tbuckley/cabot-search huggingface dataset:
Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) with measurable asymptomatic inoperable brain metastases (BM): A multicenter phase II trial (GFPC 07-01).
Authors: G. Robinet, F. Barlesi, R. Gervais, H. Lena, J. Hureaux, H. Berard, D. Paillotin, S. Bota, I. Monnet, A. Chajara
Journal: Journal of Clinical Oncology (2010)

7595 Background: BM occur in 10% of patients (pts) at diagnosis of NSCLC and in 40% during the course of the disease, and are associated with a poor prognosis. Optimal treatment for inoperable BM is controversial: whole brain radiotherapy (WBRT) is broadly use but several clinical data showed the role of chemotherapy. This study assessed the safety and efficacy of pemetrexed-cisplatin in NSCLC pts with BM. Methods: NSCLC chemonaïve pts with BM at first diagnosis not amenable to surgery or radiosurgery, age > 18, PS 0-2 and adequate organ functions were eligible for up to 6 cycles of cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on d1 (d1 = d22). WBRT was given in case of disease progression or CT completion. Primary endpoint was objective response rate (RR) on BM. Secondary endpoints included extra cerebral and overall response rate, safety and survival. Results: Forty-three pts were enrolled, initial characteristics were: mean age 60.4 ± 7.96 years, males 29, PS: 0-1-2 were 37.2%, 60.5% and 2.3%, weight loss 3.28 ± 4.09%, squamous carcinoma 3 pts, adenocarcinoma 36 pts and large cells 4 pts (nonsquamous 93%). BM were multiple 83.7% and bilateral 58.1%. Functional classification of neurological status was: stage I/II 86.0%, III 2.3% and IV 11.6%. One pt was not assessable for objective response (withdrawn early due to unrelated adverse event ). Dose intensity and number of cycles received were: cisplatin 95.9 ± 9.06 % and 3.72 ± 1.52, pemetrexed 98.10 ± 5.29 % and 3.84 ± 1.60. Grade (G) 3-4 haematological toxicities: neutropenia 11 pts (febrile neutropenia 1 pt), anemia 6 pts. Non haematological toxicities: G3 pneumopathy 2 pts, G2 urinary infection 1 pt, G3 hypoacousia 1 pt. RR in ITT: cerebral 41.9% (95%CI: 27-57.9), extra-cerebral 34.9% (95%CI: 21-50.9) and overall 34.9% (95%CI: 21-50.9). Median survival time was 7.4 months (95%CI: 5.87-9.63) and median time to progression was 4.01 month (95%CI: 2.77- 6.2). Overall and BM RR in nonsquamous were respectively 37.5% (95%CI: 22.7-54.2) and 42.5% (95%CI: 27-59.1). Conclusions: For NSCLC pts with BM, pemetrexed-cisplatin is an effective and well tolerated option in first-line treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly, Roche Lilly, Pfizer, Roche, sanofi-aventis
Bendamustine and rituximab (BR) are effective in the treatment of relapsed or refractory indolent and mantle-cell lymphomas: Long-term follow-up of a phase II study
Authors: M. J. Rummel, J. Atta, M. Welslau, D. Kofahl-Krause, U. von Gruenhagen, K. Schalk, H. P. Boeck, A. G. Banat, W. Knauf, N. Niederle
Journal: Journal of Clinical Oncology (2007)

8034 Bendamustine combines a purine-like benzimidazol and bifunctionally alkylating nitrogen mustard group. The aim of this multicenter- study was to evaluate the progression-free survival (PFS), response rate and toxicity of BR in patients with mantle-cell or low-grade lymphomas in 1st to 3rd relapse or refractory to previous treatment. A median of 4 courses per patient were administered to 63 pts. Bendamustine was given at a dose of 90 mg/m 2 on day 1 and 2 combined with 375 mg/m 2 Rituximab on day 1 for a max. of 4 cycles every 4 weeks. Histologies: 24 follicular, 16 mantle cell, 17 lymphoplasmacytoid, 6 marginal zone lymphoma. 57 of 63 pts responded to BR corresponding to an overall response rate of 90% with a CR-rate of 60%. In mantle cell lymphomas BR showed a considerable activity achieving a response rate of 75% with a CR-rate of 50%. In an updated analysis the median time of PFS was 30 months and the median duration of overall survival has not yet been reached. With a median follow-up period of 3 years two secondary neoplasms have been observed (bronchial carcinoma). No MDS was observed to date. These results demonstrate that the combination of Bendamustine and Rituximab is a highly active regimen in the treatment of low-grade lymphomas and mantle cell lymphomas. Based upon these encouraging results the Studiengruppe indolente Lymphome (StiL) initiated two Phase III trials that compare BR to established chemo-immunotherapy regimens: BR vs R-CHOP in untreated pts, and BR vs Fludarabine- R in relapsed pts. These studies should provide considerable guidance for the appropriate role of Bendamustine in the treatment of low-grade and mantle cell lymphomas. No significant financial relationships to disclose.
Functional characterization of human cancer stem cells for targeted therapy
Authors: Michele Signore, Dario Lombardi, Fiorenza Lotti, Lucia Ricci-Vitiani, Adriana Eramo, Lance Liotta, Emanuel Petricoin, Ruggero De Maria
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4617 

Compelling evidence indicates that a rare population of tumorigenic cells is responsible for tumor formation, maintenance and spreading. Such tumor initiating cells are defined as cancer stem cells (CSCs) for their ability to self-renew and produce a progeny of non-tumorigenic cells that form the vast majority of tumor cell mass.    The obvious consequence of this paradigm is that CSC targeting should represent the primary goal of effective cancer therapies. However, CSCs seems particularly resistant to conventional chemotherapy and, at least in the case of glioblastoma, to radiotherapy. The molecular pathways responsible for tumorigenic activity and chemotherapy resistance of CSCs are largely unknown. Thus, given the central importance of signaling in underpinning cellular growth and survival and their key roles as targets for therapeutics, we performed the first ever comprehensive analysis of CSC signal pathway activation in hopes of beginning a functional classification of CSC by cellular signaling portraits.    CSCs were isolated from human colorectal, melanoma, lung and glioblastoma tumor specimens by selection in serum-free medium specific for primitive cells, which allows the expansion of cancer stem and progenitor cells from solid cancers as tumor spheres in the presence of EGF and FGF-2. Early passages of CSC cultures were lysed and subjected to Reverse Phase Protein Microarray analysis using a panel of 33 total and 50 phospho-specific antibodies to proteins involved in key cancer-related signaling pathways. Some CSCs share EGF-R signaling activation, regardless of organ origination, while also displaying tumor-specific signatures, such as PI3-K/Akt pathway specific signaling in glioblastoma CSCs and p70S6K specific activation in melanoma CSCs. In vitro cytotoxicity studies, performed through the use of a selection of specific inhibitors of key components of the pathways active in CSCs, indicate that targeting of single proteins is generally insufficient to kill CSCs. The inhibition of multiple pathways or the combined use of targeted and conventional therapies is required for increasing the killing activity at possible therapeutic levels. These new data, if validated in further experimentation, may provide key and missing information about potential combinations of targeted therapeutic strategies for cancer treatment based on CSC signaling pathway and kinase substrate activation.    We are currently evaluating the therapeutic efficacy of such combinations on CSC-based mouse xenografts, which may represent a valuable preclinical model of human cancer.
Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results.
Authors: I F Khouri, M J Keating, H M Vriesendorp, C L Reading, D Przepiorka, Y O Huh, B S Andersson, K W van Besien, R C Mehra, S A Giralt
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was undertaken to evaluate the feasibility and therapeutic effect of high-dose chemoradiotherapy with autologous or allogeneic bone marrow transplantation (BMT) in patients with advanced chronic lymphocytic leukemia (CLL) who relapse after fludarabine treatment. PATIENTS AND METHODS Twenty-two patients with advanced CLL received high-dose cyclophosphamide, total-body irradiation, and BMT. Eleven patients with relapsed CLL received autologous BMT with marrow collected during a prior fludarabine-induced remission; leukemia cells were depleted from the autologous marrow in seven patients using an anti-CD19 monoclonal antibody and immunomagnetic separation. Eleven patients received allogeneic or syngeneic BMT, seven of whom had refractory Rai stage III or IV disease. RESULTS Six autologous transplant recipients achieved a complete remission (CR), four a nodular CR (nCR), and one a partial remission (PR). Two recurred with CLL, and three developed Richter's transformation. Two patients had recurrence of immune cytopenias while in morphologic remission; one of these patients died of cytomegalovirus pneumonia. Six of 11 patients survive in remission 2 to 29 months following BMT. Of the 11 patients who received allogeneic or syngeneic BMT, seven achieved a CR, two a nCR, and one a PR; 10 survive 2 to 36 months following BMT. CONCLUSION These data indicate that high-dose chemotherapy with allogeneic BMT is effective at producing CRs in patients with CLL. Autologous transplantation in CLL is feasible and is capable of producing remissions in patients with advanced CLL. Further studies are warranted to assess the role of BMT in the treatment of CLL.
AB1157-HPR Intimate Relationships as Perceived by Patients with Early Rheumatoid Arthritis: A Qualitative Interview Study (The Swedish Tira Study)
Authors: G. Ostlund, M. Björk, E. Valtersson, A. Sverker
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recent research has described in detail how participation restrictions in relation to rheumatoid arthritis (RA) are experienced in everyday life from patients9 perspective [1- 3]. However, the knowledge of how intimate relationships are affected is still scarce [4]. <h3>Objectives</h3> The aim of this study was to analyze RA patients9 descriptions of intimate relationships to understand more about if and how it is affected. <h3>Methods</h3> This study is part of the Swedish TIRA-project [5]. The data collection includes 60 interviews with 37 women and 23 men, aged 20-63, that were taped and transcribed verbatim. The Critical Incident Technique was used in the data collection [6] and content analysis was used to categorize the results. <h3>Results</h3> A preliminary result shows that 17 of 54 patients described that RA affected their intimate relationships. Tiredness and body pain were factors that had an impact according to these patients and for some aging was part of the problem. Adverse reactions to medication was another aspect. Some refrained from having sex and said that closeness and caresses could suffice. Others had worries of being rejected as a partner when lacking enough sexual capacity. Women also described feelings of being less attractive due to RA. Patients reported the importance of having an open conversation with the partner to find solutions to make this important part of life work. <h3>Conclusions</h3> A quarter of this sample talked about how RA influenced the intimate relationship this calls for further investigation in research as well as in clinical interventions. <h3>References</h3> Sverker A, Thyberg I,Östlund G, Valtersson E, Thyberg M (2013). Participation in work in early rheumatoid arthitis: A qualitative interview study intepreted in terms of ICF.Disability &amp; Rehabilitation May (3)ISSN:1464-5165. Sverker A, Östlund G, Thyberg M, Valtersson E, Björk M, Thyberg, I. Dilemmas of participation in everyday life in early rheumatoid arthritis: a qualitative interview study (The Swedish TIRA study). (Submitted) Östlund G, Björk M, Valtersson E, Thyberg M, Thyberg I, Sverker, A. Emotions experienced by patients in early rheumatoid arthritis: a qualitative interview study (The Swedish TIRA study). (Submitted) National Rheumatoid Arthritis Society (2013). Emotions, relationships and sexuality. http://www.nras.org.uk/ Björk M, Thyberg M, Rikner K, Balogh I, Gerdle B. (2009). Sick leave before and after diagnosis of rheumatoid arthritis: a report from the Swedish TIRA project. J Rheumatol; 36:1170-1179. Flanagan C (1954). The critical incident technique. Psychol Bull 51: 327-358. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2395
Time for root and branch reform
Authors: A. Scott-Samuel
Journal: BMJ (2009)

<h3>Background</h3> Type-1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterised by the progressive immune-mediated destruction of pancreatic β-cells. Genetic predisposition solely fails to justify the increasing global prevalence of T1DM in recent years. Environmentally triggered disruption in gut microbiota composition has been hypothesised as one of the contributing factors. Mounting animal studies have testified to the phenomenon and witnessed how probiotic administration helps to restore homeostasis. However, direct clinical evidence of probiotics efficacy is lacking and the mechanisms remain unclear. Hence, this systematic review aims to critically examine the effectiveness of probiotic supplementation in T1DM patients and decipher its mechanisms of action. <h3>Methods</h3> A systematic search for RCTs was conducted in accordance with PRISMA guidelines in PubMed, EMBASE, and Web of Science from inception to June 2022. ‘diabetes’, (‘gut’ OR ‘microbiome’ OR ‘microbiota’), and ‘probiotics’ were employed as the primary search terms. Covidence was used as a platform for primary screening. All retrieved studies were refined based on the pre-identified inclusion and exclusion criteria. <h3>Results</h3> Four studies were selected for qualitative analysis from the 569 articles screened (IDDF2022-ABS-0231 Figure 1). Pooling the selected studies gives a total of 312 newly diagnosed T1DM participants (2–18 years). The effectiveness of probiotics in glycaemic control (HbA1c and fasting blood glucose) was evident. Probiotic supplementation significantly helps reduce insulin requirements and increases remission. The effect correlates to the modulation of gut microbiome composition. At the genus level, probiotic intervention is associated with an increase in <i>Bifidobacterium</i>, <i>Lactobacillus</i> and <i>Akkermansia.</i> Probiotics did not alter C-peptide levels but substantially elevated anti-inflammatory cytokine (TGF-β1), and lowered inflammatory cytokines (TNF-α, IL-1β, IL-17, IL-18, IL-21, RANTES and MIP-1b) expression (IDDF2022-ABS-0231 Figure 2). Discrepancies in probiotic choice, dosage, duration of treatment and subject demographics could affect treatment outcomes. <h3>Conclusions</h3> Our findings suggest that probiotics are a promising adjunctive therapeutic option for T1DM. However, quality clinical study is still scant. This area of research warrants further attention. Deciphering the gut modulatory effect and elucidating the mechanisms of action of probiotics will quicken the quest for precision probiotics tailored for T1DM patients.
The impact of palliative irradiation on the management of patients with acquired immune deficiency syndrome.
Authors: M P Nobler, M E Leddy, S H Huh
Journal: Journal of Clinical Oncology (1987)

We have studied the natural history of the acquired immune deficiency syndrome (AIDS), and the part that irradiation plays in the management of this devastating and fatal disease. The radioresponsiveness of the two most common malignancies associated with AIDS, Kaposi's sarcoma (KS) and malignant lymphoma (ML), has been demonstrated. We have documented satisfactory time-dose relationships for the management of multiple manifestations of KS, including cutaneous and deep subcutaneous extremity involvement, visceral lesions, and AIDS-associated lymphadenopathy. A similar time-dose construct has been documented for ML, involving the brain and both central and peripheral lymph nodes. Irradiation can provide good to excellent palliation with only minimal side effects, and will produce a lesser impact on the hematological and immunological systems than chemotherapy. Therefore, we advocate the liberal employment of palliative radiation therapy in patients with AIDS.
The lymphotoxin β receptor is a potential therapeutic target in renal inflammation
Authors: Gitta Seleznik, Harald Seeger, Judith Bauer, Kai Fu, Julie Czerkowicz, Adrian Papandile, Uriana Poreci, Dania Rabah, Ann Ranger, Clemens D. Cohen, Maja Lindenmeyer, Jin Chen, Ilka Edenhofer, Hans J. Anders, Maciej Lech, Rudolf P. Wüthrich, Nancy H. Ruddle, Marcus J. Moeller, Nicolas Kozakowski, Heinz Regele, Jeffrey L. Browning, Mathias Heikenwalder, Stephan Segerer
Journal: Kidney International (2015)
Phase II trial of aflibercept (VEGF Trap) in previously treated patients with metastatic colorectal cancer (MCRC): A PMH phase II consortium trial
Authors: P. Tang, S. J. Cohen, G. A. Bjarnason, C. Kollmannsberger, K. Virik, M. J. MacKenzie, J. Brown, L. Wang, A. P. Chen, M. J. Moore
Journal: Journal of Clinical Oncology (2008)

4027 Background: Vascular endothelial growth factor (VEGF) is an important target in MCRC. Aflibercept (VEGF Trap) is a recombinant fusion protein of the human VEGFR1 and R2 extracellular domains and the Fc portion of human IgG1. Methods: This is an open-label, multi-centre, 2-stage phase II trial in pts with MCRC. Eligibility criteria: >1 prior systemic therapy for MCRC, ECOG < 2. Exclusion criteria: prior treatment with a VEGF or VEGFR inhibitor other than bevacizumab (BEV). IV VEGF Trap (4 mg/kg) was administered every 2 weeks (1 cycle). The primary endpoint was RR and 4-month PFS. Pts were enrolled in two cohorts: BEV naïve and prior BEV. Planned sample size in each cohort was 40 pts. Results: In total, 51 pts were enrolled (BEV naive = 24 pts; prior BEV = 27; median age=59, range 39–80; M:F = 30:21; ECOG 0:1:2 = 21:27:3; median # prior regimens for MCRC = 2, range 1–6). After 287 cycles of therapy, most common treatment adverse events (TAEs) of any grade were (#pts): fatigue (40), hypertension (28), proteinuria (25), headache (22), voice alteration (16), anorexia (12), and joint pain (9). Grade 3+ TAEs in > 1 pt were (#pts): hypertension (4), proteinuria (4), fatigue (3), headache (3). One pt died on treatment due to PD. In the BEV naïve cohort (n=24), 4 pts were inevaluable: 7 pts maintained 4-mo PFS, disease control rate (PR + SD > 16 wks) = 29% [95% CI 13–51%], and median PFS was 2.0 mo [95% CI 1.7- not reached (NR)]. In the prior BEV cohort (n=27), 1 pt was inevaluable. There was 1 confirmed PR and 7 pts maintained 4-mo PFS, disease control rate 30% [95% CI 14–50%], and median PFS was 3.4 mo [95% CI 1.9-NR]. Conclusions: Aflibercept (VEGF Trap) is well tolerated in pretreated pts with MCRC. Single agent activity has been observed in the prior BEV cohort, and accrual is ongoing in this stratum. Based on the study results, studies of aflibercept as single agent or in combination should be explored. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Johnson & Johnson, Pfizer Oncology
Unusual Tumors Involving the Head and Neck Region
Authors: Päivi Toivonen, Tero Kivelä
Journal: Journal of Clinical Oncology (2001)

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.2001.19.21.4174 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11689587 Unusual Tumors Involving the Head and Neck Region Case 2. Malignant Uveal Melanoma in Ocular Melanocytosis Päivi ToivonenxPäivi ToivonenSearch for articles by this author , Tero KiveläxTero KiveläSearch for articles by this author Show More Helsinki University Central Hospital, Helsinki, Finland https://doi.org/10.1200/JCO.2001.19.21.4174 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Nonchromogenic Acid-Fast Bacilli Isolated from Tuberculous Swine
Journal: JAMA (1963)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Rampant Parasexuality Evolves in a Hospital Pathogen during Antibiotic Selection
Authors: Kathryn Beabout, Troy G. Hammerstrom, Tim T. Wang, Minny Bhatty, Peter J. Christie, Gerda Saxer, Yousif Shamoo
Journal: Molecular Biology and Evolution (2015)

Horizontal gene transfer threatens the therapeutic success of antibiotics by facilitating the rapid dissemination of resistance alleles among bacterial species. The conjugative mobile element Tn916 provides an excellent context for examining the role of adaptive parasexuality as it carries the tetracycline-resistance allele tetM and has been identified in a wide range of pathogens. We have used a combination of experimental evolution and allelic frequency measurements to gain insights into the adaptive trajectories leading to tigecycline resistance in a hospital strain of Enterococcus faecalis and predict what mechanisms of resistance are most likely to appear in the clinical setting. Here, we show that antibiotic selection led to the near fixation of adaptive alleles that simultaneously altered TetM expression and produced remarkably increased levels of Tn916 horizontal gene transfer. In the absence of drug, approximately 1 in 120,000 of the nonadapted E. faecalis S613 cells had an excised copy of Tn916, whereas nearly 1 in 50 cells had an excised copy of Tn916 upon selection for resistance resulting in a more than 1,000-fold increase in conjugation rates. We also show that tigecycline, a translation inhibitor, selected for a mutation in the ribosomal S10 protein. Our results show the first example of mutations that concurrently confer resistance to an antibiotic and lead to constitutive conjugal-transfer of the resistance allele. Selection created a highly parasexual phenotype and high frequency of Tn916 jumping demonstrating how the use of antibiotics can lead directly to the proliferation of resistance in, and potentially among, pathogens.