5 research outputs found
Association of anti-apoptotic Mcl-1L isoform expression with radioresistance of oral squamous carcinoma cells
Association of anti-apoptotic Mcl-1L isoform expression with radioresistance of oral squamous carcinoma cells
Abstract Background Oral cancer is a common cancer and a major health problem in the Indian subcontinent. At our laboratory Mcl-1, an anti-apoptotic member of the Bcl-2 family has been demonstrated to be overexpressed in oral cancers and to predict outcome in oral cancer patients treated with definitive radiotherapy. To study the role of Mcl-1 isoforms in radiation response of oral squamous carcinoma cells (OSCC), we investigated in the present study, the association of Mcl-1 isoform expression with radiosensitivity of OSCC, using siRNA strategy. Methods The time course expression of Mcl-1 splice variants (Mcl-1L, Mcl-1S & Mcl-1ES) was studied by RT-PCR, western blotting & immunofluorescence, post-irradiation in oral cell lines [immortalized FBM (radiosensitive) and tongue cancer AW8507 & AW13516 (radioresistant)]of relatively differing radiosensitivities. The effect of Mcl-1L knockdown alone or in combination with ionizing radiation (IR) on cell proliferation, apoptosis & clonogenic survival, was investigated in AW8507 & AW13516 cells. Further the expression of Mcl-1L protein was assessed in radioresistant sublines generated by fractionated ionizing radiation (FIR). Results Three to six fold higher expression of anti-apoptotic Mcl-1L versus pro-apoptotic Mcl-1S was observed at mRNA & protein levels in all cell lines, post-irradiation. Sustained high levels of Mcl-1L, downregulation of pro-apoptotic Bax & Bak and a significant (P P P  Conclusion Our studies suggest that Mcl-1L isoform has an important role in the survival and radioresistance of OSCC and may be a promising therapeutic target in oral cancers.</p
Induction of lymphomas on implantation of human oral squamous cell carcinomas in nude mice
111-118<span style="font-size:
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cells from five oral cancer patients and pleomorphic adenoma cells from one
individual were inoculated as single cell suspension in to subcutis of 30 Swiss
nude mice and tail vein of additional 30 mice. Further, tumor tissue pieces from
three oral cancer patients were xenografted sc in 18 nude mice, and 10 mice
were kept as controls. In animals implanted with tumor pieces, 7/18 (39%) mice,
developed squamous cell carcinoma at the site of inoculation within 8-15 days,
while tumors were not observed in mice inoculated with single cell suspension, up
to 60/90 days. In 8/68 (12%) mice,
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foci were observed in several tissues, with hepatomegaly and splenomegaly noted
in 27/68 (39%) mice. Histopathological examination of various tissues revealed
presence of large cell lymphoma in several organs in 14/68 (2 1 %) mice. No
regional or distant metastasis of the implanted oral tumor cells was detected.
Mice injected with cells from pleomorphic adenoma, also demonstrated large cell
lymphoma in 2/10 (20%) mice, whereas none of the 10 control animals showed any
gross abnormalities or microscopic abnormalities in several organs. 2/16 (12%)
lymphomas exhibited positive reaction with mouse B cell antibodies illustrating
the murine origin of the lymphomas, and these were immunophenotyed as
<span style="font-size:
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lymphomas. The lymphomas were also examined with mouse T cell antibodies and
none reacted positively with the mouse T cell antibodies. The lymphomas also
failed to react with human T cell, B cell and human Leucocyte common antigen
(LCA) antibodies, indicating that the induced lymphomas were not of human
origin. The tumor specimens from seven of eight oral cancer patients and the
pleomorphic adenoma patient induced lymphomas in nude mice. Thus it appears that
xenografting oral tumor cells into nude mice may cause induction of the murine
lymphomas, and this needs further investigation.
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