2005, Vol 3, No 1
Hypoxia in cervical cancer and response to therapy
GIN ONKOL, 2005, 3 (1), p. 9-14
ABSTRACT

Hypoxia in malignant tumors is associated with resistance to radio- and chemotherapy. Studies of patients with cervical cancer revealed a correlation between anoxia in tissues containing tumor cells and a worse 3-year survival rate. Assay of hypoxia markers: HIF-1α, CA 9 and GLUT 1 using immunochemical techniques in biopsy material or surgical specimens of uterine cervix represents a less invasive approach than assessment of hypoxia using the Eppendorf probe. Assessment of anoxia enable optimal tailoring of therapy and it’s monitoring. It is hoped, that YC-1 may have a favorable therapeutic effect by suppressing HIF-1α.

Keywords: hypoxia, hypoxia markers, cancer of the uterine cervix, HIF-1α, YC-1
DOWNLOAD ARTICLE (PDF)
Hypoxia can stimulate angiogenesis by degranulation of mast cells
GIN ONKOL, 2005, 3 (1), p. 15-21
ABSTRACT

The placental angiogenesis is crucial for the proper course of pregnancy. The trophoblast cells are able to grow invasively. The oxygen concentration can modulate the degree of invasiveness of the trophoblastic tissue e.g. by changes in the intensity of angiogenesis. The human placenta is a relatively good source of mast cells (MC), whose secretory granulations contain angiogenic factors (e.g. VEGFs). On hypoxia, the placental cells have been proved to physiologically increase the expression of VEGFs. The aim of this study was to assess the influence of hypoxia on the process of MC degranulation in an extracorporeal culture of human trophoblastic cells. The cells from full-term pregnancies as well as most cells from the umbilical blood were obtained to form in vitro co-cultures. After 30 minutes of incubation in hypoxic environment (2% O2), a computer analysis assessed the degree of mast cells degranulation. The cells had been stained with 0.001% ruthenium red and osmium tetroxide. The results were compared with those obtained at normoxia. Control tests included incubation with the compound 48/80 (which causes degranulation) and disodium cromoglycate (DSCG, mast cells stabilizer). Hypoxia led to increased degranulation of MC (p<0.05) in the co-culture with trophoblastic cells. Maximum intensity of this process was similar to this observed with 48/80, but the rate of this reaction was lower. Prior incubation with DSCG inhibited the degranulation, both at hypoxia and in response to 48/80. Due to the presence of numerous mediators in their secretory granulations, mast cells at hypoxia are able to affect e.g. the placental angiogenesis, the vessels permeability and the trophoblast invasiveness. Changes in the number of MC or in the proportion between their subtypes (MCTC and MCT) can play an important role in the physiology and pathology of the human placenta.

Keywords: mast cells, angiogenesis, human trophoblast, degranulation, hypoxia
DOWNLOAD ARTICLE (PDF)
The evaluation of the treatment tolerance in cervical cancer patients, FIGO stage II and III, treated with radiotherapy in dependence on the brachytherapy method and the type of radioactive source used
GIN ONKOL, 2005, 3 (1), p. 22-32
ABSTRACT

Introduction: The disadvantageous effect of the irradiation in cervical cancer patients is the radiation injury, especially in the bladder and rectum. Objective: The aim of the study was the assessment of the frequency and intensity of early and late radiation injury in dependency on the radioactive source and the brachytherapy method used in radical treatment of cervical cancer patients. Material and methods: The retrospective analysis of 314 cervical cancer patients FIGO II and III stage, treated with radiotherapy at the Gynecological Oncology Department at Centre of Oncology in Lublin was performed. The two groups of patients were separated. Group I – 148 women, treated between 1990 and 1992. In this group the brachyterapy was performed with the afterloading system, using radium or cesium as the radioactive source. Group II – constituted 166 women, treated between 1994 and 1996. In this group, the automatic afterloading system with cesium was used. Results: The percentage of early rectal and bladder sequelae was similar in both groups, and amounted for 43.92% in the group I, and 45.78% in the group II. The difference observed was not statistically significant (p=0.82). There was demonstrated, that early sequelae in both comparable groups more frequent appeared in rectum, than in bladder (p<0.0001). There was proved more frequent late radiation injury in the group I. Late radiation sequelae was noted among 34.46% of patients in the group I, and among 16.27% of patients in the group II. The difference was statistically significant (0.00033). Conclusions: The method of automatic afterloading with cesium is safer and causes less risk of late complications, than manual afterloading, using radium.

Keywords: carcinoma of the uterine cervix, LDR brachytherapy, radiation therapy, early and late radiation complications
DOWNLOAD ARTICLE (PDF)
Changes in oxygen concentration may involve angiogenesis changing an expression of VEGF receptors – in vitro trophoblast culture study
GIN ONKOL, 2005, 3 (1), p. 33-39
ABSTRACT

Angiogenesis is essential for tissue growth, particularly for the development of fetus and placenta, but also plays a crucial role in pathologic phenomena, e.g. retinopathy or tumors. The key mediator involved in the development of new vessels is vascular endothelial growth factor (VEGF), acting by specific receptors – VEGF-R1, VEGF-R2 and VEGF-R3. These receptors are present on the surface of cells of developing trophoblast as an expression of auto- and paracrine proangiogenic activity of trophoblast. The aim of this study was to assess the expression of VEGF receptors on cultured trophoblastic cells in vitro, in normoxic or hypoxic conditions. Material and methods: Placentae (n=12) were collected on the occasion of scheduled cesarean sections terminating normal, full-term pregnancies. After excision of tissue fragments, placental tissue was crumbled and trophoblastic cells were isolated by the Kliman technique. Cells were cultured and randomized into two groups. Culture conditions were as follows: group 1: CO2 – 5%; O2 – 20%, N2 – completed; group 2: CO2 – 5%, O2 – 5%, N2 – completed. After 96 hours’ incubation cultures were terminated, supernatant was removed and solid material was fixed in 4% formalin. Immunocytochemical staining for VEGF-R1 and VEGF-R2 was performed. Preparations were evaluated using the morphometric software Quantimet C500+ (Leica). Intensity and surface area of color reaction were analyzed in 20 randomly selected fields of vision (200x). The level of expression of receptors was shown as a product of analyzed parameters and was compared in both groups. Results: The level of expression of VEGF-R1 and VEGF-R2 was greater in the group 2 as compared with the group 1 by 113.9% and 83.6% respectively. Conclusions: Trophoblast culture in hypoxic conditions leads to a greater expression of VEGF receptors than in normoxemic culture.

Keywords: trophoblast, VEGF, hypoxia, angiogenesis, morphometry
DOWNLOAD ARTICLE (PDF)
The role of the PTEN gene alterations in the pathogenesis of the endometrial carcinoma
GIN ONKOL, 2005, 3 (1), p. 40-46
ABSTRACT

Sporadic endometrial carcinoma, most frequently diagnosed in routine practice, can be divided into two biologically and clinically distinctive subtypes of which one is estrogen-related (type I), the other estrogenunrelated (type II). The type I of endometrial carcinoma usually shows mutations of tumor suppressor phosphatase tensin homologue (PTEN) accompanied by K-Ras and β-catenin genes mutations and microsatellite instabilities whereas alternations of genes encoding p53 and p16 proteins or her2/neu amplifications are observed infrequently. Mutations of PTEN gene, localized on chromosome 10, leading to loss of gene function can increase the neoplastic transformation. PI3-k phosphorylation and accumulation of active forms of Akt within neoplastic cells lead to up-regulation of Bad protein resulting in Bcl-2, Bcl-xl proteins and caspase- 9 mediated apoptotic pathway inhibition. Heterogeneity of PTEN gene expression observed in surgical specimens correlates to histological stage of carcinoma and prognosis. PTEN expression is an important prognostic factor reflecting longer overall survival in group of patients diagnosed with advanced stages of endometrial cancer treated with adjuvant chemotherapy. Loss of PTEN gene expression can suggest tumor progression. However, incorporation of PTEN expression analysis into routine diagnostic procedure is limited by the presence of PTEN pseudogene, which is actively transcribed in various neoplastic tissues including endometrial cancer but not in normal endometrial tissue.

Keywords: endometrial cancer, PTEN, mutations, carcinogenesis
DOWNLOAD ARTICLE (PDF)
Palliative radiotherapy of bone metastases in gynecological malignancies
GIN ONKOL, 2005, 3 (1), p. 47-52
ABSTRACT

In spite of significant progress in diagnostic and therapeutic methods, bone metastases are still the diagnostic and therapeutic problem. They do not give any uniform clinical signs. They may be asymptomatic in some cases, in the others, they are very painful and may cause pathological fractures. The treatment method employed in these events has a significant meaning. The aim of the study was the bone metastases frequency in gynecological malignancies analysis and the assessment of direct analgesic effect of palliative irradiation. Material and method: The subject of analysis was the group of 1359 patients with gynecological malignancies, treated between 1996 and 1998 at Gynecological Department of Maria Sklodowska-Curie Memorial Cancer Centre in Warsaw. All diagnoses were confirmed with histopathological examination, clinical exams and the digital exams. The clinical stage was assessed according to FIGO classification. They were qualified to the intent – to treat treatment, according to in force protocols. From the above group, 20 patients with bone metastases were separated. In all cases, palliative radiotherapy with analgesic intent was performed. Photons γ Co60, or X energized 4, 9 or 15 MeV, with one or two – field technique. The hypo fractionation schemes were performed: 3, 4, 8 Gy per fraction, suitably in 10, 5 or 1 fraction. The analgesic effect was evaluated, based on the subjective patient’s opinion and the analgesic drugs limitation possibility. Results: Direct analgesic effect was obtained in 17/20 (85%) patients. The fractionation scheme had no influence on direct analgesic effect. Conclusions: External beam irradiation is an effective palliative treatment of pain caused by bone metastases. The fractionation schedule has no significant influence on analgesic effect.

Keywords: palliative radiotherapy, bone metastases, gynecological malignancies, hypofractionation, analgesic effect
DOWNLOAD ARTICLE (PDF)
The comparison of two chemotherapy schemes adverse side effects in adjuvant treatment of advanced ovarian cancer
GIN ONKOL, 2005, 3 (1), p. 53-58
ABSTRACT

Objective: To compare tolerance of first-line chemotherapy with cisplatin-cyclophosphamide (PC) and cisplatin- paclitaxel (TP) in patients with ovarian cancer stage IIIC. Material and methods: A retrospective review of clinical course in 145 patients treated in Dept. of Gynecology at Medical University of Gdańsk was performed. All patients underwent primary surgery and received adjuvant chemotherapy with six cycles of cisplatin (75 mg/m2) and cyclophosphamide (750 mg/m2) with 21-day intervals – 83 women, and six cycles of cisplatin (75 mg/m2) and paclitaxel (135 mg/m2, 24-hour infusion period) at 21-day intervals – 62 women (1999-2001). Toxicity was reviewed and compared in accordance to Common Toxicity Criteria and World Health Organization toxicity scale. Results: Neutropenia, anemia, thrombocytopenia and gastrointestinal toxicity were similar in the two regiment of chemotherapy. Grade 3 and 4 anemia and grade 2 and 3 fatigue were more common in TP group. The peripheral neurotoxicity was more common in TP group than PC group (32% vs. 1.2%). Dose reduction or prolongation of treatment occurred in 16% of PC group and 27% of TP group. The treatment was discontinued in 4 cases – one in PC group and three in TP group. There was one death in PC group due to myelosuppression and progression of disease. Conclusion: The TP regiment was associated with higher frequency of anemia and neurotoxicity than PC. Dose reduction and prolongation of treatment interval due to toxicity concerned more often TP combination.

Keywords: ovarian cancer, chemotherapy, paclitaxel, cisplatin, cyclophosphamide
DOWNLOAD ARTICLE (PDF)