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J Viallet

Publications and source records attributed to J Viallet.

46 records · Page 3Linked to original sources

Dominant oncogenes and tumor suppressor genes in the pathogenesis of lung cancer.

An understanding of the molecular pathogenesis of lung cancer has evolved from classic cytogenetic studies and the use of restriction fragment length polymorphisms to encompass the definition of specific genetic abnormalities associated with this disease. Activation of the dominant class of oncogenes is frequent, with involvement of the ras and myc families of genes being the best defined. Several examples of inactivation at specific loci exist and have been related to the presence of tumor suppressor genes, most notably the retinoblastoma gene, p53, and a putative gene located on the short arm of chromosome 3. As our understanding of the nature and interactions between these numerous genetic events evolves, new opportunities for early diagnosis, prevention, and treatment will arise.

Animals↗

Cholera toxin inhibits signal transduction by several mitogens and the in vitro growth of human small-cell lung cancer.

Cholera toxin (CT) inhibited the in vitro growth of three of four human small-cell lung carcinoma (SCLC) cell lines with a 50% inhibitory concentration of 27-242 ng/ml. Loss of surface membrane ruffling and the capacity of [Tyr4]-bombesin, vasopressin, and fetal calf serum to stimulate increases in intracellular free calcium clearly preceded effects on cellular metabolic activity and cell growth. 125I-[Tyr4]-bombesin binding was unaffected by CT treatment but [Tyr4]-bombesin stimulated phospholipase C activity was decreased in membranes from CT-treated SCLC cells. CT stimulated a rapid but transient increase in intracellular cyclic AMP ([cAMP]i) in SCLC. The effects of CT on susceptible SCLC were not reproduced by elevations of [cAMP]i induced by forskolin or cyclic AMP analogues. GM1 ganglioside, the cellular binding site for CT, was highly expressed in the CT-sensitive but not the CT-resistant SCLC cell lines. In contrast, expression of guanine nucleotide binding protein substrates for ADP-ribosylation by CT was similar. These data demonstrate the existence of a CT-sensitive growth inhibitory pathway in SCLC-bearing GM1 ganglioside. Addition of CT results in decreased responsiveness to several mitogenic stimuli. These results suggest novel therapeutic approaches to human SCLC.

Adenosine Diphosphate Ribose↗

jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun.

We have cloned the human jun-B gene and determined its sequence and transforming and trans-activating activities. jun-B is less potent that c-jun in transforming and immortalizing primary rat embryo cells in cooperation with activated ras (effects enhanced by c-fos and TPA); unlike c-jun, jun-B does not transform Rat-1A cells alone. However, cotransfection of c-jun and jun-B into primary rat embryo cells with c-Ha-ras results in a significant decrease in transformation compared with c-jun alone, an event reversed by TPA. Cotransfection of c-jun and jun-B with or without c-fos into F9 teratocarcinoma cells results in decreased trans-activation of AP-1 compared with either gene alone. Introduction of jun-B into primary rat c-jun/ras transformants or c-jun into jun-B/ras transformants also results in a decrease in trans-activation. These findings demonstrate that, whereas jun-B and c-jun each participate in AP-1 trans-activation and malignant transformation, interactions between them involve negative regulation.

Amino Acid Sequence↗

Gastrin-releasing peptide (GRP, mammalian bombesin) in the pathogenesis of lung cancer.

Established human lung cancer exhibits a complex pattern of genetic changes as well as several distinct autocrine growth factor loops for regulatory peptides. The best studied example is that of gastrin-releasing peptide (GRP), the mammalian homolog of the amphibian bombesin. It is produced by up to 70% of small cell lung cancers and 10-20% of non-small cell lung cancers. GRP stimulates the growth of normal bronchial epithelium as well as that of small cell lung cancer, and its blockade with the use of antibodies or synthetic antagonists inhibits the growth of these tumors. Study of its molecular biology has revealed a complex pattern of mRNA processing which has lead to the recent isolation of a novel family of peptides termed gastrin-releasing peptide gene-associated peptides (GGAPs), present in normal and malignant human tissues. Additional efforts have been directed at characterizing the GRP receptor as well as its intracellular signaling pathways which have been reported both as G protein phospholipase C coupled events as well as activation of a membrane associated tyrosine kinase. In view of its expression in normal bronchial epithelium and its mitogenic effects on this tissue, GRP appears to play a central role in the early events of pulmonary carcinogenesis.

Animals↗

Trichinosis in the Canadian Arctic: report of five outbreaks and a new clinical syndrome.

Trichinosis is a serious but understudied medical problem in the Arctic. Forty-nine consecutive cases in the Inuit population of northeastern Canada are described. Most developed the disease after eating raw walrus, and the clinical presentation of most of these cases differed from previously reported descriptions of classic trichinosis due to Trichinella spiralis. Unlike the classic syndrome of a brief period of diarrhea followed by fever, myalgia, muscle weakness, and edema, the most common presentation in these cases was a prolonged diarrhea without fever and with brief muscle symptoms. High peripheral eosinophilia, high Trichinella antibody serotiters, and little direct or indirect evidence of muscle invasion in many of those with the chronic diarrheal presentation suggest a new clinical syndrome due to a different species of Trichinella seen in the Arctic or to reinfection with Trichinella.

Animals↗

Arctic trichinosis presenting as prolonged diarrhea.

We describe an outbreak of trichinosis after the consumption of raw walrus meat in 10 Inuit inhabitants of a northern community. During the presentation of the illness, diarrhea was found in all subjects and was the dominant symptom in 8 of the 10 cases. Myalgia (60%) and muscle weakness (50%) were much less prominent complaints. The diarrhea was characteristically prolonged, lasting up to 14 wk (average 5.8 wk), as opposed to comparatively short episodes of myalgia (average 5.4 days) and muscle weakness (average 4.5 days). Prolonged diarrhea with little or no muscle symptomatology in an epidemic form represents a previously unrecognized clinical presentation of trichinosis. It remains to be determined whether this new clinical presentation is related to variant biological behavior of arctic Trichinella, to previous exposure to the parasite, or to other factors.

Adult↗