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Mapping the sites of putative tumor suppressor genes at 6p25 and 6p21.3 in cervical carcinoma: occurrence of allelic deletions in precancerous lesions.
Allelic deletions on the short arm of chromosome 6 (6p) are one of the common, possibly early, genetic changes that occur in the pathogenesis of cervical carcinoma (CC). Previous loss of heterozygosity (LOH) studies in CC identified a number of critical regions of deletions on 6p. However, the precise location of minimally deleted regions and their role in precancerous lesions have not been well characterized. To address these questions, we first performed a detailed LOH analysis on 6p in 59 cases of invasive CC. The pattern of LOH identified two minimal regions of deletions, one spanning a 5 cM genetic distance at 6p25 and a second site of 10.3 cM deletion mapping to 6p21.3. The 6p21.3 minimal deletion spans HLA class I genes. To understand the role of 6p genetic alterations in the development of CC, we also investigated 12 high-grade and 4 low-grade cases of cervical intraepithelial neoplasia (CIN) for LOH after laser microdissection. The high-grade CINs exhibited 91.7% LOH, and low-grade CINs had 50% LOH. These findings implicate the presence of at least two tumor suppressor genes on 6p relevant to CC and suggest that these genetic alterations occur very early in CC development. This study should therefore facilitate the identification of tumor suppressor genes on 6p and may identify which CINs are at high risk of progressing to invasive CC.
[First report on ultrasonic therapy in Colombia].
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Bronchography with dionosil (propyliodone); a new absorbable bronchographic medium.
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Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.
PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.
[Electrodehydration and electrolytic depilation].
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Culture and domestic violence: the ecology of abused Latinas.
This study examined the predictors of domestic violence within a sample of 60 immigrant Latinas, of whom 30 had sought assistance for abuse and 30 had sought other family services. Hypotheses were derived from several frameworks relevant to understanding abuse--intrapsychic (learned helplessness), interpersonal (family violence), and feminist theory. Findings related to the specific formulations were subsequently combined into a model of abuse in which the mutuality of communication within the couple mediates the effects of husband's intoxication and environmental stressors on the occurrence/severity of abuse. The study points out the inadequacy of relying on any one existing theory and supports the idea of taking an ecological approach to the study of abuse in specific populations.