Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unconjugated monoclonal antibodies (mAb) may induce tumour regression in patients. The mechanisms of action are complex. Antibody-dependent cellular cytotoxicity (ADCC) is considered one of the effector functions. Augmentation of the killing capacity of cytotoxic cells may thus be a way to increase the therapeutic potential of mAb. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) has been shown to enhance this function in vitro. Eighteen patients with metastatic colorectal carcinoma received GM-CSF (250 micrograms m-2 day-1 s.c.) for 10 days and a single infusion of the anti-(colon carcinoma) mAb 17-1A (mouse IgG2A) (400 mg) on day 3 of the cycle. The cycles were repeated once a month four times. Neutrophils, eosinophils, monocytes and lymphocytes increased significantly in a biphasic way. However, at the fourth cycle the rise in white blood cells was significantly lower compared to the preceding courses. ADCC (SW948, a human CRC cell line,+mAb 17-1A) or peripheral blood mononuclear cells (PBMC) was significantly (P less than 0.05) augmented by day 6 of a cycle and then declined gradually and, at the end of a cycle, the ADCC activity had returned to the pretreatment level. The spontaneous cytotoxicity of PBMC against the natural-killer-resistant cell line, SW948, varied in a similar way. During GM-CSF treatment there was also a significant increase in FcRI+ (CD64), FcRII+ (CD32), FcRIII+ (CD16) and CD14+ cells but not of CD56+ cells.
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PMID:Cytotoxic functions of blood mononuclear cells in patients with colorectal carcinoma treated with mAb 17-1A and granulocyte/macrophage-colony-stimulating factor. 163 51

We report a patient with severe paraneoplastic encephalomyeloneuritis, occult small-cell carcinoma of the lung, and high titers of circulating antineuronal antibody who died shortly after developing limbic encephalitis. The antibody was of IgG class and reacted specifically with nuclei and cytoplasm of all neurons in the pattern typical for encephalomyelitis and subacute sensory neuropathy associated with small-cell carcinoma (type II, anti-Hu). At autopsy, perivascular inflammatory infiltrates were prominent. All samples of serum, CSF, and postmortem peritoneal and pleural fluid contained high titers of antibody. Direct immunofluorescence of frozen tissue revealed IgG bound to most remaining neurons in multiple brain regions in a pattern similar to indirect immunofluorescence of normal brain tissue. IgG was also bound to tumor. Attempts to elute antibody from tissue decreased background staining but did not remove neuronal immunofluorescence. These results indicate that antibody can access and bind specifically to neuronal antigens in the brain during the course of paraneoplastic disease.
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PMID:Localization of antibody in the central nervous system of a patient with paraneoplastic encephalomyeloneuritis. 165 26

Progress in genetics now enables the synthesis of molecules acting on the regulation of the immune system which are called cytokines. Currently there are several cytokines, Interferon (IFN), Interleukin 2 (IL2), tumour necrosis factor (TNF) as well as haematopoietic growth factors and these are the object of study in clinical trials. Interferon has already been used in the therapy of hairy cell leukaemia, Kaposi sarcoma associated with AIDS(SIDA) and metastasis of malignant melanoma. Interleukin 2 allows for an increase in the cytotoxic activity of NK cells in producing LAK cells, the lymphocyte infiltrating the tumour (TIL). Therapeutic combinations combining IL2 associated with LAK or of TIL have been evaluated in some private studies. These treatments have shown some interesting response levels on those tumours which are usually resistant, such as malignant melanoma or carcinoma of the kidney. TNF is active in vitro on human tumours; its potential toxicity is important; it is the object of a phase 1 clinical trial. Haematopoietic growth factors, G-CSF and GM-CSF, stimulate the production of leucocytes which will be valuable to correct toxic affects on the marrow during chemotherapy. This will enable chemotherapy to be given at a high dose.
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PMID:[Immunotherapy of cancer using cytokinins. Use and perspectives in lung oncology]. 169 91

Granulocyte colony-stimulating factor stimulates the proliferation and differentiation of progenitor cells committed to the neutrophil lineage, and it has been shown to improve survival to bacterial challenge in neutropenic mice. We studied recombinant human granulocyte colony-stimulating factor (rhG-CSF), cloned from bladder cell carcinoma line 5637, in a nonneutropenic infection model of Streptococcus pneumoniae pulmonary infection in splenectomized and sham-operated control mice. The rhG-CSF improved survival in the splenectomized mice but not in the sham-operated mice. Circulating leukocyte counts were greatest for the rhG-CSF-treated splenectomized mice compared with all other groups, presumably due to a loss of splenic sequestration. Clearance of live pneumococci from mouse lung pairs was impaired after splenectomy. The rhG-CSF improved lung clearance in both splenectomized and sham-operated mice compared with saline solution-treated controls. The number of live pneumococci recovered from tracheobronchial lymph nodes at 24 hours after aerosol challenge was greatest in the splenectomized mice vs sham-operated mice. Decreased numbers of viable pneumococci were recovered from tracheobronchial lymph nodes from the rhG-CSF-treated splenectomized mice and the sham-operated mice vs saline solution-treated controls. The rhG-CSF may be a useful adjuvant for treating infections in individuals with immunologic dysfunctions other than neutropenia.
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PMID:Protective effect of recombinant human granulocyte colony-stimulating factor against pneumococcal infections in splenectomized mice. 169 96

A patient with pleomorphic giant cell carcinoma of the gallbladder also had mild neutrophilia, and this tumor was found to be human granulocyte colony-stimulating factor (G-CSF)-positive on immunohistochemical staining. CSF activity in urine and serum was not examined, but leukocytosis disappeared immediately after cholecystectomy. These findings suggest that this was a G-CSF-producing tumor.
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PMID:A case of gallbladder cancer producing granulocyte-colony-stimulating factor. 170 76

A new mutant protein of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was produced for the studies on receptors for human G-CSF. The mutant protein [(Tyr1, Tyr3]rhG-CSF), the biological activity of which was almost equal to that of rhG-CSF, was prepared by the replacement of threonine-1 and leucine-3 of rhG-CSF with tyrosine. The radioiodinated preparation of the mutant protein showed high specific radioactivity and retained full biological activity for at least 3 weeks. The binding capacity of the radioiodinated ligand was compared with that of [35S]rhG-CSF. Both radiolabeled ligands showed specific binding to murine bone marrow cells. Unlabeled rhG-CSF and human G-CSF purified from the culture supernatant of the human bladder carcinoma cell line 5637 equally competed for the binding of labeled rhG-CSFs in a dose-dependent manner, demonstrating that the sugar moiety of human G-CSF made no contribution to the binding of human G-CSF to target cells. In contrast, all other colony-stimulating factors and lymphokines examined did not affect the binding. Scatchard analysis of the specific binding of both labeled ligands revealed a single class of binding site with an apparent dissociation constant (Kd) of 20-30 pM and 100-200 maximal binding sites per cell. These data indicate that the radioiodinated preparation of the mutant protein binds the same specific receptor with the same affinity as [35S]rhG-CSF. The labeled mutant protein also showed specific binding to human circulating neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutant protein of recombinant human granulocyte colony-stimulating factor for receptor binding assay. 171 70

We studied the effects of in vivo administrations of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the metastasis of murine hematogenous and non-hematogenous tumors in spontaneous and experimental metastasis models. Spontaneous lung metastasis caused by intra-footpad injections of B16-BL6 melanoma and Lewis-lung-carcinoma (3LL) cells were inhibited by intravenous (i.v.) and subcutaneous (s.c.) injections of rhG-CSF after excision of the primary tumors. Recombinant hG-CSF significantly inhibited liver metastasis when administered i.v. after i.v. injection of L5178Y-ML25 T-lymphoma cells. Multiple i.v. administration of rhG-CSF after the tumor inoculation prolonged the survival times of mice inoculated i.v. with L5178Y-ML25 lymphoma cells. Recombinant hG-CSF did not directly affect the growth of B16-BL6 and L5178Y-ML25 cells in vitro. During the administration periods, both i.v. and s.c. injections of rhG-CSF increased the number of total white blood cells (WBC) in peripheral blood to approximately 3 times the normal level in normal and tumor-bearing mice. We also found that the administration of rhG-CSF stimulates neutrophils to become cytostatic against these tumor cells. Our results indicate that the injection of rhG-CSF is effective in inhibiting lung and liver metastases by activating neutrophils and increasing cell number.
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PMID:Recombinant human granulocyte colony-stimulating factor inhibits the metastasis of hematogenous and non-hematogenous tumors in mice. 171 86

Thirty-four patients with meningeal carcinomatosis were treated at The Center for Adult Diseases, Osaka, from 1984 through 1990. The major origin of meningeal carcinomatosis was carcinoma of the lung (14 cases) and breast (8 cases). The most frequent histological type of carcinoma was adenocarcinoma (23 cases). Twenty cases still had active lesions and/or primary lesions in the lung, liver or bone at the time of diagnosis of the meningeal carcinomatosis. The primary lesions were treated surgically in 22 cases, with chemotherapy in 4 cases and with radiotherapy in 2 cases. Metastatic brain tumors were treated by surgical removal followed by chemo-radiotherapy in 12 cases, and with radiotherapy alone in 2 cases. The interval from the time of diagnosis of the primary lesion to the time of diagnosis of the meningeal carcinomatosis varied from one month to eight years, and the interval between surgical removal of metastatic brain tumors and the diagnosis of meningeal carcinomatosis ranged from 0 to 3 years. With regard to the diagnosis of meningeal carcinomatosis, positive cytology was seen in initial standard lumbar puncture in 32 of the 34 patients. CT scan showed abnormal findings in 28 of the 34 patients, including ventricular dilatation only (12 cases), and small enhancing lesions along the CSF space (12 cases). The EEG showed abnormal patterns in 14 of 15 cases. Intrathecal chemotherapy with methotrexate alone or combined methotrexate with cytosine arabinoside via the Ommaya reservoir or standard lumbar puncture alternately with or without radiation therapy was successful as treatment, and 22 of 29 treated patients showed symptomatic improvement of the meningeal irritation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Study of meningeal carcinomatosis: diagnosis and treatment]. 173 24

A mouse monoclonal antibody (MAb17-1A) (IgG2A) against colorectal carcinoma cells was used to treat patients with metastatic disease. Major direct effector functions of MAb seem to be ADCC (antibody dependent cellular cytotoxicity), CDC (complement dependent cytolysis) and apoptosis ('programmed cell death'). Thus, a high tumor cell saturation of the MAb should be achieved. Increasing doses of MAb to the patients increased the total area under the concentration curve and thus the exposure of tumor cells to MAb. However, the response rate (with complete + partial + minor response + stable disease defined as response) was not augmented. In total, 10/52 (19%) patients responded and in fact lower doses (less than 2 g) might induce a higher response frequency (9/52) than higher doses (greater than 2 g) (1/52). During treatment, the numbers of cytotoxic cells (lymphocytes and monocytes) increases in the tumor lesion and complement components were deposited. As ADCC may be important, effector mechanism attempts were made to augment the cytolytic capability of the effector cells by simultaneously giving the patients GM-CSF. The combination of MAb17-1A + GM-CSF augmented the ADCC activity of blood mononuclear cells and a heavy infiltration of monocytes could be noted in the tumor. Out of 15 available patients 6 (40%) showed a response.
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PMID:Therapy of colorectal carcinoma with monoclonal antibodies (MAb17-1A) alone and in combination with granulocyte monocyte-colony stimulating factor (GM-CSF). 177 44

Recombinant human (rh) erythropoietin (EPO) is attracting increasing interest as an agent for treating cancer-related anemia. Thus, we have tested the effects of rhEPO on the clonal growth of 22 different cell lines derived from a wide range of human solid tumors (head and neck 3, lung 2, breast 2, stomach 1, colorectal 3, hepatocellular 1, pancreas 1, ovary 1, choriocarcinoma 1, osteogenic sarcoma 1, glioblastoma 2, neuroblastoma 1, prostate 1, renal 2) in vitro. RhEPO (dose range 0.01-100 U/ml) caused no significant and reproducible stimulation of clonal growth as measured by a capillary modification of the human tumor cloning assay in agar in any of the cell lines tested. In particular, there was no sensitivity for rhEPO of those cell lines which were shown to be responsive to interleukin-3 and GM-CSF. On the other hand, there were no growth inhibitory effects of rhEPO on the cell lines of this study. Finally, neutralizing anti-human EPO antibody had no effect on the clonal growth of two kidney carcinoma cell lines, making autocrine growth regulation by hEPO in these lines unlikely.
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PMID:Studies on the role of recombinant human erythropoietin in the growth regulation of human nonhematopoietic tumor cells in vitro. 187 24


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