Biomedical subjects

N H Mulder

Publications and source records attributed to N H Mulder.

364 records · Page 21Linked to original sources

PubMedDate not supplied

Effects of c-myc oncogene modulation on drug resistance in human small cell lung carcinoma cell lines.

Small cell lung carcinoma (SCLC) is characterized by rapid development of resistance to drugs, such as cisdiamminedichloroplatinum (II) (cDDP) and anthracyclines. The molecular basis for resistance to cDDP and adriamycin (Adr) is poorly understood. One of the genetic alterations observed in SCLC, which is correlated with poor prognosis, is amplification and overexpression of c-myc oncogene. Therefore, activation of the c-myc oncogene might form a basis for resistance. The relationship between c-myc and cDDP as well as Adr resistance was analyzed by down-regulation of endogenously expressed c-myc in the human SCLC cell line GLC4, and its cDDP and Adr resistant sublines (GLC4-cDDP and GLC4-Adr). Cells were incubated with an unmodified antisense (AS) oligodeoxynucleotide complementary to the first 5 codons of the c-myc mRNA in serum free culture medium. Pre-incubation with 15 microM AS c-myc, reduced c-myc protein expression and induced 30-35% growth inhibition in all 3 cell lines. It resulted in increased cDDP sensitivity in GLC4-cDDP but not in GLC4. However, this pre-incubation did not affect Adr sensitivity in all lines. The effect of AS c-myc pretreatment on cDDP resistance was not mediated by changes in cell cycle distribution. These findings suggest that c-myc plays a role in cDDP resistance by effects other than those on cell cycle distribution.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Pulmonary function after high-dose chemotherapy with autologous bone marrow transplantation and radiotherapy in patients with advanced loco-regional breast cancer.

Our aim was to study the extent of pulmonary toxicity after high-dose chemotherapy and radiotherapy in breast cancer patients. In a retrospective study the pulmonary symptoms and chest X-rays were analyzed before, during and after treatment in 17 patients, treated with loco-regional radiotherapy to the breast/chest wall and the regional lymph nodes after the completion of high-dose chemotherapy and autologous bone marrow transplantation for locally advanced breast cancer. Lung function was evaluated between 15 and 46 months after completion of the irradiation. Nine patients (53%) had pulmonary symptoms during and/or within two months from irradiation. Radiographic changes were seen in twelve patients (71%) and a decreased diffusion capacity occurred in nine patients (53%). The spirometric values (VC and FEV1) were abnormal in two patients (12%). There is a high incidence of radiation pneumonitis, although no consistent correlation between the various parameters (pulmonary symptoms, chest X-rays and lung function tests) could be found.

Adult↗

PubMedDate not supplied

The anatomical substrate for a difference in surgical approach to rectal cancer in male and female patients.

This review emphasizes' gender related anatomical differences warranting a difference in surgical approach to the problem of rectal cancer in men and women. Differences in the anatomy of the bony pelvis, the pelvic viscera and the lymphatics of the rectum, inspired the authors to extend the margins of the rectal resection in the anterior plane in female patients. Between 1978 and 1992 a rectal resection was carried out for cancers confined to the pelvis in 158 patients. Of these patients 152 were available for review, 95 male and 57 female. In 24 out of 57 female patients extension of the rectal resection towards the genital tract by en bloc excision of posterior vaginal wall and/or uterus was considered necessary to be confident about obtaining tumour free margins. After a median follow-up of 8 years the risk of local recurrence and cancer related death were significantly lower in female patients.

Female↗

PubMedDate not supplied

Expression of proteins correlated with the unique cisplatin-sensitivity of testicular cancer.

Cisplatin (CDDP) has a curative effect in approximately 80%, of patients with testicular cancer, in contrast to the frequent development of resistance in patients with small cell lung cancer and ovarian cancer, and to the natural resistance of colon cancer. At present it is unknown which factors explain the unique curability of testicular cancer. Since it is very likely that the absence or presence of specific proteins plays an important role in cellular sensitivity towards CDDP, we have screened the protein patterns of various human CDDP-sensitive cell lines and cell lines with acquired or intrinsic resistance to CDDP of testicular, lung and colon origin. The expression of several proteins appeared to correlate with in vitro CDDP sensitivity. The most striking difference found was a relative increase in expression lactate dehydrogenase (LDH) H-subunit expression in the germ cell lines. In testis and colon tumour samples some of these proteins, LDH-H included, also appeared to correlate with in vivo CDDP sensitivity. In the analysis of the mechanisms of drug-resistance, screening of the protein patterns of intrinsic sensitive and resistant cell lines could be a valuable approach.

Antineoplastic Agents↗