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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor activity of eight new metal complexes (three platinum, one titanium, four ruthenium derivatives) was investigated in a cisplatin (DDP)--sensitive (O-342) and a DDP-resistant (O-342/DDP) ovarian tumor line using the bilayer soft-agar assay. A continuous exposure set up at logarithmically spaced concentrations was used to test the drugs; to uncover possible pharmacokinetic features, a short-term exposure was additionally included for selected compounds. DDP served as the reference drug. The following compounds were investigated: 18-crown-6-tetracarboxybis-diammineplatinum(II) (CTDP), cis-aminotrismethylenephosphonato-diammine-platinum(II) (ADP), cis-diamminecyclohexano-aminotrismethylenephosphonato-platin um(II) (DAP), diethoxybis(1-phenylbutane-1,3-dionato)titanium(IV) (DBT, budotitane), trans-imidazolium-bisimidazoletetrachlororuthenate(III) (ICR), trans-indazolium-tetrachlorobisindazoleruthenate(III) (IndCR), cis-triazolium-tetrachlorobis-triazoleruthenate(III) (TCR) and trans-pyrazolium-tetrachlorobispyrazoleruthenate(III) (PCR). Of the new metal complexes, CTDP was the most active compound in O-342, resulting in a percentage of control plating efficiency (+/- SE) of 1 +/- 1, 12 +/- 8 and 40 +/- 21 following continuous exposure to 10, 1 and 0.1 microM, respectively, and was thus comparable to DDP at equimolar concentrations. In the resistant line, 10 microM CTDP reduced colony growth to 18% +/- 8%, whereas an equimolar concentration of DDP effected a reduction to 26% +/- 9%. During short-term exposure. CTDP was inferior to DDP, which may be ascribed to the stability of the bis-dicarboxylate platinum ring system. The titanium compound DBT, in contrast, showed promising effects at its highest concentration (100 microM) during short-term exposure in both lines; at this concentration the activity in O-342/DDP was higher than that in O-342 (7% +/- 7% vs 34% +/- 17% of control plating efficiency at 100 microM). All ruthenium complexes showed higher activity in the resistant line O-342/DDP than in the sensitive counterpart. ICR was the most active compound. Following continuous exposure of O-342/DDP cells to 10 microM ICR, colony growth was reduced to 18% +/- 4% that of controls. Further studies should concentrate on CTDP and ICR for the following reasons; the activity of CTDP was equal to that of DDP at equimolar concentrations during continuous exposure; considering that the in vivo toxicity of DDP was 3-fold that of CTDP, an increase in the therapeutic index of CTDP would be expected. ICR showed the best effect of all ruthenium complexes; it was superior to DDP in the resistant line.
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PMID:In vitro evaluation of platinum, titanium and ruthenium metal complexes in cisplatin-sensitive and -resistant rat ovarian tumors. 199 86

Cisplatin is the single most active cytotoxic agent in the treatment of patients with recurrent or metastatic squamous cell cancer of the cervix; no other standard drug has been associated consistently with objective response rates of 25% or higher. However, cervical cancer is a relatively drug-resistant disease and prolonged cisplatin treatment appears to induce multiple mechanisms of tumor resistance. The majority of objective responses to cisplatin are partial and relatively short-lived and, therefore, have little impact on survival duration. Complete responses to cisplatin are seen predominantly in patients with extrapelvic metastases rather than pelvic recurrences. This article examines the role of cisplatin in the management of advanced cervical cancer with emphasis on its efficacy in the following circumstances: as a single agent; in combination with other cytotoxic drugs; in previously treated patients; and when administered before surgery or before or concurrent with definitive radiation therapy.
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PMID:Cisplatin in advanced cancer of the cervix: an update. 200 24

To enhance the therapeutic effect of conventional TRC using intra-arterial (i.a.) DDP plus simultaneous i.v. STS, we combined the AT-II-induced hypertension method with TRC and evaluated its efficacy for a rat uterine tumor, using the simulation of intra-arterial chemotherapy for human uterine tumors. During interruption of arterial blood flow by vascular manipulations, DDP plus AT-II were injected for 10 min through the abdominal aorta in the direction of the uterus. Then STS was administered i.v. for a further 5 min and all the arterial restrictions were released. This modified TRC using AT-II showed a much higher anti-tumor effect than that seen in conventional TRC without AT-II and was free from DDP-induced renal damage. On the other hand, severe nephrotoxicity was unavoidable in the rats given the delayed i.v. administration of STS to i.a. DDP alone. The feasibility of post-administration of STS without obvious nephrotoxicity in modified TRC was explained by transient inhibition of DDP delivery to the kidney during the AT-II-induced hypertension. The loss of body weight and the decrease in the number of leukocytes after this therapy were tolerable. Modified TRC showed a higher anti-tumor effect and a lower nephrotoxicity compared with other treatments, as follows: DDP i.a. with or without AT-II; i.v. infusion of DDP alone. Such a superior anti-tumor effect of modified TRC consists of the following 2 factors: (i) the post-administration of STS leading to the delayed neutralization of DDP at the tumor site; (ii) the selective enhancement of DDP delivery to the tumor tissue during AT-II-induced hypertension.
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PMID:Therapeutic efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with the angiotensin-II-induced hypertension method in a rat uterine tumor. 201 Feb 32

From January 1, 1984 to April 30, 1990, 38 patients were surgically found to have an intraabdominal disease resembling epithelial ovarian cancer. This diagnosis was confirmed in 31 patients; the remaining 7 met the criteria of primary peritoneal papillary serous carcinoma. Five of these were diagnosed retrospectively and two during surgery. The mean age at diagnosis was 61.2 years. Tumor histology revealed papillary serous carcinoma in six and mixed (papillary serous and papillary clear cell carcinoma) in one patient. Optimal debulking was achieved in three of seven cases (42.8%). Cisplatin-based combination chemotherapy was administered to all in the study group. Complete response was obtained in four patients, with one surviving for 76 months. The median survival in these patients was 34.5 months (range 6-76 months). Currently, three patients with complete response are alive with clinically undetectable disease. CA-125 assays were available in three cases and blood levels corroborated the clinically determined status of the disease. Tumor steroid hormone receptor status was determined in one case and revealed low levels of estrogen and progesterone receptors. To the best of our knowledge, the usefulness of CA-125 in the diagnosis, management, follow-up, and determination of tumor steroid hormone receptor status, mixed papillary serous and clear cell subtype histological patterns for primary peritoneal papillary serous carcinoma are first described in this report. It seems that this neoplasm may be treated and followed up as in epithelial ovarian cancer, obtaining long-term survival; however, the biologic behavior and management problems of this relatively new entity deserve further clinical experience.
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PMID:Primary peritoneal papillary serous adenocarcinoma: clinical and management aspects. 201 45

Fifty-four patients with inoperable cancers were treated with a combination of cisplatin and radiotherapy from May 1984 to February 1989. Cisplatin was administered at a dose of 40 mg/week, for a total dose of 160-320 mg, during radiation therapy. In 4 cases with brain metastases, the cisplatin dose was 40 mg/m2. Cisplatin concentration in blood was measured using the flameless atomic absorption spectrophotometric method. Radiation therapy was delivered by a 6 MV X-ray or a cobalt-60 unit up to a total dose of 50-70 Gy. Among the 54 patients, 89% (48) responded to the treatment regimen; complete responses (CR) and partial responses (PR) were 56% and 33%, respectively. Six patients were stable in their disease. Among the 30 patients who had CR's, the 1-year survival rate was 88% (21/24). Two patients (7%) had local relapse. However, among PRs, the 1-year survival rate was 33% (4/12) and local failure (61%) (11/18). Objective tumor response was observed in 4 cases with brain metastasis, 2 of the 4 patients were alive for more than 6 months. Toxic effects were moderate and consisted of emesis and myelosuppression. Grade III bone marrow suppression amounted to 11%, and the interval of recovery was relatively long compared with that reported in the literature. Further prospective controlled studies are recommended.
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PMID:Cisplatin as a radiosensitizer in clinical practice: a pilot study. 201 93

The authors report on one case of pharyngolaryngeal extraosseous Ewing's sarcoma. This is a very rare tumor which preferentially has a paravertebral or retroperitoneal location. The difficult histological diagnosis is greatly facilitated by the use of tumoral markers. The treatment implemented consisted of a "conventional" Cisplatin 5 FU chemotherapy, which allowed an almost complete clinical recession after 3 courses, then of external radiation therapy. The evolution of these tumors still remains unpredictable. Regional metastases to the lymph nodes are rare, and they are usually remote and mainly pulmonary. Lastly, the merits of computed tomography for the follow-up of these intramural lesions of the larynx must be emphasized.
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PMID:[Extraskeletal pharyngolaryngeal Ewing's sarcoma. Apropos of a case]. 201 81

Prolonged arterial infusions of cisplatin (DDP) have been effective in the treatment of regionally confined malignancies. It is unclear whether the route or schedule of DDP administration was responsible for the observed therapeutic benefit. To resolve this issue, tumor and normal tissue platinum (Pt) levels were determined in rats bearing hind-limb rat mammary tumors after intravenous (IV) and intra-arterial (IA) DDP infusions of constant dose and varying lengths. Infusions of DDP at 6 mg/kg were conducted IA over 30 minutes, and 3, 6, 24, and 48 hours and IV over 30 minutes and 48 hours. After infusion, Pt concentrations in solubilized tissue homogenates were measured by flameless atomic absorption spectroscopy. Maximum tumor Pt levels were seen after 48-hour IA infusion (29.3 micrograms Pt/mg tissue). IA infusions of 24 hours or less resulted in significantly lower Pt levels. Maximum tumor Pt concentration after IV administration was only 0.98 micrograms/mg tissue (48-hour infusion). Muscle Pt levels adjacent to the tumor were highest in the IA infused extremities, but at the 48-hour interval, were 53-fold less than tumor levels. Tumor and adjacent muscle Pt levels were not significantly different from each other after IV administration. This study provides pharmacologic evidence that lengthening the duration of IA DDP infusion increases tumor levels of Pt over that of IV or rapid IA administrations. The benefit of prolonged IA DDP infusions is dependent upon both route and schedule of drug administration.
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PMID:Increased cisplatin tissue levels with prolonged arterial infusion in the rat. 202 48

We investigated the efficacy of the combination of cisplatin and etoposide in endometrial cancer using mice bearing human endometrial cancer. Cisplatin (5 mg/kg) plus etoposide (10 mg/kg) caused markedly greater inhibition of the growth of medium-sized tumors (96.1% inhibition) than cisplatin alone at the same dose. Similarly, the combination of cisplatin (7.5 mg/kg) and etoposide (10 mg/kg) produced a significantly higher complete remission rate in small tumors, compared with cisplatin alone at the same dose (82.6% vs 35.3%, P less than 0.01). As a single agent, etoposide had almost no inhibitory effect on tumor growth and produced a considerably lower complete remission rate. Total platinum and etoposide concentrations in serum and tumor tissue were unaltered when these agents were used either singly or in combination. Our results suggested that combination cisplatin-etoposide therapy was synergistic against endometrial cancer.
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PMID:Anticancer activity of the combination of cisplatin and etoposide in endometrial cancer-bearing nude mice. 202 58

DNA protein cross-links (DPC), DNA interstrand cross-links (ISCL), and DNA single strand breaks following treatment of experimental ovarian tumor cells (O-342) with five new metal complexes (three platinum, one titanium, one ruthenium compounds) were investigated at 6, 24, and 48 h after drug exposure and compared with their in vitro growth inhibitory potential. cis-Diamminedichloroplatinum(II) (cisplatin, DDP) served as reference drug. The following new compounds were tested: 18-crown-6-tetracarboxybis-diammineplatinum(II) (CTDP), cis-aminotrismethylenephosphonato-diammineplatinum(II) (AMDP), cis-diamminecyclohexano-aminotrismethylenephosphonato-platin um(II) (DAMP), diethoxybis-(1-phenylbutane-1,3-dionato)-titanium(IV) (budotitane), and trans-indazolium-tetrachlorobisindazole-ruthenate(III) (IndCR). At equimolar concentrations DNA cross-linking activity of the platinum agents decreased in the order cisplatin, CTDP, AMDP, DAMP; this was paralleled by growth inhibition in a cell proliferation assay. CTDP-induced interstrand cross-linking occurred more slowly compared to cisplatin (DDP) (6 h: CTDP, 73 +/- 15 versus DDP, 365 +/- 72 rad equivalents), but reached a peak similar to cisplatin 24 h after exposure (CTDP, 317 +/- 68 versus DDP, 392 +/- 116 rad equivalents). At this time point in contrast to DDP no DNA protein cross-links were observed for CTDP (total cross-links: CTDP 310 +/- 71, DDP 1987 +/- 436 rad equivalents). Thus, at 24 h, CTDP was found to be distinctly less reactive to proteins than DDP, and it is suggested that CTDP might be similar in its toxicity pattern to the structurally related compound carboplatin which was also reported to be less reactive to protein than DDP. By 48 h, CTDP- and DDP-induced interstrand cross-links were 65 +/- 21 and 180 +/- 33 rad equivalents, respectively. Although at a lower level, by 24 h, AMDP showed a ratio of ISCL to total cross-links (179 +/- 39 versus 213 +/- 31 rad equivalents), which was comparable to CTDP. The second biphosphonate complex DAMP was the least active platinum compound in terms of DNA damage, effecting only 16 +/- 7 rad equivalents ISCL and 63 +/- 28 rad equivalents total cross-links; similar to DDP, DAMP displayed a higher DPC fraction at 24 h. The titanium complex diethoxybis-(1-phenylbutane-1,3-dionato)-tita-++ +nium(IV) showed dose-dependent inhibition of cell proliferation, while no significant DNA damage could be detected with the alkaline elution technique. These results, together with observations from other authors, indicating that space-filling planar aromatic ring systems are important for its antitumor activity, suggest as possible mechanism of action of diethoxybis-(1-phenylbutane-1,3-dionato)-titanium(IV) intercalation into the DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New platinum, titanium, and ruthenium complexes with different patterns of DNA damage in rat ovarian tumor cells. 203 32

Surgery was attempted in a case of stage IV ovarian cancer with a hepatic metastatic lesion measuring 119 x 96 mm. However, radical surgery was impossible and the operation ended up as no more than exploratory laparotomy. Before closing, Cisplatin 100 mg and Etoposide 200 mg were instilled into the intraperitoneal cavity. Two courses of systemic chemotherapy with PAC (Cisplatin 50 mg, Pirarubicin 40 mg, Cyclophosphamide 400 mg) were instituted. To examine shrinkage of the hepatic metastasis and the peritoneal tumors, A "Second look" operation was conducted. Abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, omentectomy and partial sigmoidectomy resulted in no residual lesions in the peritoneal cavity with the exception of the hepatic metastatic lesion (69 x 57 mm). Two additional courses of PAC therapy were administered after the "Second look" operation. The hepatic metastatic lesion shrank to 45 x 41 mm; a decrease of 83.8% compared to the pre-therapy in size. Liver function tests and tumor chemical markers (TPA, CA 125, SLX) revealed decreased values that were consistent with a tumor size reduction. Good PR was achieved with only a systemic chemotherapy; i.e., without resorting to local injections of chemotherapeutic agents into the liver.
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PMID:[A case of ovarian cancer with liver metastasis successfully treated by PAC therapy]. 205 78


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