First-line bevacizumab-paclitaxel in 220 patients with metastatic breast cancer: results from the AVAREG study.

BACKGROUND: First-line bevacizumab-paclitaxel therapy demonstrated a median progression-free survival (PFS) of 11 months in three randomized phase III trials on metastatic breast cancer (mBC) (E2100, TURANDOT and CALGB 40502). We assessed the efficacy and safety of bevacizumab-paclitaxel in a routine oncology practice study. PATIENTS AND METHODS: Patients with previously untreated mBC received bevacizumab-paclitaxel according to the approved indication in Hungary. The primary end-point was PFS. Secondary end-points included time-to-treatment discontinuation, 1-year survival rate, PFS in patients with triple-negative breast cancer (TNBC) and safety. RESULTS: Median PFS in the 220 treated patients was 9.3 (95%CI 7.8-10.8) months. The 1-year survival rate was 68%. In patients with TNBC (N=106), median PFS was 8.3 months (95%CI 7.8-8.8). Adverse events were consistent with the established safety profile of bevacizumab-paclitaxel. CONCLUSION: Bevacizumab-paclitaxel is an active and well-tolerated first-line treatment for mBC, with notable activity in TNBC.

Effect of glutathione-S-transferase M1 and T1 allelic polymorphisms on HPV-induced cervical precancer formation.

AIM: The effect of GSTM1 and GSTT1 allelic polymorphisms was studied on the HPV-induced cervical carcinogenesis. PATIENTS AND METHODS: Two hundred and fifty-three women with persistent high-risk HPV infection were involved in the study; 117 of them developed cervical high-grade dysplasia and/or cervical intraepithelial neoplasia grade III during the 7-year follow-up period. Occurrence of GSTM1 and GSTT1 null genotypes was compared between women with and without dysplasia. RESULTS: Presence of GSTM1 (OR=1.78, 95% CI=1.06-2.97; p=0.028) and GSTT1 (OR=1.89, 95% CI=1.10-3.26; p=0.022) null genotypes was statistically significantly more frequent among women with cervical dysplasia than in the group without dysplasia. Participants with dual null genotype had an even more elevated risk of precancerous lesion (OR=2.35, 95% CI=1.17-4.73; p=0.017). CONCLUSION: Our study demonstrated the role of both GSTM1 and T1 null genotypes in the development of high-grade cervical dysplasia in a Caucasian population.

The effect of fenugreek on the gene expression of arachidonic acid metabolizing enzymes.

The main bioactive compounds of Trigonella foenum graecum L. (fenugreek) seeds are protodioscin, trigoneoside, diosgenin and yamogenin, which have anticarcinogenic potency through inhibition of cell proliferation and inhibition of prostaglandin synthesis. The effect of fenugreek on ALOX and COX genes was examined in AKR/J H-2(k) mice exposed to dimethylbenz[α]anthracene (DMBA), a potent carcinogen. The expression pattern of these genes was determined by detecting the mRNA expression in various tissues (the lungs, liver, spleen and the kidneys) in four groups of mice. Two groups were fed with normal and two of them with fenugreek containing nutriment. Each group divided into DMBA treated and control groups. Mice were autopsied on day 7 after DMBA treatment for mRNA isolation. Fenugreek consumption itself did not change gene expression compared with the control group. DMBA could increase the expression of ALOX12, ALOX15, ALOX5 genes mainly in all organs. Fenugreek consumption was generally protective in each organ in a different manner. DMBA treatment increased COX2 gene expression, but fenugreek was protective in all tissues examined. In COX1 gene, the fenugreek diet could suppress the expression, except for spleen, independently from carcinogen exposure. Therefore by inhibiting the arachidonic acid metabolism fenugreek may prevent tumorigenesis.

Early modification of c-myc, Ha-ras and p53 expressions by chemical carcinogens (DMBA, MNU).

7,12-Dimethylbenz[a]anthracene (DMBA) and N-methyl-N-nitrosourea (MNU) are important environmental carcinogens. Their different biological effects were examined in CBA/Ca H-2(K) haplotype inbred mice on the gene expression of c-myc, Ha-ras and p53 through a 24 hour period. Elevated expression of c-myc and Ha-ras genes was found in the spleen, lung, thymus and lymph nodes 6 and 12 hours after DMBA treatment and in the lung and thymus 3 hours after MNU treatment. In the liver, DMBA induced strong onco/suppressor gene expression as early as 6 hours after the treatment, but MNU increased the p53 gene expression 12 hours after the treatment. The gene expression patterns reflected the different mechanism of the direct acting MNU and metabolically activated DMBA. This phenomenon provides evidence as to the usefulness of detection of onco/supressor key gene expression as early molecular epidemiological biomarkers of carcinogenesis and carcinogenic exposure in animal model, useful in human cancer prevention practice as well.

Early modification of c-myc, Ha-ras and p53 expressions by N-methyl-N-nitrosourea.

Methylnitrosourea (MNU) is a well-known pluripotent direct-acting carcinogen. Formation of MNU following incubation of various meats with additional nitrite under in vitro acidic conditions is possible. It is possible that many species, including humans, are exposed to carcinogenic MNU, generated in their alimentary tract. Previously, an animal model was developed by our research group to investigate the expression of three genes c-myc, Ha-ras and p53 as early molecular epidemiological biomarkers of carcinogenic exposure or carcinogenesis caused by DMBA (dimethylbenz[alpha]anthracene). The aim of this study was to investigate the early effect of MNU on the gene expression levels. MNU is a direct-acting carcinogen which spontaneously and rapidly degrades, so any effect on the gene expression is observed in 24 hours. Our results show the maximum effect in vivo on the gene expression at 12 hours after the MNU treatment; on the other hand, 24 hours after the treatment, the elevated gene expressions decreased in target organs (bone marrow, lung, lymph nodes). Our results correspond to "long-term" experiments of the carcinogenic effect of MNU in different target organs. Our findings suggest that MNU has an impact on the expression of c-myc, Ha-ras and p53 genes in 12 hours, especially in bone marrow. Overexpression of these genes occurs as an early biological effect of exposure to chemical carcinogens. According to our results, the high expression of these genes could indicate MNU exposure and these genes could take part in MNU-induced tumorigenesis.

[The results of ovarian cancer therapy in the Hungarian Centers in 2002-2003]. / Petefészekrákos betegek kezelési eredményei a hazai centrumokban 2002-2003-ban.

UNLABELLED: Authors presented data of treatment results and course of disease in 487 ovarian cancer patients treated by primary surgery and paclitaxel-carboplatin combination chemotherapy between July 1, 2002 and December 31, 2003. PATIENTS: Most of our patients (87.8%) belonged to the age-group between 40-70 years. Distribution of their histological diagnosis was as 69.6% serous, 10.7% mucinous, 5.1% endometrial and 4.7% undifferentiated carcinoma. The grade distribution was found as 8.4% grade 1, 40.9% grade 2 and 35.9% grade 3. RESULTS: The primary surgery was evaluated as optimal in 41.7%, suboptimal in 37.3% and exploration was performed in 21.1%. Most patients started chemotherapy 20 days after surgery and 74.2% of them got six courses. During the evaluation period 61 intervallum laparotomies were performed, and resulted on 55.7% optimal debulking. Complete remission was found in 58.9%, and partial remission in 14.7% of patients. This treatment resulted on a complete remission in 40.9% at the follow-up of 12 months.

[Status report on the chemotherapy of ovarian cancer at special cancer centers in Hungary (2002-2003)]. / A petefészekrák gyógykezelésének helyzete a különkeretes Centrumokban 2002-2003-ban Magyarországon.

Data on the first-line treatment of ovarian cancer in special centers of Hungary 2002 and 2003 are presented, involving 283 and 416 patients, respectively. Patients' age, clinical stage and histological type of the tumor were highly similar to literature data, while grades were different. Surgical effectiveness in case of IIIc staged tumors with >1 cm residual mass was 37%. The ratio of interval laparotomy was about 15%. Overall response rates of the first-line treatment of ovarian cancer was 82%, while the rate of complete remissions was 60%. The authors provide detailed analysis of factors that can improve the chemotherapy of ovarian cancer in Hungary.