tbuckley/cabot-search huggingface dataset:
Thalidomide use in general oncology practice: A single institution experience
Authors: M. Billstrand, L. P. Duong, F. C. Lee
Journal: Journal of Clinical Oncology (2004)

3161 Background:Since the approval of thalidomide by the FDA in 1998, there has been wide off-label use in oncology based on its purported cytokine modulating and anti-angiogenesis properties. We conducted a retrospective review on the use of thalidomide in a single institution to evaluate its role in cancer treatment and palliation. Methods: From Dec 1, 1999 to July 31, 2003, an estimated 110 patients have been enrolled in the thalidomide education (STEPS Program) database. Patients enrolled but did not take thalidomide were excluded. 45 patients have been evaluated so far. All cancer diagnoses are included. Clinical response is recorded by using a 1–4 ranking (1-responsive, 2-stable, 3-progressive, 4-death). A 1 or 2 ranking is considered a positive response to thalidomide. Patients are further divided into two groups: treated with thalidomide alone or treated with any concurrent chemotherapy agents. Results: 38 of the 45 reviewed charts contained adequate information to evaluate tumor response. All had prior chemotherapy before starting thalidomide (median 2 regimens, range 1–4). Mean dose of thalidomide is 169 mg/day (50–500 mg/day). 23/38 (60.5%) had a 1 or 2 tumor response to thalidomide. No complete responder. Eighteen patients were treated with thalidomide alone and had a 17% response rate (3/18). Twenty patients were treated concurrently with other agents and had a 65% response rate (13/20). Excluding myeloma diagnosis the tumor response rate is 50% (13/26) and the average response duration is 11 months (2- >24). The table lists the responding tumor types. Weight changes data available in 12 responders with a mean weight gain of 1.9 kg. Conclusions: Unpredictable but some long-term disease control was seen with relatively low dose thalidomide alone or in combination with other agent(s). Objective weight gain as a surrogate marker for improved functional status is noted among the majority of responders. No significant financial relationships to disclose.
Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications
Authors: Alessandra Biffi
Journal: Molecular Therapy (2017)

Lysosomal storage disorders (LSDs) are a broad class of monogenic diseases with an overall incidence of 1:7,000 newborns, due to the defective activity of one or more lysosomal hydrolases or related proteins resulting in storage of un-degraded substrates in the lysosomes. The over 40 different known LSDs share a life-threatening nature, but they are present with extremely variable clinical manifestations, determined by the characteristics and tissue distribution of the material accumulating due to the lysosomal dysfunction. The majority of LSDs lack a curative treatment. This is particularly true for LSDs severely affecting the CNS. Based on current preclinical and clinical evidences, among other treatment modalities, hematopoietic stem cell gene therapy could potentially result in robust therapeutic benefit for LSD patients, with particular indication for those characterized by severe brain damage. Optimization of current approaches and technology, as well as implementation of clinical trials for novel indications, and prolonged and more extensive follow-up of the already treated patients will allow translating this promise into new medicinal products.
Early intervention with epoetin-alfa during platinum-based chemotherapy
Authors: J. Savonije, C. Van Groeningen, A. Van Bochove, H. Pinedo, G. Giaccone
Journal: Journal of Clinical Oncology (2004)

8111 Background: There is good evidence that epoetin alfa (EPO) is effective in the treatment of moderate to severe chemotherapy-associated anemia (CAA). Further research is required to clarify its role in mild CAA. Methods: This multicenter randomized trial assessed the effect of EPO on hemoglobin level (Hb), transfusion requirements and quality of life (QOL) in patients (pts) with mild CAA. Pts with Hb ≤12.1 g/dl, likely to receive 2–6 more cycles of platinum-based chemotherapy (CT) for a solid malignancy, were randomized (2:1) to EPO (10,000 U t.i.w.) or best supportive care (BSC). If after 4 wks of EPO therapy, Hb <12.1 g/dl and Hb increase <1 g/dl, EPO dose was increased to 20,000 U t.i.w. FACT-An (Functional Assessment of Cancer Therapy-Anemia) and CLAS (Cancer Linear Analogue Scale) scores after 2 cycles of CT (QOL-2) and at study completion (4 wks after the last cycle of CT; QOL-end) were compared to QOL-baseline. Results: A total of 315 pts (211 EPO vs 104 BSC) were enrolled. There were no statistically significant differences in gender, age, and tumor type between groups. The mean study period was 97 vs 102 days. Median baseline Hb was 10.7 vs 10.8 g/dl (EPO vs BSC). Hematological response was significantly higher in the EPO group. The percentage correctors (Hb >12.1 g/dl and not transfused in previous 28 days) was 67 vs 30%1 (EPO vs BSC), the percentage responders (Hb increase >2 g/dl and not transfused in previous 28 days) 69 vs 31%1, and the percentage hematopoietic responders (corrector or responder) was 76 vs 45%1. The percentage of patients transfused during the study period was lower in the EPO group (37 vs 65%1). QOL was comparable between groups after 2 cycles of CT (QOL-2), but both CLAS and FACT-An scores were significantly higher in the EPO group at QOL-end (See Table). Conclusions: EPO therapy for mild anemia results in significant increases in QOL and Hb and reduces transfusion requirements in patients receiving platinum-based CT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech, a division of Janssen-Cilag BV Ortho Biotech, a division of Janssen-Cilag BV Ortho Biotech, a division of Janssen-Cilag BV Ortho Biotech, a division of Janssen-Cilag BV Ortho Biotech, a division of Janssen-Cilag BV
Optimal selection of individuals for BRCA1 and BRCA2 gene testing
Authors: P. James, M. Harris, R. Doherty, M. Young, E. Niedermayr, A. Hunter, C. Scott
Journal: Journal of Clinical Oncology (2004)

1009 Background: Targeting BRCA1 and BRCA2 mutation analysis to those most likely to carry a mutation is desirable. We examined the performance of 6 different methods of selecting individuals for BRCA gene testing with the aim of identifying the optimal strategy. Methods: 266 families who were seen at a single Familial Cancer Centre between 1997 and 2003 where at least one affected family member had completed full BRCA1 and 2 mutation screening were included in this retrospective study. 68 individuals (25.5%) carried a gene mutation (33(12.5%) BRCA1, 35(13%) BRCA2). Each family was assessed using the BRCAPRO computer program, the models published by Couch et al (1997), Frank et al(2002), as well as the Family History Assessment Tool ( Gilpin et al 2000), the Australian National Breast Cancer Centre guidelines, and an assessment tool developed by the South Australian Family Cancer Centre. The performance of each method as a selection criterion was compared with the result of the gene test to produce sensitivity, specificity, predictive values and receiver operating curve data. The effect of using different levels of pre-test probability as a cut-off for gene testing, as well as the impact of breast pathology data on the assessment were analysed. Results: Use of the probability data generated by the BRCAPRO program produced the highest area under the receiver operated curve ( 0.78) compared with the other methods. Applying a cut-off of 10% or higher probability for testing gave a sensitivity of 79% and a specificity of 61% for BRCA mutation detection. These data were further improved by the incorporation of breast cancer pathology information ( tumour grade and ER/PR status). The probability generated by BRCAPRO was adjusted on the basis of the pathology of the breast cancers in the families using Bayes theorem. A cut-off of 10% or more for testing resulted in further improvements in both sensitivity and specificity in comparison to the BRCAPRO score alone. Conclusions: The BRCAPRO score with a Bayesian adjustment incorporating breast cancer pathology data, with a cut-off of 10% or greater, was the optimal method for selecting individuals for BRCA1 and 2 mutation analysis. No significant financial relationships to disclose.
Feasibility of adjuvant chemotherapy with doxorubicin plus docetaxel followed by sequential capecitabine in patients with node positive breast cancer
Authors: R. Lara, J. I. Mayordomo, A. Modolell, M. Burillo, J. Sanz, L. Murillo, J. Janariz, V. Perez, R. Andres, A. Tres
Journal: Journal of Clinical Oncology (2004)

782 Background: Anthracyclines, taxanes and more recently capecitabine are among the most active drugs for patients with breast cancer. Sequential administration of active chemotherapy agents may result in improved clinical outcomes with lower toxicity than concurrent administration. We have tested the safety profile of adjuvant doxorubicin plus docetaxel followed by sequential capecitabine in patients with node-positive breast cancer. Methods: Patients with histologically confirmed stage II-III breast cancer and at least one positive node, previous complete surgery, age older than 18 years, performance status 2 or better (ECOG) and adequate bone marrow, renal, hepatic and cardiac functions were eligible. Treatment consisted of 6 courses of doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2, both given on day 1 of a 21-day cycle for 6 courses, followed by 6 additional courses of capecitabine 1250 mg/m2 bid on day 1–14 of a 21-day cycle. Vitamin B6 300 mg bid days 1–21 was also given. Patients subsequently received hormonal therapy, with radiotherapy if indicated by the investigator. Primary endpoint was safety. Results: Forty-seven patients have been enrolled and treated. Median age was 47 years (range: 32–73). Median number of positive axillary nodes was 4. Median received dose intensity was 0.99 for doxorubicin, 1.0 for docetaxel and 0.96 for capecitabine. Grade 3–4 toxicities of doxorubicin plus docetaxel included neutropenia (4 courses or 3 patients), febrile neutropenia (4 episodes in 3 patients) and constipation (4 courses in 1 patient). No grade 3–4 toxicities were reported with capecitabine, even if grade 1–2 palmoplantar erytrodisesthesia occured in one third of courses. Conclusions: Sequential chemotherapy with doxorubicin plus docetaxel followed by capecitabine is well tolerated when given as adjuvant chemotherapy to patients with node-positive breast cancer, and deserves evaluation within large randomised trials. No significant financial relationships to disclose.
Addressing the risk of infertility in young women with breast cancer (BC): A quality improvement (QI) intervention.
Authors: Karen L. Smith, Enoch Cheung, Beth Thompson, Stacie Jeter, Jill Mull, Jennifer Ensminger, Mary Capano, Catherine Klein, Meghan McTague, Mindy Christianson, Vered Stearns
Journal: Journal of Clinical Oncology (2017)

72 Background: Many young women with early BC require systemic therapy (ST) which can result in ovarian damage leading to infertility. Fertility preservation (FP) can be performed prior to ST, however uptake is low. Data suggest oncology providers do not routinely discuss the risk of treatment related infertility (TRI) or FP with young women with BC. Methods: We created a QI protocol to ensure providers address fertility needs of young women with early BC. Non-pregnant women age 18-44 years with stage I-III BC who have not initiated ST are identified by screening clinic schedules. Clinicians are asked to follow a QI protocol requiring assessment of patients’ childbearing potential (CBP), risk for TRI and fertility goals (FG). If appropriate, FP is discussed and consultation with a fertility specialist arranged. A clinical team member completes a provider documentation form (PDF) summarizing the QI protocol steps accomplished. Results: Since implementation of the QI protocol, there have been 80 eligible women (mean age 38.6). At least one PDF was completed for 56 (70%), with the majority completed by breast surgeons. Among those with a completed PDF, 48 (86%) were of CBP, all but one of whom planned ST associated with a risk of infertility. According to the PDF, the risk of TRI was discussed in 34 (72%) while FG were assessed in 44 (94%), with 8 (18%) desiring fertility and 8 (18%) undecided about FG. Discussion of FP by the provider and/or a fertility specialist was documented in the PDF for 85% of those who desired fertility or who were undecided. In comparison to the PDF, discussion of FG was recorded in provider notes in 36 (45%) women with documentation in both provider notes and the PDF for 29 (36%). Provider notes documented discussion of FG in 94% of the women who desired fertility or who were undecided according to the PDF. Conclusions: Implementation of a QI protocol with required documentation ensures providers address fertility needs of young women with BC. Providers do not discuss the risk of TRI as frequently as assessing FG. Efforts are ongoing to increase completion rate of our PDF and to incorporate it into the electronic medical record. Follow-up regarding ST and uptake of FP in our cohort is ongoing.
Comprehensive thymidylate synthase genotyping in adjuvant therapy of CRC
Authors: A. Villanueva, E. Dotor, M. Cuatrecasas, L. Pareja, M. Martinez, M. Navarro, V. Moreno, M. A. Peinado, G. Capella, J. R. Germa
Journal: Journal of Clinical Oncology (2004)

3588 Background: Adjuvant chemotherapy treatment, mainly based in the inhibition of thymidylate synthase (TS) enzyme with 5-FU (5-fluorouracil) is offered to all Dukes C and indications for Dukes B2 cases are being evaluated. TS levels of expression as well the presence of different TS gene polymorphisms have been postulated as a potential marker of 5-FU response. The aim of this study was to evaluate TS genotyping as a predictor of 5-FU response in a series of primary resected CRC. Methods: 213 patients resected of stage II-IV colorectal tumors [63 Dukes B2, 121 Dukes C and 29 Dukes D] were treated with 5-FU plus levamisole or leucovorin as a standard treatment. TS protein expression was immunohistochemically assessed using commercial and a newly generated polyclonal antibody. TS polymorphisms [TSER, the G/C polymorphism based in the second repeat of the 3R allele of TSER, and TS 1494del6], point mutations and allelic imbalances were analyzed in 128 of the 213 cases after tumor cell enrichment. Results: 174 tumors (81.7.%) had high intratumoral TS expression and associated with poorer 5-year overall survival (76.97% vs. 69.77% at 5 years, p=0.079). No correlation was observed between TSER and TS1494del6 polymorphisms and TS protein immunostaining. The presence of the TS1494del6 polymorphism was associated to a better 5-year OS (p=0.006). TSER genotype did not predict for longer DFS (p=0.341) or OS (p=0.255). Inclusion of the presence of the G/C allele in the 3R allele did not modify these results. Allelic imbalances were present in 35% of all informative tumors. No point mutations were detected in the 128 tumors analyzed. Conclusions: A 6-bp deletion in the 3'-untranslated region of the TS and high TS protein expression are effective in predicting outcome of adjuvant chemotherapy in patients with resected CRC. TS allelic imbalances are a frequent event in human colorectal tumorigenesis of unknown significance. No significant financial relationships to disclose.
Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia
Authors: Anne P. Beigneux, Kazuya Miyashita, Michael Ploug, Dirk J. Blom, Masumi Ai, MacRae F. Linton, Weerapan Khovidhunkit, Robert Dufour, Abhimanyu Garg, Maureen A. McMahon, Clive R. Pullinger, Norma P. Sandoval, Xuchen Hu, Christopher M. Allan, Mikael Larsson, Tetsuo Machida, Masami Murakami, Karen Reue, Peter Tontonoz, Ira J. Goldberg, Philippe Moulin, Sybil Charrière, Loren G. Fong, Katsuyuki Nakajima, Stephen G. Young
Journal: New England Journal of Medicine (2017)

A protein that is expressed on capillary endothelial cells, called GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1), binds lipoprotein lipase and shuttles it to its site of action in the capillary lumen. A deficiency in GPIHBP1 prevents lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides, and severe hypertriglyceridemia (chylomicronemia). During the characterization of a monoclonal antibody-based immunoassay for GPIHBP1, we encountered two plasma samples (both from patients with chylomicronemia) that contained an interfering substance that made it impossible to measure GPIHBP1. That finding raised the possibility that those samples might contain GPIHBP1 autoantibodies.Using a combination of immunoassays, Western blot analyses, and immunocytochemical studies, we tested the two plasma samples (as well as samples from other patients with chylomicronemia) for the presence of GPIHBP1 autoantibodies. We also tested the ability of GPIHBP1 autoantibodies to block the binding of lipoprotein lipase to GPIHBP1.We identified GPIHBP1 autoantibodies in six patients with chylomicronemia and found that these autoantibodies blocked the binding of lipoprotein lipase to GPIHBP1. As in patients with GPIHBP1 deficiency, those with GPIHBP1 autoantibodies had low plasma levels of lipoprotein lipase. Three of the six patients had systemic lupus erythematosus. One of these patients who had GPIHBP1 autoantibodies delivered a baby with plasma containing maternal GPIHBP1 autoantibodies; the infant had severe but transient chylomicronemia. Two of the patients with chylomicronemia and GPIHBP1 autoantibodies had a response to treatment with immunosuppressive agents.In six patients with chylomicronemia, GPIHBP1 autoantibodies blocked the ability of GPIHBP1 to bind and transport lipoprotein lipase, thereby interfering with lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins and causing severe hypertriglyceridemia. (Funded by the National Heart, Lung, and Blood Institute and the Leducq Foundation.).
Maternal Obesity and Epilepsy
Authors: William L. Bell
Journal: JAMA Neurology (2017)

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 Neurology 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 Neurology journal
Identification of factors that may influence the selection of first‐line biological therapy for people with psoriasis: a prospective, multicentre cohort study
Authors: N.J. Davison, R.B. Warren, K.J. Mason, K. McElhone, B. Kirby, A.D. Burden, C.H. Smith, K. Payne, C.E.M. Griffiths
Journal: British Journal of Dermatology (2017)

The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium has a collective aim to develop a prescribing algorithm to help stratify eligible patients with psoriasis to the most appropriate biological treatment. To facilitate the adoption of a stratified approach, it is necessary to first understand the factors driving the choice of first-line biological therapy.To identify and quantify factors that influence the selection of the first-line biological therapy for people with psoriasis.Multinomial logistic regression was used to determine the factors that influenced the probability of treatment selection, using data from the British Association of Dermatologists Biologic Interventions Register from January 2012 to December 2015. Sensitivity analyses were performed to assess the robustness of the findings to key assumptions.The main analysis was based on a dataset comprising 3040 people with psoriasis. The identified factors affecting first-line biological selection within the available therapies were: presence of psoriatic arthritis; patient weight; employment status; country of registration; and baseline disease severity. Importantly, the analysis showed a general shift in prescribing behaviour over time. These results were robust to sensitivity analysis.This study offers important insights into the factors influencing current prescribing practice for first-line biological therapies for people with psoriasis. It provides baseline data to inform the evaluation of future potential changes that may affect prescribing behaviour, such as stratified medicine.
Imatinib mesylate inhibits STAT5 phosphorylation in response to IL-7 and promotes T cell lymphopenia in chronic myelogenous leukemia patients
Authors: S Thiant, M M Moutuou, P Laflamme, R Sidi Boumedine, D M Leboeuf, L Busque, J Roy, M Guimond
Journal: Blood Cancer Journal (2017)

Abstract Imatinib mesylate (IM) therapy has been shown to induce lower T cell counts in chronic myelogenous leukemia (CML) patients and an interference of IM with T cell receptor (TCR) signaling has been invoked to explain this observation. However, IL-7 and TCR signaling are both essential for lymphocyte survival. This study was undertaken to determine whether IM interferes with IL-7 or TCR signaling to explain lower T cell counts in patients. At diagnosis, CML patients have typically lower CD4 + counts in their blood, yet CD8 + counts are normal or even increased in some. Following the initiation of IM treatment, CD4 + counts were further diminished and CD8 + T lymphocytes were dramatically decreased. In vitro studies confirmed IM interference with TCR signaling through the inhibition of ERK phosphorylation and we showed a similar effect on IL-7 signaling and STAT5 phosphorylation (STAT5-p). Importantly however, using an in vivo mouse model, we demonstrated that IM impaired T cell survival through the inhibition of IL-7 and STAT5-p but not TCR signaling which remained unaffected during IM therapy. Thus, off-target inhibitory effects of IM on IL-7 and STAT5-p explain how T cell lymphopenia occurs in patients treated with IM.