Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of IFN-alpha has been studied in patients with carcinoid tumours. More than 300 patients have been treated with IFN-alpha for long periods of time (median 2.5 years). IFN-alpha exerts many pleiotrophic effects in carcinoid tumours. Antiproliferative effects are manifest mainly by a cell cycle block in GO-G1 phase and prolongation of the S-phase. Hormone synthesis is impaired with reduced circulating hormone levels after IFN-alpha therapy and the mechanism includes reduction of mRNA expression for various hormones. Induction in vitro of the nuclear enzyme 2'-5-A synthetase in tumour cells correlates with biochemical response and might account for reduced mRNA expression. IFN-alpha induces significantly increased intratumoral fibrosis in carcinoid metastases without significant changes in tumour size. Finally IFN-alpha causes alteration of the major histocompatibility complex (MHC) with increased expression of class I antigens on the tumour cells. The net result of all these effects of IFN-alpha is an antitumour effect in 70-80% of carcinoid tumour patients with biochemical control and abrogated tumour growth for extended periods of time. However, when IFN-alpha therapy is withdrawn tumour progression occurs within 3-9 months, indicating a controlling but not curing effect.
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PMID:The action of interferon alpha on human carcinoid tumours. 135 93

In a group of 30 human tumors, comprising 12 lung, 14 ovarian, 2 breast carcinomas, 1 hypernephroma and 1 mid-gut carcinoid, the expression of major histocompatibility complex (MHC) class I molecules and the intercellular adhesion molecule 1 (CAM-1, CD54) was found to vary independently. Some tumors expressed both or neither of these molecules. Among 9/13 ICAM-1+ tumors, in which greater than 50% cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) (LB-2), the class I antigen was also detected on greater than 50% of the cells. Only 2 ICAM-1+ tumors were class-I-. In 5/17 cases the tumors were MHC-class-I+ and ICAM-1-. Lymphocytes collected from the blood or from the tumor site were assayed for recognition on the tumor cells in the auto-tumor cytotoxicity test and in mixed lymphocyte tumor cell culture (MLTC). Positive results were obtained only with the MHC-class-I+/ICAM-1+ tumors. In vitro treatment of the tumor cell suspensions with interferon gamma and tumor necrosis factor alpha (TNF alpha) induced or enhanced the ICAM-1 and/or class I antigen expression in 8/12 cases. Of the tumor samples treatged, 8/9 acquired stimulatory capacity and 3/10 became susceptible to lysis by the lymphocytes. In 6/6 MLTC performed with the cytokine-treated tumor cells, cytotoxicity against the autologous tumor was generated. Three of these MLTC lymphocytes also lysed the untreated targets. mAb directed to class I antigens or to ICAM-1 inhibited both the stimulation by and the lysis of tumor cells when confronted with fresh lymphocytes. The cytotoxicity generated in the MLTC was also inhibited. If, however, the cytotoxic function was induced in MTLC containing interleukin-2 (5 U/ml), inhibition was obtained only by pretreatment of the targets with mAb against ICAM-1. The results show thus (a) that the lymphocytes react in vitro with tumor cells only if these express both MHC class I molecules and ICAM-1; (b) that expression of these molecules can be induced by interferon alpha and TNF alpha; (c) that cytotoxic effectors generated in the MLTC with cytokine-treated tumors can also act on the untreated tumor cells. The requirement of the two surface moieties for the interaction with lymphocytes was also substantiated by blockade with relevant mAb.
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PMID:Expression of the adhesion molecule ICAM-1 and major histocompatibility complex class I antigens on human tumor cells is required for their interaction with autologous lymphocytes in vitro. 196 61

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and beta 2-microglobulin, beta 2m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced beta 2m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining beta 2m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-alpha therapy. Before IFN treatment, 3/4 SCLC tumors and 5/7 mid-gut carcinoids did not express beta 2m. By contrast, all tumors showed considerable expression of beta 2m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.
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PMID:Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids. 301 23

Cell lines established from small cell lung cancer (SCLC), a neuroendocrine tumor, have low or absent expression of class I major histocompatibility complex antigens. To determine whether this phenomenon occurs also in vivo, 244 routine paraffin-embedded tumors including 32 SCLC and 79 non-SCLC (NSCLC) lung cancers were studied for expression of beta 2-microglobulin (beta 2m) by an avidin-biotin coupled immunoperoxidase technique. The majority of SCLC tumors lacked beta 2m expression, while some had weak, focal expression. In contrast, most NSCLC expressed beta 2m, often strongly. The difference between SCLC and NSCLC was highly significant statistically, suggesting that beta 2m can be used as a clinical immunodiagnostic marker for distinguishing NSCLC from SCLC. In addition, certain other neuroendocrine tumors (neuroblastoma, bronchial and midgut carcinoid tumors) lacked beta 2m expression, whereas some (pheochromocytoma, medullary thyroid carcinoma, and peripheral neuroectodermal tumors) usually stained positively. Such non-neuroendocrine tumors as colon, breast, and prostate carcinomas showed moderate to high expression of beta 2m. Selective absence of beta 2m expression by certain neuroendocrine tumors appears to be a phenomenon of biological and diagnostic importance.
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PMID:Paucity of beta 2-microglobulin expression on small cell lung cancer, bronchial carcinoids and certain other neuroendocrine tumors. 352 83

We studied the expression of major histocompatibility complex (MHC) class I molecule in 52 ex-vivo tumor samples comprising 29 ovarian, 15 lung, 1 breast, and 4 colon carcinomas; 1 midgut carcinoid; and 2 malignant mesenchymal tumors obtained from surgical specimens or from malignant effusions. The allelic products were visualized in untreated and interferon gamma + tumor necrosis factor alpha treated aliquots of tumor cells and in the patient's blood lymphocytes by the one-dimensional isoelectric focusing method. Generally, the tumor cells contained lower amounts of MHC class I molecules compared to the lymphocytes. In vitro exposure to interferon gamma and tumor necrosis factor alpha elevated the level of MHC class I expression in 24 of 52 tumors and corrected the assembly defect seen in 2 cases. In 20 tumors one or several human leukocyte antigen alleles were undetectable even after cytokine treatment. Correlation was seen with the grade of differentiation; the proportion of tumors with selective losses in poorly, moderately, or well differentiated tumors were 16 of 30, 3 of 13, and 1 of 9, respectively. Selective losses occurred in ovarian carcinoma cells collected from malignant effusions (12 of 22, 54%) but not in 7 primary tumors. In primary lung carcinomas the frequency was 36% (5 of 14 cases). Thirty-nine patients were serologically typed; thus the MHC alleles on the tumor cells could be identified. In this panel of tumors 30 human leukocyte antigen alleles were represented. Among these the expression of 15 was found to be down-regulated in some but not all tumors of the same histology.
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PMID:Selectively down-regulated expression of major histocompatibility complex class I alleles in human solid tumors. 848 28