Akt Phosphorylation Orchestrates T11TS Mediated Cell Cycle Arrest in Glioma Cells.

The novel anti-neoplastic glycopeptide T11TS retards glioma both in in-vitro clinical samples and in-vivo models. This study investigates the correlation between altering the glioma microenvironment with glioma arrest and death. Flow cytometry, immunoblotting, ELISA, and co-immunoprecipitation were employed to investigate glioma cell arrest and death. Results include a decline in phosphorylation of Akt and attenuation of p21 phosphorylation (Thr145,Ser146) and disassociation of p-Akt-Mdm2 and p-Akt-BAD facilitating death by Akt>BAD. T11TS influence phosphorylation patterns in two focal axes Akt>p21 and Akt>Mdm2>p53. The current article provides crucial insight in deciphering the mechanism of T11TS induced glioma cell arrest and death.

Induction of G1 arrest in glioma cells by T11TS is associated with upregulation of Cip1/Kip1 and concurrent downregulation of cyclin D (1 and 3).

In our laboratory, a novel therapeutic probe, T11TS, a membrane glycoprotein, was isolated which had antineoplastic activity against experimental glioma. Development of a novel therapeutic strategy with T11TS has unearthed a newer dimension of its mechanism of action: modulation of the cell cycle. In this study, we have presented evidence to support the finding that T11TS induces G1 cell cycle arrest of rat glioma cells. Results of flow cytometric studies showed that the treatment produced a marked increase in the proportion of cells in the G1 phase. Flow cytometry, immunoblotting, immunoprecipitation, and kinase assays were performed for investigating the involvement of G1 cell cycle regulators. T11TS induces downregulation of the cyclin-D (1 and 3) expression with the concurrent upregulation of p21 and p27 and their concomitant association with cyclin-dependent kinase 4, proliferating cell nuclear antigen and cyclin E respectively leading to a decrease in cyclin-dependent kinase 4 kinase activity. A transient rise in retinoblastoma protein level and coordinated binding of retinoblastoma protein with E2F coincided with the accumulation of cells in G1 phase. Thus, our observations have uncovered an antiproliferative pathway for T11TS, causing retardation of glioma cell cycle.

The first cross sectional survey on intracranial malignancy in Kolkata, India: reflection of the state of the art in southern West Bengal.

Recent increase in the occurrence of intracranial malignancies and poor performance of therapeutic measures have established the disease as an important concern of medical sciences. The lack of information about the disease pattern throughout India creates problems for maintaining community health for prevention. The present study on the hospital population of Kolkata was conducted to determine the incidence pattern of the disease in the population of southern West Bengal, focusing on distribution with age, sex, occupation and religion in different districts of the region, and characterizing diagnostic and therapeutic measures. Among a total of 39,509 cancer patients from 21 health centers of Kolkata, 2.4% had brain cancers and among these more than 60% are gliomas. A cross-sectional study for a period of 3 years reported the occurrence of 15 types of intracranial malignancy, which demonstrated astrocytomas (36.8%), glioblastoma multiforme (GBM) (7.9%) and meningiomas (11.6%) to be predominant. Brain tumors occur more frequently in males with few exceptions and the incidence was found to be highest among the 40-49 year old group (20.2%). No specific trend for religion and occupation was apparent. However, the district wise distribution showed maximum incidences among industrial areas, namely, Kolkata (33.1%), North 24-Parganas (18.2%), Howrah (9.3%) and Hoogly (7.6%). Diagnosis of the disease was by CT scan, MRI and histological identification (pre and post operative). Therapeutic procedures rely mainly on surgery and radiotherapy, whereas chemotherapy was used as an adjuvant for about 10% of the cases. Evaluation of the scenario regarding intracranial malignancy in this region was a long awaited requirement which should ultimately serve an important function in pointing to risk zones within the population and allow better control measures to be introduced for the disease.