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J Gogusev

Publications and source records attributed to J Gogusev.

57 records · Page 4Linked to original sources

Cellular and genetic constitution of human endometriosis tissues.

For many years, endometriosis has been an enigmatic and confusing disorder, but there have been recent contributions to the subject, provided by modern techniques in cellular and molecular biology, regarding the cell lineage involved, the stage of differentiation, and genomic features. This review deals mainly with the cellular, cytochemical, cytogenetic, and molecular cytogenetic features of primary endometriotic lesions and cultured endometriotic cells. The FbEM-1 cell line, taken as an in vitro model, showed cell proliferation and differentiation features suggesting an immature endometriosis-related cell lineage. Chromosomal analysis of these cells demonstrate a complex karyotype including a rearrangement interpreted as der(5) t(5q34;6p11) indicating a clonal cell proliferation. Data of recurrent DNA sequence copy number alterations detected by the comparative genomic hybridization in a series of primary endometriotic lesions also are described. Predominant recurrent anomalies were found on chromosome 1p and 22q in 50% of the studied samples. Additional losses were seen on chromosomes 5p(33%), 6q(27%), 7p(22%), 9q(22%), and 1q(22%), as well as on 17q segments in one case. Gain of DNA sequences was seen on chromosomes 6q, 7q, and 17q. The potential role of the genetic changes identified are discussed in relation to the putative oncogenes and/or tumor suppressor genes possibly involved in development of endometriosis.

Animals↗

Modulation of c-myc, c-myb, c-fos, c-sis and c-fms proto-oncogene expression and of CSF-1 transcripts and protein by phorbol diester in human malignant histiocytosis DEL cell line with 5q 35 break point.

Following exposure to phorbol ester (TPA), DEL cell line, a human malignant histiocytosis (MH) cell line, is able to differentiate along a macrophage phenotype and thus it provides a suitable model for analyzing the sequential and differential gene expression associated with monocyte/macrophage differentiation. C-myc, c-myb, c-fos, c-sis and c-fms expression were determined by Northern analysis at various times following TPA treatment. The results showed that TPA down-modulated the constitutive expression of c-myc, c-myb, and c-fms, mRNA to low but still detectable levels. Conversely, TPA-induced differentiation resulted in transient appearance of c-fos, whereas no change in the level of c-sis and actin transcripts were observed. Thus, the c-fms and c-sis genes appear to be regulated in a specific manner in this malignant histiocytosis derived cell line. Furthermore, these investigations demonstrated a constitutive CSF-1 gene expression which transiently increased at mRNA and also at protein level as evaluated by a murine bone marrow CFU bioassay. Through this drug-induced modulation, the DEL cell line offers an additional model for studying some of the subtle interrelations existing between a growth factor (CSF-1) and its receptor (c-fms) in the monocyte/macrophage system.

Cell Differentiation↗

Regulation of TNF-alpha and IL-1 gene expression during TPA-induced differentiation of "Malignant histiocytosis" DEL cell line t(5;6) (q35:p21).

The production of TNF-alpha and IL-1 alpha and beta molecules has been shown to be associated with the proliferation and activation of cells of the monocyte/macrophage series, the intermediate steps in the synthesis of these molecules have been less investigated. Unstimulated and TPA stimulated DEL cells (a CD30-positive, t(5;6)(q35;p21) malignant histiocytosis cell line) were used to study the expression of TNF-alpha and IL-1 genes and to evaluate, by nuclear run-on assay and biological measurements, the control of their transcription and the level of protein production. To refine this analysis, the effects of cycloheximide and actinomycin D were also evaluated in this investigation. Following TPA stimulation, transcription of TNF-alpha (constitutively present) increased threefold as early as 30 mins and started decreasing by 24h. Cycloheximide superinduced the expression of TNF-alpha mRNA and, accordingly, the release of its protein. By contrast, transcription of IL-1 molecules appeared de novo and did not result in a biologically detectable protein. Measurements of RNA half line after actinomycin D indicated that TNF-a and IL-1 alpha mRNAs are not as stable as that of IL-1 beta. These results indicate that, despite their common synergistic activity, the transcriptional and post-transcriptional mechanisms regulating the synthesis of TNF-alpha and IL-1 alpha and IL-1 beta involve different pathways.

Blotting, Northern↗