Relativistic anisotropic charged fluid spheres with varying cosmological constant

Static spherically symmetric anisotropic source has been studied for the Einstein-Maxwell field equations assuming the erstwhile cosmological constant $\Lambda$ to be a space-variable scalar, viz., $\Lambda = \Lambda(r)$. Two cases have been examined out of which one reduces to isotropic sphere. The solutions thus obtained are shown to be electromagnetic in origin as a particular case. It is also shown that the generally used pure charge condition, viz., $\rho + p_r = 0$ is not always required for constructing electromagnetic mass models.Comment: 15 pages, 3 eps figure

Antiangiogenic Activity of 2-Deoxy-D-Glucose

During tumor angiogenesis, endothelial cells (ECs) are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO) N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR), which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay). Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETA)T(AG) transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies

Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death

Nutrient deprivation has been shown to cause cancer cell death. To exploit nutrient deprivation as anti-cancer therapy, we investigated the effects of the anti-metabolite 2-deoxy-D-glucose on breast cancer cells in vitro. This compound has been shown to inhibit glucose metabolism. Treatment of human breast cancer cell lines with 2-deoxy-D-glucose results in cessation of cell growth in a dose dependent manner. Cell viability as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay and clonogenic survival are decreased with 2-deoxy-D-glucose treatment indicating that 2-deoxy-D-glucose causes breast cancer cell death. The cell death induced by 2-deoxy-D-glucose was found to be due to apoptosis as demonstrated by induction of caspase 3 activity and cleavage of poly (ADP-ribose) polymerase. Breast cancer cells treated with 2-deoxy-D-glucose express higher levels of Glut1 transporter protein as measured by Western blot analysis and have increased glucose uptake compared to non-treated breast cancer cells. From these results we conclude that 2-deoxy-D-glucose treatment causes death in human breast cancer cell lines by the activation of the apoptotic pathway. Our data suggest that breast cancer cells treated with 2-deoxy-D-glucose accelerate their own demise by initially expressing high levels of glucose transporter protein, which allows increased uptake of 2-deoxy-D-glucose, and subsequent induction of cell death. These data support the targeting of glucose metabolism as a site for chemotherapeutic intervention by agents such as 2-deoxy-D-glucose

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

Clinical and pathological response rates of docetaxel-based neoadjuvant chemotherapy in locally advanced breast cancer and comparison with anthracycline-based chemotherapies: Eight-year experience from single centre

Introduction: The administration of neoadjuvant chemotherapy (NACT) prior to local therapy is advantageous for women with locally advanced breast cancer (LABC), since it can render inoperable tumors resectable and can increase rates of breast conservative surgeries. Materials and Methods: We retrospectively analyzed LABC patients who received NACT from January 2000 to December 2007. Out of 3000 case records screened, 570 (19%) were LABC and 110/570 (19%) treatment-na\uefve patients started on NACT were analyzed. Ninety-one (37 docetaxel [D], 54 anthracycline [A]) patients were eligible for response and survival analysis. Pathological complete remission (pCR) was defined as no evidence of malignancy in both breast and axilla. Results: Median age of the whole cohort was 45 years (range 25-68 years). Premenopausal were 42% and estrogen receptor + 49.5%. Most (90%) were T4 tumors and 70% were Stage IIIB. Median numbers of preoperative cycles were six and three in the D and A group respectively. Overall clinical response rates for breast primary were 74.3% and 53.7% (CR 28.6% vs. 16.7%, P=0.58) while for axilla ORR were 75.7% vs. 54.8% (51.4% vs. 40.4% CR, P=0.77) respectively for D and A. Corresponding pCR rates were 19% vs. 13% respectively. There was no significant difference in disease-free (three-year 56.84% vs. 61.16%, P=0.80) and overall survival (three-year 70% vs. 78.5%, P=0.86) between the two groups. Conclusions: Although pCR rates were higher with docetaxel-based NACT, it did not translate into superior disease-free survival / overall survival compared to anthracycline-based chemotherapies

Clinical and pathological response rates of docetaxel-based neoadjuvant chemotherapy in locally advanced breast cancer and comparison with anthracycline-based chemotherapies: Eight-year experience from single centre

Introduction: The administration of neoadjuvant chemotherapy (NACT) prior to local therapy is advantageous for women with locally advanced breast cancer (LABC), since it can render inoperable tumors resectable and can increase rates of breast conservative surgeries. Materials and Methods: We retrospectively analyzed LABC patients who received NACT from January 2000 to December 2007. Out of 3000 case records screened, 570 (19%) were LABC and 110/570 (19%) treatment-naïve patients started on NACT were analyzed. Ninety-one (37 docetaxel [D], 54 anthracycline [A]) patients were eligible for response and survival analysis. Pathological complete remission (pCR) was defined as no evidence of malignancy in both breast and axilla. Results: Median age of the whole cohort was 45 years (range 25-68 years). Premenopausal were 42% and estrogen receptor + 49.5%. Most (90%) were T4 tumors and 70% were Stage IIIB. Median numbers of preoperative cycles were six and three in the D and A group respectively. Overall clinical response rates for breast primary were 74.3% and 53.7% (CR 28.6% vs. 16.7%, P=0.58) while for axilla ORR were 75.7% vs. 54.8% (51.4% vs. 40.4% CR, P=0.77) respectively for D and A. Corresponding pCR rates were 19% vs. 13% respectively. There was no significant difference in disease-free (three-year 56.84% vs. 61.16%, P=0.80) and overall survival (three-year 70% vs. 78.5%, P=0.86) between the two groups. Conclusions: Although pCR rates were higher with docetaxel-based NACT, it did not translate into superior disease-free survival / overall survival compared to anthracycline-based chemotherapies

Results of radical radiotherapy in carcinoma of the Uterine cervix stage I-III

A retrospective analysis is described of 271 diagnosed cases of carcinoma of the uterine cervix who were treated with radical radiotherapy between January 1987 and July 1988 at the Institute Rotary Cancer Hospital. The mean age at presentation was 49 years and 89% of the tumours were FIGO Stage II and III. The median duration of follow-up was 60 months. The early cases were treated with two intracavitary insertions of 34 Gy each to point A with a Selectron LDR intracavitary system, followed by 36 Gy external radiotherapy to the parametrium. Late stage disease was treated with 50 Gy of external radiotherapy, followed by a single intracavitary insertion of 30 Gy to point A. To compensate for the higher dose rate of the Selectron (180 cGy/h) a dose reduction factor of 15% was applied over the intracavitary dose. There were 2.5% and 4.7% of late Grade III bladder and bowel complications, respectively, requiring surgical intervention. There was no relationship between haemoglobin level at diagnosis and the development of late complications. The actuarial 5-year survivals were 65%, 63% and 35% for Stages I, II and III disease, respectively. This study from the Indian subcontinent shows the effectiveness of radiotherapy in Stages I, II and III carcinoma of the uterine cervix, with acceptable morbidity rates