Faculty Bibliography
Searched for:
person:yangj16
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70
The Extent of Pathologic Response to Anthracycline-Based Neoadjuvant Therapy in Triple Negative Breast Carcinomas [Meeting Abstract]
ORIGINAL:0011091
ISSN: 1543-2165
CID: 2090162
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10â»â¹ to P = 1.8 × 10â»â´â°) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10â»Â³ to P = 1.2 × 10â»Â¹Â³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
PMID: 20935629
ISSN: 1546-1718
CID: 3845432
c-Kit expression and mutations in phyllodes tumors of the breast
BACKGROUND: Phyllodes tumors (PTs) represent uncommon fibroepithelial lesions of the breast that express c-Kit and platelet-derived growth factor receptor-alpha, similar to gastrointestinal stromal tumors (GISTs). 'Activating' mutations in these genes underlie responsiveness of GISTs to imatinib. Standard treatment for breast PTs is wide local excision, with no role for targeted therapies. PATIENTS AND METHODS: c-Kit (CD117) expression was investigated by immunohistochemistry in 17 cases of breast PTs. Fourteen of these cases were also subjected to KIT mutation analysis by dideoxynucleotide sequencing. RESULTS: Five out of 17 (29%) tumors showed weak stromal staining for CD117. No previously described 'activating' mutations were found in exons 9, 11, 13, or 17 of the KIT gene. A silent germline point mutation was found in exon 17 of one case. CONCLUSION: These data do not suggest a pathogenetic role for KIT in breast PTs. Inhibition of c-Kit signaling is unlikely to be helpful in this condition.
PMID: 21115932
ISSN: 1791-7530
CID: 2489012
Synchronous Pancreatic Adenocarcinoma, Multiple Gastrointestinal Stromal Tumors, and Periampullary Carcinoid in a Patient With Neurofibromatosis Type 1 [Meeting Abstract]
ORIGINAL:0011092
ISSN: 1543-2165
CID: 2090172
Magnetic resonance spectroscopy of the brain under mild hypothermia indicates changes in neuroprotection-related metabolites
Brain hypothermia has demonstrated pronounced neuroprotective effect in patients with cardiac arrest, ischemia and acute liver failure. However, its underlying neuroprotective mechanisms remain to be elucidated in order to improve therapeutic outcomes. Single voxel proton magnetic resonance spectroscopy ((1)H-MRS) was performed using a 7 Tesla MRI scanner on normal Sprague-Dawley rats (N=8) in the same voxel under normothermia (36.5 degrees C) and 30min mild hypothermia (33.5 degrees C). Levels of various brain proton metabolites were compared. The level of lactate (Lac) and myo-inositol (mI) increased in the cortex during hypothermia. In the thalamus, taurine (Tau), a cryogen in brain, increased and choline (Cho) decreased. These metabolic alterations indicated the onset of a number of neuroprotective processes that include attenuation of energy metabolism, excitotoxic pathways, brain osmolytes and thermoregulation, thus protecting neuronal cells from damage. These experimental findings demonstrated that (1)H-MRS can be applied to investigate the changes of specific metabolites and corresponding neuroprotection mechanisms in vivo noninvasively, and ultimately improve our basic understanding of hypothermia and ability to optimize its therapeutic efficacy.
PMID: 20362032
ISSN: 1872-7972
CID: 2449802
In vivo MRI of endogenous stem/progenitor cell migration from subventricular zone in normal and injured developing brains
Understanding the alterations of migratory activities of the endogenous neural stem/progenitor cells (NSPs) in injured developing brains is becoming increasingly imperative for curative reasons. In this study, 10-day-old neonatal rats with and without hypoxic-ischemic (HI) insult at postnatal day 7 were injected intraventricularly with micron-sized iron oxide particles (MPIOs), followed by serial high-resolution MRI at 7 T for 2 weeks. MRI findings were correlated to the histological analysis using iron staining and several immunohistochemical double staining. The results indicated that in normal and HI-injured brains the NSPs from the subventricular zone (SVZ) were labeled by MPIOs, and migrated as newly created cells (iron+/BrdU+), neuroblasts (iron+/nestin+), astrocytes or astrocytes-like progenitor cells (iron+/GFAP+), and mature neurons (iron+/NeuN+). In normal brains, the endogenous NSPs mainly exhibited a tangential pattern in both rostral and caudal directions. The NSP radial migratory pattern could be observed in some rats. In the HI-injured brains during the same developmental period, the NSPs mainly migrated towards the HI lesion sites. The tangential, rostrocaudal migrations could be observed but impaired. These findings suggest that the NSP migratory pathways in SVZ change in response to the HI insult, likely due to the self-repairing efforts known in the neonatal brains. The MRI approach demonstrated here is potentially applicable to the in vivo and longitudinal study of NSP cell activities in developing brains under normal and pathological conditions and in therapeutic interventions.
PMID: 19591946
ISSN: 1095-9572
CID: 2449852
MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction
Several recent reports have suggested that microRNAs (miRNAs) might play critical roles in acute myocardial infarction (AMI). However, the miRNA expression signature in the early phase of AMI has not been identified. In this study, the miRNA expression signature was investigated in rat hearts 6 h after AMI. Compared with the expression signature in the noninfarcted areas, 38 miRNAs were differentially expressed in infarcted areas and 33 miRNAs were aberrantly expressed in the border areas. Remarkably, miR-21 expression was significantly down-regulated in infarcted areas, but was up-regulated in border areas. The down-regulation of miR-21 in the infarcted areas was inhibited by ischemic preconditioning, a known cardiac protective method. Overexpression of miR-21 via adenovirus expressing miR-21 (Ad-miR-21) decreased myocardial infarct size by 29% at 24 h and decreased the dimension of left ventricles at 2 weeks after AMI. Using both gain-of-function and loss-of-function approaches in cultured cardiac myocytes, we identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that was associated with its target gene programmed cell death 4 and activator protein 1 pathway. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by decreased cell apoptosis in the border and infarcted areas of the infarcted rat hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI.
PMCID:2785585
PMID: 19706597
ISSN: 1083-351x
CID: 4521152
Neoadjuvant therapy with celecoxib to women with early stage breast cancer
Cyclooxygenase-2 (COX-2) is preferentially expressed in breast cancer cells compared to normal breast tissue. COX-2 inhibitors are, therefore, potential therapeutic options for patients with breast cancer. Women newly diagnosed with non metastatic breast cancer were enrolled into the study after undergoing a diagnostic core needle biopsy. Patients received celecoxib treatment at 400 mg orally twice a day for 14 days, and then underwent surgical excision of their tumor. Core biopsies obtained at the time of initial diagnostic procedure and surgical excision specimens were stained for Ki-67, as well as COX-2 and cleaved poly (ADP-ribose) polymerase (PARP) expression (as an apoptosis marker). Appropriate negative and positive controls were included. We assessed the difference in Ki-67, COX-2 and cleaved PARP expression levels, before and after treatment using the Wilcoxon's matched-pair ranks test and the McNemar's test with continuity correction. Sixteen patients were enrolled. The median age was 54 years. ER and/or PR expression was present in 81% of tumors; Her-2 neu overexpression was present in 25%. No significant change in COX-2 or cleaved PARP expression was noticed in the post intervention specimen compared to the core biopsies. Surprisingly, there was a significant increase in the Ki-67 expression (p < 0.009). This short term prospective study was conducted to assess the effects of celecoxib, on the proliferative and apoptotic indexes in patients with early stage breast cancer. We have found an increase in the Ki-67 activity, with no significant down regulation of COX-2 or increase in cleaved PARP expression with 14 days of therapy. This could be partly due to the small sample size.
PMID: 18237249
ISSN: 0028-2685
CID: 2488942
Disseminated Cutaneous Histoplasmosis in a Severely Immunocompromised HIV/AIDS Patient [Meeting Abstract]
ORIGINAL:0011806
ISSN: 1543-2165
CID: 2490632
Expression of the vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukemia: incidence and feasibility of immunohistochemical staining
Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases, VEGFR-1 and VEGFR-2, are important therapeutic targets for various cancers including AML. Paraffin-embedded bone marrow samples (PE-BM) are, in most cases, the only tissue accessible to perform retrospective analyses of novel targets such as VEGF and/or its receptors. As a result, it limits our options to immunohistochemistry (IHS), or more expensive and less practical techniques such as enzyme-linked immunosorbent assay (ELISA) or fluorescence in situ hybridization (FISH). We analyzed the feasibility of IHS to measure VEGFR-1 and VEGFR-2 expression in 28 AML samples using monoclonal antibodies (moAbs) against Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2). Medical records were reviewed for relevant clinical information. Expression of VEGFR-1 (+) and VEGFR-2 (+) were seen in 25% (7/28) and 43% (12/28) respectively. Forty-six percent (13/28) were dual-negatives for VEGFR-1 and VEGFR-2; 14% (4/28) were dual-positives for VEGFR-1 and VEGFR-2. An inferior survival was observed in patients whose myeloblasts express either VEGFR-1 (+) or VEGFR-2 (+), or both. Determination of expression of VEGF receptors (1 and 2) by IHS in PE-BM tissue is feasible. Prospective comparison of IHC to flow cytometry or other molecular techniques, and assessment of the prognostic significance of VEGF receptors in AML patients is warranted.
PMID: 16898965
ISSN: 0141-9854
CID: 2488952
