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Biomedical subjects

P Pour

Publications and source records attributed to P Pour.

At least 19 recordsLinked to original sources
PubMed1991

Immunotherapy with monoclonal antibody (Mab) in pancreatic adenocarcinoma.

Conventional therapy of pancreatic exocrine cancer is disappointing. The poor prognosis of the disease challenges development of novel therapeutic strategies. We report the results of clinical trials of the monoclonal antibody (Mab) 17-1A in patients with histologically verified unresectable pancreatic exocrine cancer. No antitumor response was seen in 18 patients treated with Mab 17-1A (500 mg) admixed with 10(9) autologous mononuclear cells, and 81% of the patients developed antimouse antibody response. Combination of recombinant gamma interferon and Mab 17-1A mixed with autologous mononuclear white cells resulted in complete response of 4-mo duration in 1 out of 25 evaluable patients and unusually stable disease from 4 to 48+ mo in another 6 patients. High intermittent doses of infused Mab 17-1A did not show any objective antitumor response and caused serious anaphylaxis in two of the patients in the trial. Because examination of six pancreatic adenocarcinoma cell lines with different doses of Mab 17-1A and IL-2 failed to augment lytic activity of mononuclear effector cells against all cancer cell lines tested, there seemed to be no rationale for pursuing clinical studies with IL-2 and Mab 17-1A in either the murine or chimeric form. Attractive therapeutic approaches include active immunotherapy with immunization using idiotypic antibodies or targeted toxicity with the use of radioimmunoconjugates, particularly 125I-labeled chimeric Mab 17-1A.

Adenocarcinoma↗
PubMed1990

Pancreatic ductal adenocarcinomas induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine contain a c-Ki-ras oncogene with a point-mutated codon 12.

We have used the polymerase chain reaction and dideoxynucleotide sequencing to amplify and sequence exons 1 and 2 of the c-Ki-ras proto-oncogene from the normal Syrian golden hamster. Similar methods were employed to screen for the presence of point mutations in the c-Ki-ras oncogene in primary hamster pancreatic ductal adenocarcinomas (PDC) induced by N-nitrosobis(2-oxopropyl)amine (BOP). A GGT to GAT point mutation was detected in codon 12 of the c-Ki-ras gene in 10 primary hamster PDCs. This same point mutation was present in two nonclonal cell lines, PC-1 and PC-1-0, established from tumors that were produced in hamsters by subcutaneously implanting a preparation of minced BOP-induced PDC. Two clonal cell lines, Cl-3 and Cl-7, were cloned from the PC-1 cell line, and these cell lines also carried the GAT point mutation at codon 12. This point mutation was the same as that detected in greater than 75% of adenocarcinomas from the human exocrine pancreas. Thus, our findings provide further validation for the use of the BOP-induced hamster PDC model as a relevant experimental model for human pancreas cancer: not only did the hamster pancreatic ductal adenocarcinomas closely resemble their human counterpart in histopathological morphology and sequential development, but they also contained the same point mutation in codon 12 of the c-Ki-ras oncogene, as has been reported for human pancreatic adenocarcinomas.

Amino Acid Sequence↗
PubMed1989

Proliferative changes in the prostate.

The prostate of the rat has several lobes which have variable responsiveness to estrogens and testosterone. Testosterone is a major stimulant of cell proliferation in the prostate. Chemical carcinogenesis models in the rat prostate have taken advantage of administering the carcinogen during the peak proliferative period following testosterone administration with subsequent testosterone administered to continue the proliferative stimulus. Invasive adenocarcinomas of the prostate have been induced utilizing such methods.

Aging↗
PubMed1986

Effect of pure zinc deficiency on glucose tolerance and insulin and glucagon levels.

The effect of zinc deficiency on glucose tolerance was investigated using intragastric force feeding to obviate decreased food intake and altered eating patterns. Three groups of weanling male Sprague-Dawley rats were fed a purified zinc-deficient diet: zinc-deficient, ad libitum-fed animals (ZDA) were offered powdered zinc-deficient diet; zinc-replete, force-fed controls (ZRF) were tube fed a diet blended with water containing 25 ppm of zinc; zinc-deficient, force-fed animals (ZDF) were similarly tube fed the zinc-deficient diet. The ZRF and ZDF groups received a diet of identical amount based on the intake of ad libitum-fed, zinc-replete rats. After 8 days of feeding, the ZDF group had impaired glucose tolerance curves, yet blood insulin and glucagon levels were normal. The ZDA group had normal glucose tolerance with low insulin levels compared with the ZRF group. The islet cell morphology among the three dietary groups were similar. These results suggest that the glucose intolerance observed in ZDF rats is not due to altered blood insulin and glucagon levels but rather to peripheral resistance to insulin action.

Animals↗
PubMed1985

Ductal metaplasia of human exocrine pancreas and its association with carcinoma.

Monoclonal antibodies to cell surface markers of human exocrine pancreas were used to establish the cytotypic expression of cells forming "tubular complexes" in pancreases from six adults without carcinoma and in the nontumorous pancreatic parenchyma of 16 pancreases with carcinoma. These cells manifested duct cell determinants. In general, the presence of cells with duct cell surface markers within the acini corresponded to the normal distribution of centroacinar cells in the 30 control human pancreases (from cadaveric donors); however, foci of abnormal acini were seen in these pancreases independent of or intermingled with the "tubular complexes." The acini in these abnormal areas were formed by a core of cells and cell processes that expressed duct cell determinants. They were partially surrounded by acinar cells and showed slight or no lumenal dilation. While the causative agent(s), the cell(s) of origin, and the regression and/or progression of these lesions are yet to be determined, the replacement of acini by the spectrum of lesions composed of cells with duct cell surface marker is suggested to constitute ductal metaplasia.

Animals↗
PubMed1985

Test of catechol, tannic acid, Bidens pilosa, croton oil, and phorbol for cocarcinogenesis of esophageal tumors induced in rats by methyl-n-amylnitrosamine.

Catechol (CAS: 120-80-9), given in drinking water to rats, was the most effective of 5 phenols in enhancing [3H]thymidine incorporation [( 3H]dThd-l) into esophageal DNA. To test for esophageal cocarcinogenesis, groups of 30 male MRC-Wistar rats received 3 weekly ip injections of 25 mg methyl-n-amylnitrosamine [(MNAN) CAS: 13256-07-0]/kg. From the time of the first MNAN injection, each group also received catechol, tannic acid (CAS: 1401-55-4), dried leaves of Bidens pilosa L., or croton oil (CAS: 8001-28-3) (respectively, 2, 10, 50, and 2 g/kg semipurified diet), or were given 20 ip injections of 6 mg phorbol (CAS: 17673-25-5)/rat. The rats were killed after 20-45, 46-52, or 53-72 weeks (subgroups A, B, and C). In the group given MNAN alone, most esophageal papillomas developed during the first 45 weeks. Both catechol and B. pilosa significantly increased the esophageal papilloma multiplicity (No. of papillomas/rat) induced by MNAN, with a maximum tumor yield of 2.2 times that in the corresponding subgroup treated with MNAN alone. Papilloma multiplicity increased from subgroup A to subgroup C in the MNAN plus B. pilosa group but not in the MNAN plus catechol group. No tumors were induced by the test cocarcinogens given without MNAN. We concluded that a) an increased esophageal [3H]dThd-I indicates potential cocarcinogenicity and b) catechol and B. pilosa were weak esophageal cocarcinogens. These results support the view that catechol in cigarette smoke and B. pilosa as eaten in South Africa contribute to the etiology of human esophageal cancer.

Animals↗
PubMed1979

Comparative studies of neoplastic response to a single dose of nitroso compounds. 6. The effect of diethylnitrosamine in Syrian golden hamsters.

The effect of a single subcutaneous injection of different DEN doses was examined in adult Syrian hamsters observed for life. The minimal effective dose (threshold dose) for neoplastic response, reflected by induction of papillary polyps in the larynx and/or trachea, was 1.03 mg DEN/kg body weight. No tumors were found which could be related to treatment in other segments of the respiratory epithelium nor in other tissues.

Animals↗
PubMed1979

Ductular origin of pancreatic cancer and its multiplicity in man comparable to experimentally induced tumors. A preliminary study.

The histologic features of 3 randomly selected pancreatic cancer cases are compared with those found in Syrian hamsters after treatment with N-nitrosobis(2-oxopropyl)amine (BOP). The 3 human cases all exhibited hyperplastic, preneoplastic and malignant changes which were markedly multicentric, and which arose predominantly from ductules, as well as from small ducts. The findings were comparable to those in the hamster mode. Proliferation and malignant alterations of the intrainsular ductules were commonly seen in both human and experimental tumors. The data is consistent with the concept that cells of the small ducts and especially of the ductules represent a potential source of human, as well as experimental, tumors. The small number of human cases studied does not allow generalization, but the marked resemblances in all 3 randomly selected pancreatic cancer cases were remarkable.

Adenocarcinoma↗
PubMed1979

The morphologic and biologic patterns of chemically induced pancreatic adenocarcinoma in Syrian golden hamsters after homologous transplantation.

A pancreatic adenocarcinoma induced by N-nitrosobis(2-oxopropyl)amine in the Syrian golden hamster was successfully transplanted to a homologous host by subcutaneous inoculation through 10 successive passages. The rate of 'tumor take' increased progressively with each generation from 60% to 100%, and the latency period after inoculation was reduced simultaneously from 6 weeks to 1 week in the second and following passages. The tumors grew rapidly, ulcerated the overlying skin, and metastasized to the regional lymph nodes and lungs. The animals usually died with multiple lung metastases between the 5th and 20th weeks. All transplanted tumors and their metastases retained the pattern of the original, well-differentiated adenocarcinomas.

Adenocarcinoma↗
PubMed1979

Spontaneous tumors and common diseases in three types of hamsters.

Hamsters of three types designated as inbred cream (Epp/e/e), linebred white (EPP/cdcd/RB/A), and linebred albino (EPP/cdcde/e) were thoroughly examined histopathologically for spontaneous diseases. All hamsters were maintained simultaneously for life under identical standard laboratory conditions. Marked differences were found in longevity of the animals and in incidence, sites, patterns, and types of spontaneous diseases. In cream hamsters (CH), survival time was shorter than in white hamsters (WH) and albino hamsters (AH). More tumors and malignant lesions unrelated to survival were found in AH compared to CH and WH; also, the multiplicity of neoplasms were more pronounced in AH. The predominating tumor types differed in each line: Pancreatic islet cell neoplasms were most common in CH, adrenal gland tumors predominated in WH, and thyroid gland tumors in AH. Also, the relative incidence of spontaneous tumors varied among the lines. Some tumors seemed strain-specific and were not seen in other lines; malignant melanomas, for example, occurred only in CH and WH. Certain neoplasms, e.g., those of the thyroid and adrenal glands, were found more often in one sex than the other. The three hamster groups differed also in nonneoplastic diseases. Detailed histopathologic findings are presented and compared with data on the Syrian golden hamster, the ancestral line of these three groups.

Amyloidosis↗
PubMed1979

Carcinogenic effect of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, a postulated proximate pancreatic carcinogen in Syrian hamsters.

N-Nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) proved to be a potent carcinogen in Syrian golden hamsters. The compound is an in vivo metabolite of N-nitrosobis(2-hydroxypropyl)amine, N-nitrosobis(2-oxopropyl)amine (BOP), and N-nitroso-2,6-dimethylmorpholine and a postulated proximate pancreatic carcinogen in hamsters. As with BOP, HPOP induced a higher incidence of pancreatic ductular adenocarcinomas than did N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine, and these neoplasms showed a great tendency for invasion and metastasis. Also, HPOP induced tumors of the forestomach, liver, gallbladder, kidneys, and vagina (as did BOP). However, HPOP [unlike BOP, but like N-nitrosobis(2-hydroxypropyl)amine and N-nitroso-2,6-dimethylmorpholine] led to tumor development in the nasal cavity, larynx, trachea, intestine, Harderian gland, lips, and flank organ. The possible mechanisms of HPOP carcinogenicity are discussed.

Animals↗
PubMed1979

Metabolism of three radiolabeled pancreatic carcinogenic nitrosamines in hamsters and rats.

The in vivo metabolism and disposition of three radiolabeled N-nitrosamines which are carcinogenic for the pancreas of the hamster but not the rat have been examined. N-[1-14C]Nitrosobis(2-oxopropyl)amine (BOP), N-[1-14C]nitrosobis(2-hydroxypropyl)amine (BHP), and their suggested proximate pancreatic carcinogenic metabolite N-[1-14C]nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) were metabolized and exhaled as 14CO2 to various extents somewhat proportional to their carcinogenic potency. More than 50% of the dose of BOP and HPOP was exhaled as 14CO2, whereas 26% of BHP was excreted this way, and 40% of BHP was excreted unchanged in the urine. Administered BOP was excreted to a small extent in the urine of both species as HPOP and BHP. No other nitrosamine metabolites were detected in urine. HPOP and BHP were detected in the pancreatic juice and bile of both species after administration of BOP and BHP. The results suggest that pancreatic ductular carcinogenesis in the hamster as a result of exposure to BOP is not due to secretion of carcinogenic metabolities in the pancreatic juice or reflux of bile containing nitrosamine metabolites into the ducts. Carcinogen metabolic activation appears to be by an oxidative pathway.

Animals↗
PubMed1979

Carcinogenicity of N-nitrosobis(2-hydroxypropyl)amine and N-nitrosobis(2-oxopropyl)amine in MRC rats.

Weekly sc injections of equitoxic doses of N-nitrosobis(2-hydroxypropyl)amine (BHP) and N-nitrosobis(2-oxopropyl)amine (BOP) to Wister-derived MRC rats induced tumors. The incidence, latency, multiplicity, morphologic type, and distribution of these tumors varied according to the compound given. The esophagus was the main target organ for BHP (100%), followed by the respiratory tract (87%), pharynx (80%), colon and liver (each 73%), kidneys (20%), thyroid gland (20%), and urinary bladder and urethra (each 7%). BOP was ineffective in the esophagus and pharynx but induced a higher incidence of tumors in the kidneys (27%), thyroid gland (60%), urinary bladder (33%), and urethra (73%) and fewer neoplasms in the respiratory tract (20%), colon (67%), and liver (53%). In addition, BOP caused a few, apparently primary, prostate squamous cell carcinomas. The results are compared with results of BHP treatment in Sprague-Dawley rats and with results of BHP and BOP treatment in Syrian golden hamsters.

Animals↗
PubMed1978

Induction of thyroid follicular adenomas and carcinomas by N-nitrosobis(2-oxopropyl)amine.

Subcutaneous injection of N-nitrosobis(2-oxypropyl)amine (BOP) induced thyroid follicular adenomas and carcinomas in MRC rats. The tumor yield was 50% following a single dose and 60% after weekly treatment for life. In males the tumor incidence was slightly higher and the latency period shorter, while in females, the tumors were larger. Sites of origin, size, multiplicity and morphologic patterns of tumors were analyzed in relation to dose and sex. The possible mechanisms involved in tumorigenesis are discussed.

Adenocarcinoma↗