Genotype-phenotype association of TGF-pi and GST with chemo-radiotherapy induced toxicity

Background: Normal tissue toxicity continues to remain as a major challenge for radiation oncologists for delivering the total dose to the tumour cells in cancer patients. Cellular, molecular and plasma based early biomarkers to predict the overreactions and non-overreactions of normal tissue toxicity before the initiation of radiotherapy can be valuable for personalised treatment. The aim of the current study was to analyse the interrelationship between polymorphisms in Glutathione S- Transferases [GSTs] and Transforming Growth Factor-pi [TGF-J31], the plasma level/activity of these proteins with the development of chemo-radiotherapy induced oral mucositis and skin reaction in head and neck cancer [HNC] patients

Materials and Methods: We analysed polymorphisms in TGF-fil and GST by restriction digestion of the PCR amplified products and we also assessed circulating TGF-pl levels and GST activity by Enzyme Linked Immunosorbent Assay [ELISA]

Results: The results indicate that pre-radiotherapy plasma TGF-P1 levels and total GST activity has no correlation with radiation induced normal tissue skin reaction and oral mucositis in HNC patients

Conclusion: The selected polymorphisms in TGF-fil and GST had no influence on TGF-P1 levels and total GST activity. Plasma TGF-P1 and GST activity was not affected by the presence of selected polymorphisms and lacks significance in predicting skin reaction and oral mucositis prior to chemo-radiotherapy

Successful treatment of cerebral toxoplasmosis with clindamycin: a case report

Toxoplasmosis is caused by infection with the obligate intracellular parasite Toxoplasma gondii. Toxoplasmosis is generally a late complication of HIV infection and usually occurs in patients with CD4 + T-cell counts below 200/micro l. Co-trimoxazole [trimethoprim plus sulfamethoxazole] is the most common drug used in India for the treatment of AIDS-associated cerebral toxoplasmosis. Other alternative drugs used for the treatment of cerebral toxoplasmosis are clindamycin plus pyrimethamine and clarithromycin with pyrimethamine. A 30-year-old male known case of retroviral disease presented to Kasturba Medical College, India, with complaints of fever, headache and vomiting. Computed tomography scan of his brain showed irregular ring enhancing lesion in the right basal ganglia. Toxoplasma serology revealed raised IgG antibody levels. Based on the CT features and serology, diagnosis of cerebral toxoplasmosis was made. He was treated with clindamycin alone as he had history of sulfonamide allergy. The patient was symptomatically better after 48 hours. After 21 days, repeat CT of brain was done which was normal. The patient showed good clinical improvement within 48 hours and the lesion resolved completely within 3 weeks. The authors recommend using clindamycin without pyrimethamine in resource poor settings and in patients who do not tolerate sulfa drugs

Induction of micronuclei in a transplantable murine tumor after multimodality treatment with cis-platin, radiation and hyperthermia

Tumor response after multimodality treatment using combination of radiation, chemotherapeutic drugs and hyperthermia usually assessed by parameters such as tumor growth delay, volume doubling time and regression response. The study herein was conducted to investigate the usefulness of micronucleus assay for assessing the multimodality treatment. The induction of micronuclei [MN] in a transplantable solid tumor grown in inbred Balb/c mice was analyzed after treating the tumors with cis-platin [cDDP], radiation [RT] and hyperthermia [HT]. The MN frequency in tumor was measured at 1, 3, 5 and 7 days of post-treatment. On day 1, all the cDDP and RT groups, except HT treatment produced significantly higher MN counts from that of the untreated tumors. Cis-platin treatment resulted in a dose-dependent linear increase in the frequency of MN induction on day one. Combination of radiation with cDDP or HT, as bimodality treatment further increased the MN counts. In the tri-modality group [cDDP+RT+HT] the MN counts were not significantly higher than the bi-modality treatments, however there was an immediate tumor shrinkage indicating the contribution of other forms of cell death. Although, MN counts were declined after day five post-treatment, remained significantly higher than the control on day seven-post treatment in hyperthermia alone or its combination with RT and RT+ cDDP groups. Micronucleus assay may be useful for assessing the post-treatment regression response of resistant tumors, while monitoring the response of sensitive tumors the parameters such as apoptosis and necrosis may also contribute considerably to tumor cell loss contributing immediate tumor regression

Androgen & vitamin D nuclear receptor expression in archival breast tumour samples.

BACKGROUND & OBJECTIVE: Breast tumour cells have receptors for androgen and vitamin D and their clinical significance is not completely understood. Therefore, the present study was undertaken to analyze androgen and vitamin D receptor levels in human primary infiltrating ductal breast carcinomas (IDC) and benign breast tumour archival samples and to find out their correlation, if any, with the clinical findings. METHODS: Paraffin blocks of benign and malignant breast tumours were sectioned, deparaffinized, and nuclei released by pepsin digestion. After antigen retrieval, nuclei were stained with primary antibodies for androgen or vitamin D receptors and secondary fluorescein isothiocyanate (FITC) labeled antibodies and propidium iodide respectively, to quantitative receptor expression and DNA content by flow cytometry. RESULTS: Androgen receptor positive nuclei ranged from 16-66 per cent in the IDC tumours as compared to 36-67 per cent in the benign tumours. Based on flow cytometric comparison of AR expression in AR positive and negative cell lines established earlier, 24 of 28 tumours from postmenopausal women were AR positive compared to all benign tumours and 32 of 33 tumours from pre-menopausal patients. Vitamin D receptor positive nuclei ranged from 14-89 and 2-75 per cent in IDC and benign tumours, respectively. All pre- or post-menopausal tumours were VDR positive as compared to 10 of 15 benign tumours that were VDR positive. No correlation was seen between nuclear androgen and vitamin D receptor expression of the IDC or benign tumours. There was a positive correlation between per cent of receptor positive nuclei and antigen density as measured by ratio of the mean log fluorescence channel value (MFC). No statistically significant correlation was found between nuclear receptor expression (per cent positive nuclei or antigen density) with that of tumour stage, lymph node status, tumour grade, patient age or menopausal status. INTERPRETATION & CONCLUSION: There was no significant correlation between androgen or vitamin D receptor expression and clinical findings. The expression of AR and VDR and the antigen density in the nuclei of the archival breast tumour samples were highly variable because of the tumour heterogeneity. Future studies with fresh biopsy samples of tumour on AR and VDR levels and their up- or down-regulation may be useful while stratifying the patients for hormonal therapy.