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Improved Response (improved + response)

Distribution by Scientific Domains

Medical Sciences	83%

Selected Abstracts

Immune enhancement of nitroreductase-induced cytotoxicity: Studies using a bicistronic adenovirus vector

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2003
Nicola K. Green
Abstract The nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in preclinical studies and is currently being assessed in phase I clinical trials. It is well established that there is an immune component to the bystander effect observed with other systems such as thymidine kinase and cytosine deaminase; however, such an effect has not previously been described using NR. We have preliminary data suggesting an immune bystander effect with NR to further examine these effects and their potential enhancement by cytokines, an adenoviral vector containing CMV-NR, an internal ribosome entry site (IRES) and the gene for murine GM-CSF (mGM-CSF) was constructed. The NR-GM-CSF virus was validated in 2 experimental models and demonstrated increased therapeutic efficacy in the MC26 murine colorectal tumour model. These data illustrate that the combination of suicide gene therapy using NR and CB1954 with immune stimulation via GM-CSF gives an improved response compared to either modality alone and suggests that the immune component of this response may be beneficial in combating unresectable, metastatic disease and preventing tumour recurrence. © 2002 Wiley-Liss, Inc. [source]

Influence of the copolymer architecture and composition on the response and mechanical properties of pH-sensitive fibers

JOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2007
Anasuya Sahoo
Abstract A series of copolymers based on acrylonitrile (AN) and acrylic acid (AA) with varying architecture and composition were synthesized using free radical polymerization. The distribution of monomers in the copolymer chains could be successfully controlled by regulating the addition of more reactive monomer (AA). Copolymers having nearly random distribution of comonomer moieties to block type distribution with different composition (10,50 mol % AA) were synthesized to investigate the effect of polymer architecture and composition on pH response and mechanical properties of resultant structures. These copolymers were solution spun from dimethylformamide-water system, drawn in coagulation bath, and annealed at 120°C for 2 h to make pH-sensitive fibers which were structurally stable without the need of chemical crosslinking. The fibers from block copolymers showed significantly better tensile strength (34.3 MPa), higher retractive forces (0.26 MPa), and enhanced pH response (swelling 3890%) in comparison with fibers from random copolymer (13.55 MPa, 0.058 MPa, and 1723%, respectively). The tensile strength and retractive forces could be further improved to a value of 72 MPa and 0.36 MPa, respectively, by changing the composition of the block copolymer while retaining the swelling percentage similar to the random copolymer mentioned above. It is proposed that on processing to fibers, the block copolymers could form a segregated domain structure with separate domains of AA and AN, where AN domains were responsible for high structural integrity by providing connectivity among polymer chains, while AA domains showed improved response to changing pH of the environment. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007 [source]

Neo-Adjuvant Hormonal Therapy

THE BREAST JOURNAL, Issue 3 2008
Marcia Valenzuela MD
Abstract:, Neo-adjuvant endocrine therapy has opened new alternatives for locally advanced breast cancer. Such therapy, which has permitted us to expand the treatment role of neo-adjuvant therapies, may be of great benefit to patient groups such as the elderly, those not suited for chemotherapy, and those whose response may not be optimal. This therapy also may be able to help us identify agents that could improve outcomes in the adjuvant setting as well as possible biologic predictors for outcome. The latest generation of endocrine therapy for breast cancer, aromatase inhibitors, has proved superior to tamoxifen in terms of toxicity and efficacy in the adjuvant setting and is currently being studied in other clinical trials. Current findings indicate that these agents are less toxic and better tolerated than neo-adjuvant chemotherapy and that third-generation anti-hormomal therapy offers improved tumor response compared with tamoxifen, which has resulted in increased breast conserving surgery. Biomarker findings of improved response in tumors that are both estrogen receptor positive and HER-2 positive as well as progesterone receptor positivity only will be important for planning future selective treatment and clinical trials. [source]

Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas

APMIS, Issue 11 2003
HELGA B. SALVESEN
Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours. [source]

Improvement of muscle healing through enhancement of muscle regeneration and prevention of fibrosis

MUSCLE AND NERVE, Issue 3 2003
Kenji Sato MD
Abstract Skeletal muscle is able to repair itself through regeneration. However, an injured muscle often does not fully recover its strength because complete muscle regeneration is hindered by the development of fibrosis. Biological approaches to improve muscle healing by enhancing muscle regeneration and reducing the formation of fibrosis are being investigated. Previously, we have determined that insulin-like growth factor,1 (IGF-1) can improve muscle regeneration in injured muscle. We also have investigated the use of an antifibrotic agent, decorin, to reduce muscle fibrosis following injury. The aim of this study was to combine these two therapeutic methods in an attempt to develop a new biological approach to promote efficient healing and recovery of strength after muscle injuries. Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis. This improvement was not associated with improved responses to physiological testing, at least at the time-points tested in this study. Muscle Nerve 28: 365,372, 2003 [source]

Systematic review of high dose chemotherapy and autologous haematopoietic stem cell transplantation for chronic lymphocytic leukaemia: what is the published evidence?

BRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2007
Mohamed A. Kharfan-Dabaja
Summary Despite improved responses, chronic lymphocytic leukaemia (CLL) remains incurable with conventional chemotherapy. Patients with poor-risk factors or who fail conventional chemoimmunotherapy are offered autografts, preferably after achieving remission. This report presents the totality of evidence through a systematic review that assessed the efficacy of autografts in CLL. A search of MEDLINE databases from 1966,2006 and hand-search of references identified 82 prospective-randomized, non-randomized comparisons or single-arm trials, of which only nine met our inclusion criteria: two trials were funded by public/government, one by private foundations, one jointly by private/public, and was unclear in five. No randomized controlled trials comparing autografts versus conventional chemotherapy (or chemoimmunotherapy) were found. Six studies were single-arm and three were non-randomized with a control-arm (autologous versus allogeneic). Overall, 361 patients were enrolled, but only 292 were transplanted. Transplant-related mortality ranged from 0% to 9%. Complete responses ranged from 74% to 100% and molecular responses ranged from 57% to 88%. Overall survival ranged from 68% at 3 years to 58% at 6 years. It is uncertain whether autograft is superior to conventional therapy. The high incidence of myelodysplastic syndrome (9,12%) is particularly concerning in CLL, where median survival is 9 years. [source]