Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Curative treatment modalities for patients with malignant melanoma (MM) in advanced stages are limited. Temporary successes with chemotherapy have so far mainly been achieved after removal of all accessible tumor masses. Extensive experience with cytostatic measures has been gained over more than two decades both with therapeutic and with adjuvant schedules. Dacarbazine (DTIC), which is associated with a remission rate of approximately 20%, continues to be the most effective cytostatic drug in the treatment of MM. Systemic (poly) chemotherapeutic schedules with and without DTIC have improved the response rates in metastasizing MM in numerous phase II trials. However, these results have not been confirmed in randomized studies comparing these schedules with DTIC monochemotherapy. For the BOLD schedule (bleomycin, Oncovin, lomustine, dacarbazine), the BELD schedule (Eldisine instead of Oncovin), and the DVP combination (dacarbazine, vindesine, Platinex), initial response rates of 40-49% have been reported. However, lower response rates were recently described (DVP: 24%; BOLD: 22% and 4%). Therefore, there is still no definite evidence that polychemotherapy is superior to DTIC monotherapy in MM. In our opinion, expected response rates of 20-30% justify the use of chemotherapy in disseminated MM; in cases of further progression, therapy should be interrupted early - after 2-3 cycles. Systemic (poly) chemotherapy of metastasizing MM is indicated in patients whose general condition is good, mainly in those who have skin, soft tissue, or lung metastases. These metastases usually respond well to cytostatic treatment. In future, the combined use of cytostatics together with new antitumour molecules may reduce the general toxicity and improve the efficacy of systemic cytostatic therapy in MM. The benefits of adjuvant chemotherapy in the treatment of MM have still to be confirmed definitively. While adjuvant therapy with DTIC has proved to be ineffective in stage I, irrespective of the tumor thickness, some studies suggest that adjuvant therapy with DTIC, or combinations including DTIC, may improve the prognosis of patients in clinical stage II.
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PMID:[Chemotherapy of malignant melanoma--current status]. 218 Aug 55

A 38-year-old man was admitted to Nara Medical University Hospital on Feb.7,1983, because of swelling of the scrotal contents on the right side and elevated serum AFP, beta-HCG and LDH suggestive of testicular tumor. Right orchiectomy was carried out and a pathological diagnosis of embryonal cell carcinoma of the right testis (pT3N0M1) was made. The patient, upon evidence of multiple pulmonary metastases, was treated with a combination chemotherapy of cis-Diamminedichloroplatinum, vincristine and peplomycin. After three courses of combination chemotherapy, pulmonary metastases were decreased, but their foci persisted. The patient was then treated with Etoposide 62 mg/m2 daily for 5 days every three weeks, and after this course, complete remission of pulmonary metastases was obtained. The patient recieved 3 courses of Etoposide and retroperitoneal lymph node dissection, and has since shown no evidence of disease for 2 years and 4 months after surgery.
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PMID:[Complete remission obtained in advanced testicular cancer treated by etoposide (NK-171)]. 242 Feb 82

Clinical features of 644 surgically treated cases of cancer of the uterine cervix were analyzed according to their histological type. Large cell non-keratinizing carcinomas (L) showed node metastasis proportional to the grade of invasion in the cervix, and the lowest recurrence rate. Small cell non-keratinizing carcinomas (S) tended to have widely spread metastasis from an early stage of the primary lesion. Lateral recurrence from metastatic foci was common in this type. Keratinizing carcinomas (K) were localized in the cervix until the primary tumor became enlarged to a certain size. Central recurrence from invasive foci in the surrounding tissue or organ occurred more often than lateral recurrence in this type. Metastasis pattern of pure adenocarcinomas (A) was similar to that of S, but recurrence was delayed. Adenosquamous carcinomas (AS) showed a similar metastasis pattern to that of K, but recurrence was rapid and the ratio high. Prophylactic maintenance chemotherapy with Tegafur (800 mg/day) or Carboquone (0.5 mg/day) was performed in 187 cases for a period of 2 years after surgery. The effect of maintenance chemotherapy depended on the histological type. A marked effect was obtained in the groups of S and A, in which no recurrence has appeared so far. The recurrence rate of L dropped to 1/5 that of the control. However, unsatisfactory results were shown in the groups of K and AS including the keratinizing cell component. It is of significance that maintenance chemotherapy showed the highest effectiveness in S and A on which conventional adjuvant therapy, i.e. postoperative radiotherapy, has had the least effect. This has led us to consider that a proper selection of adjuvant therapies would contribute toward improving the postoperative prognosis of patients with cancer of the uterine cervix.
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PMID:[Differing progress patterns in cancer of the uterine cervix and variant effects of adjuvant chemotherapy based on histological type]. 308 Sep 62

Total growth of transplanted human or rodent tumors in the subrenal capsule of mice was much improved by treatment with cyclosporine (CSA, cyclosporin A). Tumor size increased rapidly between days 6 and 12 after implantation, CSA injected on days 1-5 or 2-8 prevented tumor regression. In contrast, immunologic regression occurred after 6 days in absence of the drug. Tumor growth was comparable in CSA-treated mice, athymic nude mice with human tumors, or normal mice with syngeneic rodent tumors. Studies with rodent tumors in syngeneic mice showed that the CSA treatments had no antitumor effect. Inflammatory infiltration was seen on days 6-12 after tumor implantation into control mice. Immunoperoxidase staining showed murine T cells to be prominent in the infiltrate. In contrast, tumors in CSA-treated mice contained minimal inflammatory infiltrate even 12 days after implantation. Allogeneic tumors in CSA-treated mice caused neovascularization, metastases, and local invasion into the kidney. cis-Diamminedichloroplatinum showed highly significant activity against human tumors in CSA-treated mice during the period 6-10 days after tumor implantation but showed no statistically significant antitumor activity 0-6 days after implantation in mice not treated with CSA. We suggest that in CSA-treated mice the subrenal capsule assay for tumor growth provides a rapid, economical model for investigations in vivo of mouse or human tumor biology, for drug screening with a standard tumor, or for determination of optimal treatment of particular human tumors.
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PMID:Transplantation of human or rodent tumors into cyclosporine-treated mice: a feasible model for studies of tumor biology and chemotherapy. 659 66

Intravenous cis-Diamminedichloroplatinum-II (CDP) was administered to 10 patients with osteosarcoma to treat the primary tumor in 8 and bone metastases in 2. Three patients also had pulmonary metastases. The intent was to deliver 7 courses (150 mg/M2 q 2 weeks) over 3 months (total cumulative dose 1050/mg/M2). However, this was only accomplished in 2 patients; in the remaining 8 the full course was not administered because of temporary renal insufficiency (3), tumor escape (1) and apparent response after 4-6 courses suggesting that no further benefit would accrue (4). Overall, clinical and/or radiologic responses were observed in 9 patients. In 6 of 9 tumors subjected to surgical resection (66%), necrosis in excess of 65% was observed. Optimum results were achieved with a cumulative dose of 600 mg/M2 administered over 6 weeks. These results suggest that intravenous CDP may be as efficacious as intra-arterial CDP which has produced similar responses.
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PMID:Pediatric osteosarcoma - treatment of the primary tumor with intravenous cis-diamminedichloroplatinum-ii (cdp) - comparison of the results with the reported efficacy of intraarterial cdp. 2157 59

The incidence rates of cutaneous melanoma in non-Hispanic whites show an increasing tendency with age. While uveal melanoma in general is a rare disease, representing only 4% of all melanomas with an incidence rate of 0.6 per 100 000, it is still the most frequent malignancy of the eye. Synchronous occurrence of ocular and cutaneous melanoma is an exceptional rarity, due to the distinct genetic background of the diseases. We report the case of a 80-year-old man who underwent total excision of a cutaneous melanoma in 2008. In 2013, he was diagnosed with uveal melanoma as part of a routine work-up for reduced vision. The uveal melanoma was treated by brachytherapy. In 2015, liver metastases were suspected by routine ultrasonography. Core biopsy was carried out, and the histology confirmed melanoma metastases. The molecular analysis of the cutaneous lesion showed gain of function mutation of the BRAF V600 K gene, while we found a wild-type BRAF gene in the metastatic lesion. Based on the recommendation of the oncoteam, hepatic intra-arterial Epirubicin-Platidiam therapy was introduced. He received 11 doses of intra-arterial chemotherapy (IAC), in 21 cycles. IAC was well tolerated without any catheter-related complications or toxicities. Partial regression of the hepatic metastases were documented in February 2016. After completing the eleventh cycle of intrahepatic chemotherapy, the disease remained in complete remission for over a year. The parallel occurrence of cutaneous and ocular melanoma is rare, however, the metastatic progression in such cases make the selection of optimal medical therapy challenging. The distinct genetic background of two melanoma types may help the identification of the source of the metastatic lesions, in order to guide the treatment decisions. Orv Hetil. 2018; 159(16): 642-647.
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PMID:[Treatment of metastatic progression following the synchronous occurrence of cutaneous and ocular primary melanomas]. 2965 81

Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin-bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells.
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PMID:Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway. 3235 Sep 53