Sodium Valproate Enhances the Urethane-Induced Lung Adenomas and Suppresses Malignization of Adenomas in Ovariectomized Female Mice.

In the present study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in female mice has been evaluated. BALB/c mice (n = 60; 4-6 weeks old, females) were used in the following groups: (1) urethane-treated; (2) urethane-NaVP-treated; (3) only NaVP-treated; (4) control. In the same groups, ovariectomized female mice (n = 60) were investigated. Urethane was given intraperitoneally, with a total dose of 50 mg/mouse. In NaVP-treated mice groups, 0.4% aqueous solution of NaVP was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in ovariectomized mice and in those treated with urethane and NaVP was significantly higher than in mice treated with urethane only (8.29 ± 0.58 versus 6.0 ± 0.63, p < 0.02). No significant difference in the number of tumors per mouse was revealed while comparing the nonovariectomized urethane- and urethane-NaVP-treated groups (p = 0.13). A significant decrease of adenocarcinoma number in ovariectomized mice treated with a urethane-NaVP as compared with ovariectomized mice treated with urethane only was found (p = 0.031). NaVP together with low estrogen may have a protective effect on the malignization of adenomas in ovariectomized mice.

Endometrial cancer and microsatellite instability status.

Microsatellite instability (MSI) is an important factor in the development of various cancers as an identifier of a defective DNA mismatch repair system. The objective of our study was to define the association between microsatellite instability status and traditional clinicopathologic characteristics of endometrioid type adenocarcinoma. MATERIAL AND METHODS: MSI status of endometrial cancer was examined by employing the Promega MSI Analysis System. This system uses 5 mononucleotide markers to identify MSI in tumour and normal tissue DNA (BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. In this study, we investigated MSI status in 109 endometrial carcinomas. RESULTS AND CONCLUSIONS: One hundred (92%) of 109 endometrial cancers showed endometrioid type histology and only 9 (8%) non-endometrioid type. MSI-high was found in 17% (17/100) of endometrioid type adenocarcinomas, in 0% (0/9) of non-endometrioid carcinomas. Selected clinicopathologic parameters for endometrioid type adenocarcinomas were compared to the MSI status which was separated into two groups - MSI-high and MSI stable. The results showed that MSI-high status was related to clinicopathologic parameters such as deep myometrial invasion and higher histologic grade in endometrioid type adenocarcinomas.

Sodium valproate enhances urethane tumorigenicity in lungs of male but not female mice.

In the study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in mice has been evaluated. BALB/c mice (n = 120; 4-6 weeks old, both sexes) were used in the following groups: 1) urethane-treated, 2) urethane-NaVP-treated, 3) only NaVP-treated, 4) control. In the same groups, castrated male mice (n = 48) were investigated. Urethane was given by intraperitoneal injections 10 mg/mouse, twice a week, the total dose 50 mg/mouse. In NaVP-treated mice, the 0.4 % NaVP aqueous solution was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in urethane-NaVP-treated males was significantly higher than in those treated with urethane only (13.82 ± 1.12 vs 6.77 ± 0.43, p < 0.0001). No significant difference in the number of tumors per mouse was revealed while comparing the female urethane- and urethane-NaVP-treated groups (6.50 ± 0.79 vs 8.15 ± 0.55, p = 0.105). No difference in the number of tumors per mouse was found in urethane-NaVP-treated castrated males as compared with urethane-treated castrated males. However, in the urethane-NaVP-treated castrated males the number of tumors per mouse was significantly lower than in analogous non-castrated males (7.8 ± 1.67 vs 13.82 ± 1.12, p < 0.01). NaVP combined with urethane potentiates urethane tumorigenicity in BALB/c non-castrated but not in female and castrated male mice. These data indicate an important role of testosterone in the urethane-NaVP induced lung tumorigenesis.

[Microsatellite instability and loss of heterozygosity in cancer]. / Mikrosatelitu nestabilumas ir heterozigotiskumo praradimas sergant veziu.

Literature review on genetic alterations (microsatellite instability and loss of heterozygosity) in different types of cancer is presented. Microsatellite instability and loss of heterozigosity are significant processes in carcinogenesis. The evaluation of microsatellite instability in cancer patients might be of clinical importance as a prognostic and predictive factor. The most of up-to-date data available are on microsatellite instability in colorectal cancer. For other types of cancer, the number of publications on microsatellite instability is rapidly increasing.

[Risk factors of main cancer sites]. / Dazniausiu vezio lokalizaciju rizikos veiksniai.

Cancer prevention is a system of various measures devoted to avoid this disease. Primary cancer prevention means the identification, avoidance, or destruction of known risk factors. The main risk factors are smoking, diet, alcohol consumption, occupational factors, environmental pollution, electromagnetic radiation, infection, medicines, reproductive hormones, and lack of physical activity. Approximately one-third of cancers can be avoided by implementing various preventive measures. The aim of this article was to acquaint medical students, family doctors with risk factors of main cancer sites (lung, breast, colorectal, and prostate).

Human papillomavirus and p53 polymorphism in Lithuanian cervical cancer patients.

BACKGROUND: Cervical cancer is the fourth most common cancer for women in Lithuania. One of the important cervical cancer risk factors is human papillomavirus (HPV) infection. Recent literature has considered p53 allelic polymorphism to be a putative predisposing factor for cervical carcinoma development. OBJECTIVE: The aim of this study was to elucidate the prevalence of HPV, especially HPV 16, in cervical cancer patients and in healthy women, to investigate the distribution of p53 gene 72 codon polymorphism and to correlate these to cervical cancer risk in Lithuanian women. METHODS: 588 women were included in the study: 212 women with primary diagnosed cervical cancer (case group) and 376 healthy volunteers (control group). RESULTS: A high prevalence of HPV DNA was detected in cervical cancer patients, 92.0%, and in control women, 23.6% (P < 0.0001). HPV 16 is the most frequent HPV type in cervical cancer patients. In the case of squamous cell carcinoma, this type was detected in 55.8%, in adenocarcinoma - 35.3%. In the control group, this type was detected in 19.0%. A statistically significant difference in the distribution of p53 alleles between the case and the control groups was found. CONCLUSIONS: Cervical cancer risk in Lithuanian patients is associated with HPV infection (OR = 75.39; 95% CI 33.61-192.98), especially HPV 16 type (OR = 100.3; 95% CI 46.05-238.59) and p53 homozygous Arg/Arg allele (OR = 2.10; 95% CI 1.10-4.19).

Investigation of ethyl alcohol and beta-carotene effect on two models of carcinogenesis.

The effects of ethyl alcohol and synthetic beta-carotene have been studied on two models of carcinogenesis in mice BALB/c. Lung tumours were induced with organotropically acting urethane (given by i.p. injections, total dose--100 mg/mouse) subcutaneous tumours were induced with locally acting benzo(a)pyrene (single injection, 2 mg/mouse) beta-Carotene was given 3 times per week 0.4 mg/mouse by gastric intubations and 10% ethanol was given instead of drinking water until the end of experiments (4-6 months). Results showed that beta-carotene did not significantly inhibit lung adenomogenesis and may moderately delay subcutaneous tumours occurence. In ourstudies chronic ethanol intake did notshow significant influence on this delay.

N-acetil-l-cysteine and 2-amino-2-thiiazoline N-acetyl-l-cysteinate as a possible cancer chemopreventive agents in murine models.

The aim of this study was to investigate N-acetyl-cysteine (NAC) and its 2-amino-2-thiazoline salt (NACAT) as potential chemopreventive agents on experimentally induced lung tumours by urethane (U) in mice. Female BALB/c mice were used. U was given by intraperitoneal injections during 2 weeks (single dose - 10 mg/mouse, total - 50 mg/mouse). Mice were treated daily per os with NAC 1/10 LD50, NACAT 1/10 or 1/100 LD50 starting 2 weeks prior U administration, then during U treatment and thereafter for 2 months. The duration of experiment was 4 months. The results showed that NAC (1000 mg/kg) reduced the lung tumour incidence to 30% that of controls, P < or = 0.05. Most effective of NACAT was 100 mg/kg dose; it reduced an average of lung adenomas per mouse by 26%, P < or = 0.05, but lower dose (10 mg/kg) was less effective. In order to achieve similar chemopreventive effect (approximately 30%) on mice, it is necessary to use 0.38 mM/kg of NACAT or 6.13 mM/kg of NAC. It means that 16 times less of NACAT is required, if calculated by molar concentration. In general, NAC and NACAT have a moderate chemopreventive effect on lung tumorigenesis induced by urethane in mice.

Carcinogenicity of Sulfuric Acid in Rats and Mice.

An International Agency for Research on Cancer (IARC) committee recognized aerosol of sulphuric acid as a human carcinogen on the basis of epidemiological studies. No experimental studies on the carcinogenicity, either of sulfuric acid aerosol or of sulfuric acid itself was available. Our aim was to determine whether sulfuric acid is a causal or modifying factor in carcinogenesis, especially in the respiratory tract. We used two species of laboratory animals (both sexes) 315 Wistar rats and 219 CBAxC57Bl mice in a long term experimental study. The rats were treated with sulfuric acid (maximal tolerated doses, by chronic intratracheal instillations or by gastric intubations) and/or benzo(a)pyrene (by intratracheal instillations). The mice were treated with sulfuric acid (by chronic gastric intubations) and/or urethane (by intraperitoneal injections). We observed the animals throughout their lives and performed gross and microscopic examination of all organs. The results of the first year of study did not provide clear evidence either for sulfuric acid carcinogenicity or for co-carcinogenicity. However, in the second year tumors appeared in those organs where sulfuric acid acted directly. A modifying (stimulating) effect of sulfuric acid on carcinogenesis induced with benzo(a)pyren was observed in rats. Sulfuric acid did not influence lung carcinogenesis induced with urethane in mice.