Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subcutaneous growth of immunogenic chemically induced rat sarcomata and a hepatoma was restricted when cells were injected into syngeneic animals in admixture with MER. Rats rejecting mixed inocula were immune to further challenge with the same tumour. Growth of a chemically induced mammary carcinoma which lacks detectable immunogenicity was suppressed when low cell inocula were injected in admixture with MER or intact BCG organisms, although animals were not immune to re-challenge. These studies indicate that clinically MER may be a suitable alternative to BCG for contact suppression of tumour growth or incorporation into tumour cell:adjuvant vaccines for active immunotherapy.
 ...
PMID:Methanol extraction residue of BCG in the treatment of transplanted rat tumours. 16 61

A Graffi murine leukemia was utilized as a model system to investigate the effect of chemoimmunostimulation therapy. Subcutaneous inoculation of approximately 1.0 times 10(6) tumor cells resulted in a rapidly growing tumor at the site of inoculation and subsequent development of splenomegaly and lymphoadenopathy. All animals succumbed to the leukemia within 24 to 30 days. Treatment of diseased animals with two courses of cytoxan over a 2-week period resulted in a remission period of approximately 16 to 18 days before relapse and eventual death of approximately 70% of the drug-treated animals. A significant number of long-term survivors (50 to 83%) was obtained in groups of animals that received combined drug plus BCG or C. parvum therapy. In contrast, the administration of MER (a methanol-extracted residue of BCG) to animals in a drug-induced remission period was no more effective than drug alone. The protective effect afforded by BCG and C. parvum was dependent on the time interval between drug therapy and the administration of the immunostimulators. Treatment of leukemic animals with BCG, C. parvum, or MER alone proved ineffective as all mice died at approximately the same time as untreated control animals. No leukemic cells were observed in any of the histologically examined tissues taken from long-term survivors. The implication of these results for cancer therapy is discussed.
 ...
PMID:Histological and combined chemoimmunostimulation therapy studies against a murine leukemia. 17 Feb 12

The local reaction to gingival injections of methanol extraction residue of BCG (MER/BCG) was investigated in guinea pigs to help determine the potential of this agent in treating oral carcinoma. The drug was used in a standard and diluted form. Both concentrations were well tolerated and caused no ulceration or necrosis. Histological examinations performed at predetermined intervals showed an inflammatory response to the standard and the diluted solution. This reaction was more pronounced when the higher concentration was used. No changes in the alveolar bone were found in either of the groups. Complete healing with scar formation was evident four to six weeks later. The absence of severe reactions after injections of MER should encourage further investigations of this agent in the local treatment of neoplastic processes in the oral cavity.
 ...
PMID:Local reaction to gingival injections of MER/BCG in guinea pigs. 28 60

Twenty-four patients with advanced cancer not reacting to conventional therapy were treated with 97 courses of i.v. MER (methanol extraction residue of BCG). MER was administered by i.v. infusion over a 4-h period, twice a week, in dosages varying from 0.05 mg to 1.25 mg. The skin reactivity to 5 recall antigens was evaluated in the patients. All patients except 4 were anergic. Twelve patients had no side-effects. Anergic patients had less side-effects than ergic patients. The side-effects recorded in the others were fever, chills, vomiting and tachycardia. The reaction subsided within 24 h after treatment and was tolerable for most patients. In 2 patients an objective improvement was observed. No changes in cutaneous reactivity, renal and hepatic functions were found. A significant increase in peripheral leucocyte count was noted in two patients and slight a increase in the remainder.
 ...
PMID:A preliminary study of intravenous methanol extraction residue of BCG in treatment of advanced cancer. 33 70

The combination of vincristine, methyl-CCNU, and methotrexate with or without MER-BCG achieved a 2% complete response (CR) and a 11% partial response (PR) with a median duration of 25-29 weeks in 124 evaluable patients with advanced adenocarcinoma of the colon and rectum. Responses were seen in previously untreated patients and in patients refractory to 5-fluorouracil. The median survival of these objective responders (CR + PR) was 57 weeks. The addition of MER-BCG did not appear to influence response rate or duration of survival and was accompanied by significant toxicity. Response was significantly correlated with performance status, sex, and disease free interval and survival with alkaline phosphatase and performance status. Patients with advanced colorectal carcinoma should be stratified according to these variables.
 ...
PMID:Chemotherapy versus chemoimmunotherapy in advanced adenocarcinoma of the colon and rectum: a prospective randomized study. 36 76

Peripheral blood lymphocytes (PBL) from normal human donors were sensitized in vitro against allogeneic human acute myelocytic leukemia (AML) cells by means of an unidirectional mixed lymphocyte-tumor cell culture (MLTC) technique. The cytotoxic responsiveness of the sensitized lymphocytes, as determined in vitro by the 51Cr-release assay, varied among individual lymphocyte donors and was greatly dependent on the sensitization culture conditions. Induction of cytotoxic effector cells was augmented appreciably by adding to the cultures minute amounts of the immunopotentiating agent MER-BCG. Responding lymphocytes and stimulating leukemia cells cryopreserved for several weeks in liquid nitrogen were as effective as fresh cells in generating effector lymphocytes; the cytotoxic capacity of already sensitized lymphocytes was fully retained by cryopreservation. The implications of these findings for possible clinical employment of in vitro sensitized lymphocytes in adoptive immunotherapy of cancer are discussed.
 ...
PMID:In vitro induction of cytotoxic effector cells against human neoplasms. I. Sensitization conditions and effect of cryopreservation on the induction and expression of cytotoxic responses to allogeneic leukemia cells. 38 44

BCG immunotherapy often has severe complications in cancer patients despite lack of toxicity in the immunocompetent individual. MER, a cell wall fraction of BCG, has been reported to cause immunopotentiation similar to that of BCG without equivalent toxicity. Recently, animal models have been reported to develop MER complications, especially disseminated granuloma formation, like those of BCG. For the past several years, MER has been used as adjuvant immunotherapy for treatment of malignant tumors with minimal systemic toxicity reported. A patient with malignant melanoma was treated with intralesional MER at the site of local metastases. He developed military pulmonary granulomatosis and a severe cutaneous eruption in association with MER therapy. The toxicities of BCG and MER therapy were compared with the pathogenesis of granuloma formation reviewed. This patient's complications were consistent with a hypersensitivity reaction to MER. Pulmonary granulomatosis and rash must be added to the list of known MER toxicities.
 ...
PMID:Systemic complications of MER immunotherapy of cancer: pulmonary granulomatosis and rash. 42 Nov 77

6 patients with cutaneous malignant melanoma and multiple secondary cutaneous lesions were treated with intralesional methanol extraction residue of bacillus Calmette Guerin (MER-BCG). Separate lesions were injected with purified protein derivatives (PPD) in 5 of the study patients. 5 of the 6 MER-BCG injection lesions developed marked inflammation clinically. Excisional biopsy 7-14 days later demonstrated complete dissolution of tumor in 2 patients and was accompanied by infiltration with acute and chronic inflammatory cells; 3 lesions revealed necrosis with residual tumor, and in 1 patient there was no apparent host response. Clinical tumor regression was not observed with PPD applied intralesionally, although histopathologic analysis revealed a granulomatous inflammatory response in 3 of 5 patients. No patient demonstrated regression of uninjected cutaneous lesions (4 evaluable patients) or visceral lesions (2 patients). The critical determinants of tumor regression are the size, site and depth of the lesion in relationship to the cutaneous surface. The mechanism of tumor eradication may be related to 'innocent bystander' necrosis secondary to nonspecific inflammation rather than immunologically mediated via host sensitization.
 ...
PMID:Intralesional immune therapy: methanol extraction residue of BCG or purified protein derivative. 48 45

Intradermal injections of MER-BCG 0.1 mg or 0.2 mg at each of 10 multiple sites, led to local granuloma formation. The nodules reached approximately 10 mm in diameter, ulcerated and were accompanied by granulomatous changes in the regional lymph nodes. Six or twelve successive treatments (each including 10 injections) at 4 week intervals produced the same histopathological lesions but no changes in hematological and blood chemical parameters or general morphology and no changes in general condition with exception of occasional weight loss in a few animals. Injection with 0.01 or 0.001 mg/site produced similar, though less severe, skin lesions but no changes in the draining lymph nodes. The immunogenicity of MER-BCG was characterized by granuloma formation, a positive skin response to old tuberculin, and a positive lymphocyte transformation to PPD tuberculin, thus indicating stimulation of cell-mediated immune responses. However, there was a decreased responsiveness to PHA and PPD with continuing treatment with MER-BCG. The decreased responsiveness and accumulation of numerous depots of antigen would suggest an "immunologic paralysis" contraindicating the administration of excessive amounts of MER-BCG during immunotherapy. A specific humoral response to the administration of MER-BCG was not detected, but an MER-BCG dose independent decrease in albumin associated with a non-specific, dose related elevation in serum IgG was observed.
 ...
PMID:MER-BCG (NSC-143769): immunogenicity and toxicity of single and repeated intradermal injections in dogs. 55 13

Nine patients with advanced cancer who were receiving the methanol extraction residue of BCG (MER-BCG) intradermally or intratumorally underwent biopsies from the injected sites or from locally enlarged lymph nodes. Most preparations showed a chronic granulomatous reaction consisting of lymphocytes, histiocytes, and epithelioid cells as well as either Langhans's or foreignbody type giant cells, or both. The degree of granuloma formation and giant cell infiltration varied. In only one case did the reactions consist merely of chronic lymphocytic and histiocytic inflammation with no granuloma formation. Examination of melanoma nodules injected with MER showed, in addition to granulomas, large numbers of giant cells penetrating the tumour.
 ...
PMID:Granuloma formation in patients after injection of methanol extraction residue (MER-GCG). 60 61


1 2 3 4 5 Next >>