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Biomedical subjects

M Z Khan

Publications and source records attributed to M Z Khan.

81 records · Page 5Linked to original sources

Lack of expression of P-glycoprotein in 7 small cell lung cancer cell lines established both from untreated and from treated patients.

The establishment and characterisation of 7 small cell lung cancer cell lines is described. Four cell lines were established from biopsies taken from untreated patients and one of these was from primary tumour taken via the fibreoptic bronchoscope. The other three were from biopsies taken from patients who had relapsed after chemotherapy. All grow as non-adherent aggregates of cell and express a range of neuroendocrine and epithelial features characteristics of small cell lung cancer cell lines. No relationship was observed between the characteristics of the cell line in vitro and the treatment status of the patient from whom the biopsy was taken. Furthermore, none of the cell lines expressed p-glycoprotein even though 3 were derived from relapse biopsies where chemotherapy included drugs associated with the multidrug resistance phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Identification and characterisation in vitro of cells with a non-SCLC cell-like phenotype derived from a continuous SCLC cell line.

Two adherent sublines, H69V and H69VZ, have been isolated from the classic SCLC cell line NCI-H69. Significant morphological differences were observed between the parental and the derivative cell lines. While NCI-H69 grew as densely packed free floating cellular aggregates the derivative lines grew as a monolayer of epithelioid cells. The growth rates of both the derivative lines were faster than the parental line with doubling times closer to non-SCLC cell lines in the derivative lines. Both H69V and H69VZ either express very low levels or do not express neuroendocrine cell markers including L-dopa-decarboxylase (DDC), creatine kinase-BB isoenzyme (CK-BB), bombesin-like immunoreactivity (BLI), neuron specific enolase (NSE), and neurosecretory type dense core granules (DGCs), compared to the parental cell line. All the lines stained positive for epithelial markers such as CAM5.2. LDH isoenzyme and chromosome analyses confirmed the human origin of all the cell lines. Therefore, it appears that cell line NCI-H69 contains stem cell subpopulation capable of generating cells of both small and non-small cell like phenotypes.

Carcinoma, Non-Small-Cell Lung↗

Oncogene transfection of mink lung cells: effect on growth characteristics in vitro and in vivo.

Three sublines have been derived from the parental line Mv1Lu by transfection with normal and mutated Ha-ras, and myc oncogenes, and subsequent cloning. All the oncogenes have increased the growth rate of the cell in vitro, increased their plating efficiency in monolayer and suspension, and reduced their serum dependence. Growth in vivo as xenografts in nude mice has also been increased. Very few tumours were generated from the parental line and those that did form did so after a prolonged lag period, while the transfected lines produced tumours with 100% efficiency, and a short lag period. In general the effects of ras transfection were more extreme, with the highest growth rates and plating efficiencies in vitro and the shortest lag period and doubling times in vivo. There was no increase in plasminogen activator activity as a result of transfection, and the invasive behaviour of the lines in organotypic culture was broadly similar.

Animals↗

The effect of H-ras oncogene transfection on response of mink lung epithelial cells to growth factors and cytotoxic drugs.

Mink lung epithelial cells were transfected with c-myc and activated H-ras genes. The transfected sublines formed colonies in soft agar and were tumorigenic when injected subcutaneously into athymic nude mice. DNA synthesis was measured in each of the cell lines by 3H-thymidine incorporation and in the parent line there was dose related stimulation of DNA synthesis by epidermal growth factor (EGF) and inhibition by transforming growth factor-beta (TGF-beta). The c-myc transfected line had a reduced inhibitory response to TGF-beta and an exaggerated stimulatory response to EGF whereas the activated H-ras1 transfected line did not respond to TGF-beta or EGF. The activated H-ras1 transfected line was significantly more resistant to doxorubicin (ID50, 4.4 nM) and vincristine (ID50, 4.9 nM) than the parent mink lung epithelial cell line (ID50, 2.7 nM and 2.4 nM respectively). It would appear that oncogene transfection can alter the sensitivity of mink lung epithelial cells to both exogenous growth factors and cytotoxic drugs.

Animals↗

Association of socio-economic factors with drug use among college students in an Indian town.

The paper examines the association of various socio-economic factors with the use of drugs by college students in a town in central India. Data were collected from a large sample, using a self-reporting questionnaire. It was found that analgesics, tobacco and alcohol were the most commonly used drugs amongst some 30 per cent of the students. Factors such as age, urbanity, sex, marital status as well as the family's educational and economic status were seen to be relevant. Inter-parental and inter-generational tensions in the family also had a bearing. Drug use by one or more members of the family was seen as a highly significant factor. The data thus suggest that an inclination towards drug taking might be embedded in the social matrix itself.

Adolescent↗

Sociocultural differences between former and current users of psychoactive drugs in a sample of college student.

The paper present the results of a study on the underlying sociocultural factors which distinguish "former users" of drugs from "current users" among the college youth. Belonging to a similar social milieu, the two sets showed little difference in many respects. There were, however, features on which the two differed. Those who gave up drug use were mostly from the middle or lower strata of society, and had tolerant but drug abstaining family members. They were mostly junior students pursing "professional courses", and had fewer drug-using friends. Also they did not view drugs with favour. Giving up drug use had been mainly their personal decision, perhaps prompted by the influence of their family members and peer-group and by their own experience with drugs. Thus the former users have been found to differ noticeably from the current users.

Adolescent↗

[Regulation of genetic activity by thyroid hormones. II. Specificity of interaction of cytoplasmic thyroxine receptor isolated from human embryonal fibroblasts and HeLa cells with DNA].

The work concerns a new approach to evaluating the receptor and hormone-receptor complex specific interaction with DNA and revealing the cause of the absence of the hormone-receptor complex acceptation with HeLa cell chromosomes. It has been shown that hormone-receptor complexing should precede specific interaction with DNA. The purified receptor-thyroxin complex is saturatable and specifically competes with Hae III restrictase, protecting specific sites of DNA recognition from this enzyme. Specificity of the hormone-receptor complex interaction with DNA depends on the sequences surrounding Hae III restriction site. The HeLa cell hormone-receptor complex does not interact with the recognition site for the normal hormone-receptor complex.

Cells, Cultured↗

Research on drug dependence in India.

The persistent problem of drug dependence has been studied in India from several disciplinary angles. The present exercise attempts to answer the question of whether these efforts have been able to build up a dependable and comprehensive body of literature. While available studies show the magnitude of the problem in different population groups, there are obvious information gaps which discourage attempts to evolve countrywide estimates. This is also the case with such aspects as personal attributes of drug users, socio-cultural background and psychological characteristics. Such data gaps show up further when processes of experimentation or abstinence, as well as psychosocial implications, are examined. These considerations call for the intensification of research activities, development of a co-ordinated research programme and the investigation of the problem from different disciplinary perspectives.

Adolescent↗

Tumorigenicity, invasion and metastasis of the small cell lung cancer cell line NCI-H69 and two derivative lines MOG-H69V and MOG-H69VZ.

Two adherent cell lines MOG-H69V and MOG-H69VZ have been isolated from a continuous cell line, NCI-H69, derived from human small cell lung cancer by Carney et al, [1987]. They have been established and characterised morphologically, biochemically, and for growth characteristics in vitro Khan et al (19). In the present study both the parental and the derivative lines have been investigated for invasiveness in vitro and in vivo. The parental line showed an early invasiveness compared with both the derivative cell lines. All cell lines formed tumours in nude mice with 100% take rate. Xenograft histology of all the cell lines revealed pleomorphic tumours, however the derivative lines showed areas of focal, large, spindle cells containing both acidic and neutral mucin, and spaces between the cells were found filled with alcianophilic, amorphous material. The parental line was invasive and metastatic. Tumours of both the derivative lines were non-metastatic under similar conditions. They were also investigated for neuroendocrine-cell marker expression. These data show that while the behaviour of the parental line was compatible with small cell lung cancer, that of the derivative lines was more indicative of non-small cell lung cancer, both in vitro and in vivo. As previous data suggested a common origin of the parental and the derivative lines, probably from a stem cell subpopulation present in the parental line, these lines represent a useful model for the study of phenotypic changes in lung cancer.

Animals↗