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)

Twenty-two patients with cutaneous metastases of malignant melanoma were treated with intralesional injections of the methanol extraction residue of bacillus Calmette-Guerin (MER). The local reaction consisted of erythema and pustule formation followed by ulceration and tumor necrosis. Side effects included fever, chills, headache and malaise in the majority of patients; nausea, vomiting, cyanosis and hypotension occurred infrequently. Hypersensitivity reactions were not observed. Temporary abnormalities in liver function were seen in 11 of 19 patients tested. Reversible lymphopenia and thrombocytopenia developed in 7 of 17 and 7 of 18 patients, respectively. Immune function, as measured by skin tests for delayed hypersensitivity and the in vitro response of isolated lymphocytes to mitogens and microbial antigens, was not influenced by treatment with MER. Transient increases were observed in total hemolytic complement, complement components and the reduction of nitroblue-tetrazolium by neutrophils. Eight of eighteen evaluable patients showed a complete disappearance of all injected lesions. We conclude that intratumoral injection of MER is effective treatment for cutaneous metastases of malignant melanoma, with a complete response rate comparable to that observed after intralesional injection of BCG.
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PMID:Intralesional injection of the methanol extraction residue of Bacillus Calmette-Guerin (MER) into cutaneous metastases of malignant melanoma. 72 66

The therapeutic efficacy of intralesional BCG (Bacillus Calmette-Guerin; one immunizing dose every 2 weeks for a minimum of five treatments) was studied in 19 melanoma patients. Of 15 patients evaluable for response, five experienced significant objective improvement (two complete and three partial remissions). Objective improvement was limited to those patients with dermal metastatic disease. In vitro cytotoxicity in the presence of patient's serum bore, on average, a relationship to the clinical disease. In certain individual cases, serum blocking and/or lymphocyte stimulation may have had prognostic significance.
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PMID:Intralesional BCG in the treatment of metastatic malignant melanoma. 76 47

Experiments were undertaken to test the hypothesis that a major component of BCG contact-induced inhibition of syngeneic tumour growth in rats is not dependent on the participation of thymus-processed (T) cells. Hosts were deprived of T cells by thymectomy followed by either lethal irradiation (850 rad) and bone marrow reconstitution, or repeated whole body irradiation to a total dose of 1,000 rad. After 6 weeks had elapsed to allow for bone marrow restitution, rats were challenged with trypsinized sarcoma cells admixed with Glaxo strain BCG. For sarcoma P7, host T-cell deprivation did not significantly diminish the capacity of BCG to prevent the progressive development of this neoplasm from an inoculum of one million cells. Under similar conditions, the incidence of sarcoma CC5 development in maximally deprived hosts was significantly greater (7/19) than in normal controls (1/16) (P is less than 0.05), but the majority of rats (58%) did not succomb to tumour outgrowth. In the case of a third neoplasm--a spontaneously metastasizing fibrosarcoma (P8)--the effect of BCG on primary tumour development was comparable in normal and deprived recipients and was limited to temporary arrest as distinct from complete inhibition. Assessment of the influence of BCG on lung metastases was more complex since the extent of metastatic disease from subcutaneous tumour cells alone was greater in deprived rats than in normal rats. It is concluded that T-cell participation is not a major requirement for BCG contact-induced inhibition in this system and some implications for the mechanism of action are discussed.
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PMID:Inhibition of transplanted sarcomas mediated by BCG in rats with a defined immunological deficit. 77 43

Twenty-one patients with malignant melanoma received immunotherapy with BCG. Thirteen patients had adjuvant immunotherapy on a monthly schedule. Of these, eight with regional lymph node metastases (stage III) had been treated by lymphadenectomy. Two of the stage III patients had tumor recurrences within one year, while six are alive and free of melanoma at a median interval of 22 months. The remaining five patients (stage I or II) had level 4 or 5 (Clark classification) primary lesions. Their average tumor-free survival has been 18 months, but there was one regional recurrence in six months. Eight patients received intralesional treatment with BCG. The extent of local response correlated inversely to the stage of their disease. Higher doses of BCG or multiple simultaneous injections into the same lesion did not produce complete resolution of nodules in patients with far-advanced melanoma. In none was the course altered by intralesional therapy.
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PMID:BCG immunotherapy in patients with malignant melanoma. 77 25

This study assess the effects of oral BCG, as a single agent, on tumor progression and on cell-mediated immune function in patients with metastatic malignant melanoma. Thirty patients were studied including 22 with measurable metastatic lesions and 8 with no detectable disease, following treatment of metastases by surgery, radiotherapy, or 5-(3, 3-dimethyl-1 -triazeno)-imidazole-4-carboxamide (DTIC; DIC). Oral BCG was given in doses of 120--240 mg, 1--3 times per week for periods ranging from 9 to 80 weeks and to total doses of from 1.2 to 20.1 gm. Patients were assessed by direct measurements of tumor mass, PPD skin test and in vitro blastogenic responses to PPD PHA. Of the 22 patient with measureable disease, 19 showed tumor progression and none showed regression of any lesion. Of the 8 without apparent disease, 5 remained stable and 3 had tumor recurrence. Of the total group of 30 patients, 8 showed some increased sensitivity to skin testing with PPD. Of 19 tested, 3 showed an increased PPD response in vitro, while 3 showed a decreased response. Six of 20 tested showed an increased PHA response in vitro. Oral BCG alone was not effective as an antitumor agent in patients with metastatic malignant melanoma.
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PMID:The use of oral BCG in the treatment or metastatic malignant melanoma. 78 99

Immunotherapy of malignant melanoma with BCG may be divided into two basic groups: 1. treatment of minimum residual disease. 2. direct intralesional application of BCG. In 19 patients with a histologically confirmed malignant melanoma, direct intralesional application of BCG was used to treat relapsing patients. In 10 of the 19 patients (group A) the relapse was confined to the primary region without signs of distant dissemination. In the remaining 9 patients (group B) signs of the lesion were present prior to BCG application. Our clinical and cytological evaluation bore on local reactions, systemic side reactions and response of non-injected lesions. In patients without signs of distant dissemination, local regression, characterized by a flattening and disappearance of lenticular metastases with scar formation, was achieved in 8/10 patients, while in the noninjected lesions, regression was noted in only 4/10 patients. In 4 patients of group A complete remission lasting 4-6 months was achieved. In the group of patients with signs of distant dissemination, local regression was observed in 6/9, while noninjected lesion regressed in only 1/9. Systemic response to BCG was characterized by febrile reactions with, in the majority of the patients, nausea till vomiting, muscular pain, pain of joints. In the majority of the patients the reaction passed away within 24 hr. A pretreatment with antipyretic and antihistaminic drugs proved of great help. The effect of BCG on the subsequent fate and survival of the patients is not discussed.
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PMID:Intralesional BCG application in malignant melanoma. 79 45

Accumlated evidence suggests that human neoplasms contain antigens that elicit humoral and cellular immunity in the immunocompetent host. A recent summary report showed that Stage II melanoma patients with metastases to regional lymph nodes had a lowered incidence of recurrence and a higher incidence of survival following surgery and postoperative BCG immunotherapy. To verify these findings, clinical trials are now under way in which we radomized melanoma patients into groups to compare treatment by surgery alone with surgery and BCG only, or surgery and BCG in combination with allogeneic melanoma cell vaccine. Serum samples from each patient are monitored by in vitro techniques to define those methods which best correlate to clinical course. Hopefully, such correlations can be used to monitor response to immunotherapy before disease is clinically apparent. Although immunotherapy does not cause regression of far advanced disease, it undoubtedly will be beneficial against subclinical, microscopic tumor.
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PMID:Immunotherapy in malignant melanomaa. 79 63

Immunocompetence and prognosis are related in solid tumors, malignant lymphomas, and acute leukemia. Among the parameters of immunocompetence vigorous delayed-type hypersensitivity responses to recall antigens or to primary immunization with Keyhole limpet hemocyanin, vigorous in vitro lymphocyte blastogenic responses to mitogens such as PHA, and relatively high B-lymphocyte levels, all correlate with a good prognosis. The spectrum of immune reactivity as measured by established delayed-type hypersensitivity to recall antigens and in vitro blastogenic responses to mitogens and antigens is similar in melanoma patients and their nontumor-bearing spouses. In melanoma, only patients with widespread inoperable metastatic disease show severe immunological deficiency and this is selective for certain antigens. There are highly significant differences in response to specific antigens when patients with melanoma and lung cancer are compared. Immunotherapy with BCG and C. parvum can boost immunocompetence as measured by recall DTH skin testing. However, the relationship between the initial immunocompetence and prognosis still holds in patients receiving BCG immunotherapy to prevent recurrence of melanoma. These data indicate that a broader survey of immunological reactivity in cancer patients is needed, that immunological testing is useful in cancer prognosis clinically, and that the results of immunological testing can be used to evaluate therapy and to indicate new pathways for improved treatment.
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PMID:Immunocompetence, immunodeficiency and prognosis in cancer. 80 Mar 24

We determined the optimal conditions for conducting experiments with the solid and ascites sublines of the 13762 rat mammary adenocarcinoma and examined the response of the tumor growth rate to BCG administered in admixture with tumor cells or separately at a remote site. Versene dissociation of the 13762 solid tumor produced better growth rates than did pronase-DNase, but the former decreased cell viability and yields. A dose of 10(6) or 10(5) tumor cells produced 100% growth by the sc and iv routes. Both sublines grew slower but produced metastases slightly sooner in the intradermal than in the sc site. The frequency of axillary lymph node metastases from the sc site increased as a function of the duration of the time interval between tumor implantation and surgical excision. Both solid and ascites tumors were weakly immunogenic. Administration of BCG in a split adjuvant protocol did not improve tumor immunity. Admixture of tumor cells with BCG suppressed tumor growth but when given at a remote site, BCG was ineffective. We concluded that the 13762 rat mammary adenocarcinoma is a useful system for BCG immunotherapy.
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PMID:Suitability of rat mammary adenocarcinoma 13762 as a model for BCG immunotherapy. 81 63

The effect of systemic BCG therapy on advanced melanoma was studied in 42 patients with stage II and stage III disease. Evaluation of the immune response prior and during therapy revealed that patients who failed to convert a negative purified protein derivative (PPD) reaction and those having a low stimulation ratio of lymphocyte cultures had rapidly progressive disease and short survival. Neither tumor regression nor prolongation of survival could be appreciated in patients with stage III disease. Furthermore, aggravation of symptoms was observed in patients with visceral metastases. Fifty percent of the patients with stage II melanoma treated by operation and adjuvant immunotherapy had recurrent or metastatis disease within two years. No adverse effects were noted in patients with early disease who received adjuvant therapy. Two patients who had a full course of systemic BCG therapy developed severe reactions after intralesional injection of the vaccine. Further experience with various immunotherapeutic regimens and longer follow-up are necessary to evaluate its value in the early stages of melanoma.
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PMID:Effectiveness of systemic BCG therapy in advanced melanoma. 84 15


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