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1.
Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL. 相似文献
2.
Scagliotti GV Novello S Schiller JH Hirsh V Sequist LV Soria JC von Pawel J Schwartz B Von Roemeling R Sandler AB 《Clinical lung cancer》2012,13(5):391-395
We present the rationale and design for MARQUEE, a phase III, randomized, double-blind, placebo-controlled study of ARQ 197 plus erlotinib versus placebo plus erlotinib in previously treated subjects with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer (NSCLC). The design of MARQUEE is based on preclinical data, the current understanding of the role of cellular N-methyl-N'-nitroso-guanidine human osteosarcoma (MNNG HOS) transforming gene (MET) in NSCLC, and clinical data from a randomized phase II study. The available evidence suggests that dual inhibition of MET and the epidermal growth factor receptor (EGFR) may overcome resistance to EGFR inhibitors. In the phase II study, the combination of tivantinib plus erlotinib significantly improved progression-free survival (PFS) and overall survival (OS) compared with placebo plus erlotinib in the subset of patients with nonsquamous histology, a population enriched for MET overexpression. The primary endpoint in MARQUEE is OS. Secondary and exploratory objectives include determination of PFS, OS in molecular subgroups (defined by EGFR and KRAS mutation status, amplification or overexpression of MET, and serum hepatocyte growth factor), and safety. All patients will be tested for biomarkers, and the results will provide a wealth of information on the role of tivantinib in treating nonsquamous NSCLC. 相似文献
3.
Cancers so much resemble self that they prove difficult for the immune system to eliminate, and those that have already escaped natural immunosurveillance have gotten past the natural immune barriers to malignancy. A successful therapeutic cancer vaccine must overcome these escape mechanisms. Our laboratory has focused on a multistep "push-pull" approach in which we combine strategies to overcome each of the mechanisms of escape. If tumor epitopes are insufficiently immunogenic, we increase their immunogenicity by epitope enhancement, improving their binding affinity to major histocompatibility complex (MHC) molecules. If the anti-tumor response is too weak or of the wrong phenotype, we use cytokines, costimulatory molecules, Toll-like receptor ligands, and other molecular adjuvants to increase not only the quantity of the response but also its quality, to push the response in the right direction. Finally, the tumor invokes multiple immunosuppressive mechanisms to defend itself, so we need to overcome those as well, including blocking or depleting regulatory cells or inhibiting regulatory molecules, to pull the response by removing the brakes. Some of these strategies individually have now been translated into human clinical trials in cancer patients. Combinations of these in a push-pull approach are promising for the successful immunotherapy of cancer. 相似文献
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LV Riella A Chandraker 《JAMA : the journal of the American Medical Association》2012,308(2):130; author reply 130-130; author reply 131
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Home-based primary care has a long history in American medicine, and its prevalence is again increasing slowly in the United States in response to a changing demographic, societal, and health-policy climate. There are many models of home-based primary care, including private practice, academic, Veterans Affairs-associated, and concierge practices. There is a growing body of literature supporting the effectiveness of the medical house-call model. New healthcare reform initiatives could further impact the number and size of home-based primary-care practices, including the Independence at Home and the Accountable Care Organization demonstration projects. 相似文献
8.
Giannasi LC Matsui MT Batista SR Hardt CT Gomes CP Amorim JB Aguiar IC Collange L Oliveira EF Santos IR Dias IS Nassif SR Oliveira CS Oliveira LV Gomes MF 《BMC musculoskeletal disorders》2012,13(1):71
ABSTRACT: BACKGROUND: Few studies demonstrate effectiveness of therapies for oral rehabilitation of patients with cerebral palsy (CP), given the difficulties in chewing, swallowing and speech, besides the intellectual, sensory and social limitations. Due to upper airway obstruction, they are also vulnerable to sleep disorders. This study aims to assess the sleep variables, through polysomnography, and masticatory dynamics, using electromiography, before and after neuromuscular electrical stimulation, associated or not with low power laser (Gallium Arsenide- Aluminun, = 780nm) and LED ( = 660 nm) irradiation in CP patients. Methods/Design: 50 patients with CP, both gender, aged between 19 and 60 years will be enrolled in this study. The inclusion criteria are: voluntary participation, patient with hemiparesis, quadriparesis or diparetic CP, with ability to understand and respond to verbal commands. The exclusion criteria are: patients undergoing / underwent orthodontic, functional maxillary orthopedic or botulinum toxin treatment. Polysomnographic and surface electromyographic exams on masseter, temporalis and suprahyoid will be carry out in all sample. Questionnaire assessing oral characteristics will be applied. The sample will be divided into 5 treatment groups: Group 1: neuromuscular electrical stimulation; Group 2: laser therapy; Group 3: LED therapy; Group 4: neuromuscular electrical stimulation and laser therapy and Group 5: neuromuscular electrical stimulation and LED therapy. All patients will be treated during 8 consecutive weeks. After treatment, polysomnographic and electromiographic exams will be collected again. Discussion: This paper describes a five arm clinical trial assessing the examination of sleep quality and masticatory function in patients with CP under non-invasive therapies. 相似文献
9.
Levchenko EV Dvoretskiĭ SIu Kanaev SV Shcherbakov AM Barchuk AS Matsko DE Tiuraeva EI Radzhadova ZA Semenova AI Karelov AE Gorokhov LV Komarov IV Avanesian AA Khokhlova EA 《Voprosy onkologii》2012,58(2):260-264
The locally advanced cancer of thoracic esophagus was treated by induction chemo-irradiation therapy (IHRT) with intraluminal medium dose-rate brachytherapy (IMBT). From July 2009 to February 2012 twenty five patients (mean age 54.3 +/- 1.3 years) were included in the study. The length of the primary tumor was up to 6 cm in 10 pts and more than 6 cm in 15 pts. Induction therapy consisted of three IMBT sessions (7 Gy X 3; q7d) and two cycles of chemotherapy (PF; q28d), 26-31 days later the surgery was performed. Subtotal resection of the esophagus type of I Lewis was performed in 23 pts, transtracheal extirpation of the esophagus was performed in 2 pts.In all the cases 3F lymphodissection was performed. After IHRT in 15 of 25 pts. was obtained complete or partial response, in 10 of 25 pts was obtained disease stabilization. Perioperative complications occurred in 17 (68%) patients receiving conservative treatment, one patient (4%) died of treatment complications. In 6 cases (24%) morphology had shown the complete regression of primary tumor. Thus, the combination of intraluminal medium dose-rate brachytherapy and chemotherapy lead to reduction of primary tumor local spread and can be an efficient factor in improving the results of surgical treatment. 相似文献