chromomycin-a3 and Ovarian-Neoplasms

A new fluoropyrimidine antitumor agent, carmofur (HCFU, Mifurol) was administered to patients with malignant ovarian tumor. Two of these patients revealed favorable results. The first patient was a 72-year-old female, who was diagnosed as having ovarian serous cystadenocarcinoma with metastatic omental tumor at exploratory laparotomy, its size was newborn child head size. She was started on with a combination chemotherapy of Mifurol (600 mg p.o. daily), Endoxan (4 mg/kg i.v. twice a week), Mitomycin C (0.04 mg/kg i.v. twice a week) and Toyomycin (0.01 mg/kg i.v. twice a week). After four weeks, this combination therapy brought her a complete response with disappearance of pleural effusion, ascites and metastatic tumor. The second case was a 39-year-old female, who underwent adnexectomy elsewhere which led to the discovery of Krukenberg tumor, and was referred to our hospital. After the first course of the same combination chemotherapy, second look operation was performed. Histological examination of the specimen obtained by metastatic tumor of uterosacral ligament showed the degeneration (grade II b-III, Oboshi and Shimozato) of cancer cell. It is suggested that this combination chemotherapy including Mifurol is effective and useful for the patients with ovarian carcinoma.

Topics: Adult; Aged; Antineoplastic Agents; Chromomycin A3; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Female; Fluorouracil; Humans; Hysterectomy; Mitomycin; Mitomycins; Ovarian Neoplasms

Differential cleavage at three restriction enzyme sites was used to determine the specific binding to DNA of the antitumour antibiotics mithramycin A (MTA), chromomycin A(3) (CRO) and six chromophore-modified analogues bearing shorter side chains attached at C-3, instead of the pentyl chain. All these antibiotics were obtained through combinatorial biosynthesis in the producer organisms. MTA, CRO and their six analogues showed differences in their capacity for inhibiting the rate of cleavage by restriction enzymes that recognize C/G-rich tracts. Changes in DNA melting temperature produced by these molecules were also analyzed, as well as their antiproliferative activities against a panel of colon, ovarian and prostate human carcinoma cell lines. Moreover, the cellular uptake of several analogues was examined to identify whether intracellular retention was related to cytotoxicity. These experimental approaches provided mutually consistent evidence of a seeming correlation between the strength of binding to DNA and the antiproliferative activity of the chromophore-modified molecules. Four of the analogues (mithramycin SK, mithramycin SDK, chromomycin SK and chromomycin SDK) showed promising biological profiles.

Topics: Antibiotics, Antineoplastic; Cell Line, Tumor; Chromomycin A3; Chromomycins; Colonic Neoplasms; Deoxyribonucleases, Type II Site-Specific; DNA Restriction Enzymes; Female; Flow Cytometry; Humans; Male; Ovarian Neoplasms; Plicamycin; Prostatic Neoplasms; Structure-Activity Relationship