Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The compound 4'-(9-acridinylamino)methanesulfon-m-anisidide is a new derivative that was evaluated in a Phase 1 clinical trial. The schedule of drug administration consisted of daily i.v. injection for 3 consecutive days, repeated at 3-week intervals. Twenty-six patients received a total of 63 courses of 4'-(9-acridinylamino)methanesulfon-m-anisidide in a dose range from 4 to 50 mg/sq m/day. Hematopoietic toxicity was dose limiting, but it was of short duration and rapidly reversible. Mild nausea and vomiting were observed in 16% of the courses, and a mild degree of phlebitis was observed in 10% of the courses. Responses were observed in two patients with adenocarcinoma of the lung and one each of melanoma and acute myeloblastic leukemia. Phase 2 studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide are planned at a starting dose of 40 mg/sq m/day for 3 days in good-risk patients and at 25 to 30 mg/sq m/day for 3 days in poor-risk patients. Course of treatment would be repeated at 21-day intervals.
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PMID:Phase 1 clinical investigation of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992), a new acridine derivative. 27 97

Spontaneous sister chromatid exchanges and banded karyotypes were studied in blood lymphocytes from 96 individuals: seven patients with chronic myelogenous leukemia, 15 normal controls, and five "cancer families" comprising 12 cancer patients, 40 tumor-free blood relatives and 22 spouses. The families had: malignant melanoma; Epstein-Barr virus-associated malignancies and a birth defect syndrome; non-Hodgkin lymphoma and diverse carcinomas; Hodgkin's lymphoma and adenocarcinomas; and acute myelogenous leukemia. In addition to the Philadelphia chromosome in chronic myelogenous leukemia patients, karyotypic abnormalities, especially breaks and fragments, were found in 29% of cancer family members, but were inconsistent and usually attributable to radiotherapy. Mean sister chromatid exchange values were normal in chronic myelogenous leukemia, but low (by t-test) in tumor patients and their blood relatives in cancer-prone families. In tumor patients, mean sister chromatid exchange levels fell as age increased. After adjusting for this age effect, no significant differences remained among groups. In patients at high risk of cancer (because they have chronic myelogenous leukemia or a strong family history of cancer), spontaneous sister chromatid exchange rates were not a marker of cancer risk.
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PMID:Sister chromatid exchanges and chromosomes in chronic myelogenous leukemia and cancer families. 28 71

Nineteen patients are reported who developed acute myeloblastic leukemia following treatment for a variety of solid tumors, including seminoma (four cases), melanoma (one case), and cancer of the ovary (six cases), colon or rectum (three cases), bladder (two cases), cervix, endometrium, and larynx (one case each). There were nine men and ten women, with a median age of 49.8 years (range 29 to 75). The mean interval between the diagnosis of solid tumors and acute leukemia is 5.8 years. In two patients the two diseases occurred simultaneously or within six months of each other. One patient was treated only surgically. Eight patients were treated with radiotherapy, five with chemotherapy, and five received both chemotherapy and radiotherapy. Pancytopenia was commonly noted prior to the onset of leukemia with chromosomal abnormalities observed in four cases in which a karyotype was performed. Three patients achieved complete hematological remission following antileukemic therapy. One hundred and six additional patients with non-hematopoietic neoplasms and acute leukemia are reviewed. Although acute leukemia may occur in a higher than expected frequency in patients with solid tumors because of a possible increased risk of a second neoplasm, it seems more likely that the acute leukemia is related to the radiotherapy and/or chemotherapy administered to treat the first neoplasm.
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PMID:Acute myeloblastic leukemia following treatment for non-hematopoietic cancers: report of 19 cases and review of the literature. 29 52

The Southeastern Cancer Study Group has been particularly interested in the use of immunological adjuvants in the treatment of melanoma and acute myelogenous leukemia. A study of chemotherapy versus chemoimmunotherapy in randomly selected patients with metastatic malignant melanoma revealed no significant increase in either complete remissions or overall survival in the group receiving chemoimmunotherapy. Preliminary results in a study involving maintenance of patients with acute myelogenous leukemia (chemotherapy versus chemoimmunotherapy) revealed suggestive but not statistically significant increases in remission duration and survival in the group receiving immunotherapy. Data from these ongoing studies and plans for new group studies are presented in this paper.
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PMID:Clinical immunotherapy experiences in the Southeastern Cancer Study Group. 34 10

This brief review of the more promising clinical trials suggests that immunotherapy is indeed beneficial for selected cancer patients. Because of its limited potency, it should not be used as primary treatment for malignant disease except as local immunotherapy for certain accessible tumors. It is effective for eradication of primary neoplasms of the skin as well as cutaneous metastases of malignant melanoma and breast carcinoma. The most important role for immunotherapy is in combination with other modalities. It may help control occult micrometastases that cause recurrence and death following surgical procedures or irradiation. Results of adjuvant immunotherapy appear promising for malignant melanoma, for carcinoma of the lung, breast, and colon, and for soft-tissue sarcomas. In combination with chemotherapy, immunotherapy appears to prolong remission and survival in acute myelogenous leukemia and in disseminated tumors of the lung and breast. Clearly, immunotherapy is not a panacea for malignant disease, but it could become an important arm in a multimodality attack on cancer.
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PMID:Clinical trials of immunotherapy: present status. 36 56

Piperazinedione was administered to 79 patients with solid tumors on an intermittent schedule with single doses of 1.5-36 mg/m2. Courses were usually repeated at 4-week intervals. Twenty-five patients with leukemia were treated at doses of 18-36 mg/m2 (occasionally for 2 successive days) every 1-4 weeks. Of 48 evaluable patients with malignant melanoma, three (6%) achieved partial remission and nine (20%) had stable disease. Eight of 17 (47%) patients with adenocarcinomas and one of two (50%) patients with lymphomas also had stable disease. Six of 14 (43%) patients with acute myelogenous leukemia showed hematologic improvement, as did one of 11 (9%) patients with blast cell crisis of chronic myelogenous leukemia. The principal toxic effect was myelosuppression, which occurred in 69% of the patients with solid tumors. Profound bone marrow aplasia occurred in 19% of the patients, resulting in six deaths (8%). Risk factors for marrow aplasia included extensive prior therapy, prior nitrosoureas, cumulative toxicity from piperazinedione, and abnormal liver function tests. The recommended doses for further studies are 9 mg/m2 for patients with risk factors for marrow aplasia, 12 mg/m2 for patients with prior therapy, 15 mg/m2 for previously untreated patients, and 24-36 mg/m2 for patients with acute leukemia.
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PMID:Phase I-II study of piperazinedione in adults with solid tumors and acute leukemia. 38 Aug 2

The hazards and complications of BCG immunotherapy, as well as the potential for enhanced tumor growth, make it imperative that the clinician know the clinical setting in which BCG can offer therapeutic benefit. This would include the intratumor injection of localized intradermal tumor deposits of melanoma and breast cancer, chemoimmunotherapy with BCG to prolong remission in acute myelogenous leukemia, and possibly the use of BCG as an adjuvant to control minimal residual disease. Aside from these situations, it is advisable to treat patients only on clearly defined experimental protocols.
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PMID:Hazards and complications of BCG immunotherapy. 127 90

The expression of c-fms oncoprotein in different primary tumours as well as in their metastases in bone marrow, was shown. All the samples were fixed and processed by the acetone, methyl benzoate, xylene procedure (AMeX), which was suitable for studying oncoprotein expression not only in primary tumours but also in bone marrow (BM) biopsies. Among the patients suffering from acute myeloid leukaemia (AMeL), positive c-fms cells were found in 55% cases. On the contrary, patients with lymphocytic cell disorders have not had detectable c-fms oncogene product in BM biopsies.c-fms oncoprotein was also detected in some primary tumour specimens (lung carcinoma, cervical carcinoma, gastric carcinoma, breast carcinoma and melanoma) and their metastases in BM, while it was not present in normal uterine tissue. There was a positive correlation between c-fms oncoprotein expression in primary and metastatic tumours. Our results showed that c-fms product is confined, not only to some normal, but also to the variety of malignant cells of different origin.
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PMID:c-fms is present in primary tumours as well as in their metastases in bone marrow. 139 Jan 97

In this review we shall discuss the biological rationale and the clinical findings obtained using Interleukin 2 (IL2)-based immunotherapy in the management of cancer patients. Objective and long-lived clinical responses have been documented in a proportion of cases, particularly renal cell carcinoma, melanoma and acute myeloid leukaemia. Though encouraging, the clinical use of IL2 has so far been limited by toxicity, as well as by the heterogeneous and unpredictable responses and by the lack of specific anti-tumour effect. These considerations have led to the belief that more sophisticated technologies aimed at introducing the IL2 gene into the neoplastic cells may potentially overcome some of the limitations coupled to the in vivo infusion of high doses of IL2. The data accumulated in animal models and, more recently, also with human tumour cells indicate that the IL2 gene may be successfully inserted into neoplastic cells. The constitutive secretion of IL2 by the tumour cells leads to a reduced or abrogated tumorigenicity in several different tumour models. The evidence that in some experimental tumours the transduction of the IL2 gene into the neoplastic cells may elicit a specific cytotoxic response and confer anti-tumour memory, suggests that vaccination protocols based on this innovative strategy may represent a potential new tool in the management of cancer patients.
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PMID:IL2 treatment for cancer: from biology to gene therapy. 145 68

Interleukin-2 (IL-2) therapy generates killer cells with major histocompatibility complex (MHC)-unrestricted cytotoxicity against most tumors but not normal tissues. Cyclosporine A (CsA) has been reported to break tolerance to self and to induce killer cells with specificity against class II MHC (Ia) antigens both on the host and the tumor cells, resulting in a mild graft-versus-host disease (GVHD) in an autologous bone marrow transplantation (BMT) setting in the rat. We used these two agents in a syngeneic BMT model in a strain of mice that does not develop GVHD with CsA. Therapy with either agent alone was ineffective, whereas a combination of CsA plus IL-2 after BMT induced a potent graft-versus-tumor (GVT) effect against a melanoma and an acute myeloid leukemia. The antitumor effect could be adoptively transferred by infusing spleen cells harvested from mice treated with CsA plus IL-2 into secondary recipients that received chemoradiotherapy. The cytotoxicity of these cells was not influenced by treatment of tumor cells with gamma-interferon or Ia antibody. The cytotoxic effect was mediated by Thy 1+ and asialo GM 1+ cells. There was no GVHD either in the primary recipients of CsA and IL-2 or in those receiving the adoptively transferred spleen cells. Our findings show that combination therapy with CsA and IL-2 after syngeneic BMT induces a potent GVT effect in a non-MHC-restricted manner, and point to the existence of differences between the mechanisms of GVT and GVHD.
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PMID:Synergism of interleukin-2 and cyclosporine A in induction of a graft-versus-tumor effect without graft-versus-host disease after syngeneic bone marrow transplantation. 161 Oct 84


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