K-ras exon 2 point mutations in human endometrial cancer.

In the present study, we screened for the K-ras exon 2 point mutations in a group of 87 gynecological neoplasms (82 endometrial carcinomas, four carcinomas of the uterine cervix and one uterine carcinosarcoma) using the non-isotopic PCR-SSCP-direct sequencing techniques. Direct sequencing analysis revealed CAA-->CAC (Gln-->His) K-ras codon 61 point mutations in two (2.4%) of the 82 endometrial carcinomas mentioned above. These two cases were endometrial endometrioid carcinomas at an early clinical stage of disease (stage IB and IC due to FIGO). Those endometrial carcinomas that showed K-ras exon 2 point mutations revealed a strong positivity for heterogeneous nuclear retinoblastoma protein staining; none of these, however, have had the K-ras codon 12 point mutation. In addition, there were no K-ras gene point mutations in three endometrial carcinomas lacking the Rb protein immunohistochemically. None of the cervical carcinomas tested had K-ras gene point mutations, whereas one carcinosarcoma harbored K-ras codon 61 point mutation (CAA-->CAC). In conclusion, our data support the view that K-ras exon 2 point mutations are rare events in human endometrial cancer. Rb and K-ras gene abnormalities may occur independently of each other during endometrial carcinogenesis in humans.

Total serum sialic acid concentration as a supporting marker of malignancy in ovarian neoplasia.

The present study was undertaken to establish the diagnostic utility of total sialic acid (SA) determination in the serum of patient with ovarian neoplasia. In a group of 29 patients with histopathologically confirmed ovarian neoplasia, concentrations of total SA was determined. In addition, the two tumor markers: CA125 antigen level and lactic dehydrogenase (LDH) activity were determined. The mean value of serum total SA in patients (1.76 mmol/L) was significantly higher than in the control group of healthy women (1.52 mmol/L). The elevation of serum total SA was associated with the burden of the tumor: higher total SA levels were observed in the cases of more developed malignancies. A significant correlation has been found between serum total SA content and CA125 level in patients with undifferentiated ovarian cancers. It has been concluded that total serum sialic acid level reflects the development of malignancy and should be considered as a supporting tumor marker in ovarian cancer diagnosis.

Analysis of p53 and K-ras genes and their proteins in a sarcoma botryoides of the uterine cervix.

Several data indicate that the activation of oncogenes and growth factors as well as inactivation of the tumor suppressor genes are implicated in the development of human neoplasms, including sarcomas. In the present study we described a case of the extremely rare, but highly malignant neoplasm of the female genital tract known as sarcoma botryoides of the uterine cervix and assessed, using molecular and an immunohistochemical analysis, p53 and K-ras alterations in the tumor. A point mutation in exon 6 of the p53 tumor suppressor gene was found but no K-ras gene point mutations at codons 12, 13 and 61 were detected using molecular analysis. p53 protein was overexpressed in more than half of the neoplastic cells, however, ras p21 protein expression was not immunohistochemically detected. Our data indicate that p53, but not K-ras gene alterations may play a role in the development and progression of sarcoma botryoides of the uterine cervix.

Sialic acid concentration in serum and tissue of endometrial cancer patients.

Serum total sialic acid (TSA) level was determined in the group of 45 patients with endometrial neoplasia. Moreover, the sialic acid content in 23 surgically obtained tumor tissue specimens has been estimated. The mean value of serum total sialic acid level of the cancer patients (2.38 mmol/l) was significantly higher (P < 0.0001) than the sialic acid level in the control group (1.52 mmol/l). The elevation of serum total sialic acid level was associated with the burden of the tumor (2.30 mmol/l and 2.68 mmol/l for stages I and II + III, respectively). Tissue sialic acid content showed no significant differences between early and advanced clinical stage of the disease.

K-ras gene point mutations in human endometrial carcinomas: correlation with clinicopathological features and patients' outcome.

In order to evaluate the role of K-ras gene point mutations in the progression of endometrial carcinoma, we applied the polymerase chain reaction/restriction-fragment-length polymorphism technique to 57 tumours surgically removed from women of Polish origin. We assessed the relationship between K-ras gene activation and clinicopathological features as well as patients' outcome. Mutational activation in codon 12 of the K-ras gene was detected in 8 out of 57 (14%) endometrial carcinomas, while in codon 13 of the K-ras gene no point mutations were noted. A correlation between the histological type of the tumour and codon 12 K-ras gene mutation was noted (P < 0.05; Fisher exact test). K-ras gene mutation was not related to the patients' age, surgical stage, histological grade or to the depth of myometrial invasion. A trend towards a poorer prognosis was noted during the follow-up of patients whose tumours had shown K-ras codon 12 point mutations, but the difference was not significant (P = 0.06; log-rank test). Our data indicate that point mutations in codon 12 of the K-ras gene are a rare event in human endometrial carcinomas. The lack of correlation between K-ras point mutations and clinicopathological features (except histological type) supports the hypothesis of a random activation of the K-ras gene in human neoplastic endometrium.

Detection of K-ras mutations in cancerous lesions of human endometrium.

The many genetic changes associated with human carcinogenesis include the activation and/or inactivation of various genes. Polymerase-chain reaction and single-strand conformation polymorphism analysis [PCR-SSCP] was used to detect alterations at exon 1 of the K-ras gene in 20 lesions of human endometrium. Six cases of endometrial hyperplasia, 13 of endometrial carcinoma and one of endometrial metastasis of ovarian cancer were analyzed. Mutations at exon 1 of the K-ras gene were detected in two of 13 human endometrial carcinoma [15%]; both were histologically defined adenocarcinomas, stage Ib and stage IIa according to the FIGO. Alterations were also observed in the single case of endometrial metastasis of ovarian cancer. It is worthy of note that among the six women with hyperplasic endometrial lesions K-ras gene mutation were not reported. These data suggest that K-ras activation is rare in Polish women and when it does occur it is in cancerous, but not in precancerous, lesions of human endometrium.

[Antioncogenes--tumor suppression genes]. / Antyonkogeny--geny supresji nowotworowej.

Recent knowledge about biological role of tumor suppressor genes and their products: RB1, p53, WT1, DCC, APC/FAP, NF1, NF2, VHL, MCC and MTS1 is presented. The main approaches of these agents as physiological regulators of cell growth and proliferation are discussed. Views on the tumor suppressor genes involvement in the development of inherited and sporadic forms of cancer have been reviewed.

[Level of sialic acid in blood serum as a tumor marker]. / Poziom kwasu sialowego w surowicy krwi jako wskaznik choroby nowotworowej.

In the recent quick development of cancer diagnostic methods, attention of researchers is focused onto tumor-derived compounds as possible markers of neoplasia. In this article we have reviewed researchers' opinions about sialic acid as a tumor marker. According to majority of researchers, blood sialic acid may be regarded as a useful marker for a variety of cancers although its specificity is not high.

[P53 protein in adenocarcinoma of the large intestine]. / Bialko p53 w gruczolakorakach jelita grubego.

P53 gen mutations play significant role in neoplastic transformation of colorectal mucosa. We investigated p53 immunostaining in 80 cases of spontaneous human colorectal adenocarcinomas (with monoclonal DO7 antibody and LSAB+ kit). We found positive, nuclear p53 immunostaining in 64% of nonmucinous adenocarcinoma tissues and in 19% of mucinous adenocarcinomas tissues. P53 protein deposits were most often found in colorectal adenocarcinomas localised in rectum (66.67%) and in advanced (Dukes C, D) colorectal adenocarcinomas (59.38%) as well. There was no statistical significance between the p53 positive immunostaining and the histological differentiation of the colorectal adenocarcinomas. The overall survival of patients with tumours positive for p53 protein was significantly shorter than that of patients with colorectal cancers negative for p53 protein. We conclude that p53 immunohistochemical analysis may be treated as a supplementary prognostic marker for patients with colorectal adenocarcinoma, especially it may be useful for adjuvant therapy selection.

[High molecular weight forms of aminoacyl-tRNA synthetases in animals. I. Amount and enzymatic composition of high molecular weight synthetase in cytosol from rabbit liver]. / Wielkoczasteczkowe postacie syntetaz aminoacylo-tRNA w organizmach zwierzecych. Czesc I. Wielkosc i sklad enzymatcyzny wielkoczasteczkowego kompleksu syntetazowego z cytosolu watroby królika.

A high-molecular-weight complex composed of 15 amino acid-tRNA synthetases occurs in the rabbit liver cytosol apart from the free enzymes. The greatest activities in the complex are exhibited by lysyl- and arginyl-tRNA synthetases. The complex has the mass of about 4,000 kDa and the sedimentation constant about 19 S.

[High molecular weight forms of aminoacyl-tRNA synthetases in animals. II. High molecular weight aminoacyl-tRNA synthetase complexes in lower animals]. / Wielkoczasteczkowe postacie syntetaz aminoacylo-tRNA w organizmach zwierzécych. Czesc II. Wielkoczasteczkowe kompleksy syntetaz aminoacylo-tRNA w organizmach nizszych zwierzat.

High-molecular-weight aminoacyl-tRNA synthetase complexes have been found in hen, frog and carp liver cytosol as well as in cytosol from snails and Paramecium. The complexes from vertebrates and snails contained 13-15 aminoacyl-tRNA synthetases, revealed mass of about 4,000 kDa and sedimentation constant about 19 S. The complex from Paramecium containing 11 aminoacyl-tRNA synthetases, revealed a mass of about 1,600 kDa and sedimentation constant 15 S. The results of the present study support the view that the high-molecular-weight synthetase complexes are common entities in the animal kingdom.

Comparison of the thermolability and hydrophobic properties of high- and low-molecular-weight forms of rabbit liver arginyl-tRNA synthetase.

Two preparations with arginyl-tRNA synthetase activity have been obtained from rabbit liver post-microsomal fraction: a) a high-molecular-weight containing the multienzyme aminoacyl-tRNA synthetase complex and b) a low-molecular-weight preparation containing free enzymes. Thermal inactivation of arginyl-tRNA synthetase in both preparations has been compared in a solution which was successively supplemented with tRNA, reduced glutathione, L-ascorbic acid, ZnCl2 and Triton X 100. Moreover, hydrophobic properties of both enzyme preparations have been compared. It was found that the complexed arginyl-tRNA synthetase is more stable than the free enzyme. A role of hydrophobic interactions in the maintenance of the complexed enzyme stability is suggested.

Heavy and light forms of some aminoacyl-tRNA synthetases in fraction X, microsomes and cytosol of rabbit liver.

Aminoacyl-tRNA synthetase activity for alanine, glutamic acid, lysine and phenylalanine was studied in the three subcellular fractions of rabbit liver: fraction X, microsomes and cytosol. From 60 to 80% of the enzyme activities were found in fraction X and microsomes. Fraction X was especially rich in the synthetase activities. By means of gel chromatography, heavy (over 10(6) daltons) and light (below 480 X 10(3) daltons) forms of lysyl- and phenylalanyl- but only light ones of alanyl- and glutamyl-tRNA synthetase activities were found in all the subcellular fractions studied. It is concluded that in higher organisms (mammals) all aminoacyl-tRNA synthetases, at least in part, are associated with cell structural constituents.