thromboembolism, or proteinuria were seen. Drug plasma concentrations exceeded the maximally active plasma trough levels identified in preclinical models. Disease stabilization through ∼6 months and ∼4.5 months was observed in 2 patients at 1.2-mg/kg BID of PTC299 in stage 1. A complete response by CT scan and a complete response by PET scan occurred in 2 patients receiving PTC299 and letrozole in stage 2. Reductions in tumor perfusion and metabolism were observed in additional patients. Conclusions: In patients with metastatic breast cancer, PTC299 is generally well tolerated, achieves target plasma concentrations, and shows antitumor and pharmacodynamic activity. Supported by a grant award from the Department of Defense. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PTC Therapeutics PTC Therapeutics
3D Quantitation of Sinonasal Inflammation Correlates with Symptoms and Disease-Specific Quality of Life in Patients with Rhinosinusitis
Authors: Sooyoung Lim, Michael Ramirez, Katherine McKeough, Adam Starkey, Fawwaz Qayyum, Jonathan Garneau, Megan K. Ford, William F. Sensakovic, Daniel T. Ginat, Samuell G. Armato, Fuad M. Baroody, Jayant M. Pinto
Journal: Journal of Allergy and Clinical Immunology (2016)
Health Care Delivery Innovations That Integrate Care? Yes!
Authors: Regina E. Herzlinger, Stephen M. Schleicher, Samyukta Mullangi
Journal: JAMA (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 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
Therapy-related leukemia: a necessary complication of successful systemic chemotherapy?
Authors: G P Canellos
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.10.1077 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6491695 Therapy-related leukemia: a necessary complication of successful systemic chemotherapy? G P CanellosxG P CanellosSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.10.1077 First Page PDF © 1984 by American Society of Clinical Oncology
Chemotherapeutic Activity of New 2-Chloroethylnitrosoureas in Rat L5222 Leukemia: Comparison of Bifunctional and Water-Soluble Derivatives With 1,3-Bis(2-chloroethyl)-1-nitrosourea
Authors: W. Jens Zeller, Gerhard Eisenbrand, Heinz H. Fiebig
Journal: JNCI Journal of the National Cancer Institute (1978)

The chemotherapeutic activity of eight nitrosourea derivatives was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in transplantable rat leukemia L5222 cells. Bifunctional 1,1′-polymethylenebis-3-(2-chloroethyl)-3-nitrosoureas effected cure rates between 30 and 75% in single equitoxic doses in the therapy of advanced ip implanted L5222 [staging of L5222 leukemia development (hr before median day of death in controls): early=<120; advanced=120-61; late=60-25; and preterminal= 24-0). Of three water-soluble monofunctional alkylatlng 1-(ω-hydroxyalkyl)-3-nitrosoureas, 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea yielded more cures (90%) than did BCNU (cure rate, 70%) and was also superior to the other substances. Against preterminal ip implanted and late intracerebrally implanted L5222, the hydroxyethyl compound was significantly superior to BCNU.
Reply to Matsushita et al.
Authors: K.-M.  Chu
Journal: Endoscopy (2003)

I would like to thank Dr. Matsushita and colleagues for their interest in my article [1]. Apart from stromal tumors, submucosal lesions of the stomach are uncommon. Ectopic pancreas and, more rarely, adenomyoma are occasionally reported. The histological features of adenomyoma were first described in 1903 by Magnus-Alsleben after incidental identification of five cases at autopsy [2]. While only fewer than 40 cases of gastric adenomyoma had been described up to 1993 [3], ectopic pancreas is relatively more common, with a reported incidence of about 0.25 % during abdominal operations [4].
Differentiation dependent expression of P-glycoprotein in the normal and neoplastic human kidney
Authors: C.K. van Kalken, P. van der Valk, M.M.N. Hadisaputro, R. Pieters, H.J. Broxterman, C.M. Kuiper, G.L. Scheffer, A.J.P. Veerman, C.J.L.M. Meyer, R.J. Scheper, H.M. Pinedo
Journal: Annals of Oncology (1991)
Charles Edmunds Darby Taylor
Authors: Anita Rampling
Journal: BMJ (2016)

Charles Edmunds Darby Taylor (widely known as Eddie) was educated at Malvern College, Emmanuel College, Cambridge, and Middlesex Hospital Medical School. He qualified in 1946 and gained experience in a variety of posts. He met his future wife, Eileen, while serving in the Royal Army Medical Corps in the British Military Hospital, Berlin. He joined the Public Health Laboratory Service (PHLS) in 1954 as a trainee. This gave him the opportunity to …
Paralytic Disease Due to Infection with Echo Virus Type 9
Authors: John F. Foley, Tom D. Y. Chin, Clifton R. Gravelle
Journal: New England Journal of Medicine (1959)

DURING the past two years infections with ECHO virus Type 9 have been widespread in the United States. In 1957 they appeared in epidemics in Minnesota1 and in Wisconsin.2 Their prevalence in the Boston area during 1958 has recently been pointed out in this journal.3 Infections with this virus have principally been associated with benign aseptic meningitis and minor febrile illness, either with or without a rubelliform type of rash. Only a few patients have been reported to have paralysis as a part of the symptom complex. The paralytic case reported below was well documented by virologic and antibody studies. . . .
Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy
Authors: John Eng, Renee F. Wilson, Rathan M. Subramaniam, Allen Zhang, Catalina Suarez-Cuervo, Sharon Turban, Michael J. Choi, Cheryl Sherrod, Susan Hutfless, Emmanuel E. Iyoha, Eric B. Bass
Journal: Annals of Internal Medicine (2016)

Background: Iodine contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN). Purpose: To compare CIN risk for contrast media within and between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures. Data Sources: PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015. Study Selection: Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging. Data Extraction: Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results. Data Synthesis: None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 [95% CI, 0.65 to 0.99]; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk. Limitations: Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment. Conclusion: No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance. Primary Funding Source: Agency for Healthcare Research and Quality.
Acute Vasodilator Response in Pediatric Pulmonary Arterial Hypertension
Authors: Johannes M. Douwes, Tilman Humpl, Damien Bonnet, Maurice Beghetti, D. Dunbar Ivy, Rolf M.F. Berger, R.G. Weintraub, R. Geiger, M. Marx, Z.C. Jing, L. Sondergaard, C. Apitz, A. Hager, A. Szatmari, O. Milanesi, T. Saji, T. Pulido, J. Moll, K.W. Michalak, W. Kawalec, M. Zuk, M. Fasnacht Boillat, R. Olguntürk, S. Kula, D. Alehan, I. Schulze-Neick, A.M. Atz, G.B. Mallory, E.D. Austin, D.J. Moore, J.A. Feinstein, R.W. Day, D. Yung, J.T. Berger
Journal: Journal of the American College of Cardiology (2016)
Preliminary phase II SOCRATES study results: Capecitabine (CAP) combined with oxaliplatin (OX) and preoperative radiation (RT) in patients (pts) with locally advanced rectal cancer (LARC)
Authors: R. Glynne-Jones, D. Sebag-Montefiore, A. McDonald, S. Falk, T. Maughan
Journal: Journal of Clinical Oncology (2004)

3575 Background: CAP, an oral fluoropyrimidine preferentially activated to 5-FU in tumors by the enzyme thymidine phosphorylase (TP), has superior antitumor activity and favorable safety compared with bolus i.v. 5-FU/LV in pts with metastatic colorectal cancer (MCRC). OX plus 5-FU/LV further improves outcomes in MCRC. Preclinical xenograft models show that RT and OX both upregulate tumor TP vs normal tissue. The aim of this study was firstly to determine the recommended dose of neoadjuvant CAP in combination with OX and pelvic RT in pts with LARC, and secondly to assess the efficacy and safety of this regimen. Methods: Pts with primary unresectable LARC took CAP (500, 650, 825mg/m2 twice daily) 7 days/week during RT and received i.v. OX 130mg/m2, days 1 and 29, and RT (25 fractions of 1.8Gy; 45Gy total over 25 days). After identifying the maximum tolerated dose (MTD) of CAP, the study continued into phase II for a total sample size of 80 pts. Results: Currently we have enrolled 52 patients; six in each phase I cohort, and another 34 in phase II. Median age is 55 years (24–75); most pts are male (76%), and Caucasian (97%). All pts were staged T3/T4 by pre-operative MRI. Dose-limiting toxicities (DLTs) occurred in 2/6 pts receiving CAP 825mg/m2 (grade 3 diarrhea and moist desquamation), establishing the MTD at this dose. CAP 650mg/m2 twice daily is being used in the ongoing phase II. To date, 42 pts have undergone surgery. Complete pathologic responses occurred in 9 (21%) of pts, a further 10 (24%) were downstaged to ypT1T2N0 and 36 (77%) had tumor-free circumferential resection margins. Among 34 pts evaluable for safety, the most common (≥20%) treatment-related adverse events (AEs) were paresthesia (79%), diarrhea (62%), neuropathy (38%), and nausea (38%). Most AEs were mild (64% G1–2). In phase II 2/34 pts had G3–4 diarrhea and 1/34 had G3–4 lethargy. Conclusions: The recommended dose of neoadjuvant CAP is 650mg/m2 twice daily with OX 130mg/m2 (days 1 and 29) and pelvic RT. The regimen is well tolerated and shows promising activity in LARC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche; Sanofi Roche Roche
Center Experience and Calendar Year Of Transplantation Strongly Influence Short Term Survival After Autologous Peripheral Blood Transplantation In 1315 Patients With Light Chain Amyloidosis: An EBMT Analysis
Authors: Stefan O Schonland, Ute Hegenbart, Simona Iacobelli, Jennifer Hoek, M Rovira, Guustaaf van Imhoff, G Bandini, Ulf-Henrik Mellqvist, Veronique Leblond, Kristina Carlson, Samo Zver, Didier Blaise, Emilio Paolo Alessandrino, Laurent Garderet, Nicolaus Kröger
Journal: Blood (2013)
A functional polymorphism in the CEBPE gene promoter influences acute lymphoblastic leukemia risk through interaction with the hematopoietic transcription factor Ikaros
Authors: J L Wiemels, A J de Smith, J Xiao, S-T Lee, M O Muench, M E Fomin, M Zhou, H M Hansen, A Termuhlen, C Metayer, K M Walsh
Journal: Leukemia (2015)
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia
Authors: Tatjana Pandzic, Jimmy Larsson, Liqun He, Snehangshu Kundu, Kenneth Ban, Muhammad Akhtar-Ali, Anders R. Hellström, Anna Schuh, Ruth Clifford, Stuart J. Blakemore, Jonathan C. Strefford, Tycho Baumann, Armando Lopez-Guillermo, Elias Campo, Viktor Ljungström, Larry Mansouri, Richard Rosenquist, Tobias Sjöblom, Mats Hellström
Journal: Clinical Cancer Research (2016)

To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control.We used piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line.In total, this screen identified 782 genes with transposon integrations in fludarabine-resistant pools of cells. One of the identified genes is a known resistance mediator DCK (deoxycytidine kinase), which encodes an enzyme that is essential for the phosphorylation of the prodrug to the active metabolite. BMP2K, a gene not previously linked to CLL, was also identified as a modulator of response to fludarabine. In addition, 10 of 782 transposon-targeted genes had previously been implicated in treatment resistance based on somatic mutations seen in patients refractory to fludarabine-based therapy. Functional characterization of these genes supported a significant role for ARID5B and BRAF in fludarabine sensitivity. Finally, pathway analysis of transposon-targeted genes and RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL.To our knowledge, this is the first forward genetic screen for chemotherapy resistance in CLL. The screen pinpointed novel genes and pathways involved in fludarabine resistance along with previously known resistance mechanisms. Transposon screens can therefore aid interpretation of cancer genome sequencing data in the identification of genes modifying sensitivity to chemotherapy. Clin Cancer Res; 22(24); 6217-27. ©2016 AACR.