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EGFR and HER2 exert distinct roles on colon cancer cell functional properties and expression of matrix macromolecules. - Biochimica et biophysica acta
ErbB receptors, EGFR and HER2, have been implicated in the development and progression of colon cancer. Several intracellular pathways are mediated upon activation of EGFR and/or HER2 by EGF. However, there are limited data regarding the EGF-mediated signaling affecting functional cell properties and the expression of extracellular matrix macromolecules implicated in cancer progression.Functional assays, such as cell proliferation, transwell invasion assay and migration were performed to evaluate the impact of EGFR/HER2 in constitutive and EGF-treated Caco-2 cells. Signaling pathways were evaluated using specific intracellular inhibitors. Western blot was also utilized to examine the phosphorylation levels of ERK1/2. Real time PCR was performed to evaluate gene expression of matrix macromolecules.EGF increases cell proliferation, invasion and migration and importantly, EGF mediates overexpression of EGFR and downregulation of HER2. The EGF-EGFR axis is the main pathway affecting colon cancer's invasive potential, proliferative and migratory ability. Intracellular pathways (PI3K-Akt, MEK1/2-Erk and JAK-STAT) are all implicated in the migratory profile. Notably, MT1- and MT2-MMP as well as TIMP-2 are downregulated, whereas uPA is upregulated via an EGF-EGFR network. The EGF-EGFR axis is also implicated in the expression of syndecan-4 and TIMP-1. However, glypican-1 upregulation by EGF is mainly mediated via HER2.The obtained data highlight the crucial importance of EGF on the expression of both receptors and on the EGF-EGFR/HER2 signaling network, reveal the distinct roles of EGFR and HER2 on expression of matrix macromolecules and open a new area in designing novel agents in targeting colon cancer. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.Copyright Â© 2014 Elsevier B.V. All rights reserved.
Evaluation of the coordinated actions of estrogen receptors with epidermal growth factor receptor and insulin-like growth factor receptor in the expression of cell surface heparan sulfate proteoglycans and cell motility in breast cancer cells. - The FEBS journal
Estradiol (E2)-estrogen receptor (ER) actions are implicated in initiation, growth and progression of hormone-dependent breast cancer. Crosstalk between ERs, epidermal growth factor receptor (EGFR) and/or insulin-like growth factor receptor (IGFR) is critical for the observed resistance to endocrine therapies. Cell surface heparan sulfate proteoglycans (HSPGs) are principal mediators of cancer cell properties and the E2-ER pathway as well as those activated by EGFR and IGFR have significant roles in regulating the expression of certain cell surface HSPGs, such as syndecan-2 (SDC-2), syndecan-4 (SDC-4) and glypican-1. In this study, we therefore evaluated the role of EGFR-IGFR signaling on the constitutive expression and E2-mediated expression of ERs and HSPGs as well as the effect of E2-ERs and IGFR/EGFR-mediated cell migration in ERÎ±+ (MCF-7) and ERÎ²+ (MDA-MB-231) breast cancer cells using specific intracellular inhibitors of EGFR and IGFR. We report that the expression of ERÎ± is mainly enhanced by IGFR, whereas ERÎ² expression is mainly coordinated by EGFR. Moreover, constitutive SDC-2 expression in ERÎ±+ and ERÎ²+ cells is mainly mediated through the IGFR, whereas in ERÎ±+ E2-treated cells EGFR is the active one. In contrast, SDC-4 expression is regulated by IGFR in the presence and absence of E2. E2 also seems to diminish the inhibitory effect of EGFR and IGFR inhibitors in breast cancer cell migration. These data suggest that the coordinated action of ERs with EGFR and/or IGFR is of crucial importance, providing potential targets for designing and developing novel multi-potent agents for endocrine therapies.Â© 2013 The Authors Journal compilation Â© 2013 FEBS.
Extracellular matrix-associated (GAGs, CTGF), angiogenic (VEGF) and inflammatory factors (MCP-1, CD40, IFN-Î³) in type 1 diabetes mellitus nephropathy. - Clinical chemistry and laboratory medicine : CCLM / FESCC
The aim of the present study was to evaluate the role of extracellular matrix-associated glycosaminoglycans (GAGs), connective tissue growth factor (CTGF), angiogenic vascular endothelial growth factor (VEGF) and inflammatory factors (MCP-1, CD40, IFN-Î³) in the development of diabetic nephropathy in type 1 diabetes (T1DM).Plasma and urine samples from 30 T1DM patients and 20 healthy controls were used to measure the levels of CTGF, VEGF, MCP-1, CD40 and IFN-Î³ by ELISA. Plasma and urine GAGs were measured using a spectrophotometric method.Plasma levels of GAGs, CD40 and MCP-1 and urine levels of GAGs and CTGF were significantly elevated in normoalbuminuric T1DM patients. A tendency to higher plasma VEGF levels was found in patients compared to controls. The urine/plasma GAGs ratio of T1DM patients was almost similar to that of healthy subjects (HS), whereas the urine/plasma CTGF ratio was about three times greater in diabetic patients compared to HS.Conclusively, increased GAGs and CTGF excretion are evident in T1DM normoalbuminuric juveniles, possibly reflecting early renal injury signs, before the initiation of albuminuria.
Metastasis to the breast from an adenocarcinoma of the lung with extensive micropapillary component: a case report and review of the literature. - Diagnostic pathology
Breast metastasis from extra-mammary malignancy is rare. Based on the literature an incidence of 0.4-1.3% is reported. The primary malignancies most commonly metastasizing to the breast are leukemia-lymphoma, and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 73-year-old female presented with dyspnea and dry cough of 4 weeks duration and a massive pleural effusion was found on a chest radiograph. Additionally, on physical examination a poorly defined mass was noted in the upper outer quadrant of the left breast. The patient underwent bronchoscopy, excisional breast biopsy and medical thoracoscopy. By cytology, histology and immunohistochemistry primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Both the primary and metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient received chemotherapy but passed away within 7 months. Accurate differentiation of metastatic from primary carcinoma is of crucial importance because the treatment and prognosis differ significantly.
Simultaneous cytological diagnosis of herpes simplex virus infection and primary lung cancer: report of two cases. - Diagnostic cytopathology
Herpes simplex is an uncommon cause of lower respiratory tract infection that requires prompt diagnosis and treatment to prevent late complications. We report two cases with simultaneous herpes simplex virus infection of the lower respiratory tract and lung carcinoma. Cytology of bronchial brushing and washing fluids and postbronchoscopic sputum established the diagnosis, which was further corroborated by real-time polymerase chain reaction.
Study of the eye and lacrimal glands in experimental iron overload in rats in vivo. - Anatomical science international
A variety of syndromes leading to hemosiderosis in men cause ocular lesions. The purpose of the present study was to determine the distribution of iron and of transferrin in the eyes and lacrimal glands of rats in experimental hemosiderosis, so as to achieve a better understanding of the formation of the ocular lesions observed in patients with advanced hemosiderosis. In order to achieve hemosiderosis the rats were fed 3% (w/w) carbonyl iron or received i.p. or i.v. polymaltose iron. Hemosiderin deposits were detected in macrophages lying in the interlobular connective tissue of lacrimal glands, in the interstitial connective tissue of the choroid, in the ciliary body, in the iris and extracellularly in the sclera in all animals that received iron i.v. Also, scanty hemosiderin laden macrophages were found to a lesser degree in interstitial connective tissue of the choroid and in the interlobular connective tissue of lacrimal glands in animals that received iron i.p. No iron deposits were detected in the eye and lacrimal glands of control rats and in rats that were on an iron enriched diet. No transferrin was detected in the eye and in the lacrimal glands, neither in the control rats nor in the rats that received iron. Experimental iron overload leads to increased iron deposition in tissues of the eye and lacrimal glands, whereas no transferrin could be detected in the aforementioned organs.
Rarity of bacterial and viral meningitis in areas of Western Greece with fewer than 2,000 inhabitants. - Japanese journal of infectious diseases
The purpose of the present study was to compare the incidence of childhood meningitis in regions with fewer than 2,000 inhabitants (rural regions) and regions with more than 2,000 inhabitants (urban regions) in the prefecture of Achaia in Western Greece during 1991-2005. Included were all 555 children hospitalized for meningitis. The criteria for bacterial meningitis were (i) positive blood/cerebralspinal fluid (CSF) culture, Gram stain, or latex agglutination and/or (ii) increased beta-glucuronidase in CSF. In case of suspected bacterial meningitis, the following findings were considered: compatible clinical and laboratory findings, and whether or not a cure was achieved with antibiotic treatment and finally resulted in negative cultures. In cases of suspected viral meningitis, compatible clinical and laboratory findings were considered, together with observation of a cure without antibiotic treatment. Only 28 of 555 meningitis patients were from rural regions. The incidence per 10,000 children in rural and urban regions, respectively, was as follows: meningitis, 1.13 and 8.99; bacterial meningitis, 0.16 and 2.40; suspected bacterial meningitis, 0.52 and 3.00; and viral meningitis, 0.44 and 3.58. The incidence ratio for bacterial, suspected bacterial, and viral meningitis in urban versus rural regions was 14.85, 5.72, and 8.10, respectively. Only 2 of the 79 cases with a confirmed causative pathogen came from rural regions. In conclusion, compared to those living in urban regions, children living in rural regions are relatively spared from bacterial and viral meningitis.
Prognostic impact of Deoxyribonucleic acid (DNA) image analysis cytometry and immunohistochemical expression of Ki67 in surgically resected non-small cell lung cancers. - Cancer detection and prevention
The aim of the present study was to evaluate the prognostic significance of DNA ploidy and Ki67 expression in non-small cell lung carcinoma (NSCLC).This prospective study included 96 patients with stages I-IIIA NSCLC who underwent surgical excision. DNA image analysis cytometry was applied on imprints. Calculation of the DNA index (DI) and the 5c exceeding rate (5cER) was performed and the histograms were classified as peridiploid, peritetraploid, and x-ploid-multiploid. The Ki67 immunoreactivity was determined according to the avidin-biotin complex immunoperoxidase method.DNA histogram classification disclosed 30 peridiploid cases, 15 peritetraploid and 51 x-ploid-multiploid. Forty-eight cases (50%) had 5cER > 5%. The Ki67 immunoreactivity was below 25% in 53 tumors (62.4%) and above 25% in 32 (32.6%). Our results revealed the existence of a statistically significant relationship of DNA ploidy with nodal status (p = 0.042) and grade (p = 0.005). Adenocarcinomas and large cell carcinomas were more frequently encountered in x-ploid-multiploid tumors as compared to squamous cell carcinomas, which were more frequently peridiploid (p = 0.003). 5cER showed statistically significant association with nodal status (p = 0.037). Univariate analysis with respect to survival revealed significant association with stage (p < 0.001), nodal status (p < 0.001), tumor status (p < 0.001), DNA ploidy (p = 0.008) and 5cER (p = 0.0124). Multivariate analysis revealed stage and ploidy status as independent factors: peridiploid tumors were associated with better survival as compared to x-ploid-multiploid tumors (p = 0.022).Our results suggest that DNA ploidy, as determined by image analysis, provides an independent prognostic parameter for patients with NSCLC and thus, could be used to identify a subset of patients with more aggressive tumors.
First urinary tract infection in neonates, infants and young children: a comparative study. - Pediatric nephrology (Berlin, Germany)
In an attempt to evaluate first urinary tract infection (UTI) in neonates and infants, we estimated retrospectively in 296 patients (62 neonates and 234 infants) clinical and laboratory findings, occurrence of vesicoureteral reflux (VUR), urinary tract abnormalities and pyelonephritis. First UTI occurred more often in male than female neonates, whereas male and female infants/young children were affected at an equal rate. The pathogens isolated in urine cultures of neonates and infants did not statistically significantly differ (P>0.05); Escherichia coli predominated. Gram-negative bacteria other than E. coli affected boys more often than girls (P=0.0022). Fever was the most frequent symptom. Neonates had lower-grade fever of shorter duration than infants (P<0.05). The incidence of reflux and urinary tract abnormalities did not differ between neonates and infants, male and female neonates and infants (P>0.05). Pyelonephritis affected neonates and infants at an equal rate; it was more prevalent among female patients (P=0.038) and patients with VUR or urinary tract abnormalities other than VUR (P<0.0001). Neonates with reflux were more often affected by Gram-negative bacteria other than E. coli than were neonates without reflux (P=0.0008).
Presentation of childhood brucellosis in Western Greece. - Japanese journal of infectious diseases
The purpose of this study was to evaluate clinical and laboratory findings, treatment modalities and final outcomes of brucellosis in children and to compare our data with those of other studies performed in Greece. Fifty-two children treated for brucellosis in the Department of Pediatrics during the decade 1995-2004 were analyzed. Of the 52 children, 47 were reexamined during July 2005. Fever, arthritis or arthralgia, hepatomegaly and splenomegaly were the main findings. Young children had positive blood cultures and lower or negative antibody titers statistically significantly more often than did older children. Brucella abortus was isolated in 9 of 18 patients with positive blood cultures. Antibiotic treatment lasted for 28 days on average. There were no complications or relapses, except one, and the final outcomes were excellent.
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