MedicalResearch.com Interview with:
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Dr. Hua Lu[/caption]
Dr. Hua Lu MS PhD
Department of Biochemistry & Molecular Biology
Reynolds and Ryan Families Chair in Translation Cancer
Tulane Cancer Center
Tulane University School of Medicine
New Orleans, Louisiana 70112
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It has been well appreciated and acknowledged that p53 is the most important tumor suppressor in human body. However, approximately 50% of human cancers still sustain the wild type form of its gene, and also oddly, some cancers, such as breast cancer, which contain wild type p53, are often less sensitive to chemotherapy than those harbor mutated p53. Although a number of oncoproteins, including MDM2 and MDMX (MDM4), have been shown to be highly expressed and to inactivate p53 in those wild type p53-containing cancers, more molecules need to be discovered to keep p53 in control in order to let cancer cells to proliferate and growth.
Our study as described in our recent publication in Nature Communications unveils a new p53 target gene that encodes pleckstrin homology domain-containing protein (PHLDB3) as another p53 inhibitor in a negative feedback fashion. Interestingly and mechanistically, PHLDB3 can work with MDM2 by boosting its E3 ubiquitin ligase activity, consequently leading to degradation of p53. Biologically, PHLDB3 can promote cancer cell proliferation and growth in culture and in xenograft tumor models by in part inactivating p53 activity. More interestingly, PHLDB3 is highly amplified and expressed in a number of human cancers, such as pancreatic, prostate, colon and breast cancers. High expression of PHLDB3 is well correlated with the wild type status of p53 in certain portion of breast cancer. These findings uncover PHLDB3 as another
oncoprotein that can promote cancer growth by partially inactivate p53, and thus might serve as a potential target for future development of anti-cancer therapy. Our study also suggests that PHLDB3 has a p53-independent function important for cancer growth.
Dr. Spyridoula Maraka[/caption]
Dr. Spyridoula Maraka
Assistant professor of medicine
Division of Endocrinology and Metabolism
Center for Osteoporosis and Metabolic Bone Diseases
University of Arkansas for Medical Sciences and
Central Arkansas Veterans Health Care System
Little Rock Arkansas
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Subclinical hypothyroidism, a mild thyroid dysfunction, has been associated in pregnancy with multiple adverse outcomes. Our aim was to estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism.
Using a large national US dataset, we identified 5,405 pregnant women diagnosed with subclinical hypothyroidism. Of these, 843 women, with an average pretreatment TSH concentration of 4.8 milli-international units per liter, were treated with thyroid hormone. The remaining 4,562, with an average pretreatment TSH concentration of 3.3 milli-international units per liter, were not treated.
Compared with the untreated group, treated women were 38 percent less likely to experience pregnancy loss. However, they were more likely to experience a preterm delivery, gestational diabetes or preeclampsia. Moreover, the benefit of thyroid hormone treatment on pregnancy loss was seen only among women with higher TSH levels (4.1 to 10 mIU/L) before treatment. We also found that for women with lower levels of TSH (2.5–4.0 mIU/L), the risk of gestational hypertension was significantly higher for treated women than for untreated women.
