Biomedical subjects

Qianqian Zhao

Publications and source records attributed to Qianqian Zhao.

4 recordsLinked to original sources

PubMed2026

Charting host structural variations in cervical cancer by long-read sequencing pinpoints a functional deletion in PIAS1.

Host structural variations (SVs) are critical in cancer development but their landscape and interaction with HPV integration in cervical carcinogenesis remain unclear. In this study, we performed Nanopore long-read sequencing on five HPV-positive cervical cancer tissues and two cell lines to profile host SVs. We identified thousands of SVs and statistically demonstrated their significant enrichment in genomic windows ±25 to ±50 kb from HPV integration sites. Cross-sample analysis revealed 60 shared SVs, including a recurrent deletion within the PIAS1 gene. Multi-omics integration (Hi-C, H3K27ac ChIP-seq, and TCGA data) showed that this deletion is associated with reduced PIAS1 expression, disruption of local topologically associating domains, advanced pathological tumor stage, and poorer overall survival. Functional assays confirmed that PIAS1 deficiency inhibits cervical cancer cell proliferation and migration. Our findings identify a PIAS1 deletion as a candidate driver event, and underscore the pivotal role of host genomic instability in HPV-associated oncogenesis.

Cervical cancer↗

PubMed2006

Comparison of three interventions to increase mammography screening in low income African American women.

BACKGROUND: Low-income African American women are more likely to die of breast cancer than their Caucasian counterparts, and at least part of the difference in mortality results from differential screening adherence. The purpose of this study was to identify more efficacious methods of promoting routine mammography screening in underserved populations. METHODS: A prospective randomized intervention study of 344 low income African American women compared the impact of three interventions on mammography adherence and stage of readiness: (1) pamphlet only; (2) culturally appropriate video; and (3) interactive computer-assisted instruction program. RESULTS: The interactive computer intervention program produced the greatest level of adherence to mammography (40.0%) compared to the video group (24.6%) and the pamphlet group (32.1%). When subjects in the pamphlet and video groups were combined to form a non-interactive group, this group had a significantly lower adherence than the group who received the interactive computer intervention (27.0% versus 40.0%). There was also significantly more forward movement in mammography stage of readiness among participants in the computer group (52.0%) compared to those in the pamphlet group (46.4%) or the video group (31.3%). When combining the non-interactive technology (pamphlet and video) there was also more forward movement in mammography stage of readiness for those in the interactive intervention group (52.0% moved 1 or 2 stages) compared to those in the non-interactive group (36.2%). CONCLUSIONS: These data indicate that tailored approaches are more effective than targeted messages either in print or video format. Another finding of this study is that interactive interventions are more effective than non-interactive interventions in increasing adherence and moving African American women forward in their mammogram stage of readiness.

Adult↗

PubMed2006

Endoxifen, a secondary metabolite of tamoxifen, and 4-OH-tamoxifen induce similar changes in global gene expression patterns in MCF-7 breast cancer cells.

We recently demonstrated that endoxifen (4-hydroxy-N-desmethyl-tamoxifen), a pharmacogenetically regulated metabolite of tamoxifen, is equipotent to 4-hydroxy-tamoxifen (4-OH-Tam) with respect to estrogen receptor binding and inhibition of 17beta-estradiol (E2)-induced cell proliferation. Endoxifen was also found to be more abundant in human plasma than 4-OH-Tam, and its formation has been shown to be primarily catalyzed by cytochrome P450 2D6 (CYP2D6). Here, we report studies evaluating the effects of endoxifen, 4-OH-Tam, and E2 on gene expression in MCF-7 cells using Affymetrix U133A GeneChip Arrays (Santa Clara, CA). We detected 4062 genes that were E2-regulated (1924 induced; 2138 suppressed), and the ratio of E2-induced versus E2-suppressed genes was consistent regardless of the cutoff value. In the presence of E2, 2444 and 2390 genes were affected by 4-OH-Tam and endoxifen, respectively, when no minimal -fold change cutoff was implemented. The majority of genes regulated by the tamoxifen metabolites were also E2-responsive (74.4 and 73.3%, respectively). Endoxifen and 4-OH-Tam had overlapping effects on 1365 E2-sensitive genes, whose -fold effects between these metabolites were highly correlated (R2 = 0.99). A significant correlation was also found between the -fold effects of 249 E2-insensitive genes coregulated by both metabolites (R2 = 0.99). Hierarchical clustering analysis demonstrated similar gene regulation patterns between these metabolites, which were distinct from E2 or vehicle treatment patterns. Using real time-polymerase chain reaction, we validated the gene expression patterns of five genes that were differentially regulated by endoxifen and 4-OH-Tam. We conclude that endoxifen and 4-OH-Tam have similar effects on global gene expression patterns in MCF-7 cells and that the majority of the affected genes are estrogen-regulated genes.

Breast Neoplasms↗

PubMed2005

Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension.

Hypertension in blacks is more prevalent and less often controlled than the hypertension of other ethnic groups. We sought to explore the benefit of adding inhibitors of the epithelial sodium channel (ENaC), an aldosterone-regulated site of sodium reabsorption in the distal nephron, to the antihypertensive regimen of black hypertensive patients. In a prospective, randomized, placebo-controlled, double-blind clinical trial, we used a 2-by-2 factorial design with 4 treatment groups: amiloride (a direct inhibitor of ENaC), spironolactone (an aldosterone receptor antagonist), the combination of both drugs, and placebo. The subjects (n=98) had an elevated blood pressure despite treatment that included a diuretic and a calcium channel blocker; the level of plasma renin activity was < or =0.56 ng/L per second. The primary end points were changes from baseline in systolic and diastolic blood pressure over a 9-week period of treatment. The reductions in systolic and diastolic blood pressures (mm Hg) were, respectively, 9.8+/-1.6 (SE) and 3.4+/-1.0 for amiloride (P<0.001) and 4.6+/-1.6 (P=0.006) and 1.8+/-1.0 for spironolactone (P=0.07). Treatment with either amiloride or spironolactone or the combination was well tolerated; no patient experienced hyperkalemia. In a substudy, plasma endothelin-1 levels were observed to decrease after 3 weeks of treatment with spironolactone (P<0.001), consistent with a non-ENaC-related potential benefit of spironolactone. In conclusion, treatment with either amiloride or spironolactone can provide an additional reduction in blood pressure in blacks already receiving conventional antihypertensive therapy.

Amiloride↗