Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study pertains to an entity characterized by the presence of multiple intrapulmonary nodules, which consist of an admixture of bundles of well-differentiated smooth muscle cells and epithelial-lined spaces. These lesions have been frequently interpreted as a variant of hamartomas. However, in this review of the literature, and careful analysis of nine cases of this entity, we concluded that they should be considered metastases from smooth muscle tumors which incorporate some structures of mature lung parenchyma as they slowly expand. We affirm that the designation "fibroeliomyomatous hamartoma" should be discarded. Our cases occurred in six female and three male patients. In all but one female the primary source for lung metastases was uterus, while the male patients had primary lesions in the saphenous vein, diaphragm, and soft tissues. These lung lesions increase in size and number and are potentially fatal, though this may take many years. Even though the smooth muscle cells of the lung nodules appear bland on light microscopy, we were always able to demonstrate mitotic activity; electron microscopy indicated immaturity of the cells. For these reasons, we believe the tumors to represent metastatic leiomyosarcomas.
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PMID:Pulmonary metastases (with admixed epithelial elements) from smooth muscle neoplasms. Report of nine cases, including three males. 39 47

Phospholipase C-gamma (PLCgamma) has been implicated in tumor cell motility required for invasiveness and metastasis. Diminished tumor dissemination has been demonstrated in xenograft models, but studies in naturally-occurring tumors are lacking, having been limited by the timing of the interventions. Therefore, we generated mice that express a doxycycline (DOX)-inducible dominant-negative fragment of PLCgamma, PLCz; this approach avoids the in utero lethality caused by the absence of PLCgamma. As we targeted two de novo-occurring carcinomas of the mammary (MMTV-driven polyoma middle T antigen model, PyVmT) and prostate (TRAMP model) glands, we limited expression to these epithelial cells by driving DOX transactivator from the prostatein C3 promoter. This avoids the confounding variable of potentially abrogating motility in stromal and endothelial cells. These mice developed normally in the presence of DOX, except for limited mammary development if treated before 6 weeks and immaturity of the prostate gland if treated before 2 weeks of age. DOX-mediated induction of PLCz from age 8 to 16 weeks in PyVmT mice decreased the number of lung metastases by >10-fold (P<0.06) without a detectable effect on in situ tumor cell proliferation or tumor size. Lung metastases were also significantly decreased in the TRAMP model in which the mice expressed the PLCz fragment (P<0.05). DOX treatment itself had no effect on tumor size or metastasis in control mice, nor did it affect tumor dissemination in nontransgenic littermates. In conclusion, abrogation of the PLCgamma signaling pathway can limit the metastatic potential of carcinomas.
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PMID:PLC gamma contributes to metastasis of in situ-occurring mammary and prostate tumors. 1713 Aug 35