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This paper focuses on the influence of chemoresistance on the herpes simplex virus (HSV-tk)/ganciclovir (GCV)-induced bystander effect (BE), as studied in a human small cell lung cancer (SCLC) cell line (GLC4) and its sublines with in vitro acquired resistance to adriamycin (GLC4/ADR), mitoxantrone (GLC4/MITO) and cisplatin (GLC4/CDDP). Chemoresistance for adriamycin, mitoxantrone and cisplatin significantly changed GCV sensitivity. A significant BE was found in all GLC4 cell lines. Compared to the parental GLC4 cell line, the BE was significantly higher only for the GLC4/ADR cell line. No expression of the nucleoside transporters MRP4 and MRP5 was detected. In all cell lines expression of connexin 43 was found, but modulation of gap junctional intercellular communication (GJIC) by 18-alpha-glycyrrhetinic acid did not significantly change the BE in any of the GLC4 cell lines. In conclusion, chemoresistance can influence the HSV-tk/GCV-induced BE, which seems not to be related to differences in MRP4/MRP5 expression or to differences in GJIC.

The purpose of the study was to investigate whether cycle-related variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would increase the metastatic potential at specific times during the menstrual cycle.VEGF levels in serum and whole blood were evaluated during the normal menstrual cycle in premenopausal women. Determination of the menstrual phase was based on hormonal measurements.A total of 46 samples were taken of six menstrual cycles. Serum VEGF was inversely related with progesterone levels (r = -0.6, p = 0.012). Throughout the menstrual cycle the serum VEGF decreased indicating that the lowest VEGF level occurs during the secretory phase, which is compatible with the inverse relationship between serum progesterone and VEGF.These findings, however, do not suggest that individual VEGF levels can direct the optimal timing of surgical intervention in breast cancer.

The aim of this study was to determine the relationship between survival and value of molecular markers in the primary tumour in a group of patients with irresectable rectal cancer, treated with preoperative chemo-radiotherapy.Immunohistochemistry for p53, p21, bcl-2 and Ki-67 was performed on pre-treatment biopsy specimens of 34 patients with irresectable rectal cancer. Preoperative treatment consisted of pelvic irradiation of 45-56 Gy, combined with 5FU and leucovorin (350/20 mg/m2 x 5 d; in weeks 1 and 5 during radiotherapy). The median follow-up was 38 months. Endpoints were pathological T-stage and survival after surgery.Expression of p21 correlated significantly with survival (p=0.005). Survival and p21 expression also correlated significantly, when adjusted for tumour response (p=0.005, RR=4.8 (1.6-14.7)).Expression of p21 predicts a worse survival in irresectable rectal cancer treated with preoperative chemo-radiotherapy. No relationship was found between tumour response in chemo-radiotherapy and p53, bcl-2 or Ki-67.