Tata Memorial Hospital

About: Tata Memorial Hospital is a healthcare organization based out in Mumbai, India. It is known for research contribution in the topics: Cancer & Breast cancer. The organization has 3187 authors who have published 4636 publications receiving 109143 citations.

Peripheral dose from uniform dynamic multileaf collimation fields: implications for sliding window intensity-modulated radiotherapy

Abstract: The increase in the number of monitor units in sliding window intensity- modulated radiotherapy, compared with conventional techniques for the same target dose, may lead to an increase in peripheral dose (PD). PD from a linear accelerator was measured for 6 MV X-ray using 0.6 cm 3 ionization chamber inserted at 5 cm depth into a3 5 cm6 35 cm 6 105 cm plastic water phantom. Measurements were made for field sizes of 6 cm 6 6 cm, 10 cm 6 10 cm and 14 cm 6 14 cm, shaped in both static and dynamic multileaf collimation (DMLC) mode, employing strip fields of fixed width 0.5 cm, 1.0 cm, 1.5 cm, and 2.0 cm, respectively. The effect of collimator rotation and depth of measurement on peripheral dose was investigated for 10 cm 6 10 cm field. Dynamic fields require 2 to 14 times the number of monitor units than does a static open field for the same dose at the isocentre, depending on strip field width and field size. Peripheral dose resulting from dynamic fields manifests two distinct regions showing a crest and trough within 30 cm from the field edge and a steady exponential fall beyond 30 cm. All dynamic fields were found to deliver a higher PD compared with the corresponding static open fields, being highest for smallest strip field width and largest field size; also, the percentage increase observed was highest at the largest out- of-field distance. For 6 cm 6 6 cm field, dynamic fields with 0.5 cm and 2 cm strip field width deliver PDs 8 and 2 times higher than that of the static open field. The corresponding factors for 14 cm 6 14 cm field were 15 and 6, respectively. The factors by which PD for DMLC fields increase, relative to jaws-shaped static fields for out-of- field distance beyond 30 cm, are almost the same as the corresponding increases in the number of monitor units. Reductions of 20% and 40% in PD were observed when the measurements were done at a depth of 10 cm and 15 cm, respectively. When the multileaf collimator executes in-plane (collimator 90˚) motion, peripheral dose decreases by as much as a factor of 3 compared with cross-plane data. The knowledge of PD from DMLC field is necessary to estimate the increase in whole-body dose and the likelihood of radiation induced secondary malignancy.

Tamoxifen-Induced Cell Death of Malignant Glioma Cells Is Brought About by Oxidative-Stress-Mediated Alterations in the Expression of BCL2 Family Members and Is Enhanced on miR-21 Inhibition

Abstract: High-grade gliomas are refractory to the current mode of treatment primarily due to their inherent resistance to cell death. Tamoxifen has been reported to inhibit growth and induce cell death of glioma cells in vitro, in an estrogen-receptor-independent manner. Delineating the molecular mechanism underlying tamoxifen-induced cell death of human glioma cells would help in identifying pathways/genes that could be targeted to induce tumor-cell-specific cell death. In the present study, tamoxifen was found to bring about autophagic cell death of human glioma cells that was accompanied by oxidative stress induction, JNK activation, downregulation of anti-autophagic BCL2 family members, viz. BCL2 and BCL-XL, and increased expression of the pro-autophagic members BCL-Xs and BAK. Oxidative stress induction appears to be primarily responsible for the tamoxifen-induced cell death since the cell death, JNK activation, and the alterations in the expression levels of BCL2 family members were abrogated on pretreatment with antioxidant vitamin E. MiR-21, an oncogenic miRNA, is known to be highly upregulated in malignant glioma. Inhibition of miR-21 activity was found to enhance tamoxifen-induced cell death of U87 MG malignant glioma cells. Tamoxifen treatment coupled with miR-21 inhibition could therefore be an effective strategy for the treatment of malignant gliomas.

Flow cytometric analysis of estrogen, progesterone receptor expression and DNA content in formalin-fixed, paraffin-embedded human breast tumors.

Abstract: Flow cytometric analysis of estrogen (ER) and progesterone (PgR) receptor expression in archival human breast tumors is relatively difficult. We have used enzyme digestion and microwave antigen retrieval procedures for multiparametric flow cytometric analysis of ER and PgR expression and DNA content in nuclei isolated from formalin-fixed/paraffin-embedded primary breast tumors. Deparaffinized rehydrated tissue sections treated with pepsin were subjected to microwave irradiation for unmasking of ER and PgR antigenic sites. Biotinylated ER antibody and streptavidin–fluorescein isothiocyanate (FITC) were used for ER labeling and PgR antibody with phycoerythrin labeled goat anti-mouse antibody was used for PgR labeling. Counter staining with propidium iodide-RNase was used for determination of cellular DNA content. Our results show that enzyme digestion and microwave treatment of formalin-fixed, paraffin-embedded breast tumors can be successfully used for the multiparametric analysis of nuclear hormone receptor expression and DNA content by flow cytometry. Cytometry (Comm. Clin. Cytometry) 38:61–69, 1999. © 1999 Wiley-Liss, Inc.