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)

We established a human carcinoma cell line (KHC 287) from a patient with large-cell-typing lung carcinoma associated with marked leukocytosis. The culture supernatant of KHC 287 cells promoted granulocytic colony formation of human bone-marrow cells in semi-solid culture. Colony formation was almost completely suppressed by treatment of the supernatant with a monoclonal anti-granulocyte colony-stimulating factor (G-CSF) antibody. Not only G-CSF but also interleukin-1 alpha (IL-I alpha), IL-I beta and IL-6 were detected in the culture supernatant by an ELISA method. Northern blot analysis of KHC 287 cells revealed distinct expression of these cytokine genes. Southern blot hybridization of KHC 287 DNA showed 20- and 40-fold co-amplification of c-myc and c-ki-ras, respectively. The chloramphenicol acetyl transferase (CAT) activity was distinctly enhanced in the KHC 287 cells which were transfected with the 360 bp upstream region of G-CSF gene inserted into pSV00CAT, but not in non-G-CSF-producing tumor cell lines. These results suggest that overproduction of the transactivating factor(s) which binds to the 360 bp of the G-CSF upstream region is responsible for the abnormal expression of G-CSF gene in KHC 287 cell line.
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PMID:Analysis of abnormal expression of g-csf gene in a novel tumor cell line (KHC 287) elaborating G-CSF, IL-1 and IL-6 with co-amplification of c-myc and c-ki-ras. 171 Feb 8

There is strong evidence implicating human papillomavirus type 16 (HPV16) in the genesis of human genital cancer. Viral DNA has been identified in invasive carcinoma of the uterine cervix and in cell lines derived from cervical carcinomas. These sequences are actively transcribed, and translation products corresponding to the early (E)-region genes have been identified. The most abundant viral protein is the E7 protein, which has been shown to possess transforming activity for both established and primary cells. In addition, it has been shown to bind to a cellular tumor suppressor, the retinoblastoma gene product (pRb-105). In view of these properties, we have undertaken the immunological analysis of this protein and have identified four T-cell epitopes and three B-cell epitopes by using a series of overlapping peptides spanning the entire HPV16 E7 sequence. Two of the B-cell epitopes were recognized by antisera from mice with three different murine (H-2) haplotypes (k, d, and s) immunized with two different E7 fusion proteins and from Fischer rats seeded with baby rat kidney cells transformed by HPV16 E7 and ras. A third B-cell epitope was recognized by antisera from CBA mice seeded with HPV16 E7-expressing L cells. Two regions of the protein contain common B- and T-cell epitopes, one of which appears to be particularly immunodominant.
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PMID:Identification of T- and B-cell epitopes of the E7 protein of human papillomavirus type 16. 171 16

Pathological diagnosis of hepatic tumors is sometimes difficult when performed with only routine examinations such as Hematoxylin and Eosin (H.E.) stain. The diagnostic usefulness of KM01 was compared to that of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9 and ras p21 in this immunohistochemical study. AFP was positive in about half of the cases of hepatocellular carcinoma and hepatoblastoma, and AFP-positive cells were frequently found at the periphery of acini in both diseases. Absorbed CEA stain was mostly negative in hepatocellular carcinoma, but was positive in the cells of mixed hepatocellular and cholangiocellular carcinoma (MHCC) and metastatic liver cancer, especially in their cytoplasm. CA19-9 immunostaining was completely negative, and was only 3% positive in hepatocellular carcinoma. KM01 stain was positive in about half of the cases of hepatocellular carcinoma, hepatoblastoma and MHCC. It was positive in proliferated bile ducts around the capsule in the former two diseases but positive in the tumor cell of both parts of the cytoplasm in the latter. The histological positivity of ras p21 was high in all tumor cells of these three types of tumors. Negative absorbed CEA and KM01 in pseudoglandular hepatocellular carcinoma differentiated from MHCC and metastatic liver cancer. However these tumor markers were occasionally positive and nonspecific in cancer-like lesions, implying no advantage for differential diagnosis between hepatocellular carcinoma and apparent cancer-like lesions. The above results demonstrate that AFP, CEA and KM01 are effective for differentiating hepatocellular carcinoma among various hepatic tumors.
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PMID:Immunohistochemical study on hepatic tumors--KM01 stains compared with AFP, CEA, CA19-9 and RAS P21. 171 40

We assayed rat colon tumors induced by N-methyl-N-nitrosourea (MNU) for transforming oncogenes by the NIH 3T3 transfection and nude mouse tumorigenicity assays. Transfection of DNA from 3 of 3 adenomas and 3 of 5 carcinomas induced transformed foci on NIH 3T3 cells. DNA from 2 of 3 primary foci also possessed focus-forming activity, and rat-specific sequences were observed in secondary focus DNAs. Furthermore, NIH 3T3 cells transfected with DNA from a carcinoma and from a primary focus derived from it, both positive in the focus-forming assay, induced tumors in nude mice. We found no evidence for rat H-ras, K-ras, or N-ras sequences in the DNA of any of 16 primary foci derived from 6 rat tumors; thus, in contrast to other animal tumor models induced by MNU, activation of the ras genes does not appear to predominantly occur in MNU-induced rat colon tumors. We also did not observe, in any of these foci, sequences corresponding to the rat neu, raf, fms, met, or hst genes, thus indicating that none of these is the transforming oncogene in our model. These results suggest that an as yet unidentified transforming oncogene may be activated in rat colon tumors induced by MNU.
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PMID:Detection of transforming oncogenes in rat colon tumors induced by direct perfusion with N-methyl-N-nitrosourea. 173 Jan 34

Transfection of primary rat embryo fibroblasts with the H-ras oncogene plus the cooperating oncogene v-myc results in the development of foci of morphologically altered tumorigenic cells. We examined radiation (X-rays) induced inhibition of DNA synthesis in cell lines derived from such transformed clones and compared the results to those obtained with the nontransformed parental cells, rat embryo fibroblasts, as well as with cells immortalized either spontaneously, or after transfection with nuclear oncogenes (v-myc, E1A). Inhibition by X-rays of DNA synthesis was higher and persisted for longer periods of time in the H-ras- plus v-myc-transformed cell lines as compared to their nontrasformed counterparts. When the rate of DNA synthesis was measured as a function of dose 3 h after irradiation, biphasic curves were observed in all cell lines tested with a radiation sensitive and a radiation resistant component, known to correspond to inhibition of replicon initiation and chain elongation, respectively. A substantially larger inhibition of DNA synthesis was observed between 0 and 30 Gy in H-ras- plus v-myc-transformed cell lines, as compared to their nontransformed counterparts, presumably caused by sustained inhibition of replicon initiation. Hypersensitive DNA synthesis to X-rays was also observed in a transformed cell line obtained by transfection of rat embryo fibroblasts with H-ras in cooperation with the oncogene E1A, but normosensitive DNA synthesis in a rare transformant obtained by transfection with H-ras alone. These results suggest a direct or indirect involvement of the oncogene H-ras in cooperation with the oncogene v-myc (or other nuclear oncogenes such as E1A) in the control of DNA synthesis in irradiated cells. This control of DNA synthesis may be mediated via a trans-acting mechanism that involves the production of a diffusible factor in response to the radiation insult, or, by a cis-acting mechanism that directly affects the replication machinery. Circumstantial evidence for possible involvement of oncogenes of the ras and myc families in DNA synthesis support this hypothesis. There was an inverse correlation between sensitivity to radiation-induced killing and prolonged inhibition by radiation of DNA synthesis, with radioresistant cell lines displaying longer inhibition of DNA synthesis. However, inhibition by radiation of DNA synthesis was similar in normal human fibroblasts (W138) and cells derived from a radiation-resistant human carcinoma cell line (SQ-20B) suspected to carry an abnormal c-raf-1 oncogene.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prolonged inhibition by X-rays of DNA synthesis in cells obtained by transformation of primary rat embryo fibroblasts with oncogenes H-ras and v-myc. 173 37

Immunocytochemistry with monoclonal antibody Y13-259 demonstrated p21 ras in paraffin sections of breast tissue from 171 women: 85 with invasive breast carcinoma, 14 with non-invasive carcinoma and 72 with benign changes only. Many different tissue elements contributed to ras expression. Semiquantitative assessment showed that intensity of immunostaining in the normal epithelium of large ducts, small extralobular ducts and terminal duct lobular units (TDLU) was usually exceeded by that of myoepithelial cells. Vascular smooth muscle and apocrine epithelium also stained strongly, but the flat epithelial cells lining cysts did not express detectable p21 ras. There was a progressive increase from normal epithelium through epithelial hyperplasia of usual type and atypical hyperplasia to carcinoma in situ, without further increase in invasive carcinoma. Expression in carcinomas was inversely related to oestrogen receptor content but independent of the prognosis-associated variables of size, histological type, vascular invasion or lymph node metastasis.
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PMID:Ras p21 in breast tissue: associations with pathology and cellular localisation. 173 41

The prevalence of Kirsten (Ki)-ras gene mutations was studied in 105 paraffin-embedded tissues obtained from 40 patients with pancreatic cancer, 48 with bile duct carcinoma (19 distal, 6 middle, and 23 proximal), 16 with ampullary carcinoma and 1 with duodenal cancer, by in vitro amplification of target sequences by the polymerase chain reaction (PCR). With regard to pancreatic cancers, the authors' data confirm the very high frequency (88.6%) of Ki-ras gene mutations occurring at codon 12. Five pancreatic carcinomas did not contain the Ki-ras mutation and included rare types of histopathology. By histologic review after the examination of Ki-ras mutations through PCR, the diagnosis of four patients could be legitimately revised from other periampullary carcinoma to pancreatic carcinoma. In the ampullary carcinoma, the prevalence of mutations in Ki-ras codon 12 was 13.3%. Although there was a large difference in incidence of mutations between distal and middle or proximal bile duct carcinoma, the prevalence of mutations in bile duct carcinoma was limited to 19.6%. Unlike other approaches to diagnose periampullary carcinoma, detection of a mutation in Ki-ras codon 12 by PCR may distinguish pancreatic carcinoma from other periampullary carcinomas that have better prognoses.
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PMID:Distinguishing pancreatic carcinoma from other periampullary carcinomas by analysis of mutations in the Kirsten-ras oncogene. 174 44

In animal systems, complete and permanent eradication of tumours can be achieved by adoptive transfer of MHC-restricted T cells, combined with IL2. In certain types of human cancer (melanoma and perhaps renal cell carcinoma), tumour-specific T cells are probably the therapeutically most active cells among LAK or TIL cells. To prove these points, it is necessary to conduct trials with cloned tumour-specific T cells. Other potentially immunogenic tumors are cervical carcinoma, associated with human papilloma virus, and Burkitt's lymphoma, associated with Epstein-Barr virus. Most other human tumours, caused by subtle mutations in proto-oncogenes, are likely to be poorly or non-immunogenic. It is worthwhile trying to overcome this by vaccination with IL2 or IFN gamma-producing tumour cells or by deliberate vaccination with desirable targets for tumour-specific CTL such as the products of point-mutated oncogenes, including ras (Jung and Schleusener, 1991) and p53 (Rodriguez et al., 1990; Halevy et al., 1990), provided the relevant peptides are processed and bound to MHC class I molecules. Other potential targets are breakpoint peptides of translocated oncogene products such as bcr/abl (Van Denderen et al., 1990). In viral systems, it has already been established that peptide vaccination for protective CTL induction is feasible (Aichele et al., 1989; Schulz et al., 1991; Kast et al., 1991).
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PMID:T-cell immunotherapy of cancer. 175 15

Assessment of the function of putative dominantly-acting oncogenes or recessive tumor-suppressor genes in human tumor development and progression must ultimately involve xenografting experiments using immune deficient animals such as nude mice. Most human tumor xenograft experiments have employed conventional subcutaneous injection procedures. However, despite the simplicity of this procedure, it poses some serious potential drawbacks as most types of human tumor will not readily grow or metastasize from a subcutaneous ('ectopic') site of injection. In contrast, 'orthotopic' injection procedures will often enhance the tumorigenic and/or metastatic ability of tumor cell populations. An example of this is summarized in the context of human malignant melanoma where the effects of subcutaneous versus subdermal injection are compared. Despite the seeming subtle and minor change in injection site, superior growth of human melanomas can be obtained by the latter, orthotopic-like, route of injection. It therefore follows that induction of tumorigenic or metastatic properties in a given human cell population by gene transfection may not be detected if the transfected cells are assayed in vivo only by subcutaneous injection procedures. An example of this is provided by experiments involving transfection of normal or mutated ras genes into a low-grade, well-differentiated human bladder carcinoma cell line, called RT-4. Thus overexpression of normal or mutated (valine 12) c-H-ras resulted in acquisition of a clinical-like invasive phenotype. However, this was clearly seen only if the cells were injected into the bladders (i.e. 'intravesically') of nude mice. In contrast, conventional subcutaneous injection of the high ras expressing transfected RT-4 cell lines did not reveal acquisition of invasive properties: all cell lines grew locally as well-encapsulated tumor masses. It is argued that similar orthotopic injection procedures should be employed when assessing the suppressive effects of various wild-type tumor-suppressor genes on human tumor growth in vivo. Utilization of subcutaneous injection procedures may grossly exaggerate the growth suppressive effects of such genes. This could explain the paradox of why, on the one hand, alterations involving many different genes (including different suppressor genes) appear to be involved in human carcinoma tumorigenesis while on the other hand, complete suppression of tumorigenicity can be caused by transfer of a single wild-type suppressor gene. Such complete suppressions might be observed only after ectopic (usually subcutaneous) injection procedures.
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PMID:Importance of orthotopic transplantation procedures in assessing the effects of transfected genes on human tumor growth and metastasis. 176 65

A poly(ADP-ribose) polymerase inhibitor, benzamide (BA), was found to induce flat revertants of NIH 3T3 cells that had been transformed by human Ha-ras, rat Ki-ras, rat c-raf, and human ret-II. These genes had been amplified in original transformants, but they were completely eliminated by BA. Contrary to this, endogenous activated Ha-ras in a human bladder carcinoma cell line, T24, was not eliminated by BA. The gene loss seemed to be restricted to exogenous and/or amplified sequences. BA also eliminated the amplified c-myc gene in HL-60 cells, concomitant with differentiation into granulocytes. We demonstrated that the amplified c-myc gene was not present as episomes. It is probably present as double minutes or a homogeneously staining region. Dimethylsulfoxide also induced differentiation at a concentration that did not inhibit poly(ADP-ribose) polymerase. The cell lost the c-myc gene in association with this differentiation. The amplified c-myc gene in a colon adenocarcinoma cell line, COLO 320HSR, and the amplified mdr-1 gene in an adriamycin-resistant myelogenous leukemia cell line, K562/ADM, were not eliminated by BA. Various poly(ADP-ribose) polymerase inhibitors also eliminated human Ha-ras in the NIH 3T3 transformant and the c-myc gene in HL-60 cells.
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PMID:Loss of amplified genes by poly(ADP-ribose) polymerase inhibitors. 177 88


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