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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to characterize an in vivo model of human pancreatic cancer suitable for chemotherapy and immunotherapy studies. In this study we report a 2-year experience in growing the MIA PaCa-2 (CRL 1420) human pancreatic cancer cell line in 92 adult (8 weeks old) and 256 young (3-6 weeks old) nude mice. Ten million tumor cells were transplanted into orthotopic (duodenal lobe of the pancreas) and/or heterotopic positions (hepatic and subcutaneous) and data on operative mortality, effect of total body irradiation (TBI), tumor growth kinetics, and survival are presented comparing the two age groups. Operative mortality was due to anesthetic intolerance which was higher in the young mouse population (13.4% versus 5.7%). Adult mice withstood TBI (500 rad) without mortality but young mice were highly sensitive to radiation damage and their maximum tolerated dose (LD50) was 425-450 rad. Subcutaneous tumors grew significantly more often in young compared to adult animals (97.9% versus 69%) and this finding was not affected by TBI (96.9% versus 75%), though tumors did appear more quickly after TBI. An average of 14.7 +/- 2.8 days was required for the subcutaneous tumors to become macroscopically apparent in the adult population compared with 3.1 +/- 0.8 days in the young mice. The largest subcutaneous tumor diameter 28 days following tumor implant averaged 9.3 +/- 0.6 mm in the young animals and 5.5 +/- 1.7 mm in the adult population (P less than 0.01). Treatment of young mice with human recombinant interleukin-2 (IL-2) (10,000 Units twice a day for 28 days) produced a 27% decrease in tumor growth. This effect was abolished by prior irradiation of the young mice with 375 rad TBI. Pancreatic tumor growth also occurred more consistently in young than in adult animals (91.2% versus 64.3%) and irradiation did not affect pancreatic tumor take in either group. Occasionally intrapancreatic tumor growth was associated with liver metastases in animals that were killed after 28 days (17.8% in young and 22.2% in adult animals). However, when more than 45 days elapsed before sacrificing the animals, the incidence of hepatic metastases increased to 57.1%. This was slightly less than the incidence of hepatic lesions found after direct injection of cancer cells into the liver by portal vein injection (71.4%). Direct extension of tumor into surrounding tissues was common with frequent involvement of the duodenum (83.7%), kidneys (30.6%), and other intraabdominal organs (43.9%). Survival was significantly longer in adult compared to young mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The nude mouse as a model for the study of human pancreatic cancer. 258 1

We studied the effects on platelet function of cells isolated from freshly dissociated human tumor tissues (11 breast carcinomas, 9 colon carcinomas and 1 lymph node metastasis from melanoma) obtained at surgery as compared with cultured human tumor cells: namely, human melanoma 1402 cell line derived from a primary tumor and two lines derived from lymph node metastases (ME 7110/2 and Me 665/1) as well as a human hepatoma cell line (Hep G2). The three melanoma cell lines activated platelets by producing ADP, as evidenced by the inhibitory effect of apyrase and by the direct measurement of the agonist in the supernatants of tumor cell suspensions; this production was much greater by the cells derived from metastases than by the cells derived from the primary tumor. On the other hand, aggregation induced by Hep G2 hepatoma cells was unaffected by apyrase and was inhibited by hirudin or concanavalin A, suggesting that the cells aggregate platelets by producing thrombin, probably through tissue factor activity of the cells themselves. Cells isolated from 16 of the 21 human tumor tissues possessed a potent platelet-aggregating effect, which was not inhibited by apyrase, hirudin or concanavalin A, but was virtually abolished by the cysteine protease inhibitors iodoacetic acid or p-hydroxymercuri-phenylsulfonate. Collectively, our data demonstrate that cells isolated from freshly dissociated tumor tissues activate platelets through tumor-associated cysteine proteinases rather than by the ADP- or thrombin-dependent mechanisms characteristic of cultured human tumor cell lines.
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PMID:Mechanisms of platelet activation by cultured human cancer cells and cells freshly isolated from tumor tissues. 276 27

Human 253J urinary carcinoma cells and the F1 (low-metastatic) and F10 (high-metastatic) variants of the B16 murine melanoma cell line have been shown to activate heparinized human platelets by an adenosine diphosphate (ADP)-dependent mechanism based on inhibition by creatine phosphate/creatine phosphokinase and the identification of aggregating concentrations (1 to 2 mumol/L) of ADP in cell-free culture supernatants by high-performance liquid chromatography. Aggregation did not occur in citrated samples, and hirudin was without effect. Studies were carried out to determine whether extracellular ADP arose from nonspecific cell damage during cell isolation and manipulation or was a specific process under control of the tumor cells themselves. Tumor cell damage during harvesting was shown not to be a factor because the amounts of ADP produced by the three cell lines (a) were inversely related to the appearance of lactic dehydrogenase in the culture supernatants and (b) were similar when measured in confluent monolayers, either in tumor cells after detachment and resuspension or after crossover studies involving culture in, alternatively, Hanks' balanced salt solution and minimal essential medium. Metabolic control of ADP production was indicated by the fact that (a) it was not dependent on cell number, which suggests feedback inhibition; (b) it was reduced 60% when tumor cells were treated with p-chloromercuribenzene sulfonate; and (c) it was completely abolished in those treated with iodoacetic acid, which might be expected to increase nonspecific leakage. These studies indicate that ADP production by these three lines does not arise due to leakage induced by nonspecific membrane damage during cell harvesting and manipulation but is a discrete process under metabolic control of the tumor cells. Moreover, in B16 murine melanoma cells the ability to produce ADP and to support platelet aggregation appears to be unrelated to metastatic potential insofar as identical results were obtained with the F1 and F10 variants.
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PMID:Platelets in tumor metastasis: generation of adenosine diphosphate by tumor cells is specific but unrelated to metastatic potential. 283 29

The present study was undertaken to examine the effects of iodoacetic acid, a non-phorbol tumor promoter, on metabolic cooperation between mutant human fibroblasts as measured by [14C]citrulline incorporation. Other thiol-reactive polyphenolic compounds such as hydroquinone and 2-hydroxyestrone were also examined. 12-O-Tetradecanoyl phorbol-13-acetate (TPA), a potent skin tumor promoter, inhibited the cell-cell communication by more than 60% at 20 ng/ml. However, iodoacetic acid, hydroquinone, and 2-hydroxyestrone, had no effect on the process even at cytotoxic concentrations. Induction of intercellular contact (agglutination) among lymphocytes during the course of phytohemagglutinin (PHA)-induced blastogenesis was monitored turbidometrically at 620 nm. Hydroquinone and 2-hydroxyestrone suppressed the PHA-induced lymphocyte agglutination at 1-2 microM in vitro concentrations while iodoacetic acid was devoid of any effects at concentrations up to 100 microM. Hydroquinone and 2-hydroxyestrone concomitantly suppressed PHA-induced lymphocyte blastogenesis at 1-2 microM in vitro concentrations while the suppression by iodoacetic acid was significant at 10 microM. All 3 compounds failed to disrupt microtubule assembly, a sulfhydryl-dependent process, in a rat brain crude extract. However, p-benzoquinone, an oxidation product of hydroquinone, did inhibit the process at 1 mM. In summary, these studies suggest that, unlike TPA, thiol-reactive non-phorbol tumor promoters and polyphenolic compounds do not inhibit cell-cell communication between mutant human fibroblasts. Although the compounds demonstrate diverse molecular mechanisms of action, they all inhibit in vitro immune functions suggesting that immunosuppression may play a role in tumor promotion.
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PMID:Iodoacetic acid and related sulfhydryl reagents fail to inhibit cell-cell communication: mechanisms of immunotoxicity in vitro. 310 20

We have investigated concomitantly the pro-aggregating and pro-coagulant activities of 11 breast and 2 colon human carcinomas. Tumor tissues, obtained at surgery, were immediately processed to prepare tumor-cell suspensions for the study of aggregating activity and tissue extracts for the study of procoagulant capacity. Nine carcinomas (8 breast and 1 colon) possessed a high, dose-dependent platelet-aggregating activity, which was present in the cell-free supernatant and was inhibited by HgCl2 and iodoacetic acid, specific cysteine proteinase inhibitors, while apyrase and hirudin had no significant effect; in contrast, the other tumors did not aggregate platelets. All the tumor extracts tested from 12 carcinomas (11 breast and 1 colon) were able to activate blood coagulation in both the presence and the absence of F VII. The activity was inhibited by HgCl2 and iodoacetamide, while Con A was less effective. Therefore, these tumors do not aggregate platelets through the production of ADP or thrombin, nor promote blood coagulation through the production and release of tissue factor; a tumor-associated cysteine proteinase plays a major role in both pro-aggregating and pro-coagulant activities.
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PMID:Human breast and colon carcinomas express cysteine proteinase activities with pro-aggregating and pro-coagulant properties. 317 28

We have previously shown that hamster H2T pancreatic ductal cancer has a receptor for vasoactive intestinal peptide (VIP) which is not present on a cell line of human pancreatic ductal cancer (MIA). The purpose of this study was to examine the effect of chronic administration of VIP on the growth of both H2T hamster pancreatic carcinoma and MIA human pancreatic carcinoma in vivo. The growth of H2T was studied in hamsters; a control group of six hamsters received 0.1% bovine serum albumin (BSA) in saline, and two treatment groups of six hamsters each received VIP (1 and 10 nmol/kg), all administered three times a day by i.p. injection for 35 days. Both doses of VIP inhibited the growth of H2T tumor (tumor area, weight, DNA, RNA, and protein content). The growth of MIA was studied in athymic Balb/c mice, one group of 10 received 0.1% BSA and the other 10 received VIP (1 nmol/kg), both three times a day by i.p. injection for 3 months. There was no difference in tumor growth rate between the two groups. Treatment with VIP did not have any effect on body weight or size of the normal pancreas in either the hamsters or the mice. We conclude that the differential response of hamster and human pancreatic cancer to VIP treatment may be due to the presence or absence of VIP receptors.
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PMID:Vasoactive intestinal peptide inhibits the growth of hamster pancreatic cancer but not human pancreatic cancer in vivo. 317 7

Malignant transformation of mouse cells by a variety of agents or treatment with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate or platelet-derived growth factor results in increased synthesis and secretion of a 39,000-dalton protein termed major excreted protein (MEP). We report here that secreted MEP is an acid-activable protease. The secreted precursor form of the protease is auto-activated at low pH and is able to digest a variety of proteins, including the extracellular matrix proteins fibronectin, collagen, and laminin. MEP protease activity has pH optimum of 3.3-3.6 and is temperature- and concentration-dependent. The activity is inhibited by sulfhydryl protease inhibitors such as leupeptin and iodoacetic acid and not by metallo-, seryl-, or carboxyprotease inhibitors. The MEP-derived protease has characteristics distinct from the cathepsins previously reported and thus may be a new acid-protease of mouse cells.
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PMID:The major excreted protein of transformed fibroblasts is an activable acid-protease. 351 Oct 49

The biodistribution, radioimmunoimaging, and high pressure liquid chromatography activity profiles of 99mTc(Sn) and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments were compared. Nude mice, bearing specific (colon carcinoma, LS174T) and nonspecific (pancreatic carcinoma, MIA) xenografts were given injections of the respective radiolabeled antibody fragments and also of irrelevant 125I-labeled antibody fragments (MOPC-21). The animals were imaged at 24 h after being given injections, they were sacrificed, and biodistribution studies were performed. Results of the study showed high kidney uptake [48.6% injected dose (ID)/g +/- 8.1% (SD)] and low tumor uptake (1.5% ID/g +/- 0.6%) for 99mTc(Sn)-labeled fragments and higher uptake (4.4% ID/g +/- 0.6%) for 131I-labeled fragments, resulting in a higher localization index for the radioiodinated monoclonal antibody fragments. Imaging results showed good tumor visualization at 24 h after injection for the 131I-labeled fragments and poor tumor visualization with predominant kidney uptake for 99mTc(Sn)-labeled fragments. After radiolabeling, high pressure liquid chromatography analysis indicated that 131I was primarily associated with F(ab')2 fragments, whereas 99mTc was mostly associated with Fab' fragments.
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PMID:Pharmacokinetics of 99mTc(Sn)- and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments in nude mice. 381 65

A monoclonal antibody (MoAb, SK-930) of the IgG2a subclass to human pancreatic carcinoma cells (MIA-PaCa 2) was obtained by hybridization of spleen cells from immunized Balb/c mice with murine myeloma cells. SK-930 was investigated for reacting in indirect immunofluorescence on FACS against a panel comprising 12 types of different origin. SK-930 reacted with seven out of 11 tumor cells and with one PBL. Immunoperoxidase techniques (ABC method) showed that SK-930 antigen was present on pancreatic adenocarcinoma cells, but could not be detected on normal pancreatic tissue. Immunoprecipitation experiments and SDS-PAGE analysis revealed that SK-930 recognized 134K dalton peptide on tumor cells. These results suggest that SK-930 reacts with a novel pancreatic cancer-associated antigen.
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PMID:[Monoclonal antibody to human pancreatic carcinoma cells]. 382 May 99

The effects of 1 mM sodium butyrate or 2% dimethylsulfoxide (DMSO) on three human pancreatic tumor cell lines were examined. The cell lines tested were MIA PaCa-2, PANC-1 and CAPAN-1. Both butyrate and DMSO inhibited the ability of all three lines to form colonies in soft agar. These results suggest that the use of these agents provides a model system for the study of the molecular changes involved in human pancreatic cancer. In butyrate all the cell lines showed a marked increase in cellular levels of alkaline phosphatase, while growth in DMSO led to a reduction in most cases. DMSO caused a rapid reduction in the attachment of all three cell lines to collagen substrates, while butyrate had no effect. These results illustrate the fact that although both butyrate and DMSO appear to greatly reduce the parameters correlated with tumorigenicity of human pancreatic cancer cells, the mechanisms involved may be very different.
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PMID:Effects of sodium butyrate and dimethylsulfoxide on human pancreatic tumor cell lines. 620 Mar 29


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