Pemetrexed-cisplatin combined with TRT followed by consolidation pemetrexed was not superior to standard chemoradiotherapy for stage III unresectable nonsquamous non-small-cell lung cancer.
The p53 tumor suppressor gene and members of the transforming growth factor- (TGF-) superfamily play central roles in signaling cell cycle arrest and apoptosis (programmed cell death) in normal development and differentiation, as well as in carcinogenesis. Here we describe a distantly related member of the TGF- superfamily, designated placental TGF- (PTGF-), that is upregulated in response to both p53-dependent and -independent apoptotic signaling events arising from DNA damage in human breast cancer cells. PTGF- is normally expressed in placenta and at lower levels in kidney, lung, pancreas, and muscle but could not be detected in any tumor cell line studied. The PTGF- promoter is activated by p53 and contains two p53 binding site motifs. Functional studies demonstrated that one of these p53 binding sites is essential for p53-mediated PTGF- promoter induction and specifically binds recombinant p53 in gel mobility shift assays. PTGF- overexpression from a recombinant adenoviral vector (AdPTGF-) led to an 80% reduction in MDA-MB-468 breast cancer cell viability and a 50 -60% reduction in other human breast cancer cell lines studied, including MCF-7 cells, which are resistant to growth inhibition by recombinant wild-type p53. Like p53, PTGF- overexpression was seen to induce both G 1 cell cycle arrest and apoptosis in breast tumor cells. These results provide the first evidence for a direct functional link between p53 and the TGF- superfamily and implicate PTGF- as an important intercellular mediator of p53 function and the cytostatic effects of radiation and chemotherapeutic cancer agents.
Resectable thymoma is associated with excellent prognosis. Aggressive resection of recurrent disease yielded excellent long-term results. Higher Masaoka stage is associated with a greater chance of incomplete resection. Higher Masaoka stage and increasing tumor size are independent factors associated with recurrence.
We describe the isolation and characterization of peroxisomal assembly mutants in the genetically manipulable yeast Yarrowia lipolytica (pay mutants). These mutants were initially identified as oleic acid‐non‐utilizers by their inability to grow on oleic acid, the utilization of which requires peroxisomal β‐oxidation enzymes. Identification of a subset of oleic acid‐non‐utilizers as pay mutants was obtained by a rapid immunofluorescence procedure using antibodies to the peroxisomal targeting signal Ser‐Lys‐Leu‐CO2H. Punctate structures characteristic of peroxisomes were not detected in pay mutants using this technique. This rapid identification by immunofluorescence should be generally applicable to the selection of peroxisomal assembly mutants in other yeasts. To take advantage of the pay mutant system, we constructed a genomic library in the autonomously replicating vector pINA445 and developed an efficient and rapid electroporation procedure for the functional complementation of these mutants. We have been successful in functionally complementing two independent pay mutants. Molecular analysis of these and other complementing genes will allow for characterization of some of the cellular elements involved in peroxisomal assembly.
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