tbuckley/cabot-search huggingface dataset:
Modulation of immune cell subpopulations in renal cell carcinoma patients by sunitinib.
Authors: B. Seliger, C. Giersberg, M. D. Staehler
Journal: Journal of Clinical Oncology (2011)

395 Background: Increased numbers of immune suppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) as well as alterations in the frequency and function of activated and memory T cells in peripheral blood mononuclear cells (PBMNC) represent immune escape mechanisms of renal cell carcinoma (RCC). The tyrosine kinase inhibitor sunitinib, which is currently successfully implemented in the treatment of RCC has been shown to modulate immune suppressive cells as well as T lymphocytes thereby shifting the immune balance in these patients to a more stimulating setting. Methods: Using flow cytometry and a large panel of antibodies directed against different immunomodulatory molecules, we here analysed the effects of (i) adjuvant sunitinib treatment (50 mg for 4 weeks, on 2 weeks off) on the composition of various immune cell populations, their function and activity in RCC patients and (ii) sunitinib treatment of PBMNC from healthy donors over time Results: A time-dependent decrease in the frequency of Treg and MDSC was found in PBMNCs during in vitro and in vivo sunitinib treatment. In addition, the number of NK cells, activated and/or memory T cells was increased in PBMNC of TKI-treated patients over time. Conclusions: This observation may have important implications for (i) the monitoring of the sunitinib activity on immune cells, (ii) the treatment schedule including duration of TKI therapy, and (iii) the implementation of sunitinib in combination with immunotherapies in RCC patients. Long-term monitoring of a larger patients' group will show whether the activation of T cells and NK cells as well as the decrease of immune suppressive cells due to sunitinib treatment is associated with enhanced antitumor responses. [Table: see text]
Flow-Cytometric Minimal Residual Disease Determination Is a Surrogate Prognosticator in Adult AML Patients Lacking Specific Molecular Signatures.
Authors: Francesco Buccisano, Luca Maurillo, Giovanni Del Poeta, Maria Ilaria Del Principe, Daniela Fraboni, Emanuele Ammatuna, Maria Irno Consalvo, Paola Panetta, Licia Ottaviani, Sabrina Faccia, Manuela Rizzo, Massimiliano Postorino, Maria Cantonetti, Francesco Lo Coco, Sergio Amadori, Adriano Venditti
Journal: Blood (2007)
Effect of adding TS-1 to neoadjuvant chemotherapy in HER2-negative, stage II-III breast cancer in a single-arm phase ll study.
Authors: S. Lee, Y. Moon, B. Park, S. I. Kim, S. Park, J. Kim, H. J. Choi, J. H. Sohn
Journal: Journal of Clinical Oncology (2011)

e11549 Background: TS-1 is an orally administered fluorinated pyrimidine, composed of tegafur, gimestat and otastat potassium at a molar ratio of 1:0.4:1 that has limited evidence for use in breast cancer. This study’s purpose was to determine the efficacy the doxorubicin/cyclophosphamide (AC) followed by docetaxel and TS-1 (DS) in the preoperative setting. Methods: Patients with HER2-negative, axillary node-positive, high-risk breast cancer received four cycles of AC (doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 on day 1 every 3 weeks), followed by four cycles of DS (docetaxel 75mg/m2 on day 1 and TS-1 30mg/m2 bid on days 1-14 every 3 weeks). Primary end point was the pathologic complete response (pCR) rate. Results: From June 2009 to December 2010, 40 of 48 patients were enrolled and 24 patients were assessable for both clinical and pathologic responses. The overall response rate was 91.7%. The pCR rate was 25% (6 of 24) which made of 3 triple-negative breast cancer patients and 3 hormone-positive breast cancer patients. Grade 3/4 neutropenia was observed in 16.7% of patients. The most common grade 3/4 non-hematologic adverse event was gastrointestinal discomfort, observed 20.8% of patients. Two patients were dropped out during DS treatment period because of TS-1 toxicity. A 25% dose reduction of docetaxel and/or TS-1 occurred in 50% (11 of 22) patients. Conclusions: Although this study is not yet completed, these data indicate that the sequential combination of AC followed by DS is an effective neoadjuvant treatment option for stage ll/lll breast cancer but the toxicity needs to be monitored closely.
A Comparison of Five Different Culture Protocols Shows That Growth of Human CD34+ Peripheral Blood Stem Cells in SCF, IL-3, Flt-3 Ligand and EPO Results in Exponential Erythroid Expansion and a Globin Gene Expression Pattern Which Is Similar to That Seen in Human Bone Marrow.
Authors: Rodwell H. Mabaera, Christopher H. Lowrey
Journal: Blood (2005)
The Positive Effect of Inpatient Care-Partners During Allogeneic Bone Marrow Transplantation; A Prospective Trial
Authors: Linda McLellan, Larry Foster, Lisa Rybicki, Jane Dabney, Michele Cooper, Hien Duong, Ronald Sobecks, Matt Kalaycio, Edward A. Copelan, Robert Dean, Brad Pohlman, Steven Andresen, Shawnda Tench, Brian J. Bolwell
Journal: Blood (2010)
A Functional Variation In the NKG2D Gene Regulates NKG2D Receptor Expression and Is Associated with Better Transplant Outcomes After Fully-HLA-Matched Unrelated Bone Marrow Transplantation
Authors: Luis J. Espinoza, Akiyoshi Takami, Katsuji Yoshioka, Katsuya Nakata, Shinji Nakao
Journal: Blood (2010)
The Class Effect of Tyrosine Kinase Inhibiotrs on Impaired Platelet Aggregation on Stimulation with Collagen and Arachidonic Acid
Authors: Warit Wangsuekul, Lalita Norasetthada, Adisak Tantiworawit, Ekarat Rattarittamrong, Chatree Chai-Adisaksopha, Sasinee Hantrakool, Thanawat Rattanathammethee
Journal: Blood (2015)
NPM1+/FLT3- Patients with Acute Myeloid Leukemia (AML) Have Excellent Clinical Outcome Independent of Age When Treated with Cytotoxic Chemotherapy: Mayo Clinic Experience
Authors: Mehrdad Hefazi Torghabeh, Mustaqeem A Siddiqui, Mrinal M. Patnaik, Alexandra Wolanskyj, Darci Zblewski, Michelle Elliott, William J Hogan, Mark R. Litzow, Aref Al-Kali
Journal: Blood (2014)
Irritability, fear, and anxiety often precede major depression in adolescents with high familial risk
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Irritability, fear, and anxiety are likely to precede the onset of major depressive disorder (MDD) in children and adolescents with a family history of the condition, a study published in JAMA Psychiatry shows.1

To examine the developmental pathways to the first episode of MDD in adolescents at high familial risk, UK researchers followed 337 families in which a parent (315 mothers, 22 fathers) had experienced at least …
Prediction of favorable outcome in a docetaxel rechallenge setting in metastatic castration-resistant prostate cancer.
Authors: Matthias Michael Heck, Mark K. Thalgott, Margitta Retz, Petra Wolf, Tobias Maurer, Juergen Gschwend, Hubert Kuebler
Journal: Journal of Clinical Oncology (2012)

68 Background: To identify predictors of favourable oncological outcome in metastatic castration-resistant prostate cancer (mCRPC) patients who are treated with docetaxel rechallenge following first-line chemotherapy with docetaxel. Methods: We retrospectively evaluated the oncological outcome of mCRPC patients who were treated with 3-weekly docetaxel (75mg/m 2 ) at first-line chemotherapy and rechallenge plus prednisone/ prednisolone. The endpoints of oncological outcome were PSA-progression-free survival (PSA-PFS) and overall survival (OS) after initiation of docetaxel rechallenge. The effect of clinical variables on PSA-PFS and OS was statistically analysed by a log-rank test or Cox regression with hazard ratios. All analyses were performed using a 0.05 level of significance. Results: 47 patients were included on analysis. At a median follow-up of 25.8 months (range 9.8-89.8 months) after the first administration of docetaxel, 27 (57.4%) patients had died. Median PSA-PFS was 5.9 months (95% CI 3.5-6.8 months) and median OS was 21.4 months (95% CI 18.9-23.9 months) after initiation of docetaxel rechallenge. PSA-reduction ≥ 30% was the only pre-treatment variable that correlated significantly with prolonged PSA-PFS (p=0.03) and OS (p=0.002). Patients with PSA-reduction ≥ 30% at first-line chemotherapy showed a median OS of 21.8 months since initiation of docetaxel rechallenge in comparison to 4.5 months in patients with &lt; 30% PSA-reduction. Conclusions: Docetaxel rechallenge represents an active treatment option in selected docetaxel-pretreated patients with mCRPC. In this retrospective study, PSA-reduction ≥ 30% at first-line chemotherapy with docetaxel predicted superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.
Mantle Cell Lymphoma Can Be Cured by Intensive Immunochemotherapy with In-Vivo Purged Stem-Cell Support; Final Report of the Nordic Lymphoma Group MCL2 Study.
Authors: Christian H. Geisler, Erkki Elonen, Arne Kolstad, Anna Laurell, Niels Andersen, Lone B. Pedersen, Anne Marie Boesen, Mikael Eriksson, Mats Jerkeman, Eva Kimby, Outi Kuittinen, Grethe F. Lauritzen, Herman Nilsson-Ehle, Marie Nordström, Elisabeth Ralfkiaer, Måns Åkerman, Mats Ehinger, Christer Sundström, Ruth Langholm, Jan Delabie, Marja-Liisa Karjalainen-Lindsberg, Peter Brown
Journal: Blood (2007)
The Beneficial Impact of KIR-Ligand Mismatch and Absence of Donor-KIR2DS3 Gene On Outcome Following Unrelated Donor Stem Cell Transplantation for Myeloid Leukemia.
Authors: Gongqiang Wu, Yanmin Zhao, Xiaoyu Lai, Yamin Tan, Yi Luo, Jimin Shi, Wanzhuo Xie, Li Li, Gaofeng Zheng, Zhen Cai, Maofang Lin, He Huang
Journal: Blood (2009)
Immune Tolerance Resulting in a Dramatic Clinical Improvement in a High-Responding Inhibitor Hemophilia A Patient Using Immunosuppression with Mycofenolate Mofetil and a Factor VIII Concentrate Containing Von Willebrand Factor.
Authors: Thierry Lambert, Cécile Goujard, Anne Rafowicz, Benoît Guillet, Yacine Taoufik, Marie Dreyfus
Journal: Blood (2005)
A South African perspective on health care resource utilization in cancer: Contextualizing the South African private sector demographic.
Authors: S. D. Moodley
Journal: Journal of Clinical Oncology (2011)

e11534 Background: Oncology drugs account for 10–20% of cancer healthcare costs. South Africa’s healthcare sector poses the challenge of providing access to new yet affordable medicines. Methods: Sanofi-aventis South Africa conducted Taxpas; an open label multi-centre survey done in a local community based setting in the private health sector. The primary objective of the survey was to assess the total cost of a patient treated with Taxotere with a secondary objective of survival. Nationally 125 oncologists from 46 centres enrolled 2,147 patients over a 6 year period. There are 1,632 breast cancer and 507 other cancer patients. Interim data of the first 789 validated breast cancer patients is available. The following is analysis of this population. Results: The average age was 51.2 years with a median BSA of 1.80. At first diagnosis 419 (57.2%) patients presented with early breast cancer and 313 (42.8%) patients presented with metastatic breast cancer with a 1 year survival of 381 (97.4%) and of 195 (65%) patients respectively. For survival we report it as per receptor status; estrogen receptor (ER), progesterone receptor (PR) and HER-2. The most interesting find was when all three receptors were negative, which fits the definition of the triple negative breast cancers. The total number of patients in this group was 119 (15%) of the total breast cancer patients. 80% of this population received Taxotere as a single agent with a survival 82% at 1 year. This triple negative receptor population fits into the incidence of triple negative breast cancers globally i.e. of 15–20 % of breast cancer patients. Conclusions: The complete cost analysis of resource utilization will be reported once those data are collated. We were able to delineate the incidence of triple negative breast cancer incidence in this South African cohort and demonstrate their survival.
Relationship of STAT3-mediated treatment resistance on activated MAPK signaling in pancreatic cancer.
Authors: Nagaraj S. Nagathihalli, Yugandhar Beesetty, Chanjuan Shi, Nipun B. Merchant
Journal: Journal of Clinical Oncology (2012)

181 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult human malignancies to treat due to its intrinsic (de novo) and extrinsic (acquired) chemoresistance. We have previously identified constitutively activated STAT3 as a mediator of treatment resistance. Src or EGFR activate STAT3 and promote STAT3 mediated tumor progression and mediate communication within the tumor microenvironment (TME). The purpose of this study was to further understand the molecular mechanisms of stromal-mediated chemoresistance in PDAC to generate new and promising targeted therapies. Methods: We characterized the expression of total and activated STAT3 and MAPK proteins in human pancreatic tissues (n=106), PDAC cell lines (n=9) and in PanIn lesions, primary PDAC and liver metastasis cell lines generated from tumors established in genetically engineered mice. Effects of STAT3 and MAPK inhibition (drug or siRNA) were assessed for phosphorylation of STAT3, Src, MAPK, EGFR and GSK3β and expression of cyclin-D1, SPARC, VEGF, fibronectin, CD31 and tumorigenicity in vitro and in vivo. Results: STAT3 activation is necessary for the malignant phenotype and affects survival in PDAC. In both human and mouse PDAC cell lines and tissues, there is an inverse correlation between activation of STAT3 on MAPK and GSK3β signaling. Inhibition of STAT3 reciprocally activated MAPK, GSK3β, Src and EGFR which led to subsequent reactivation of STAT3. Targeting both STAT3 and MAPK inhibited activation of STAT3, MAPK, GSK3β, Src, EGFR and cyclin-D1. Combined inhibition of STAT3 and MAPK overcame STAT3 mediated resistance and resulted in synergistic inhibition of tumorigenicity as well as inhibition of the tumor stroma, angiogenesis and hypoxia within the TME. Conclusions: The mechanism of STAT3-mediated treatment resistance is dependent on activation of MAPK signaling which in turn leads to reactivation of multiple oncogenic signaling pathways. Combined inhibition of STAT3 and MAPK overcomes therapeutic resistance, targets the TME and reduces tumorigenicity in PDAC. Targeting STAT3 and MAPK is a potent treatment regimen and may be a novel approach to enhance drug delivery and improve therapeutic response in PDAC.
Stimulation of B-Cell Lymphoproliferations with CpG-Oligonucleotide DSP30 Plus IL-2 Is More Effective than with TPA to Detect Clonal Abnormalities.
Authors: Stéphanie Struski, Carine Gervais, Catherine Helias, Raoul Herbrecht, Bruno Audhuy, Laurent Mauvieux
Journal: Blood (2008)
A phase I trial of combined tivozanib (AV-951) and temsirolimus therapy in patients (pts) with renal cell carcinoma (RCC).
Authors: F. F. Kabbinavar, S. Srinivas, R. J. Hauke, R. J. Amato, B. Esteves, R. Dhillon, M. M. Cotreau, M. Al-Adhami, P. Bhargava, M. N. Fishman
Journal: Journal of Clinical Oncology (2011)

330 Background: Tivozanib, a potent and selective tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3, has demonstrated antitumor activity in a phase II study in RCC (Proceedings of ASCO 2009, Abstract 5032). Temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is approved for treatment of advanced RCC. This phase Ib open-label study examined combination tivozanib and temsirolimus therapy in pts with advanced RCC to determine the safety and tolerability, maximum tolerated dose (MTD), and clinical activity of this drug regimen. Methods: Pts with advanced RCC (with clear cell component) who had failed up to 1 prior VEGF-targeted therapy received daily oral tivozanib (3 wks on, 1 wk off = 1 cycle) and intravenous temsirolimus (once weekly). A standard 3+3 dose escalation design was used at four levels: 0.5 mg/d tivozanib and 15 mg/wk temsirolimus; 1.0 mg/d and 15 mg/wk; 1.5 mg/d and 15 mg/wk; and 1.5 mg/d and 25 mg/wk. Results: As of 9/15/10, 28 pts had been treated and accrual was closed. Demographic features were: 26 male/2 female; 89% Caucasian; median age 62 years (range, 43–71); Karnofsky Performance Status of 100/90/80 for 16, 7, and 4 pts respectively (1 pt missing data). Twenty of 28 pts (71%) had received prior VEGF-targeted therapy. Median duration of treatment was 21.1 wks (range, 0.3–94.0). Treatment-related adverse events seen in ≥10% of pts were (number of pts with all grades/grade 3 toxicity): fatigue (14/3), decreased appetite (9/0), stomatitis (7/1), thrombocytopenia (6/1), diarrhea (6/0), nausea (6/1), vomiting (3/0), and decreased weight (3/0). There were no grade 4 events. The MTD of this combination was tivozanib 1.5 mg/d and temsirolimus 25 mg/wk, and no dose limiting toxicities were encountered. Clinical activity was observed, including tumor responses in pts who had failed VEGF targeted therapies. Conclusions: The combination of tivozanib with temsirolimus was well tolerated and showed clinical activity in patients with advanced RCC. Tivozanib is the first VEGFR TKI that can be combined with temsirolimus at the full dose and schedule of both agents. [Table: see text]
Stereotactic body radiotherapy for low-risk prostate cancer: Five-year outcomes.
Authors: D. Freeman, C. R. King
Journal: Journal of Clinical Oncology (2011)

94 Background: Hypofractionated, stereotactic body radiotherapy (SBRT) is an emerging treatment approach for prostate cancer. We present the outcomes for low-risk prostate cancer patients with a median follow-up of 5 years after SBRT. Methods: Between Dec. 2003 and Dec. 2005, a pooled cohort of 41 consecutive patients from Stanford, CA and Naples, FL received SBRT with CyberKnife for clinically localized, low-risk prostate cancer. Prescribed dose was 35–36.25 Gy in five fractions. No patient received hormone therapy. Kaplan-Meier biochemical progression-free survival (defined using the Phoenix method) and RTOG toxicity outcomes were assessed. Results: At a median follow-up of 5 years the biochemical progression-free survival was 93% (95% CI = 84.7% to 100%). Acute side effects resolved within 1–3 months of treatment completion. There were no grade 4 toxicities. No late grade 3 rectal toxicity and only one late grade 3 genitourinary toxicity occurred following repeated urologic instrumentation. Conclusions: Five-year results of SBRT for localized prostate cancer demonstrate the effectiveness and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are expected to further support this experience. [Table: see text]
Results of a high-throughput screen to identify compounds that modulate VHL proteostasis.
Authors: Zhiyong Ding, Peter German, Shanshan Bai, Meng Gao, Mary M. Sobieski, Clifford C. Stephan, Gordon B. Mills, Eric Jonasch
Journal: Journal of Clinical Oncology (2012)

369 Background: Mutated von Hippel Lindau (VHL) protein causes disease in sporadic renal cell carcinoma (RCC), and in the eponymous hereditary VHL disease. We developed and tested a cell-based screening tool to identify compounds that stabilize or upregulate full-length, point mutated VHL, and potentially reverse the disease phenotype. Methods: The 786-0 cell line was infected with full-length W117A mutated VHL linked to a C-terminal Venus fluorescent protein. This VHL-W117A-Venus line was used to screen the Prestwick drug library and was tested against the known proteasome inhibitors MG132 and bortezomib. Western blot validation and evaluation of downstream functional readouts, including HIF and GLUT1 levels, were performed. Results: The proteasome inhibitors bortezomib and MG132, and the Prestwick compounds 8-azaguanine, thiostrepton and thioguanosine were found to reliably upregulate VHL-W117A-Venus in 786-0 cells. Thiostrepton has also been recognized as having proteasome inhibitory effects. 8-azaguanine was found to downregulate HIF2α levels, and was augmented by the presence of VHL W117A. VHL p30 band intensities varied as a function of compound used, suggesting alternate post-translational processing. In addition, nuclear-cytoplasmic localization of pVHL varied amongst the different compounds, additionally suggesting unique effects of each of the agents on VHL homeostasis. Conclusions: We have successfully identified compounds that stabilize mutated VHL, including several proteasome inhibitors. It is possible that proteasome inhibition will have a specific clinical effect on patients with point-mutated pVHL. Further work is currently underway to further test this hypothesis in animal xenograft studies using cell lines containing various mutated VHL isoforms, and clinical trials using next-generation proteasome inhibitors are being explored.
One Step Further Toward Defining the Optimal Respiratory Care Package for Neonates
Authors: Sanja Zivanovic, Charles Christoph Roehr
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Trends in Palliative Care Use in Elderly Men and Women With Severe Heart Failure in the United States
Authors: Monique R. Robinson, Sadeer G. Al-Kindi, Guilherme H. Oliveira
Journal: JAMA Cardiology (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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Intracellular NAD+ Depletion Enhances Bortezomib-Induced Myeloma Cytotoxicity
Authors: Antonia Cagnetta, Michele Cea, Chirag Acharya, Teresa Calimeri, Yu-Tzu Tai, Teru Hideshima, Dharminder Chauhan, Franco Patrone, Marco Gobbi, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2012)