Overexpression of manganese superoxide dismutase gene changes the metastasis associated-character of the mouse fibrosarcoma, FSa-II.

The tumor metastatic ability and tumorigenicity of the mouse fibrosarcoma cell line (FSa-II) were significantly reduced due to overexpression of manganese superoxide dismutase (MnSOD) as reported previously. We investigated changes in the in vitro basic character of FSa-II cells transfected with the human MnSOD cDNA which was employed in the previous studies. FSa-II and the control vector-transfected cell line NEO, had no detectable MnSOD activity. SOD-H, into which MnSOD cDNA was transfected, is the cell line with high MnSOD activity. The malignant phenotype, characterized by serum-independence, was suppressed with elevated MnSOD activity. A quantitative comparison of transferrin receptor (TfR) by flow cytometry showed the amount of TfR on the membrane of SOD-H cells to be significantly less than that on the membrane of NEO cells. The amount of CD44 expression on SOD-H cells was almost the same as that on NEO cells. The results of this study suggest that the overexpression of MnSOD is related to suppression of the malignant phenotype and that changes of iron metabolism may play an important role in this process.

Overexpression of manganese superoxide dismutase gene suppresses spontaneous apoptosis without a resultant alteration in in vivo growth of the mouse fibrosarcoma, FSa-II.

The relationship between spontaneous apoptosis and overexpression of manganese superoxide dismutase (MnSOD) gene was examined in vivo. The mouse fibrosarcoma cells expressing high MnSOD activities due to transfection with the human MnSOD cDNA (SOD-H), or the fibrosarcoma cells transfected with the selectable marker alone (NEO), were transplanted into immune-deficient Fox Chase SCID C.B-17/Icr-scid Jcl mice. Apoptosis in tumors was visually quantified by the in situ end-labeling method. The number of apoptotic cells in the SOD-H tumors was significantly less than that in the NEO tumors. The tumor growth time of the SOD-H tumors to grow from 34 to 500 mm3 in one-half of the mice was slightly longer than that of the NEO tumors, but the difference was not statistically significant. These results suggest that overexpression of MnSOD gene is involved in the suppression of spontaneous apoptosis, without a resultant alteration in the tumor growth.

[Radiotherapy for elderly patients].

Radiotherapy is of particular benefit to elderly patients as alternative surgery, and it is widely used with curative and palliative intent. Patients aged 75 and older accounted for 5-10% of all cases, and half of them had some complications. Radical radiotherapy was performed in 63-73% of the elderly patients and 88-100% were able to complete the planned course. Several authors reported that the elderly patients adequately staged, can tolerate radical radiotherapy and have survival comparable to that of younger patients. But careful management is needed.

[Effectiveness of 3 ways method in intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy].

We analyzed 58 cases of advanced or recurrent cervical cancer treated with intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. Two separate IAIC regimens were administered since 1985: group I consisted of 5-FU + MMC +/- ADR (30 patients) and group II consisted of CDDP + MMC +/- 5-FU (28 patients). The tip of a catheter was placed in the bifurcation of the abdominal aorta (1 way method: 45 patients regimen II: 15) between 1977-1984. We have used selective catheterization (2 ways method: 9) since 1995 in order to get good drug distribution. However we experienced grade 4 toxic effect of cutaneous and pain with this method, so we have used a 3 ways method (4 patients) since 1998. The two-year survival rete was 60% with the 1 way method, and 67% with the 2 ways method and regimen II. Severe adverse effects (grade 3 + 4) were found in 53, 56, 0%, respectively, by each of the three methods (1, 2, 3 ways) hematologically, 13, 22, 0% in gastrointestinally, 0, 44, 0% in cutaneously and 0, 56, 0% in pain or neurotoxicity. These data suggest that IAIC by the 3 ways method is a useful treatment for advanced or recurrent cervical cancer. However, one should check the blood flow distribution periodically, and control concentration of drugs.