Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal hepatic metastases have a notoriously poor response to conventional systemic chemotherapy. We have synthesised cytotoxic drug (doxorubicin and mitomycin C) containing spheres 40 microns in diameter, using human albumin and ethyl cellulose as matrices. Introduction of these cytotoxic microspheres into the hepatic artery should embolise to the tumor and provide a controlled release depot for the anticancer agent. The vasoconstrictor, angiotensin II (AII) has been shown to increase tumor blood flow relative to normal tissue when administered via the hepatic artery, therefore we have investigated the effect of AII on targeting of cytotoxic microspheres to hepatic metastases. Patients with hepatic metastatic colorectal carcinoma had hepatic arterial catheters inserted at laparotomy and connected to subcutaneous injection ports. Peroperatively, 99mTc-labelled albumin microspheres were administered via the arterial catheter. Fifteen minutes later, AII was infused (10 micrograms per minuter for 4 min) via the catheter and 131I-labelled albumin microspheres were administered as a bolus at the midpoint of the AII infusion. Multiple biopsies were taken of normal liver and tumor metastasis and the tissue radioactivity counted for 99mTc and 131I. Further studies were performed postoperatively in which 99mTc-labelled microspheres were administered via the hepatic artery catheter and their distribution was followed using tomographic SPECT scanning. Combined results of this study suggested that AII can increase tumor SPECT scanning. Combined results of this study suggested that AII can increase tumor blood flow rates relative to normal hepatic tissue by approximately 3-fold.
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PMID:The effect of angiotensin II on tumor blood flow and the delivery of microparticulate cytotoxic drugs. 161 36

B1 and B3 are two newly isolated monoclonal antibodies that react uniformly with the surface of many mucinous carcinomas of the colon, stomach, and ovary but with a limited number of normal tissues, among which are glands of the stomach, epithelia of the trachea and bladder, differentiated epithelium of the esophagus, and small bowel mucin. They also react uniformly with many human tumor cell lines, including MCF7, MDA-MB-468, and HTB20 (breast), A431 (epidermoid), HT29 (colon), HTB33 (cervical), and DU145 (prostate). Immunoprecipitation experiments indicate that B1 and B3 react with epitopes present on a large number of glycoproteins, ranging in molecular weight from greater than 200,000 to less than 40,000. Using a panel of 37 different carbohydrate residues attached to albumin to form neoglycoproteins, it was found that B1 reacts with Ley and H-type 2 and B3 reacts with Ley, di-Lex, and tri-Lex antigens. Thus, each antibody reacts with a distinct portion of a carbohydrate residue. Because of the limited reactivity of these antibodies with normal tissues, they merit evaluation in the treatment of cancer.
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PMID:Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas. 164 44

It has been reported that hepatoma (HCC) cells produce abnormal proteins such as erytropietin, fibrinogen, prothrombin, and, recently, antithrombin III (AT III). In a preliminary report, we reported increased AT III levels in patients bearing HCC independent of their clinical liver status. The present study was performed to assess antithrombin III levels and other serological data present in patients with cirrhosis and in patients with cirrhosis and clinical findings of neoplastic disease. In 70 well-matched patients (47 with cirrhosis and 23 with cirrhosis and proven HCC) serum total cholesterol, albumin, prothrombin, alkaline phosphatase, AFP, aminotransferases, and AT III were determined. Together with AFP and alkaline phosphatase, patients with HCC had higher values of AT III (88 +/- 7%) and total cholesterol (184 +/- 17 mg/100 ml), as compared with cirrhotic patients (AT III 56 +/- 3.6%; total cholesterol 113 +/- 5 mg/100 ml) (P less than 0.001). No difference was observed between these two groups for albumin, prothrombin, and aminotransferases. In HCC patients, AT III levels were related to the total cholesterol level (R2 = 0.317), whereas in the cirrhotic patients it correlated with the prothrombin level (R2 = 0.274). These data suggest that in HCC patients a greater rate of synthesis of AT III occurs, whereas in cirrhotic patients lower levels of AT III occur due to impaired synthesis or increased catabolism of the protein. The serial determination of AT III in cirrhotic patients as a means of detecting neoplastic transformation is suggested.
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PMID:Hepatocarcinoma in cirrhosis. Is antithrombin III a neoplastic marker? 164 42

Short chain (C2-C6) fatty acids are produced in the colon through bacterial fermentation of mainly dietary fibre. Butyrate (C4) possesses antineoplastic effects on human colon carcinoma cells, and epidemiological studies indicate that high fibre diets may reduce the incidence of colorectal cancer. The role of dietary fibre during colorectal carcinogenesis might therefore be related to its fermentation to butyrate. Faecal concentrations of total short chain fatty acids and concentrations and ratios of the individual C2-C6 fatty acids did not differ between 16 healthy controls, 17 patients with colonic adenomas, and 17 patients with colonic cancer. Comparison of the molar production velocities (mmol/l.hour) of total and individual short chain fatty acids from glucose, ispagula, wheat bran, and albumin in six and 24 hour faecal incubations showed no differences. The ratio of butyrate production to total short chain fatty acid production from fibre, however, was reduced in patients with colonic cancer and adenomas compared with healthy controls (ispagula, six hours: 6.4, 7.6, and 11.5% respectively, p = 0.005 and 24 hour: 9.1, 9.9, and 15.4%, p = 0.002; wheat bran, six hours: 9.9, 10.2, and 14.7% respectively, p = 0.06 and 24 hours: 15.1, 16.8, and 21.0%, p = 0.01). It may be that the low ratios of colonic butyrate formation combined with low fibre diets increase the risk of colonic neoplasia.
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PMID:Colonic fermentation of dietary fibre to short chain fatty acids in patients with adenomatous polyps and colonic cancer. 165 78

An approach involving retroviral-mediated gene therapy for the treatment of neoplastic disease is described. This therapeutic approach is called "virus-directed enzyme/prodrug therapy" (VDEPT). The VDEPT approach exploits the transcriptional differences between normal and neoplastic cells to achieve selective killing of neoplastic cells. We now describe development of the VDEPT approach for the treatment of hepatocellular carcinoma. Replication-defective, amphotrophic retroviruses were constructed containing a chimeric varicella-zoster virus thymidine kinase (VZV TK) gene that is transcriptionally regulated by either the hepatoma-associated alpha-fetoprotein or liver-associated albumin transcriptional regulatory sequences. Subsequent to retroviral infection, expression of VZV TK was limited to either alpha-fetoprotein- or albumin-positive cells, respectively. VZV TK metabolically activated the nontoxic prodrug 6-methoxypurine arabinonucleoside (araM), ultimately leading to the formation of the cytotoxic anabolite adenine arabinonucleoside triphosphate (araATP). Cells that selectively expressed VZV TK became selectively sensitive to araM due to the VZV TK-dependent anabolism of araM to araATP. Hence, these retroviral-delivered chimeric genes generated tissue-specific expression of VZV TK, tissue-specific anabolism of araM to araATP, and tissue-specific cytotoxicity due to araM exposure. By utilizing such retroviral vectors, araM was anabolized to araATP in hepatoma cells, producing a selective cytotoxic effect.
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PMID:Retroviral-mediated gene therapy for the treatment of hepatocellular carcinoma: an innovative approach for cancer therapy. 165 55

Alpha fetoprotein (AFP) is present at high concentrations in fetal fluids, certain neoplasias, and regenerating liver. Its physiological function remains largely unknown. Using a primary monolayer culture system, we investigated the proliferative activity of human (h) cord blood (CB) and highly purified AFP. hAFP, purified from hCB by Cibacron blue and immunoaffinity chromatography was homogeneous on SDS-PAGE and silver stain. Porcine granulosa cells from ovarian small follicles were cultured (25,000/cm2) for 2 days in medium (Ham's F-12:DMEM, 1:1) + 5% fetal calf serum (FCS) to facilitate attachment, followed by 6 days in medium containing: FCS, hCB or h amniotic fluid (1-20%)+/- EGF (10 ng/ml); or 0.25% plasma-derived serum (PDS) containing human low density lipoprotein (LDL, 25 ug/ml), +/- AFP (0.05-5 ug), and +/- EGF and IGF-I (10 ng/ml). In this system, single growth factors do not stimulate proliferation, a characteristic also exhibited by AFP. When combined with EGF, however, AFP dose-dependently increased proliferation to levels equal to that obtained with 10% FCS (2.3-fold increase vs PDS/LDL controls). When combined with EGF+IGF-I, AFP again dose-dependently increased proliferation to levels equal to that obtained with 10% FCS+EGF (6.7-fold increase vs controls). Purified human albumin used in place of AFP was not effective. TGF-a but not PDGF could replace the proliferative activity of EGF. These results suggest that AFP at physiological levels, although not itself mitogenic, can enhance the mitogenic activity of EGF and TGF-a and may function to modulate growth factor-mediated proliferation during development and neoplasia.
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PMID:Human alpha fetoprotein enhances epidermal growth factor proliferative activity upon porcine granulosa cells in monolayer culture. 168 14

We report a case of primary endodermal sinus tumor (EST) of the endometrium in a 42-year-old female. Although numerous extragonadal EST have been reported, primary EST of the endometrium is exceedingly rare. To our knowledge this is the fourth documented case of this nature. The tumor had the typical microscopic features of EST, with papillary, tubular, reticular, and solid growth patterns; occasional Schiller-Duval bodies and many intracellular and extracellular periodic-acid Schiff positive hyaline globules were seen. The neoplastic cells stained positively for alpha-fetoprotein (AFP), alpha-1-antitrypsin (A1AT), cytokeratin, and placental alkaline phosphatase. The globules were positive for AFP, A1AT, albumin, transferrin, and fibronectin. The tumor cells were negative for type IV collagen and the beta subunit of human chorionic gonadotropin (B hcG). Electron microscopic examination showed intracellular and extracellular basement membrane-like material, intracytoplasmic lumina with microvilli, and glycogen. The patient was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by four cycles of adjunct chemotherapy (vinblastine, bleomycin, and cisplatinum) repeated every 3 weeks. The serum AFP level was elevated significantly before the surgery and the tumor response was monitored by serial determination of serum AFP level. There was no evidence of recurrence 24 months after surgery.
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PMID:Primary endodermal sinus tumor of the endometrium. A clinicopathologic, immunocytochemical, and ultrastructural study. 168 8

Hep G2, a human hepatocellular carcinoma, was grown s.c. in nude mice, as well as in tissue culture. This line retains the normal liver parenchymal cell capacity to synthesize human plasma proteins such as albumin, but there is no indication that it harbors the hepatitis B virus. We have detected the oncofetal antigens alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in both Hep G2 xenografts and spent tissue culture media by Ouchterlony double diffusion assays, enzyme-linked immunosorbent assay, and immunohistology. By enzyme-linked immunosorbent assay, the AFP levels were 544.9 ng/ml in the cell culture and 1.6 microgram/g in saline extracts of the xenograft. The CEA levels were 35.2 ng/ml in the cell culture and 5.4 micrograms/g in the xenograft. The biodistribution of a radioiodinated anti-AFP murine monoclonal antibody and an anti-CEA monoclonal antibody were studied separately in nude mice bearing s.c. Hep G2 xenografts in comparison to an isotype-matched irrelevant IgG (Ag8). Anti-CEA antibody showed a preferential localization for Hep G2, but anti-AFP antibody did not. Immunohistochemical studies of the Hep G2 tumor, using biotinylated anti-AFP and anti-CEA, indicate both cytoplasmic and luminal staining of CEA and AFP in the tumor. These results suggest that Hep G2 may be a useful cell line for radioimmunodetection and radioimmunotherapy studies using anti-CEA and possibly anti-AFP monoclonal antibodies.
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PMID:Carcinoembryonic antigen and alpha-fetoprotein expression and monoclonal antibody targeting in a human hepatoma/nude mouse model. 168 35

To determine serum thyroxine-binding globulin (TBG) levels, we used radioimmunoassay, and compared the results obtained with other tests in 231 patients with chronic hepatitis B virus infection to evaluate its clinical implications. All of these patients were hepatitis B surface antigen (HBsAg)-positive. Among them, 38 patients had hepatocellular carcinoma (HCC), 18 had chronic persistent hepatitis, 70 had chronic lobular or active hepatitis (grouped as CAH), 31 had active cirrhosis (AC), 25 had inactive cirrhosis, 20 had decompensated cirrhosis, and 29 were "healthy" HBsAg carriers. Twenty-seven patients with acute hepatitis, 12 with cancer metastasis to the liver, and 81 normal adults served as disease or normal controls. The results showed that serum TBG level increased significantly in patients with CAH, AC, or HCC. Serum TBG did not correlate with albumin or bilirubin level, but correlated with alanine aminotransferase (ALT) positively in patients with CAH (p less than 0.001) and negatively in patients with HCC (p less than 0.01) (slope difference p less than 0.05). Serial determination of serum TBG and ALT also showed parallel changes in 15 patients with CAH, but not in nine patients with HCC. In contrast, the fall and rise of serum TBG levels in patients with HCC coincided with tumor resection and recurrence. The data suggest that serum TBG elevation in patients with hepatitis activity is the result of hepatocellular damage, whereas that in patients with HCC is due to increased synthesis. Whether serum TBG elevation without concomitant rise of ALT could be used as a marker of HCC awaits further study.
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PMID:Thyroxine-binding globulin in patients with chronic hepatitis B virus infection: different implications in hepatitis and hepatocellular carcinoma. 168 51

The phenotypic response of rat liver to a carcinogenic protocol involving initiation/selection and promotion with and without phenobarbital (PB) feeding was studied in pubertal and adult male rats. Considering the early presence of preneoplastic nodular areas, it appeared that pubertal rats, initiated at 6-7 weeks, presented a higher susceptibility to the protocol than adult rats initiated at 9-10 weeks. Altered liver phenotype was characterized by: (1) gamma-glutamyl-transpeptidase (GGT) and glutathione S-transferase (GST) activities; (2) the expression of two forms of cytochrome P-450; de novo PB-inducible P-450 II B 1,2 and P-450 II C 7 normally expressed in 45-day-old rats and PB-inducible, and (3) the expression of albumin and alpha-fetoprotein cDNAs. In the absence of PB, the susceptibility of pubertal rat liver to hepatocarcinogenesis was related to a special metabolic phenotype enriched in GGT and GST activities by comparison with the quasi-normal expression of both P-450s. Adult rat liver presented a less altered pattern closer to that of noninitiated rat liver. During PB promotion, the loss of PB inducibility of P-450 II C 7 in pubertal rat liver suggested that the hormonal status of the animals could interact with initiation to modulate specific gene expression. The late phase of PB promotion revealed the loss of highly differentiated functions (P-450s, albumin), whereas enzymatic markers associated with preneoplastic foci showed a persistent high expression.
Tumour Biol 1990
PMID:Effect of rat developmental stage at initiation on the expression of biochemical markers during liver tumor promotion. 170 Aug 61


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