Biomedical subjects

J Kulmala

Publications and source records attributed to J Kulmala.

41 records · Page 3Linked to original sources

PubMedDate not supplied

Endometrial cancer cell lines are sensitive to paclitaxel.

We have previously reported a 24 fold difference in the cisplatin sensitivity and a 12 fold difference in carboplatin sensitivity of endometrial carcinoma cell lines. In this study as evaluate paclitaxel sensitivity of the same cell lines. We tested nine endometrial cancer cell lines with the 96-well plate clonogenic assay using limiting dilution. The chemosensitivity was expressed as IC50 value, the drug concentration causing 50% inhibition of clonogenic survival. IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation. The IC50 values for paclitaxel were 0.49 - 2.3 nM showing only a 4.7 fold difference between various cell lines. No correlation could be demonstrated between in vitro paclitaxel and platinum analog sensitivities of endometrial adenocarcinoma cell lines. The variance in paclitaxel sensitivity of different cell lines was little. Our results suggest that endometrial adenocarcinoma cell lines tested with the same methods. The clinical efficacy of paclitaxel in the treatment of endometrial cancer should further be evaluated in clinical trials.

Adenocarcinoma↗

PubMedDate not supplied

Paclitaxel and cisplatin sensitivity of ovarian carcinoma cell lines tested with the 96-well plate clonogenic assay.

Platinum based chemotherapy is the cornerstone of treatment in advanced ovarian carcinoma. Paclitaxel, an unique antimicrotubule agent has shown significant clinical activity in cisplatin-resistant tumours, indicating a lack of cross-resistance. To compare the in vitro sensitivity of ovarian carcinoma to cisplatin and paclitaxel, we tested 7 ovarian carcinoma cell lines with the 96-well plate clonogenic assay. Chemosensitivity was expressed as the IC50 value i.e. the drug concentration causing 50% inhibition of clonogenic survival. IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation. The IC50 values for paclitacel were 0.4-3.4 nM, showing an 8.5-fold difference between various cell lines. The IC50 values for cisplatin were 0.1-0.45 ug ml-1 showing only a 4.5-fold difference. This variance is clearly smaller than the 25-fold difference observed with the same method in endometrial carcinoma cell lines (Rantanen et al, Br J Cancer 69: 482-86, 1994). In accordance with clinical findings, no cross-resistance or correlation between sensitivity to paclitaxel and cisplatin could be demonstrated.

Adenocarcinoma↗

PubMedDate not supplied

Stage-specific apoptosis in the rat seminiferous epithelium: quantification of irradiation effects.

The effects of 3 Gy local X-irradiation on the adult rat testis were studied together with exact determination of the radiation dose distribution in the testis. Seminiferous tubule segments were isolated 8-66 hours postirradiation (p.i.), squashed between a microscope slide and a coverslip, and the exact stage of the seminiferous epithelial cycle was identified under a phase-contrast microscope. The squash preparations were subjected to in situ end labeling (ISEL) for visualization and quantification of apoptotic cells. In controls, the highest numbers of apoptotic cells were scored in stages XII-XIV and I. In situ end-label staining of cells was observed in A3-A4 spermatogonia, spermatocytes at zygotene, pachytene, and meiotic division phases, as well as in early spermatids. In irradiated testes, from 8 hours p.i. and onward, intermediate- and B-type spermatogonia were sensitive at stages II-VI. At 42 hours, in stage I, elevated numbers of degenerating spermatocytes were seen. Most of them had not undergone meiotic divisions at stage XIV and showed an apoptotic type of degeneration at stage I. At the time of irradiation, the cells were in stage XIII, suggesting that diakinetic spermatocytes are particularly sensitive to irradiation. Also, preleptotene-zygotene spermatocytes in stages VII-XII were sensitive to irradiation. Apoptotic-type of cell degeneration was confirmed by living cell squash preparations, electron microscopy, and DNA electrophoresis. In conclusion, irradiation may provide a useful model system for studying apoptosis, and its control in spermatogonia and meiotically dividing cells.

Animals↗

PubMedDate not supplied

Vulvar squamous cell carcinoma cell lines are sensitive to paclitaxel in vitro.

In the current study, paclitaxel sensitivity of eight vulvar squamous cell carcinoma (SCC) cell lines was tested using a 96-well plate clonogenic assay. The chemosensitivity was expressed as IC50 corresponding to the drug concentration causing 50% inhibition in clonogenic survival. IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation. The paclitaxel sensitivity of the eight vulvar SCC cell lines expressed as IC50 varied from 0.6 to 2.9 nM. The observed differences between the individual cell lines were surprisingly small, only 4.8-fold at the most. Paclitaxel sensitivity of vulvar SCC cell lines is of the same magnitude as the paclitaxel sensitivity of endometrial and ovarian carcinoma cell lines tested in our preliminary experiments with the same assay. We have previously studied the intrinsic radiosensitivity of these vulvar SCC cell lines. No correlation could be found between radiosensitivity and paclitaxel sensitivity. These results indicate that vulvar SCC is consistently sensitive to paclitaxel in vitro. The role of chemotherapy in the treatment of vulvar carcinoma has not been clarified yet. The efficacy of paclitaxel should be tested further in clinical trials.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Taxane sensitivity of ovarian carcinoma in vitro.

Paclitaxel, the first clinically available taxane, has proven to be effective in the treatment of ovarian carcinoma. Docetaxel is the second taxoid derivative which has also shown activity in ovarian carcinoma. These two compounds have clear differences in pharmacokinetics and side-effects. In the present study we have tested the cytotoxic effect of docetaxel in seven ovarian carcinoma cell lines using the 96-well plate clonogenic assay. These results have been compared with data obtained from our recent study on cisplatin and paclitaxel sensitivities of the same cell lines. Chemosensitivity has been expressed as IC50 value, the drug concentration causing 50% inhibition of clonogenic survival. The IC50 values for docetaxel were 0.23-2.30 nM showing a 10-fold difference between individual cell lines. On a molar basis, docetaxel was 1.2 to 2.6 times more active than paclitaxel in six out of seven cell lines. This may be explained by differences in the mechanism of action or by differences in other pharmacological properties.

Adenocarcinoma↗