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Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tract and colon.

To elicit a tumor immune response, tumor antigens represented by major histocompatibility (MHC) class I complex on the cell surface is indispensable. Some investigators demonstrated that many cancer cells reduce expression of beta2-microglobulin, a transporter of antigen presenting (TAP) or low molecular protein (LMP), due to the deletion mutant or point mutation. We investigated gene expression levels of antigen presenting machineries in 13 cell lines of the pancreas, biliary tract and colon cancer by using real-time quantitative PCR. We also evaluated the correlation between expression of MHC class I and that of antigen-processing molecules in these gastrointestinal cancer cell lines. Flow cytometric analysis showed that expression of MHC class I for the pancreatic cancer cell lines was generally lower than that for the biliary tract or colon cancer cell lines. It was further found that the colon cancer cell lines HCT-15/DLD-1 showed no MHC class I expression and lack of protein expression for beta2-microglobulin. Transfection of the wild-type beta2-microglobulin gene restored MHC class I antigen expression on the cell surface for DLD-1. Quantitative real-time PCR demonstrated lower expression for TAP1, TAP2, LMP2 and LMP7 gene in five cancer cell lines. Partial correlation analysis demonstrated that LMP2 was the only antigen presenting machinery which was significantly associated with MHC class I expression. Our results suggest that beta2-microglobulin and LMP2 are important for the expression of MHC class I in 13 gastrointestinal cancer cell lines, while the combined but complex expression of antigen presenting mechanisms was related to MHC class I expression level on the surface of cancer cells.

ATP-Binding Cassette Transporters↗

The Harvey ras 1 gene is activated in papillomavirus-associated carcinomas of the upper alimentary canal in cattle.

The possible activation of ras sequences in papillomavirus-associated carcinomas of the upper alimentary canal of cattle was investigated by restriction enzyme and hybridization analysis, and by DNA-mediated transformation of NIH3T3 cells. In three cancers, a squamous cell carcinoma of the palate, a squamous cell carcinoma of the rumen, and a transitional cell carcinoma of the urinary bladder, repetitive DNA sequences present in the Ha-ras 1 locus showed anomalous restriction patterns, indicating rearrangements and, in the case of the palate cancer, amplification. Genomic DNA from several cancers was capable of inducing focus formation in the NIH3T3 transformation test. DNA from primary, secondary and tertiary transformants was analysed by hybridization to bovine ras probes and by nucleotide sequencing of polymerase chain reaction products. Bovine Ha-ras 1 sequences were found in all transformants, but no nucleotide differences were detected in exon 1 or exon 2 between normal, cancer and transformed cells. It is concluded that the Ha-ras 1 gene is activated in alimentary canal carcinomas, although the activating mutation has not yet been mapped. The possible relationship between papillomavirus infection and activation of the ras gene is considered.

Amino Acid Sequence↗

Gastrointestinal cancer in the elderly.

The older patient population, aged 70 years and greater, represent a large proportion of patients diagnosed with gastrointestinal malignancies. Surgery remains the mainstay of treatment for these malignancy sites. Chronologic age alone should not determine the extent of surgical or medical management. The authors describe those aspects of gastrointestinal cancer detection and therapy that are unique to the aging population.

Age Factors↗

[Ultrasonographic images of liver neoplasms--comparison with histopathological findings].

Ultrasound pictures taken in 100 patients with histologically confirmed primary of metastatic neoplasms of the liver were analysed retrospectively. The most frequent were hyperechogenic foci (43%). Hypoechogenic foci were found in 33% of the patients whereas mixed changes in the liver scans (hyper- and hypoechogenic) in 22%. Thirty seven per cent of the hyperechogenic foci were attributable to metastatic process. Hypoechogenic disorders were most frequently due to the primary cancer of the liver (20%). Mixed lesions were mainly produced by the cancer of large intestine and liver (41% and 27%, respectively). Metastases into the liver produced all three types of ultrasound pictures. The obtained results confirm the opinion that ultrasound picture of metastatic liver tumours is not suitable for the diagnosis of the type and origin of the neoplasm.

Adult↗

[Diagnostic usefulness of Ca 19-9 antigen in cancer of the pancreas and neoplasms of the pancreato-biliary intersection].

Antigen CA 19-9 was measured in the serum of a group of 16 patients with pancreatic cancer, in 19 patients with non-pancreatic gastrointestinal malignancies, and in 19 others with benign pancreatobiliary disease. The test showed a high sensitivity with a low specificity and a positive predictive value for diagnosis of pancreatic cancer when confronted with a group of controls that included both benign and malignant gastrointestinal disease. The low specificity was due to high CA 19-9 values in other gastrointestinal cancers, especially in carcinoma of the ampulla and the biliary tract. When the latter were added to the group of patients with pancreatic cancer, and the diagnostic accuracy of the test was re-evaluated, sensitivity, specificity and both positive and negative predictive values increased. Values of CA 19-9 over 100 U/ml are highly predictive of malignancy in patients with pancreato-biliary disease.

Adult↗

Temporary elevation of CA 125 after abdominal surgical treatment for benign disease and cancer.

Analyses of preoperative and one to seven day postoperative determinations of CA 19-9, carcinoembryonic antigen (CEA) and CA 125 levels in 873 patients indicate that postoperative CA 19-9 and CEA serum levels were within the expected technical variance of the preoperative assay values in patients who were considered to have negative findings (below the reference value) from these tests preoperatively. If the test results were preoperatively positive in patients with cancer, they decreased postoperatively to or below normal reference values, unless the operation was palliative and significant tumor removal was not possible. For patients with a preoperative positive CA 125 level (greater than 35 units per mililiter), the postoperative serum levels were comparable with the CEA and CA 19-9 result. However, when the preoperative CA 125 level was within normal limits, 62 per cent of the patients had postoperative elevations, often to levels of less than 35 units per milliliter. Sequential postoperative determinations of CA 125 in 21 patients revealed that maximum levels of CA 125 were seen about two to four hours after the operation and that elevations persisted for as long as three months. Inferential evidence suggests that postoperative increases in serum CA 125 occur from incision and healing of the peritoneum and omentum by de novo synthesis of this antigen rather than shedding from tissues. Patients with CA 125 negative results and with carcinoma of the ovary having postoperative increases of this antigen within two months of the operation may pose a difficult problem in interpretations, and such patients require further investigation.

Antigens, Tumor-Associated, Carbohydrate↗

[A case of malignant extrameningeal meningioma of the spinal canal with multiple metastases in a 17-year-old patient. Clinical and morphologic studies].

A clinical description and pathological findings are reported in a case of extrameningeal, angiogenic malignant meningioma of the vertebral canal (Th7-Th11) in a patient aged 17 years. Clinical picture was that of transverse myelitis at the Th9 level, with spastic paraparesis, funicular loss of all sensory functions and sphincter disturbances. The authors suppose that the used combined treatment (chemotherapy and radiotherapy, surgery) improved greatly the health state inhibiting the spread of metastases and prolonged survival to 3 years. Autopsy demonstrated recurrence of he tumour in the vertebral canal and numerous metastases to the brain, lungs, liver, bones and pancreas.

Adolescent↗

Fat soluble vitamins and cancer localization associated to an abnormal ketone derivative of D3 vitamin: carcinomedin.

Many investigations suggested relations between fat soluble vitamin levels in blood and incidence of cancer. These studies are concerning both therapeutical efficiency of vitamins intake, seric levels and cancer risk, and the supposed correlation between blood fat soluble vitamin levels and the cancer localization. The purpose of the present study was to investigate whether the alterations of fat soluble vitamin levels (A-vitamin, beta-carotene and alpha-tocopherol) were correlated not only to carcinogenic processes but also to the localizations of their developments. In a former article, we have found that an abnormal ketone derivative of D3 vitamin (1-keto-24-methyl-25-hydroxycholecalciferol) or carcinomedin was present in the serum of all cancer patients and absent in that of healthy control subjects. Serum levels of the four above substances were determined in 1068 subjects suffering from differently localized cancers and in 880 healthy subjects. A statistical multidimensional analysis of data led a separate five groups of cancer types (p less than 0.001). Within each group alterations of vitamin spectra, compared to controls, were identical; between groups they were significantly different. These groups were: anal and intestinal cancer; pancreatic, hepatic, oesophageal and gastric cancer; laryngeal and lung cancer; uro-genital and breast cancer; brain cancer. All these groups are statistically different from the reference one (p less than 0.001). This grouping roughly corresponds to the embryologic origin of affected organs. This suggests that carcinogenesis may alter fat soluble vitamin metabolism, specifically in various forms of cancer, or these alterations of vitamin metabolism are in some way involved in the carcinogenic process.

Adult↗

[Analysis of tumor-associated antigen of the digestive tract by monoclonal antibody].

A sandwich enzyme immunoassay was established for measuring an adenocarcinoma-associated antigen (antigen YH206) detected by monoclonal antibody YH206. A level of antigen YH206 exceeding the cut-off value (25 U/ml) was found in the following proportions of 136 patients with digestive organ cancers: stomach cancer 37.2%, colon cancer 14.8%, pancreas cancer 43.3%, common bile duct cancer 28.6%. In contrast, only one out of 33 (3.0%) healthy donors and 7 of 104 (6.7%) patients with benign diseases had slightly elevated levels of the antigen. It was also found that perchloric acid treatment of serum might be useful for decreasing any false-positive reactions. The YH206 antigen was then purified by affinity chromatography using MoAb YH206-coupled CNBr-Sepharose. This antigen was not recognized by MoAb CA19-9. Studies on the chemical nature of the antigenic determinant of the YH206 antigen suggested that MoAb YH206 recognized a unique carbohydrate determinant of a novel adenocarcinoma-associated antigen in the sera of cancer patients. In addition, a new monoclonal antibody BM2 (IgM) was established using YH206 antigen as an immunogen. This antibody might be more useful than antibody YH206 in the detection of circulating antigen in the sera of patients with digestive tract cancer.

Adenocarcinoma↗

[Alexia and agraphia caused by a lesion of the right hemisphere in a non-aphasic right-handed patient].

Oral and written speech centers are commonly attributed to the dominant hemisphere, while body, spatial and facial recognition to the non-dominant. This paper examines the case of a 63 year old entirely right-handed male who presents alexia, agraphia, difficulties in spelling and word-finding together with left spatial and body agnosia, musical, letter and face agnosia, constructional apraxia and left hemianopsia. Computerized axial tomography confirms a right occipital tumor identified as an adeno-carcinoma probably of digestive origin. The role of right hemisphere as a spatial prerequisite to final elaborate speech is discussed.

Adenocarcinoma↗

Tumor induction in Praomys (Mastomys) natalensis by N,N'-2,7-fluorenylenebisacetamide.

Feeding N,N'-2,7-fluorenylenebisacetamide (CAS:304-28-9) at 0.025% to 15 male and 15 female mastomys considerably shortened their life-span. At death every treated mastomys had several primary tumors; untreated animals at comparable ages had none. Several mastomys with hepatoblastomas and 1 with giant cell hepatitis and a metastasizing pancreatic carcinoma are first reported here. The tumor load per animal averaged 4.0 for treated females, 2.6 for treated males, 1.5 for untreated females, and 0.6 for untreated males. Of 24 hepatic tumors in treated mastomys, 11 metastasized, compared to none of the incipient tumors in 8 of 26 untreated animals. Pancreatic adenomas developed in 27 treated and 1 untreated mastomys, and a metastasizing adenocarcinoma developed in 1 treated animal. All treated females, 3 treated males, and 1 untreated female developed multiple villous adenomas in the small intestine. One untreated female and 8 treated females developed mammary cancers, 4 of which metastasized. Primary tumors of other sites occurred infrequently.

2-Acetylaminofluorene↗

Comparative carcinogenesis by hydroxylated nitrosopropylamines in Syrian hamsters.

The relationship between the chemical structure of nitrosamines and their carcinogenic activity has been examined in Syrian golden hamsters in parallel with similar studies in rats to aid in explaining the sharp interspecies differences in response to these compounds. The relationship between the beta-oxidized N-propyl-nitrosamine structure and the induction of tumors of the pancreatic duct in Syrian golden hamsters was investigated by administration of a number of asymmetric acyclic nitrosamines containing that structure to female hamsters for 29-50 weeks. N-Nitroso-2-oxopropyl-2-hydroxyethylamine (OPE), N-nitroso-2-hydroxypropyl-2-hydroxyethylamine (NIEA), and N-nitroso-2,3-dihydroxypropyl-2-oxopropylamine (DHPOP) induced pancreatic tumors. OPE also induced a high incidence of liver neoplasms, and a number of animals given NIEA and N-nitrosoallyl-2-oxopropylamine (NAOP) also had liver neoplasms. N-Nitroso-2,3-dihydroxypropyl-2-hydroxyethylamine was very weakly carcinogenic. N-Nitroso-2,3-dihydroxypropyl-2-hydroxypropylamine and DHPOP induced a high incidence of neoplasms of the forestomach (mainly papillomas). N-Nitrosoallyl-2,3-dihydroxypropylamine, N-nitrosoallyl-2-hydroxypropylamine, and NAOP induced primarily neoplasms of the nasal mucosa but no neoplasms of the pancreatic ducts in hamsters.

Animals↗

[Correlation between the intercellular adhesion molecule (E-cadherin) and its associated protein (alpha-catenin) expression and metastasis in human digestive cancers].

The immunostaining (ABC method) of E-cadherin and alpha-catenin were performed on 46 esophageal cancers, 67 gastric cancers, 100 colon cancers. E-cadherin and alpha-catenin expression was evaluated as preserved and reduced according to the proportion of positive cells, respectively. The reduction of alpha-catenin expression was more significantly related to lymph node metastasis than that of E-cadherin. Furthermore, the frequency of hematogenous liver metastasis in preserved E-cadherin expression and reduced alpha-catenin expression was significantly higher than that in another combination of E-cadherin and alpha-catenin expression, in gastric and colon cancer. The reduction of alpha-catenin expression was associated with declined intercellular adhesiveness, which occasionally was not accompanied by reduction of E-cadherin. Therefore, the expression of alpha-catenin might more sensitively indicated cell-cell adhesion, predicting tumor metastasis.

Cadherins↗