CXCL12-Mediated Guidance of Migrating Embryonic Stem Cell-Derived Neural Progenitors Transplanted into the Hippocampus

Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus can induce lesions in the dentate gyrus (DG) that lead to cell death within the upper blade. Using a mouse model of temporal lobe epilepsy, we previously observed that embryonic stem cell-derived neural progenitors (ESNPs) survive and differentiate within the granule cell layer after stereotaxic delivery to the DG, replacing the endogenous cells of the upper blade. To investigate the mechanisms for ESNP migration and repair in the DG, we examined the role of the chemokine CXCL12 in mice subjected to kainic acid-induced seizures. We now show that ESNPs transplanted into the DG show extensive migration through the upper blade, along the septotemporal axis of the hippocampus. Seizures upregulate CXCL12 and infusion of the CXCR4 antagonist AMD3100 by osmotic minipump attenuated ESNP migration. We also demonstrate that seizures promote the differentiation of transplanted ESNPs toward neuronal rather than astrocyte fates. These findings suggest that ESNPs transplanted into the adult rodent hippocampus migrate in response to cytokine-mediated signals

Technical Report - Retrospective analysis of role of interstitial brachytherapy using template (MUPIT) in locally advanced gynecological malignancies

Aim : The aim of this retrospective study was to assess treatment outcomes for patients with locally advanced gynecological malignancies being treated with interstitial brachytherapy using Martinez universal perineal interstitial template (MUPIT) and to study the acute and late sequelae and survival after treatment by this technique. Materials and Methods : Ninety seven patients untreated with histopathological confirmation of carcinoma of cervix (37) vault (40) and vagina (20) were treated by combination of external beam RT (EBRT) using megavoltage irradiation to pelvis to dose of 4000-5000 cGy followed by interstitial brachytherapy using MUPIT between September 2001 to March 2005. Median age was 46 years. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitatory radiotherapy was found to be unlikely to encompass a proper dose distribution were treated by interstitial template brachytherapy using MUPIT application and were enrolled in this study. The dose of MUPIT was 1600-2400 cGy in 4-6# with 400 cGy /# and two fractions a day with minimum gap of six hours in between two fractions on micro-HDR. Criteria for inclusion of patients were as follows: Hb minimum 10 gm/dl, performance status - 70% or more (Karnofsy scale), histopathological confirmation FIGO stage IIB-IIIB (excluding frozen pelvis). Results : Among the 97 patients studied, 12 patients lost to follow-up and hence they were excluded from the study. Follow-up of rest of the patients was then done up to September 2006. The duration of follow-up was in the range of 20-60 months. Parameters studied were local control rate, complication rate, mortality rate and number of patients developing systemic metastasis. Local control was achieved in 56/85 (64.7%) and complication rate was 15/85 (17.6%). Local control was better for nonbulky tumors compared bulky tumors irrespective of stage of disease. Local control was better in patients with good regression of disease after external beam radiotherapy. Time of gap between EBRT and implant also had an impact on the outcome. Conclusion : Interstitial template brachytherapy by MUPIT is a good alternative to deliver high dose radiation in locally advanced gynecological malignancies where conventional brachytherapy application is either not feasible or likely to give optimal dose distribution. Loco regional control obtained is definitely better than EBRT alone and within the accepted range of complications

Technical Report - Retrospective analysis of role of interstitial brachytherapy using template (MUPIT) in locally advanced gynecological malignancies

Aim : The aim of this retrospective study was to assess treatment outcomes for patients with locally advanced gynecological malignancies being treated with interstitial brachytherapy using Martinez universal perineal interstitial template (MUPIT) and to study the acute and late sequelae and survival after treatment by this technique. Materials and Methods : Ninety seven patients untreated with histopathological confirmation of carcinoma of cervix (37) vault (40) and vagina (20) were treated by combination of external beam RT (EBRT) using megavoltage irradiation to pelvis to dose of 4000-5000 cGy followed by interstitial brachytherapy using MUPIT between September 2001 to March 2005. Median age was 46 years. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitatory radiotherapy was found to be unlikely to encompass a proper dose distribution were treated by interstitial template brachytherapy using MUPIT application and were enrolled in this study. The dose of MUPIT was 1600-2400 cGy in 4-6# with 400 cGy /# and two fractions a day with minimum gap of six hours in between two fractions on micro-HDR. Criteria for inclusion of patients were as follows: Hb minimum 10 gm/dl, performance status - 70% or more (Karnofsy scale), histopathological confirmation FIGO stage IIB-IIIB (excluding frozen pelvis). Results : Among the 97 patients studied, 12 patients lost to follow-up and hence they were excluded from the study. Follow-up of rest of the patients was then done up to September 2006. The duration of follow-up was in the range of 20-60 months. Parameters studied were local control rate, complication rate, mortality rate and number of patients developing systemic metastasis. Local control was achieved in 56/85 (64.7%) and complication rate was 15/85 (17.6%). Local control was better for nonbulky tumors compared bulky tumors irrespective of stage of disease. Local control was better in patients with good regression of disease after external beam radiotherapy. Time of gap between EBRT and implant also had an impact on the outcome. Conclusion : Interstitial template brachytherapy by MUPIT is a good alternative to deliver high dose radiation in locally advanced gynecological malignancies where conventional brachytherapy application is either not feasible or likely to give optimal dose distribution. Loco regional control obtained is definitely better than EBRT alone and within the accepted range of complications