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)

Our studies clearly show that significantly longer remission duration was attained in groups of AML patients immunized with neuraminidase treated allogeneic myeloblasts as compared to patients who received chemotherapy alone or neuraminidase treated myeloblasts plus MER. IT is clear that MER, albeit apparently active alone in certain other clinical studies impairs the immunotherapeutic value of neuraminidase treated allogeneic myeloblasts in AML patients. The in vivo and in vitro immunological tests results reflect the host's immunological status in each arm of the protocol and correlate well with the duration of remission achieved with specific vs. combination of specific plus adjuvant immunotherapy.
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PMID:Impact of specific immunotherapy in acute myelocytic leukemia. 16 58

These studies attempt to analyze the basis of the estrogenic and antiestrogenic action of three nonsteroidal clomophene-type compounds as monitored by their ability to bind to immature rat uterine cytoplasmic estrogen receptor, transfer receptor sites to the nucleus, and elicit estrogenic responses (increased uterine weight and induction of the synthesis of a specific uterine protein, called induced protein, or "IP"), and by their ability to antagonize the effects of estradiol on these receptor interactions and uterine responses. Both CI-628 (CI) and U-11, 100A (UA) [50 mug] elicit slight IP induction at 1-2 hand give pronounced uterine weight increases at 24 h but feeble increases at 72 h (3 single daily injections). Both bind to cytosol, and effect the transfer of receptor sites to the nucleus, which may account for the estrogenicity of these compounds. Both CI and UA give rapid (by 2-4 h), prolonged (for over 24 h), and complete blockage of estradiol-stimulated treatment abolishes short-term estradiol-stimulated uterine weight increase and antagonizes the 72 h estradiol-stimulated uterine weight response to the level attributable to the antiestrogen alone. MER-25, at the same dose (50 mug), had no estrogenic or antiestrogenic activity. Both CI and UA rapidly deplete the cytoplasmic estrogen binding capacity, reducing it to barely detectable levels for 24-42 h. Although during this period, no IP or uterine wet weight response can be elicited by estradiol, administration of saturating levels of [3H]estradiol in vivo or in vitro results in the appearance of considerable [3H]estradiol in the nucleus, bound to a macromolecule sedimenting identically with that of the nuclear receptor-estradiol complex (5.5S) formed in the absence of prior antiestrogen exposure. Hence, the estradiol which becomes bound in the nucleus after antiestrogen is biologically ineffective. The return of IP responsiveness after antiestrogen correlates well with the level of cytoplasmic receptor capable of translocation to the nucleus, and not with the nuclear estradiol uptake capacity, Presumably, then, the antiestrogenic action of CI and UA results from their depletion of cytoplasmic receptor sites and not from their ability to block specific estradiol-nuclear receptor binding per se. These studies indicate that one should be cautious in assuming that the magnitude of an estrogen response is necessarily related to the level of estrogen receptor complex in the nucleus.
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PMID:Antiestrogen action in the uterus: biological ineffectiveness of nuclear bound estradiol after antiestrogen. 16 21

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.
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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.
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PMID:Histological and combined chemoimmunostimulation therapy studies against a murine leukemia. 17 Feb 12

Cultured cells (chicken embryo liver cells and rat embryo fibroblasts) were treated with triparanol (MER-29) for various lengths of time. Both types of cells have developed numerous membranous whorls-myeloid bodies in the cytoplasm. Various stages in myeloid bodies development are described. Acid phosphatase activity was cytochemically demonstrated within the myeloid bodies, indicating their lysosmal nature. This activity appeared only at a late stage of the myeloid bodies formation.
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PMID:Myeloid bodies formation in triparanol treated cultured cells. 17 85

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.
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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.
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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.
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PMID:Chemotherapy versus chemoimmunotherapy in advanced adenocarcinoma of the colon and rectum: a prospective randomized study. 36 76

Fifty-three patients with colorectal cancer Dukes' B2 and C were randomized after surgery. One group was treated by radio-and/or chemotherapy and the second by radio-and/or chemotherapy and MER. After 24 and 36 months a significant longer disease free interval, lower recurrence rate and better survival was found in the group treated by radio-chemo- and immunotherapy. Treatment was well tolerated and there were few local side effects from the MER injections. The long time efficacy of this adjuvant treatment whether it increases the cure rate or only delays recurrence does require longer follow-up.
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PMID:Adjuvant therapy in colorectal cancer. (A randomized trial comparing radio-chemotherapy and radio-chemotherapy combined with the methanol extraction residue of BCG, MER). 38 71

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.
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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


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