Cell-penetrating porcine single-chain antibodies (transbodies) against nonstructural protein 1ß (NSP1ß) of porcine reproductive and respiratory syndrome virus inhibit virus replication.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine reproductive and respiratory syndrome (PRRS) worldwide, especially in domestic pigs, with an enormous economic impact, estimated at $664 million in losses every year to the pig industry. Current vaccines confer limited protection, and no direct-acting anti-PRRS treatment is available. Non-structural protein (NSP) 1ß, a cysteine-like protease (CLPro) of PRRSV plays an essential role in viral polyprotein processing, subgenomic RNA synthesis, and evasion of host innate immunity. Therefore, agents that interfere with the bioactivity of NSP1ß would be expected to inhibit virus replication. In this study, a porcine single-chain antibody (scFv)-phage display library was constructed and used as a tool for production of NSP1ß-specific porcine scFvs (pscFvs). The pscFvs to NSP1ß were linked to a cell-penetrating peptide to form cell-penetrating pscFvs (transbodies), which could be internalized and inhibit PRRSV replication in infected cells. A computer simulation indicated that the effective pscFvs used several residues in multiple complementarity determining regions (CDRs) to interact with multiple residues in the CLPro and C-terminal motifs, which might explain the mechanism of pscFv-mediated inhibition of virus replication. Although experiments are needed to determine the antiviral mechanism of the transbodies, the current data indicate that transbodies can potentially be applied for treatment and prevention of PRRSV infection.

Suppression of trinucleotide repeat expansion in spermatogenic cells in Huntington's disease.

Trinucleotide repeats (TNRs) are dispersed throughout the human genome. About 20 loci are related to human diseases, such as Huntington's disease (HD). A larger TNR instability is predominantly observed in the paternal germ cells in some TNR disorders. Suppressing the expansion during spermatogenesis can provide a unique opportunity to end the vicious cycle of genetic anticipation. Here, using an in vitro differentiation method to derive advanced spermatogenic cells, we investigated the efficacy of two therapeutic agents, araC (cytarabine) and aspirin, on stabilizing TNRs in spermatogenic cells. Two WT patient-derived induced pluripotent stem cell (iPSC) lines and two HD hiPSC lines, with 44 Q and 180 Q, were differentiated into spermatogonial stem cell-like cells (SSCLCs). Both HD cell lines showed CAG tract expansion in SSCLC. When treated with araC and aspirin, HD1 showed moderate but not statistically significant stabilization of TNR. In HD2, 10 nM of aspirin and araC showed significant stabilization of TNR. All cell lines showed increased DNA damage response (DDR) gene expression in SSCLCs while more genes were significantly induced in HD SSCLC. In HD1, araC and aspirin treatment showed general suppression of DNA damage response genes. In HD2, only FAN1, OGG1, and PCNA showed significant suppression. When the methylation profile of HD cells was analyzed, FAN1 and OGG1 showed significant hypermethylation after the aspirin and araC treatment in SSCLC compared to the control. This study underscores the utility of our in vitro spermatogenesis model to study and develop therapies for TNR disorders such as HD.

CAG Repeat Instability in the Peripheral and Central Nervous System of Transgenic Huntington's Disease Monkeys.

Huntington's Disease (HD) is an autosomal dominant disease that results in severe neurodegeneration with no cure. HD is caused by the expanded CAG trinucleotide repeat (TNR) on the Huntingtin gene (HTT). Although the somatic and germline expansion of the CAG repeats has been well-documented, the underlying mechanisms had not been fully delineated. Increased CAG repeat length is associated with a more severe phenotype, greater TNR instability, and earlier age of onset. The direct relationship between CAG repeat length and molecular pathogenesis makes TNR instability a useful measure of symptom severity and tissue susceptibility. Thus, we examined the tissue-specific TNR instability of transgenic nonhuman primate models of Huntington's disease. Our data show a similar profile of CAG repeat expansion in both rHD1 and rHD7, where high instability was observed in testis, liver, caudate, and putamen. CAG repeat expansion was observed in all tissue samples, and tissue- and CAG repeat size-dependent expansion was observed. Correlation analysis of CAG repeat expansion and the gene expression profile of four genes in different tissues, clusterin (CLU), transferrin (TF), ribosomal protein lateral stalk subunit P1 (RPLP1), and ribosomal protein L13a (RPL13A), showed a strong correlation with CAG repeat instability. Overall, our data, along with previously published studies, can be used for studying the biology of CAG repeat instability and identifying new therapeutic targets.

Surgical treatment for non-tuberculous mycobacterial pulmonary disease: analysis of prognostic factors.

BACKGROUND: The surgical treatment for non-tuberculous mycobacterial pulmonary disease (NTM-PD) has an important adjunctive role and reported outcomes have been generally good; however, the prognostic factors remain unclear.METHODS: Sixty-one patients with NTM-PD who underwent surgical resection for a therapeutic purpose from January 2000 to March 2017 at five affiliated institutions were enrolled. We explored the factors that influence complications and prognosis by retrospectively referring to the medical records.RESULTS: The mean age of the present cohort was 61.8 ± 11.4 years. The pathogen was Mycobacterium avium complex in 49 patients, M. abscessus in 5. The most common indications were refractory to medication in 39. The surgical techniques employed were lobectomy or further resection in 49, sublobar resection in 8, with video-assisted thoracoscopic surgery in 21. Sputum culture conversion rate was 95.1%. Univariate analysis of factors associated with deterioration revealed significant differences related to age (P = 0.025), pre-operative albumin level (P = 0.001) and development of postoperative complications (P = 0.037), while pre-operative albumin level alone was a significant factor in multivariate analysis (P = 0.009).CONCLUSION: Outcomes after resection were generally good in the present cases. Nutritional status, as indicated by albumin level, may affect prognosis after surgical treatment.

Novel 4-Oxoquinazoline-Based N-Hydroxypropenamides as Histone Deacetylase Inhibitors: Design, Synthesis, and Biological Evaluation.

Two series of novel 4-oxoquinazoline-based N-hydroxypropenamides (9a-m and 10a-m) were designed, synthesized, and evaluated for their inhibitory and cytotoxicity activities against histone deacetylase (HDAC). The compounds showed good to potent HDAC inhibitory activity and cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer). In this series, compounds with the N-hydroxypropenamide functionality impeded at position 7 on the 4-oxoquinazoline skeleton (10a-m) were generally more potent than compounds with the N-hydroxypropenamide moiety at position 6 (9a-m). Also, the N 3-benzyl-substituted derivatives (9h-m, 10h-m) exhibited stronger bioactivity than the N 3-alkyl-substituted ones (9a-e, 10a-e). Two compounds 10l and 10m were the most potent ones. Their HDAC inhibitory activity (IC50 values, 0.041-0.044 µM) and cytotoxicity (IC50 values, 0.671-1.211 µM) were approximately 2- to 3-fold more potent than suberoylanilide hydroxamic acid (SAHA). Some compounds showed up to 10-fold more potent HDAC6 inhibition compared to their inhibitory activity in total HDAC extract assay. Analysis of selected compounds 10l and 10m revealed that these compounds strongly induced both early and late apoptosis and arrested SW620 cells at the G2/M phase. Docking studies were carried out on the HDAC6 isoform for series 10a-m and revealed some important features contributing to the inhibitory activity of synthesized compounds.

Role of hyperoxic treatment in cancer.

IMPACT STATEMENT: Tumor hypoxia promotes cancer cell aggressiveness, and is strongly associated with poor prognosis across multiple tumor types. The hypoxic microenvironments inside tumors also limit the effectiveness of radiotherapy, chemotherapy, and immunotherapy. Several approaches to eliminate hypoxic state in tumors have been proposed to delay cancer progression and improve therapeutic efficacies. This review will summarize current knowledge on hyperoxia, used alone or in combination with other therapeutic modalities, in cancer treatment. Molecular mechanisms and undesired side effects of hyperoxia will also be discussed.

Oncologic Outcome and Morbidity in the Elderly Rectal Cancer Patients After Preoperative Chemoradiotherapy and Total Mesorectal Excision: A Multi-institutional and Case-matched Control Study.

OBJECTIVE: To determine the toxicity and oncologic outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in the elderly (≥70 yrs) and younger (<70 yrs) rectal cancer patients. BACKGROUND: Sufficient data for elderly rectal cancer patients who received definitive trimodality have not been accumulated yet. PATIENTS AND METHODS: A total of 1232 rectal cancer patients who received neoadjuvant CRT and TME were enrolled in this study. After propensity-score matching, 310 younger patients and 310 elderly patients were matched with 1:1 manner. Treatment response, toxicity, surgical outcome, recurrence, and survival were assessed and compared between the 2 groups of patients. RESULTS: The median age was 58 years for the younger patient group and 74 years for the elderly group. Pathologic complete response rates were not significantly different between the 2 groups (younger and elderly: 17.1% vs 14.8%, P = 0.443). The 5-year recurrence-free survival (younger and elderly: 67.7% vs 65.5%, P = 0.483) and overall survival (younger and elderly: 82.9% vs. 79.5%, P = 0.271) rates were not significantly different between the 2 groups either. Adjuvant chemotherapy after surgery was less frequently delivered to the elderly than that to younger patients (83.9% vs 69.0%). Grade 3 or higher acute hematologic toxicity was observed more frequently in the elderly than that in the younger group (9.0% vs 16.1%, P = 0.008). Late complication rate was higher in the elderly group compared with that in the younger group without statistical significance (2.6% vs 4.5%, P = 0.193). CONCLUSIONS: Although acute hematologic toxicity was observed more frequently in the elderly patients than that in the younger patients, elderly rectal cancer patients with good performance status who received preoperative CRT and TME showed favorable tumor response and recurrence-free survival similar to younger patients.

The prevalence of intestinal helminth infection in rural subdistricts of northeastern Thailand.

This study aimed to determine the prevalence and intensity of intestinal helminth infections (IHIs) among rural villagers in Waeng Noi district, Khon Kaen Province, northeastern Thailand. A cross-sectional study was conducted between March 1 and July 30, 2018, among rural villagers from 30 rural villages in 2 subdistricts. The participants were selected from the village enrollment list after proportional allocation of the total sample size. The background characteristic data were collected using a structured questionnaire. Specimens from patients with IHIs were prepared by concentration with a Faecal Parasite Concentrator-Solvent-Free (Mini Parasep® SF), and helminths were then detected using a light microscope. Of the 400 faecal specimens examined, 23 were positive for at least one intestinal helminth, resulting in a prevalence of 5.75%. The most prevalent helminths were Taenia spp., 10 (2.50%); followed by hookworm, 5 (1.25%); Trichuris trichiura, 4 (1.0%); Ascaris lumbricoides, 3(0.50%); and Opisthorchis viverrini, 1 (0.25%). All infected participants had a light intensity of IHI. Location (adjusted OR=2.52; 95% CI=1.30-3.52; P =0.042) showed a significant association with the prevalence of intestinal helminths. This study reveals that IHIs, particularly those with foodborne and soil-transmitted species of helminths, are prevalent in adults in rural subdistricts. A greater focus on interventions to improve personal hygiene and sanitation to prevent the spread of IHIs is required. Further studies should be performed to implement interdisciplinary research approaches in the study area.

The prevalence of intestinal helminth infection in rural subdistricts of northeastern Thailand

@#This study aimed to determine the prevalence and intensity of intestinal helminth infections (IHIs) among rural villagers in Waeng Noi district, Khon Kaen Province, northeastern Thailand. A cross-sectional study was conducted between March 1 and July 30, 2018, among rural villagers from 30 rural villages in 2 subdistricts. The participants were selected from the village enrollment list after proportional allocation of the total sample size. The background characteristic data were collected using a structured questionnaire. Specimens from patients with IHIs were prepared by concentration with a Faecal Parasite Concentrator–Solvent-Free (Mini Parasep® SF), and helminths were then detected using a light microscope. Of the 400 faecal specimens examined, 23 were positive for at least one intestinal helminth, resulting in a prevalence of 5.75%. The most prevalent helminths were Taenia spp., 10 (2.50%); followed by hookworm, 5 (1.25%); Trichuris trichiura, 4 (1.0%); Ascaris lumbricoides, 3(0.50%); and Opisthorchis viverrini, 1 (0.25%). All infected participants had a light intensity of IHI. Location (adjusted OR=2.52; 95% CI=1.30–3.52; P =0.042) showed a significant association with the prevalence of intestinal helminths. This study reveals that IHIs, particularly those with foodborne and soil-transmitted species of helminths, are prevalent in adults in rural subdistricts. A greater focus on interventions to improve personal hygiene and sanitation to prevent the spread of IHIs is required. Further studies should be performed to implement interdisciplinary research approaches in the study area

Hypotension within 1 week of life associated with poor short- and long-term outcomes in very low birth weight infants.

We examined whether hypotension in very low birth weight infants aged⩽1 week was associated with hospital morbidities and overall mortality. Further, we studied whether hypotension was associated with poor neurodevelopmental outcomes in these patients at the corrected age of 18 months. A total of 166 very low birth weight infants were studied during this period. Hospital outcomes and neurodevelopmental outcomes at the corrected age of 18 months were evaluated. Among the 166 very low birth weight infants, 95 patients (57.2%) experienced hypotension at⩽1 week and were associated with an increased incidence of morbidities and mortality. At the corrected age of 18 months, hypotension of the⩽1 week group had significantly lower scores in all three - cognitive, language, and motor - composites of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) screening tests. In addition, a multivariable logistic regression analysis showed that longer mechanical ventilation and periventricular leukomalacia were additionally associated with worse cognitive and language neurodevelopmental outcomes. Hypotension in very low birth weight infants within 1 week of life was associated with increased morbidities and overall mortality. It was also associated with an increased risk of cognitive and language outcomes.

Analysis of Patient Visits and Collections After Opening a Satellite Pediatric Emergency Department.

OBJECTIVE: Satellite pediatric emergency departments (PEDs) have emerged as a strategy to increase patient capacity. We sought to determine the impact on patient visits, physician fee collections, and value of emergency department (ED) time at the primary PED after opening a nearby satellite PED. We also illustrate the spatial distribution of patient demographics and overlapping catchment areas for the primary and satellite PEDs using geographical information system. METHODS: A structured, financial retrospective review was conducted. Aggregate patient demographic data and billing data were collected regarding physician fee charges, collections, and patient visits for both PEDs. All ED visits from January 2009 to December 2013 were analyzed. Geographical information system mapping using ArcGIS mapped ED patient visits. RESULTS: Patient visits at the primary PED were 53,050 in 2009 before the satellite PED opened. The primary PED visits increased after opening the satellite PED to 55,932 in 2013. The satellite PED visits increased to 21,590 in 2013. Collections per visit at the primary PED decreased from $105.13 per visit in 2011 to $86.91 per visit in 2013. Total collections at the satellite PED decreased per visit from $155.41 per visit in 2011 to $128.53 per visit in 2013. CONCLUSIONS: After opening a nearby satellite PED, patient visits at the primary PED did not substantially decrease, suggesting that there was a previously unrecognized demand for PED services. The collections per ED visit were greater at the satellite ED, likely due to a higher collection rate.

Cost-effectiveness Analysis of Contralateral Prophylactic Mastectomy Compared to Unilateral Mastectomy with Routine Surveillance for Unilateral, Sporadic Breast Cancer.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) rates in younger women with unilateral breast cancer have more than doubled. Studies of cost and quality of life of the procedure remain inconclusive. METHODS: A cost-effectiveness analysis using a decision-tree model in TreeAge Pro 2015 was used to compare long-term costs and quality of life following unilateral mastectomy (UM) with routine surveillance versus CPM for sporadic breast cancer in women aged 45 years. A 10-year risk period for contralateral breast cancer (CBC), reconstruction, wound complications, cost of routine surveillance, and treatment for CBC were used to estimate accrued costs. In addition, a societal perspective was used to estimate quality-adjusted life years (QALYs) following either treatment for a period of 30 years. Medical costs were obtained from the 2014 Medicare physician fee schedule and event probabilities were taken from recent literature. RESULTS: The mean cost of UM with surveillance was $14,141 and CPM was $20,319. Treatment with CPM resulted in $6178 more in costs but equivalent QALYs (17.93) compared with UM over 30 years of follow-up. Even with worst-case scenario and varying assumptions, CPM is dominated by UM in terms of cost and quality. CONCLUSIONS: From this refined model, UM with routine surveillance costs less and provides an equivalent quality of life. Patients undergoing CPM may eliminate the anxiety of routine surveillance, but they face the burden of higher lifetime medical costs.

Improving Pediatric Education for Emergency Medical Services Providers: A Qualitative Study.

OBJECTIVES: Previous studies have illustrated pediatric knowledge deficits among Emergency Medical Services (EMS) providers. The purpose of this study was to identify perspectives of a diverse group of EMS providers regarding pediatric prehospital care educational deficits and proposed methods of training improvements. METHODS: Purposive sampling was used to recruit EMS providers in diverse settings for study participation. Two separate focus groups of EMS providers (administrative and non-administrative personnel) were held in three locations (urban, suburban, and rural). A professional moderator facilitated focus group discussion using a guide developed by the study team. A grounded theory approach was used to analyze data. RESULTS: Forty-two participants provided data. Four major themes were identified: (1) suboptimal previous pediatric training and training gaps in continuing pediatric education; (2) opportunities for improved interactions with emergency department (ED) staff, including case-based feedback on patient care; (3) barriers to optimal pediatric prehospital care; and (4) proposed pediatric training improvements. CONCLUSION: Focus groups identified four themes surrounding preparation of EMS personnel for providing care to pediatric patients. These themes can guide future educational interventions for EMS to improve pediatric prehospital care. Brown SA , Hayden TC , Randell KA , Rappaport L , Stevenson MD , Kim IK . Improving pediatric education for Emergency Medical Services providers: a qualitative study. Prehosp Disaster Med. 2017;32(1):20-26.

Genetic engineered molecular imaging probes for applications in cell therapy: emphasis on MRI approach.

Recent advances in stem cell-based regenerative medicine, cell replacement therapy, and genome editing technologies (i.e. CRISPR-Cas 9) have sparked great interest in in vivo cell monitoring. Molecular imaging promises a unique approach to noninvasively monitor cellular and molecular phenomena, including cell survival, migration, proliferation, and even differentiation at the whole organismal level. Several imaging modalities and strategies have been explored for monitoring cell grafts in vivo. We begin this review with an introduction describing the progress in stem cell technology, with a perspective toward cell replacement therapy. The importance of molecular imaging in reporting and assessing the status of cell grafts and their relation to the local microenvironment is highlighted since the current knowledge gap is one of the major obstacles in clinical translation of stem cell therapy. Based on currently available imaging techniques, we provide a brief discussion on the pros and cons of each imaging modality used for monitoring cell grafts with particular emphasis on magnetic resonance imaging (MRI) and the reporter gene approach. Finally, we conclude with a comprehensive discussion of future directions of applying molecular imaging in regenerative medicine to emphasize further the importance of correlating cell graft conditions and clinical outcomes to advance regenerative medicine.

Essentials of Pediatric Emergency Medicine Fellowship: Part 6: Program Administration.

This article is the sixth in a 7-part series that aims to comprehensively describe the current state and future directions of pediatric emergency medicine (PEM) fellowship training from the essential requirements to considerations for successfully administering and managing a program to the careers that may be anticipated upon program completion. This article provides a broad overview of administering and supervising a PEM fellowship program. It explores 3 topics: the principles of program administration, committee management, and recommendations for minimum time allocated for PEM fellowship program directors to administer their programs.

Association between interleukin-27 polymorphisms and pulmonary tuberculosis.

OBJECTIVE: To investigate the effect of interleukin (IL) 27 -964A/G, 2095T/G, 4603G/A and 4730T/C gene polymorphisms on the development of pulmonary tuberculosis (PTB), radiographic characteristics and severity. DESIGN: Differences in the allele and genotype distributions of the -964A/G, 2095T/G, 4603G/A and 4730T/C polymorphisms between 224 PTB patients and 233 healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavitation, were investigated. Serum IL-27 concentration was measured using an enzyme-linked immunosorbent assay. RESULTS: There were no significant differences in the allele or genotype distributions between PTB patients and healthy controls. However, the -964A/A genotype was more prevalent in patients with single-lobe involvement than the -964A/G or -964G/G genotype in patients with multi-lobe involvement (50.0% vs. 31.3%, P = 0.01). There was no difference between patients with and without cavitation (P > 0.05). Serum median IL-27 concentration was significantly higher in patients with single-lobe involvement than in those with multi-lobe involvement (P = 0.03) and in those with -964A/A genotypes than in those with -964A/G or -964G/G genotypes (P = 0.02). CONCLUSIONS: In terms of serum IL-27 levels, the -964 A/A genotype may be associated with a protective role that prevents the intrapulmonary spread of PTB rather than its development.

Longitudinal monitoring of stem cell grafts in vivo using magnetic resonance imaging with inducible maga as a genetic reporter.

PURPOSE: The ability to longitudinally monitor cell grafts and assess their condition is critical for the clinical translation of stem cell therapy in regenerative medicine. Developing an inducible genetic magnetic resonance imaging (MRI) reporter will enable non-invasive and longitudinal monitoring of stem cell grafts in vivo. METHODS: MagA, a bacterial gene involved in the formation of iron oxide nanocrystals, was genetically modified for in vivo monitoring of cell grafts by MRI. Inducible expression of MagA was regulated by a Tet-On (Tet) switch. A mouse embryonic stem cell-line carrying Tet-MagA (mESC-MagA) was established by lentivirus transduction. The impact of expressing MagA in mESCs was evaluated via proliferation assay, cytotoxicity assay, teratoma formation, MRI, and inductively coupled plasma atomic emission spectroscopy (ICP-OES). Mice were grafted with mESCs with and without MagA (mESC-MagA and mESC-WT). The condition of cell grafts with induced "ON" and non-induced "OFF" expression of MagA was longitudinally monitored in vivo using a 7T MRI scanner. After imaging, whole brain samples were harvested for histological assessment. RESULTS: Expression of MagA in mESCs resulted in significant changes in the transverse relaxation rate (R2 or 1/T2) and susceptibility weighted MRI contrast. The pluripotency of mESCs carrying MagA was not affected in vitro or in vivo. Intracranial mESC-MagA grafts generated sufficient T2 and susceptibility weighted contrast at 7T. The mESC-MagA grafts can be monitored by MRI longitudinally upon induced expression of MagA by administering doxycycline (Dox) via diet. CONCLUSION: Our results demonstrate MagA could be used to monitor cell grafts noninvasively, longitudinally, and repetitively, enabling the assessment of cell graft conditions in vivo.

Cell-based therapies for Huntington's disease.

Cell-based therapies are a viable option for the long-term treatment of Huntington's disease (HD), which is characterized by progressive neurodegeneration predominately in the striatum and cortex. Current research focuses on genetic suppression of the mutant huntingtin (mHTT) gene and cell replacement therapy of the lost cells in HD. As we discuss here, the recent development of induced pluripotent stem (iPS) cells technology demonstrated the potential of cell-based therapy in rodent models. It was shown that iPSCs were capable of differentiating into lost neurons in HD and stem cell grafts can improve motor deficiency in HD rodent models. Altogether, these findings have shown great promise for developing the foundation of the cell-based therapy.

EGFR expression is linked to osteopontin and Nf-kB signaling in clear cell renal cell carcinoma

AIM AND BACKGROUND: Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in many important aspects of cell biology that are related to tumorigenesis. There are opposite evidences of the role of EGFR in renal cancer and the outcome of EGFR-targeted therapies, suggesting the complexity of EGFR signaling pathways. In vitro, osteopontin (OPN) and nuclear factor kappa B (NF-κB) are thought to be involved in specific ligand-independent EGFR activation that could have a role in resistance to EGFR mAb therapy. Aim of this study was to analyze the relationship between EGFR and OPN at the protein and mRNA level, as well as their relation to NF-κB in clear cell renal cell carcinoma (CCRCC). MATERIALS AND METHODS: Expression of EGFR, OPN, and p65 NF-κB protein was analyzed using immunohistochemistry and compared mutually in 88 CCRCC samples. Expression of EGFR and OPN mRNAs was analyzed using quantitative Real-time PCR in 22 CCRCC samples and compared mutually and with NF-κB protein expression. RESULTS: Epidermal growth factor receptor mRNA level was higher in CCRCC samples in comparison with normal renal tissue (p = 0.012) and was associated with high OPN mRNA level, and with NF-κB activation (p < 0.001 and p = 0.045, respectively). Immunohistochemical staining showed the inverse association; high EGFR protein expression was related with low OPN and NF-κB protein expression (p < 0.001 and p = 0.047, respectively). CONCLUSION: Epidermal growth factor receptor gene is upregulated in CRCC and associated with OPN gene expression and NF-kB signaling. The inverse relation between OPN and EGFR at the protein level could probably reflect dynamic changes that EGFR undergoes following activation (AU)