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

16 patients with cutaneous or subcutaneous melanoma recurrence on an extremity were treated with regional perfusion with Melphalan. 18 perfusions were performed on 15 patients with stage II disease, that is with tumor growth restricted to an extremity including possible regional node metastases. All patients except two had new recurrences within the observation time. However, many of the patients had been treated surgically for recurrences once or several times previously. By comparing the length of the recurrence-free period following surgery alone with that following surgery plus perfusion in the same patients it was shown that perfusion treatment gave a significant extension of the recurrence-free time. Four perfusions were performed on patients in stage III, that is those with distant metastases. These perfusions gave a moderate or good temporary palliation as regards to tumor growths on the extremity. The traditional treatment for melanoma recurrences on an extremity has been surgical excision or less often amputation. An analysis of the literature shows that perfusion, usually combined with excision, seems to give definitely better results than surgical excision alone. There is evidence to suggest that perfusion treatment is even superior to amputation as regards survival; if so an immunological mechanism might be responsible for this effect.
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PMID:The effect of regional perfusion treatment on recurrent melanoma of the extremities. 85 20

Excision of the primary and isolation-perfusion with 1-phenylalanine mustard was the treatment in 199 patients with invasive Stage I melanoma of the extremities with the goal of improving regional disease control and long-term survival. The determinant survival in patients followed 5-15 years was 83%; Berkson-Gage survivals were 98% at 2 years, 88% at 5 years, and 84% at 10 years. The site of first recurrence was determined in all 49 (25%) patients who failed treatment: three (2%) developed local recurrence, six (3%) developed intransit recurrence, 24 (13%) developed positive regional lymph nodes, 15 (8%) developed systemic metastases, and one developed local recurrence plus positive regional nodes. Of these 49 patients failing treatment, 15 (31%) are currently surviving with no evidence of disease after retreatment of the recurrence. These data are compared to historical controls in the literature. It is concluded that regional control rates are improved by perfusion and that survival has probably been improved. In 14 patients treated by perfusion without local excision, regional control and survival was poor. Single drug (L-PAM) perfusion with the techniques employed is effective in controlling regional subclinical disease, but the primary should be widely excised.
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PMID:Survival and regional disease control after isolation-perfusion for invasive stage I melanoma of the extremities. 124 54

Two patients with metastatic spread of unusual tumors responded to treatment with high-dose Melphalan and autologous bone marrow transplant. One patient had adenoid cystic carcinoma of a minor salivary gland and the other had Merkel cell tumor of the scalp. Both patients had undergone prior surgery and radiotherapy, but later relapsed with distant metastases. Both patients had progression of their disease despite conventional and salvage chemotherapy. Treatment with high-dose Melphalan and autologous bone marrow transplant resulted in partial responses for both patients. High-dose Melphalan should be considered for therapy earlier in the course of patients with these unusual cancers.
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PMID:Response of metastatic adenoid cystic carcinoma and Merkel cell tumor to high-dose melphalan with autologous bone marrow transplantation. 131 72

To increase the therapeutic efficacy of recombinant tumor necrosis factor alpha (rTNF alpha) and reduce the systemic side effects, a protocol was designed using isolation perfusion of the limbs with hyperthermia for in transit metastases of melanoma. A triple combination of high dose rTNF alpha + recombinant interferon-gamma (rIFN-gamma) + melphalan was chosen because of a synergistic anti-tumor effect of rTNF alpha with rIFN-gamma and of rTNF alpha with alkylating agents reported in the literature. Twenty-nine patients of mean age 60 years (range 22-82 years) entered the study after informed consent and received a total of 31 isolation perfusions with the triple combination. There were 24 women and 5 men with multiple progressive in transit melanoma metastases of the lower limb (stage IIIa or IIIab). rTNF alpha at the unique dose of 4 mg was injected as a bolus in the arterial line, under mild hyperthermic conditions (40 to 40.5 degrees C) for 90 minutes. rIFN-gamma was given subcutaneously on days -2 and -1 and in the perfusate, with rTNF alpha, at the dose of 0.2 mg. Melphalan was administered in the perfusate at dose giving a concentration of 40 micrograms/ml. In all the 31 isolation perfusions performed in the triple combination protocol, in order to prevent a septic shock-like syndrome which had been encountered in 2 patients treated outside this protocol for sarcoma and carcinoma, the patients received dopamine continuous infusion at 3 micrograms/kg/min from the start of isolation perfusion and for 48 hours, and only showed mild hypotension and very transient chills and temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In transit metastases of malignant melanoma treated by high dose rTNF alpha in combination with interferon-gamma and melphalan in isolation perfusion. 156 4

Common as well as unusual, heretofore unmentioned histopathologic features observed in 336 typical and 273 atypical medullary breast cancers from 6404 patients enrolled in various stage I and II protocols of the National Surgical Adjuvant Breast and Bowel Projects (NSABP) are presented. Both medullary types exhibited comparable pathologic findings, except for the infiltrative border and/or slight or absent tumor lymphoid infiltrate which by definition characterize the atypical form. Both also demonstrated a similar, high proclivity to be aneuploid, and to lack estrogen and progesterone receptors and nodal metastases. After appropriate statistical adjustments, survival (analyzed for 198 patients with typical and 149 with atypical medullary cancers) was found to be better for untreated, node-negative and node-positive patients treated with L-PAM + 5Fu who had typical medullary cancers than those with the NOS histologic type. The magnitude of this difference was 6% at 5 and 17% at 10 years post-operatively (cumulative odds = 1.81 with a 95% confidence interval of 1.08 - 3.3) for the former group, and 4% at 5 and 16% at 10 years (cumulative odds = 1.56 with a 95% confidence interval of 1.08 - 2.23) for the latter. Survival was comparable for patients with atypical medullary and NOS types in both situations. No clear difference in survival was found in untreated, positive node patients with the 3 histologic types examined, although the sample sizes in this subset were relatively small. This information as well as other pertinent considerations indicate that the prognosis of typical medullary cancer is not as 'good' as previously perceived. It is also concluded that there is insufficient evidence at present to exclude the atypical medullary variant as a histologic type of breast cancer.
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PMID:Medullary cancer of the breast revisited. 208 73

We have previously demonstrated that depletion of CD8+ T-cells by the use of a monoclonal anti-Lyt-2.2 antibody abolishes the curative effectiveness of low-dose melphalan (L-phenylalanine mustard; L-PAM) therapy for BALB/c mice bearing a large (greater than or equal to 20 mm) s.c. MOPC-315 tumor and extensive metastases (Mokyr et al., Cancer Res., 49: 4597-4606, 1989). Here we show that as a consequence of low-dose L-PAM therapy, CD8+ T-cells accumulate in the s.c. tumor nodules of MOPC-315 tumor bearers. Specifically, an 80-fold increase in the number of CD8+ T-cells was seen within 5 days after the chemotherapy. Treatment of MOPC-315 tumor bearers with low-dose L-PAM in conjunction with monoclonal anti-Thy-1.2 or anti-Lyt-2.2 antibody, in contrast to treatment with monoclonal anti-L3T4 antibody, prevented the appearance of the massive CD8+ T-cell infiltrate in the s.c. tumor nodules. Fresh CD8+ T-cells derived from s.c. MOPC-315 tumor nodules that were regressing as a consequence of low-dose L-PAM therapy exhibited a potent direct lytic activity against the MOPC-315 plasmacytoma in a short-term in vitro assay. The specificity of the lytic activity exhibited by the CD8+ T-cells was illustrated not only by the inability of the CD8+ T-cells to lyse two antigenically unrelated thymomas (the WEHI 22.1 and the EL-4) and a natural killer-sensitive lymphoma (the YAC-1), but also by their relatively weak lytic activity against an antigenically related plasmacytoma (the MOPC-104E). Thus, CD8+ T-cells that infiltrate the s.c. tumor nodules of MOPC-315 tumor bearers following low-dose L-PAM therapy most likely exploit a CTL-type lytic mechanism to eradicate at least part of the large tumor burden not eliminated by the direct antitumor effects of the drug.
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PMID:Importance of tumor-specific cytotoxic CD8+ T-cells in eradication of a large subcutaneous MOPC-315 tumor following low-dose melphalan therapy. 212 40

Pyrazine diazohydroxide (sodium salt, NSC 361456; PZDH) is a new antitumor drug with relatively broad activity in initial evaluations against murine leukemias, solid tumors, and two human tumor xenografts in vivo. The present studies were designed to address questions about PZDH activity on different treatment schedules, its activity against metastases, and the extent of its cross-resistance with established drugs. Human LOX amelanotic melanoma xenografts in athymic mice were used to explore schedule dependence and activity against natural metastases, and a series of drug-resistant murine leukemias provided an in vivo cross-resistance profile. Single-dose treatment and prolonged treatment provided equivalent therapeutic responses to PZDH by both the i.p. and i.v. routes in the i.p. LOX model. A s.c. LOX model resulting in spontaneous pulmonary metastases was adapted for bioassay and quantitation of the numbers of LOX cells killed by PZDH among both primary and metastatic cell populations. It was demonstrated that PZDH afforded about 2-log10 orders of magnitude greater cell kill among pulmonary metastases than against primary s.c. LOX tumors in the same mouse. Murine leukemias resistant to doxorubicin (ADR), vincristine (VCR), cisplatin (DDPt), methotrexate (MTX), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), and cyclophosphamide (CPA) were not cross-resistant to PZDH. However, both P388 and L1210 leukemia sublines resistant to melphalan (L-PAM) were cross-resistant to PZDH, suggesting that patients previously treated with L-PAM might have less likelihood of response to PZDH than those who had had no opportunity to develop L-PAM resistance. Although these observations should not be applied to clinical studies without due caution, they support clinical evaluation of PZDH as well as continued investigation of its molecular pharmacology.
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PMID:Schedule dependence, activity against natural metastases, and cross-resistance of pyrazine diazohydroxide (sodium salt, NSC 361456) in preclinical models in vivo. 231 Nov 70

We have previously demonstrated that the curative effectiveness of a low dose (2.5 mg/kg) of melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a large s.c. (approximately 20 mm in diameter) MOPC-315 tumor and extensive metastases requires the participation of T-cell-dependent antitumor immunity in tumor eradication (S. Ben-Efraim et al., Cancer Immunol. Immunother., 15: 101-107, 1983). Here we show that the Lyt 2+ T-cells, and not the L3T4+ T-cells, participate in the cure of such tumor-bearing mice by a low dose of L-PAM. Specifically, depletion of Lyt 2+ T-cells from mice bearing a large MOPC-315 tumor by treatment with monoclonal anti-Lyt 2.2 antibody abolished the curative effectiveness of the low dose of drug. In contrast, depletion of L3T4+ T-cells from mice bearing a large MOPC-315 tumor by treatment with monoclonal anti-L3T4 antibody did not reduce significantly the curative effectiveness of the low dose of drug. Histological examination of tumor nodules on various days following low-dose L-PAM therapy revealed widespread lymphocytic infiltration by Day 5 following the chemotherapy, and this infiltration was drastically reduced when the L-PAM-treated tumor bearers were treated with either anti-Thy 1.2 or anti-Lyt 2.2 antibody but not with anti-L3T4 antibody. The antitumor immunity exhibited by Lyt 2+ T-cells derived from mice which were in the process of eradicating a large MOPC-315 tumor following low-dose L-PAM therapy was exploited successfully to confer systemic antitumor immunity to mice bearing a barely palpable tumor. Specifically, the adoptively transferred Lyt 2+ splenic T-cells, in conjunction with a subcurative dose of L-PAM, brought about the cure of most mice. The Lyt 2+ splenic T-cells from L-PAM-treated MOPC-315 tumor bearers were also found to be capable of exerting a direct potent lytic effect against MOPC-315 tumor cells in an antigen-specific manner. Thus, it is conceivable that the direct cytotoxic activity of Lyt 2+ T-cells for MOPC-315 tumor cells is responsible, at least in part, for the ability of the Lyt 2+ T-cells from L-PAM-treated MOPC-315 tumor bearers to bring about the eradication of the tumor burden not eradicated through the direct antitumor effects of the low dose of drug.
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PMID:Importance of Lyt 2+ T-cells in the curative effectiveness of a low dose of melphalan for mice bearing a large MOPC-315 tumor. 256 74

Two cases of lymphangiosarcomas which arose 4 and 14 years after a mastectomy are reported (Stewart-Treves syndrome). One of the patients was treated by shoulder disarticulation and the other by chemotherapy (using Melphalan, Cyclophosphamide and 5-fluorouracil). Disseminated metastases and deaths occurred 6 and 18 months after the onset of the lesion. Stewart-Treves syndrome occurs in approximately 0.07 to 0.45% of mastectomy. Prognosis is worse: survival at five year is fewer than 10%. Early diagnosis is mandatory. Surgical resection of the lesions and adjunctive chemotherapy seem the best treatment.
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PMID:[Lymphangiosarcoma following mastectomy: review of the literature apropos of 2 recent cases of Stewart-Treves syndrome]. 265 58

The effects of heat and the interaction between hyperthermia and alkylating agents, such as cisplatin (CDDP) and melphalan (L-PAM) in human malignant melanoma biopsies have been investigated by a short-term assay based upon the inhibition of 3H-thymidine incorporation. Cell suspensions from 50 cutaneous and lymph nodal metastases were heated at 40.5 degrees C or at 42 degrees C for 1 h. There were significant antiproliferative effects due to heat in 10% of the tumors exposed to 40.5 degrees C and 34% to 42 degrees C. Thermal resistance was evident in 73% (at 40.5 degrees C) and 54% (at 43 degrees C) of tumors, and there was significant enhancement of cell growth in 17% and 12% of tumors. The combined effects of hyperthermia and drugs were studied on 36 tumors. Cell suspensions were exposed to different concentrations of CDDP or L-PAM for 1 h at 40.5 degrees C and 42 degrees C. Synergy between heat and CDDP was observed in 7% of cases treated with the lowest drug dose and 38% of cases treated with the highest (40.5 degrees C), with only a slight increase in the frequency of synergy at 42 degrees C. Synergy between heat and L-PAM was also observed in 12% to 44% of tumors at 42 degrees C as a function of drug concentration.
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PMID:Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma. 280 74


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