[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.

All-trans retinoic acid (ATRA) suppresses transcription of human papillomavirus type 16 (HPV16) in a dose-dependent manner.

Earlier we found that SiHa cervical squamous carcinoma cells that harbor HPV type 16 respond to ATRA treatment in a dose-dependent manner: high-dose (10(-5)-10(-4) M) but not low-dose (10(-7)-10(-6) M) ATRA induced growth arrest. Growth of HPV-infected cells is highly dependent on the expression of the viral E6/E7 proteins. Thus, targeting expression of the viral E6/E7 genes might influence growth properties of HPV-infected cells. Here, we demonstrated that high-dose ATRA inhibited expression of HPV16 E7 through suppression of the HPV16 promoter (p97) activity. Gelshift assay (EMSA) revealed that binding of the AP-1 transcription factor to an oligonucleotide originated from the HPV type 16 promoter was diminished after high-dose, but not low-dose ATRA treatment. This suggests that high-dose ATRA suppresses HPV 16 promoter activity, at least in part, via a decreased AP-1 binding. Our data might be useful in treatment of cervical dysplasias and/or carcinomas.

Polymorphisms of glutathione-S-transferase and arylamine N-acetyltransferase enzymes and susceptibility to colorectal cancer.

BACKGROUND: Glutathione-S-transferases (GSTs) and N-acetyltransferases (NATs) are involved in the metabolism of a wide range of carcinogenic chemicals. Allelic polymorphism of these enzymes is associated with variations in enzyme activity, hence it may affect the concentration of activated carcinogenic chemicals in the body. Previous studies suggest a possible cancer risk-modifying effect of these allelic polymorphisms, but the results are still controversial. We evaluated the effect of GSTM1, GSTT1, GSTP1, NAT1 and NAT2 enzymes on individual susceptibility to colorectal cancer, with particular attention to possible interactions between the studied genotypes. MATERIALS AND METHODS: Five hundred colorectal cancer patients and 500 matched cancer-free controls were included in the study. The allelic polymorphisms of GSTM1, GSTT1 and GSTP1, NAT1 and NAT2 enzymes were determined by PCR-based methods, from peripheral blood leukocytes, and allelic distributions were compared between colorectal cancer patients and controls. RESULTS: The GSTM1 0 allele (OR: 1.48, 95% CI: 1.15-1.92) and rapid acetylator genotypes of NAT2 (OR: 1.52, 95% CI: 1.17-1.98) were associated with an elevated risk No statistically significant correlation between NAT1, GSTT1, GSTP1 genotypes and colorectal cancer was found. Remarkably increased risk was associated with the GSTM1 0 allele--NAT2 rapid acetylator genotype combination (OR: 2.39, 95% CI: 1.75-3.26) and with the GSTM1 0 allele--NAT2 and NAT1 rapid acetylator triple combination (OR: 3.28, 95% CI: 2.06-5.23). Carrying 4 or 5 putative "high-risk" alleles substantially increased the risk of colorectal cancer (OR: 3.69, 95% CI: 2.33-5.86). CONCLUSION: The genotype of certain metabolizing enzymes affects the risk for colorectal cancer. This effect is particularly important when certain allelic combinations are studied. In the near future, individual level risk assessment may be reached by further increasing the number of studied polymorphisms, combining them with traditional epidemiological risk factors.

[Dual tumours in the GI tract: synchronous and metachronous stromal (GIST) and epithelial/neuroendocrine neoplasms]. / Kettôs tumorok a gasztrointesztinális traktusban: szinkron és metakron stromális (GIST) és epiteliális/neuroendokrin daganatok.

Gastrointestinal stromal tumours (GIST) constitute the most frequent group of mesenchymal tumours in the gastrointestinal tract (GI). During the last several decades major advances have been taken in the diagnostics, treatment, and understanding of its pathogenesis. However, much less is known about the either metachronous or synchronous concurrence of GIST and other tumours of different histogenesis. In the present study clinicopathological data of 43 patients with histologically proved gastrointestinal stromal tumour were studied mainly in regard of the occurrence of a secondary neoplasm. Among the 43, 7 cases were found with secondary tumour mainly of epithelial origin. In three cases (cases 3, 5, and 7) GIST concurred with colorectal adenocarcinoma, in one case (case 1) GIST occurred in a patient with a 3-years-history of chronic lymphocytic leukaemia (CLL), in other two (cases 2 and 4) the stromal tumour was combined with in situ adenocarcinoma of the stomach and carcinoid of the pancreas, respectively. In case 6, GIST concurred with a duodenal Brunner gland adenoma. In five cases the stromal tumour and the other neoplasm occurred synchronously, and in four of them, being the stromal tumour clinically silent, GISTs were intraoperative findings. This confirms the importance of surgical intraabdominal control before closure. In one hand the repeated concurrence of GIST and colorectal adenocarcinoma in our series, and on the other hand, that of GIST and adenocarcinoma of the stomach in the literature, may indicate an at least partly common factor, which may be involved in the pathogenesis of these neoplasms.

[Role of Caelyx in second line treatment of ovarian cancer]. / A Caelyx helye a petefészekrák másodvonalbeli kezelésében.

The authors published their own experiences and results of Caelyx treatment based on 40 ovarian cancer patients treated in 9 different institutions. Patients had been treated with platinum based or platinum-taxol combination chemoterapy. Their average age was 57.2 years (35-80). The average time to progression was 3.8 months (1-8). The effects of the therapy were assessed on 36 patients and the results were 3 CR, 8 PR, 7 SD and 18 PD. Summarised the Caelyx therapy caused improvement in 30.55% of the patients and stabilisation in 19.44%. Supportive therapy was needed in 8 cases.

[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.

Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial.

AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56% vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.