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)

Sixteen patients with disseminated melanoma were immunised with either BCG (8 cases) or C. parvum (8 cases) on three occasions at 21 day intervals. Blood for assay was taken immediately before the first immunisation and weekly for eight weeks thereafter. Total white count tended to increase but little change was seen in lymphocyte and monocyte counts. Serum IgG increased after BCG BUT NOT WITH C. parvum, serum IgA and IgM did not alter. The 'E' rosette % did show some increase mainly after C. parvum, and 'B' lymphoid cells (sIg staining) increased slightly after BCG; the 'EA' rosette % fell following C. parvum but not after BCG. Lymphocyte PHA blastogenesis increased after immunisation, particularly with BCG. Non-specific lymphocytotoxicity (51 Cr Chang target) demonstrated dramatic increases for 'non T' and 'K' cell function and a smaller increase in 'T' cell cytotoxicity following immunisation. These increases in cytotoxicity were maintained by the 21 day immunisation schedule.
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PMID:Effects of BCG and Corynebacterium parvum on immune reactivity in melanoma patients. 60 36

Clinically noninvolved skin of 5 patients with metastasizing malignant melanoma (MM) has been investigated under the electron microscope before and 4 weeks after repeated BCG inoculations (4 X). Increased melanin content, giant and unusual melanosomes, signs of cellular activity and some degenerative changes of the melanocytes were observed both in nontreated and in treated patients. Langerhans cells were markedly stimulated containing melanosome complexes and membrane-bound inclusions of different size and shape. Presence of amyloid, macrophage and plasma cells were also observed prior to and after repeated BCG inoculation, however, cellular infiltration was increased after this treatment and several dermal Langerhans cells appeared. These observations suggest that alterations of the melanocytes occur in MM, which are not confined to the tumor area. Moreover, BCG treatment seems to stimulate the tissue reaction against the tumor, including the activity of Langerhans cells.
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PMID:Alterations of the clinically noninvolved skin in patients with malignant melanoma. An electron microscopic study before and after repeated application of BCG. 62 28

Tumour-associated antigens and specific immune response to these antigens have been clearly demonstrated in patients with melanoma. Impaired cellular immune reactions are evident in patients with progressive and disseminated disease. Immunotherapy is used to heighten the host resistance and hence prevent recurrence and spread of the tumour. BCG vaccine has been used to produce nonspecific stimulation of the immune system. Preliminary evaluation of the effect of adjuvant systemic BCG therapy suggests that the treatment may have a beneficial effect on patients with early melanoma.
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PMID:Immune response and non-specific immunotherapy in melanoma. 63 92

A prospective trial with concurrent controls was designed to assess the effects of specific active immunotherapy in patients receiving intermittent cytotoxic chemotherapy (DTIC + Vincristine) as an adjuvant to surgery in Stage IIB malignant melanoma. The treated group received monthly irradiated allogeneic melanoma cells and BCG, and the controls BCG only. Sixteen patients in the treatment arm had a median relapse-free interval of 5 months, compared to 8 months in 12 controls given chemotherapy and BCG, and because of this we felt that continuation of the study was unjustified on ethical grounds. Although all the controls who relapsed did so at distant sites, 7/11 patients given specific active immunotherapy relapsed initially within the lymphatic drainage area of the primary tumour. The median intervals from starting treatment to relapse at distant sites, and the median survival were identical in the 2 groups. We conclude that immunotherapy comprising irradiated allogenic melanoma cells as employed in this study does not prolong survival in surgically treated Stage IIB malignant melanoma and may even promote early, local relapse.
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PMID:Specific active immunotherapy does not prolong survival in surgically treated patients with stage IIB malignant melanoma and may promote early recurrence. 64 22

Eighteen patients with multiple recurrences of malignant melanoma without evident distant spread were randomly assigned to treatment with either intralesional Bacillus Calmette-Guerin (BCG) or intralesional dinitrochlorobenzene (DNCB). Both agents were able to destroy approximately 90% of the injected intradermal nodules. Intradermal disease was more easily obliterated than subcutaneous disease with intralesional treatment with either agent, and local control of satellitosis with elimination of all clinically evident tumor was achieved in the patients who had intradermal without subcutaneous satellitosis, regardless of whether the patient was receiving BCG or DNCB. The clinical courses of the treated patients were essentially the same. Although PHA reactivity was depressed, the patients in both groups were responsive to recall and melanoma skin test antigens, demonstrated leukocyte migration inhibition with melanoma antigen and were generally within normal limits when assayed for 29 degrees C E rosettes. Our study demonstrated a dramatic difference in toxicity between the two intralesional agents without a similar difference in therapeutic efficacy or immune testing.
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PMID:Intralesional treatment of recurrent metastatic cutaneous malignant melanoma: a randomized prospective study of intralesional Bacillus Calmette-Guerin versus intralesional dinitrochlorobenzene. 65 8

Incorporation of 3H-TdR into EL4 leukemic cells in vitro was inhibited by peritoneal exudate cells (PEC) harvested from syngeneic C57BL/6J mice given an intraperitoneal (i.p.) injection of 1x10(7) viable Mycobacterium smegmatis ATCC 607 (Smeg) 4 days before. This phenomenon was also observed in the following five systems of PEC from animals and syngeneic tumor cells: C57BL/6J mice and B16 melanoma; DBA/2 mice and P815 mastocytoma; SWM/Ms mice and K5 fibrosarcoma; BALB/c, nu/nu mice and KKN-1 fibrosarcoma; and strain 2 guinea pigs and line-10 hepatoma. The in vitro cytotoxicity of the PEC activated by viable Smeg was much higher than those activated by dead-Smeg, viable BCG or proteose peptone. The activity of the adherent fraction of the PEC was stronger than that of the nonadherent one, and not influenced by either anti-theta or anti-mouse lymphocyte rabbit sera. The PEC induced with Smeg 4 days before contained a large population of mononuclear cells (88.9%) and a significant level of polymorphonuclear cells (PMN) (3.2%), and showed a much higher cytotoxicity than the PEC induced with Smeg 3 hr before, which contained a much larger population of PMN (71.9%), suggesting that PMN were not the effector cells in this system. In vitro and in vivo treatment with macrophage-inhibitors such as carrageenan, trypan blue and cytochalacin B, reduced the activity of the PEC. All of these facts suggested macrophages as the effector. Viable macrophages were required for the growth inhibition of EL4 in vitro: gamma-ray irradiated or freeze-thawed macrophages were ineffective. Kinetic studies revealed that inhibition of 3H-TdR incorporation into EL4 cells started within 3 hr of incubation together with the activated macrophages at an effector to target (E/T) ratio of 5, and the incorporation decreased gradually with the lapse of incubation time. On the other hand, 51Cr release from labelled EL4 was undetected when the E/T ratio was 5 but detected at on E/T of 10 or more. Even at the higher E/T ratio, at least 10 hr were needed until the release of 51Cr, suggesting that the activated macrophages produced growth inhibition of tumor cells followed by cell destruction.
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PMID:In vitro cytotoxicity of peritoneal macrophages activated with Mycobacterium smegmatis. 66 26

Since the introduction of BCG intralesional immunotherapy for melanoma, severe complications, including death, have been reported after treatment in hypersensitized individuals. This is a case report of BCG dissemination with ulceration, skin necrosis, lymphadenitis, and abscess formation following the first intralesional injection of a minimal dose of BCG in a PPD-negative patient. The case demonstrates that severe complications can occur in patients who are not hypersensitized, anergic, or debilitated or who have been treated multiple times. This patient's complication further suggests that migration of BCG after intralesional therapy may play a role in the regression of uninjected nodules seen in some patients.
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PMID:Severe complications of intralesional BCG therapy in an unsensitized patient. Case report and clinical implications. 67 4

From June 1975 to August 1977, 19 patients with distant metastases of malignant melanoma of the skin that were no longer responsive to chemotherapy were treated with BCG given intravenously. A single dose of lyophilized Pasteur BCG ranging from 2 X 10(7) to 3 X 10(8) viable units was given in 500 ml of saline infused in 5 to 6 h. Seven of the 16 evaluable patients benefited from treatment; 3 showed an objective regression of more than 50% of the original tumor volume, and 4 an arrest of tumor growth. The objective regressions lasted from 2 to 5 months, and 1 case had an arrest of tumor growth for 29 months. The regression rate was related to the BCG dosage: 2 X 10(8) viable units appears to be the dosage that gives severe but reversible toxicity and is able to induce objective regression. The most responsive lesions were skin and subcutaneous deposits (5 of 7) and lung metastases (1 of 4). Toxic effects seem to be related to the number of bacilli injected. In the group of 10 cases treated with less than 10(8) units, toxicity was modest: 4 patients had fever (up to 38.5 degrees C) that lasted a few days, and in 3 cases it was associated with shivering during the infusion period and weakness. One case only had vomiting and jaundice. Toxicity was severe in the 9 patients that were treated with a dosage higher than 10(8): patients had fever and weakness for at least 4 days and shivering during the infusion. Two had adrenal insufficiency and 7 had liver enlargement and jaundice with return to normality by day 21. In the whole series 8 patients had leucopenia and 5 thrombocytopenia for 2 to 3 days: only 1 patient required blood and platelet transfusion. No significant variations in immunoglobulin levels were observed. No variations of PPD or BCG skin tests were observed after treatment. Three patients expired; the first treated with 6 X 10(7) unit, had an intercurrent disease (autopsy showed a heart infarction); the second, treated with 1.8 X 10(8), showed a rapid growth of lung metastases and died 15 days after treatment; the death of the third patient was probably due to anaphylactic shock. All 3 patients had been previously treated with BCG, given by scarification or intranodular injection.
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PMID:Intravenous administration of BCG in advanced melanoma patients. 68 66

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

A prospectively controlled randomized clinical trial of adjuvant BCG immunotherapy in patients with stage 1B malignant melanoma (Clark's level 3--5) is described. The combination of intradermal and oral BCG allows approximation of the bacilli to any microscopic foci of residual disease. The trial was activated in May 1975 and to date 107 patients have been admitted to the trial, 49 patients being randomil entered patients, there have been five relapses of 49 patients in the treatment group and ten relapses of 58 patients in the control group. This encouraging trend is not yet statsitically significant at the 5% level (P = 0.17). If evaluable patients with Clark's level 3 and 4 lesions are assessed separately, there is a significant trend in favour of the immunotherapy group (P less than 0.05) with three relapses in the treatment group and ten relapses in the control group.
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PMID:Malignant melanoma (stage 1): a clinical trial of adjuvant BCG immunotherapy. 75 75


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