Focal Adhesion Kinase Induces Matrix Metalloproteinase-2 by Involving α5β1-Mediated Signaling in Breast Cancer Cell, MCF-7.

Introduction: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a pivotal role in cell invasion. Matrix metalloproteinases (MMPs) are implicated as the key players in cancer cell invasion. Hence, the role of FAK in MMP regulation is very important in understanding tumor progression. Materials and Methods: Here, we studied the role of FAK, its association with other signaling kinases and involvement in the α5β1 integrin receptor-mediated regulation of MMP-2 activity and expression in human breast cancer cell line MCF-7. Results: Immuno blot analysis revealed that FN treatment causes phosphorylation of FAK and FAK gets localized at the cell attachment focal point of MCF-7 cells. FN treatment did not change the mRNA status of FAK but enhanced mRNA level of MMP-2 and MT1-MMP, also caused downregulation of TIMP-2. Co-imunoprecipitation and inhibitor studies revealed the association of FAK with α5β1, Paxillin, PI3K and ERK. siRNA studies revealed that FAK is critical in regulation of activity and expression of MMP-2 and downstream signaling kinases. Conclusion: Th e interaction of α5β1 integrin with FN initiates a signaling cascade with FAK as its central player. FAK gets phosphorylated and in turn associates with tyrosine kinases like PI3K and ERK. FAK also activates PI3K and ERK that serve as very crucial mediators of the signaling pathway leading to induction of MMP-2 activity and resulting invasion of breast cancer cell, MCF-7.

IFNα2b augments immune responses of cisplatin+5-fluorouracil treated tongue squamous cell carcinoma patients - A preliminary study.

Background & objectives: Interferon alpha 2b (IFNα2b) has been reported to regulate several immune functions efficiently to enhance the cytotoxic activity of NK and T cells towards various forms of tumours. The objective of the present study was to evaluate the efficacy of IFNα2b in overcoming disease induced and/or treatment associated imunosuppression of tongue squamous cell carcinoma (TSCC) patients undergoing chemotherapy for better clinical outcome. Methods: Seven TSCC patients under cisplatin + 5-fluorouracil chemotherapy in combination with IFNα2b were assessed for various immunohaematological parameters before treatment, after chemotherapy and after IFNα2b therapy. Results: Deterioration of the haematological and immune responses was detected in immunosuppressed TSCC patients after chemotherapy. IFNα2b treatment led to a recovery in these parameters in most of the patients. Greater number of T/NK cells and enhanced secretion of type 1 cytokines were also noted. Haematological complications were reduced after completion of the therapy. Immune- and haematostimulation were also observed in patients with partial response. No positive clinical response was detected in one patient. Interpretation & conclusions: IFNα2b appears to be an effective immunostimulator having clinical impact to combat the immunosuppression in TSCC patients. Successful immunostimulation by IFNα2b may help TSCC patients in clinical improvement. The findings of this preliminary study need to be confirmed on a large number of patients with TSCC.

Secondary malignant giant cell tumour of bone--a study of five cases with short review of literature.

Secondary malignant giant cell tumour of bone occurs as a result of previous attempts at local control of a benign giant cell tumour of bone (GCT). Out of the total 445 conventional benign GCT of bone, therapeutic irradiation was given in 39 cases as the lesions were located in the vertebrae and pelvic bones where debulking surgery was not possible and the tumours were pressing on the spinal cord. The patients were followed up for 21 years. Out of 39 cases, 5 patients developed sarcomas of which 3 were fibrosarcomas, 1 was malignant fibrous histiocytoma while 1 was an osteosarcoma. All the patients developing post-radiation sarcomas died within a few months due to lung metastasis. In conclusion, all the patients with benign GCT of bone treated with radiation must be followed life long as they are prone to develop sarcomas.