Publications (91) View all
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Article: Integrating pathology and radiology disciplines: an emerging opportunity?
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ABSTRACT: Pathology and radiology form the core of cancer diagnosis, yet the workflows of both specialties remain ad hoc and occur in separate "silos," with no direct linkage between their case accessioning and/or reporting systems, even when both departments belong to the same host institution. Because both radiologists' and pathologists' data are essential to making correct diagnoses and appropriate patient management and treatment decisions, this isolation of radiology and pathology workflows can be detrimental to the quality and outcomes of patient care. These detrimental effects underscore the need for pathology and radiology workflow integration and for systems that facilitate the synthesis of all data produced by both specialties. With the enormous technological advances currently occurring in both fields, the opportunity has emerged to develop an integrated diagnostic reporting system that supports both specialties and therefore improves the overall quality of patient care.BMC Medicine 09/2012; 10(1):100. · 6.03 Impact Factor -
Article: Ki-67 expression in axillary lymph node metastases in breast cancer is prognostically significant.
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ABSTRACT: Several studies have documented the prognostic significance of cell proliferation in breast cancer and its positive relationship with tumor grade, size, mitotic activity, hormonal and Her-2 status, and tumor progression. The Ki-67 antigen provides an accurate measure of the growth fraction of a tumor. Ki-67 expression in 103 primary breast carcinomas and their corresponding axillary lymph node metastases was correlated with age, tumor grade, size, estrogen receptor (ER), progesterone receptor (PgR), p53, epidermal growth factor receptor (EGFR), Bcl-2, Her-2 status, and patients' overall survival. Median Ki-67 expression in primary and metastatic tumors was 20% and 15%, respectively. Although there was no difference in overall survival (P = .65, log-rank test) between primary tumors with less than or at least 10% Ki-67 expression, there was significantly better overall survival when Ki-67 expression in lymph nodes was less than 10% (P = .040). For patients whose primary tumors exhibited Ki-67 expression less than 10%, most of their metastatic lesions had a similar low Ki-67; these patients had a favorable outcome. A small subgroup was noted to have a nodal Ki-67 of 10% or more and worse survival (P = .047). For patients whose primary tumors had a Ki-67 of 10% or more, most of their metastatic lesions had similar high Ki-67 values; however, a group of 12 patients had lymph node Ki-67 less than 10% and had a better overall survival (P = .092). Our results showed that measurement of Ki-67 in lymph node is superior to its evaluation in primary tumors. Identification of subgroups of patients in whom Ki-67 expression in lymph nodes differs from expression in primary tumor may assist in the selection of therapeutic options.Human pathology 08/2012; · 3.03 Impact Factor -
Article: Critical roles of Notch and Wnt/β-catenin pathways in the regulation of hyperplasia and/or colitis in response to bacterial infection.
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ABSTRACT: Notch and Wnt/β-catenin signals play essential roles in intestinal development and homeostasis. Citrobacter rodentium induces transmissible murine colonic hyperplasia (TMCH) and various degrees of inflammation, depending upon the genetic background. We aimed at delineating the role of the Notch and Wnt/β-catenin pathways in the regulation of colonic crypt hyperplasia and/or colitis following C. rodentium infection. During TMCH, relative levels of the Notch intracellular domain (NICD) increased significantly, along with increases in Jagged-1 and Hes-1 coinciding with the progression and regression phases of hyperplasia. Blocking of Notch signaling with dibenzazepine (DBZ) for 5 days before the onset of hyperplasia also blocked Wnt/β-catenin signaling. Targeting the Notch pathway for 5 days after the onset of hyperplasia failed to inhibit Wnt/β-catenin-regulated crypt hyperplasia. Chronic DBZ administration for 10 days blocked both Notch and Wnt signaling, disrupted the intestinal barrier, and induced colitis. Core-3(-/-) mice, which are defective in mucin secretion and are susceptible to experimental triggers of colitis, also exhibited significant colitis in response to C. rodentium plus DBZ. Chronic DBZ administration in these mice did not result in depletion of the putative stem cell marker doublecortin-like kinase-1 (DCLK1) in the crypts. Dietary bael (Aegle marmelos) extract (4%) and curcumin (4%) restored signaling via the Notch and Wnt/β-catenin pathways, thereby promoting crypt regeneration, and also replenished the mucus layer, leading to amelioration of C. rodentium- and DBZ-induced colitis in NIH:Swiss mice. Thus, the balancing act between cell proliferation and mucus production to restore barrier integrity seems to depend upon the interplay between the Wnt/β-catenin and Notch pathways in the TMCH model.Infection and immunity 06/2012; 80(9):3107-21. · 4.21 Impact Factor -
Article: Inflammation-associated regulation of the macrophage inhibitory cytokine (MIC-1) gene in prostate cancer.
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ABSTRACT: Macrophage inhibitory cytokine-1 (MIC-1), also known as prostate-derived factor (PDF), is a molecule of the TGF-β superfamily and has been associated with the progression of various types of diseases including prostate cancer. Initially identified from activated macrophages, the MIC-1 gene may provide a potential link between inflammation and prostate cancer. In this context, we performed MIC-1 expression analysis using mouse prostate tissues to determine whether there was any correlation with age and inflammation. Reverse transcription PCR analysis on RNA samples isolated from prostate lobes from prostate-specific antigen transgenic mice of varying ages revealed that MIC-1 gene expression is extremely low to non-detectable in the prostate tissues obtained from young mice, while its expression increases in the prostate tissues harvested from elderly mice. Increased MIC-1 gene expression in the mouse prostate was found to be associated with an increased level of infiltrating lymphocytes. To confirm this observation, we showed that inflammation-associated cytokines (IL-1β and TNF-α) significantly upregulate the secretion of the MIC-1 protein in a human prostate cancer cell line (LNCaP cells), while cytokines IL-6 and granulocyte macrophage colony-stimulating factor were less effective. Taken together, these data indicated that inflammation-associated cytokines may play a critical role in the functional regulation of the MIC-1 gene in the early stages of prostate cancer development. More studies are required to understand the biological activity of MIC-1 gene regulation in the development and progression of prostate cancer.Oncology letters 05/2012; 3(5):1166-1170. · 0.11 Impact Factor -
Article: Clinicopathologic correlation of vitamin D receptor expression with retinoid X receptor and MIB-1 expression in primary and metastatic osteosarcoma.
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ABSTRACT: Vitamin D, in addition to its effects on bone, is important in cell cycle regulation. Vitamin D receptor (VDR) has been identified in breast, prostate, and colon cancers, as well as in canine and human osteosarcoma (OS) cell lines; however, it has not been well investigated in human OS-archived specimens. We correlated VDR, retinoid X receptor (RXR), and MIB-1 (Ki-67) expression in 110 archived OS cases with several clinicopathologic parameters including patient's age, sex, tumor location, tumor grade, and type and metastatic status. The expression of VDR and RXR was identified in human OS tissue obtained from primary and metastatic OS archival tissue. No statistically significant difference was found in VDR expression in relation with tumor grade, type, age, sex, or location. The expression of RXR was highest in higher-grade (P = .0006) and metastatic tumors but remained unchanged when correlated with tumor type, age, sex, or location. The expression of MIB-1 was statistically elevated in higher-grade tumors (P = .001), patients 25 years or younger (P = .04), tumors located in extremities (P = .005), and metastatic lesions, but was not impacted by tumor type or patient's sex. Proliferative activity was significantly reduced after treatment, as the mean MIB-1 expression dropped from 11% in primary biopsy samples to 6% in resection specimens. There appears to be a relationship between proliferative tumor activity and tumor grade, location, and metastasis. Additional studies on the analysis of the effects of vitamin D and RXR on OS proliferation, apoptosis, and differentiation are critical to further evaluate their potential role in OS treatment.Annals of diagnostic pathology 04/2012; 16(5):323-9.
