Circulating CD105 shows significant impact in patients of oral cancer and promotes malignancy of cancer cells via CCL20.

CD105 is rich in endothelium cells and is involved in angiogenesis. Higher microvascular density of tumor is also related to the prognosis in a variety of cancers. In this present study, patients with positive N classification, advanced T classification, advanced TNM stage, extracapsular spread of lymph nodes (ECS), and perineural invasion had significantly higher levels of peripheral vein (pCD105) and venous return from tumor (tCD105) in 71 patients with OSCC compared to 13 healthy volunteers. Those with higher pCD105 or tCD105 levels had significantly poorer 5-year disease-specific survival rate (DDS) and overall survival rate (OS). The tCD105 and pCD105 levels and ECS were the independent prognostic factors by the multivariate analysis according to the Cox regression model in 5-year DDS and OS rate. SAS and SCC4 cells treated with CD105 showed the increase in migration, invasion, and proliferation in vitro and in vivo. Furthermore, CCL20 expression participated in CD105-elicited cell motility in oral cancer cells. In conclusion, higher level of circulating CD105 is related to adverse pathological features among patients with OSCC. It is also a useful marker for evaluating the prognosis and targeting therapeutics of OSCC.

Enhanced accuracy of optical platelet counts in microcytic anemia.

OBJECTIVE: To determine whether microcytic erythrocytes influence the accuracy of automated platelet (PLT) counting. METHODS: We divided a total of 206 K2 ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood samples into 4 groups, as follows: In group 1 (control group), normal mean corpuscular volume (MCV > 80 fL) and PLT count equal or greater than 140,000/microL (n = 45); group 2, normal MCV, reduced PLT count (< 140 x 10(3)/microL, n = 41); group 3, microcytic samples with normal PLT count (n = 68); and group 4, microcytic samples with reduced PLT count (n = 49). We also compared the platelet counting using electroimpedance (PLT-EI), platelet count using fluorescent optical (PLT-FO), and platelet-count manual (PLT-M) methods, using the Sysmex XE 2100 automatic analyzer. RESULTS: Despite highly significant overall correlations between PLT-EI and PLT-FO, PLT-EI and PLT-M, and PLT-FO and PLT-M (r = 0.95 [all P < .001]), use of the PLT-EI method resulted in widely overestimated PLT counts in microcytic samples (MCV < 80 fL), compared with use of PLT-FO and PLT-M. Our results identify an MCV of 70 fL as the critical threshold below which PLT-EI became unreliable. CONCLUSION: The PLT-EI mode overestimated PLT counts compared with PLT-FO and PLT-M modes in microcytic blood. Therefore, PLT-FO is the preferred method for PLT counting in patients with microcytic anemia when using an automated analyzer.

Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects.

Background: Organophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years. Objectives: Investigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population. Methods: Different age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined. Results: The mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 µg/L (standard deviation (SD) of 1.91 µg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 µg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p<0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns. Conclusion: To our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships.

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan.

INTRODUCTION: This study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19. METHODS: We retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone. RESULTS: Thirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05). CONCLUSIONS: Ropeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients.

Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA)-An Accurate and Rapid Potential Companion Diagnostic and Pharmacological Interrogation Solution for Cancer Immunotherapy (PD-1/PD-L1).

Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are a critical component for determining the safety and efficacy of newly developed ICBs for cancer treatment. In this study, we strive to demonstrate the feasibility of using hollow fiber assay microtube array membrane (MTAM-HFA) in the screening of anti-cancer ICBs. The MTAM-HFA process was carried out by encapsulating peripheral blood mononuclear cells (PBMCs) and the target cancer cells (cell lines or primary cells) and subcutaneously implanting them into Balb/C mice. At predetermined time points combination regimens of PD-1/PD-L1+ were administered accordingly and at a predetermined time point, the MTAMs were retrieved, and cell viability assays were carried out. The outcomes of the MTAM-HFA were compared against the clinical outcome of patients. Clinical comparison demonstrated excellent correlation between the screening outcome of MTAM-HFA of PD-1/PD-L1+ combination therapy and the clinical outcome of the lung cancer patients. Basic cell studies revealed that the utilization of MTAM-HFA in PD-1/PD-L1+ combination therapy revealed enhanced T-cell activity upon the administration of the PD-1/PD-L1 drug; thereby resulting in the reduction of tumor cell viability by up to 70%, and the cytotoxic effects by 82%. The outcome was echoed in the in vivo cell studies. This suggested that the MTAM-HFA system is suitable for use in PD-1/PD-L1+ screening and the accuracy, rapidity and cost effectiveness made it extremely suitable for application as a companion diagnostic system in both personalized medicine for cancer treatment and could potentially be applied to screen for candidate compounds in the development of next generation PD-1/PD-L1+ combination therapies.

Exosome-derived microRNAs in oral squamous cell carcinomas impact disease prognosis.

OBJECTIVES: microRNA (miRNA) expression patterns have provided new insight as biomarkers of prognosis as well as novel therapeutic targets for several neoplasms. However, the role of exosomal miRNA in the prognosis of oral squamous cell carcinoma (OSCC) has not yet been completely clarified. Paired primary tumor and normal oral epithelial cells from OSCC patients were obtained, and the exosomal miRNA profiles between them were compared by miRNA microarray analysis. The miRNA levels in the serum exosomes of OSCC patients were verified by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Finally, the biological functions and the potential as a prognostic marker of the selected miRNA candidates were analyzed in the OSCC cells and patients, respectively. RESULTS: Exosomal miR-155 and miR-21 were significantly upregulated, and exosomal miR-126 was dramatically downregulated in the primary OSCC cells and the serum of OSCC patients. In the analysis of oncogenic behaviors, coculture with either miR-155-rich or miR-21-rich exosomes could promote cell proliferation and invasion accompanied with downregulation of PTEN and Bcl-6 tumor suppressors. Moreover, treatment with miR-126-rich exosomes inhibited oncogenic behaviors and oncogene EGFL7 expression in OSCC cells. Finally, exosomal miR-126 was reduced in the serum of the late-staged OSCC patients, and downregulation of blood exosomal miR-126 was associated with poor survival in OSCC patients. CONCLUSION: Exosomal miR-155 and miR-21 are oncogenic miRNAs which suppress PTEN and Bcl-6 expression, and exosomal miR-126 acts as a tumor suppressor which downregulates EGFL7 in OSCC. Furthermore, blood exosomal miRNAs may serve as biomarkers for the diagnosis and prognosis of OSCC.

Endotoxin and CD14 in the progression of biliary atresia.

BACKGROUND: Biliary atresia (BA) is a typical cholestatic neonatal disease, characterized by obliteration of intra- and/or extra-hepatic bile ducts. However, the mechanisms contributing to the pathogenesis of BA remain uncertain. Because of decreased bile flow, infectious complications and damaging endotoxemia occur frequently in patients with BA. The aim of this study was to investigate endotoxin levels in patients with BA and the relation of these levels with the expression of the endotoxin receptor, CD14. METHODS: The plasma levels of endotoxin and soluble CD14 were measured with a pyrochrome Limulus amebocyte lysate assay and enzyme-linked immunosorbent assay in patients with early-stage BA when they received the Kasai procedure (KP), in patients who were jaundice-free post-KP and followed-up at the outpatient department, in patients with late-stage BA when they received liver transplantation, and in patients with choledochal cysts. The correlation of CD14 expression with endotoxin levels in rats following common bile duct ligation was investigated. RESULTS: The results demonstrated a significantly higher hepatic CD14 mRNA and soluble CD14 plasma levels in patients with early-stage BA relative to those with late-stage BA. However, plasma endotoxin levels were significantly higher in both the early and late stages of BA relative to controls. In rat model, the results demonstrated that both endotoxin and CD14 levels were significantly increased in liver tissues of rats following bile duct ligation. CONCLUSIONS: The significant increase in plasma endotoxin and soluble CD14 levels during BA implies a possible involvement of endotoxin stimulated CD14 production by hepatocytes in the early stage of BA for removal of endotoxin; whereas, endotoxin signaling likely induced liver injury and impaired soluble CD14 synthesis in the late stages of BA.

Towards Wearable and Flexible Sensors and Circuits Integration for Stress Monitoring.

Excessive stress is one of the main causes of mental illness. Long-term exposure of stress could affect one's physiological wellbeing (such as hypertension) and psychological condition (such as depression). Multisensory information such as heart rate variability (HRV) and pH can provide suitable information about mental and physical stress. This paper proposes a novel approach for stress condition monitoring using disposable flexible sensors. By integrating flexible amplifiers with a commercially available flexible polyvinylidene difluoride (PVDF) mechanical deformation sensor and a pH-type chemical sensor, the proposed system can detect arterial pulses from the neck and pH levels from sweat located in the back of the body. The system uses organic thin film transistor (OTFT)-based signal amplification front-end circuits with modifications to accommodate the dynamic signal ranges obtained from the sensors. The OTFTs were manufactured on a low-cost flexible polyethylene naphthalate (PEN) substrate using a coater capable of Roll-to-Roll (R2R) deposition. The proposed system can capture physiological indicators with data interrogated by Near Field Communication (NFC). The device has been successfully tested with healthy subjects, demonstrating its feasibility for real-time stress monitoring.

Estrogen receptor overexpression in malignant minor salivary gland tumors of the sinonasal tract.

OBJECTIVES: To identify the expression of estrogen receptors in malignant minor salivary gland tumors of the sinonasal tract. STUDY DESIGN: Case series with chart review. SUBJECTS AND METHODS: A retrospective review of a pathology database identified 17 patients with malignant salivary gland tumors between December 1987 and January 2006. Clinicopathologic data were collected, and immunohistochemical staining for estrogen receptor alpha and beta was performed. RESULTS: Among these malignant tumors, adenoid cystic carcinoma was the predominant histologic type. In addition to epistaxis and nasal obstruction, the headache, facial, or ocular symptoms were also commonly noted in this cohort. Seventy-five percent of cases of adenoid cystic carcinoma were positive for estrogen receptor alpha. In contrast, only 17 percent of cases of adenoid cystic carcinoma were positive for estrogen receptor beta. CONCLUSION: Malignant minor salivary gland tumors of the sinonasal tract are rare disease entities. In the present series, adenoid cystic carcinoma was the most common form of tumor, but the prognosis was poor. Most of the cases were positive for expression of estrogen receptor alpha, which suggests that hormone therapy may have a role in the management of certain minor salivary gland tumors of the paranasal sinus and nasal cavity.

Simultaneous determination of residual thiamphenicol and florfenicol in foods of animal origin by HPLC/electrospray ionization-MS/MS.

A simple and reliable method using HPLC/MS/MS has been developed for determination of thiamphenicol and florfenicol in foods of animal origin, such as pork, porcine liver, porcine kidney, beef, bovine liver, fish, and chicken. The HPLC separation was performed on a Waters XTerra phenyl column (100 x 2.1 mm, 3.5 microm) with a gradient mobile phase system of 0.1% formic acid-methanol at a flow rate 0.35 ml/min. Negative ionization produced the molecular ions at m/z 354 and 356 for thiamphenicol and florfenicol, respectively. Two characteristic transition reactions (m/z 354-->185, 290 and m/z 356-->336, 185) in the selected reaction monitoring mode were tested for detection and confirmation of thiamphenicol and florfenicol simultaneously. The analytes were extracted with ethyl acetate and defatted with n-hexane by liquid-liquid extraction. The recoveries of thiamphenicol and florfenicol by the developed method were 72.5-97.6%. The limits of determination were 1.0 ng/g (ppb) for both compounds.

Analysis of nurse practitioner scope of practice in Taiwan using the Longest policy cycle model.

BACKGROUND AND PURPOSE: To date, there has been no policy analysis or review of the effectiveness of the current nurse practitioner (NP) scope of practice regulations in Taiwan. The purpose is of this article was to provide a policy analysis of NP scope of practice regulations in Taiwan. METHODS: The Longest policy cycle model was used to analyze the NP scope of practice regulations. Policy formation, policy implementation, and policy modification are three steps in this model. Policy formation and policy implementation are described in the first two sections. Regarding policy modification, we used the data collected from a research grant to evaluate the implementation of the NP scope of practice regulations to present the effectiveness of the policy endorsement in Taiwan. CONCLUSIONS: The impact of health care services provided by NPs was positive from the viewpoint of the hospital. The top-ranking impact was reducing physicians' workload and increasing the effectiveness of communication and coordination among the team. IMPLICATIONS FOR PRACTICE: The economic value of advanced practice nurses needs to be identified, as it can result in optimal professional growth. The Taiwan Association of Nurse Practitioners can design the metrics to measure NPs' contribution and to analyze the financial benefits bestowed by the NP profession based on the study results.

A PKC-Sp1 signaling pathway induces early differentiation of human keratinocytes through upregulation of TSG101.

The TSG101 protein has been implicated in multiple biological functions including regulation of gene transcription, vesicular trafficking, cellular growth and differentiation. However, the cellular signals that control TSG101 functions are unclear. Here, we demonstrate that TSG101 is upregulated during keratinocyte differentiation in both human foreskin tissue and reconstructed organotypic skin cultures. In addition, we found that TSG101 siRNA inhibits calcium-induced early differentiation of human foreskin keratinocytes, indicating an essential and downstream role for TSG101 in this process. Furthermore, the PKC agonist TPA promotes expression of TSG101 and keratin 10 in keratinocytes under low calcium conditions, while co-treatment with the PKC inhibitor GF 109203X blocks TPA-induced TSG101 and keratin 10 upregulation. Previous work has established that the TSG101 gene is controlled by a TATA-less promoter that harbors a Sp1-binding site. Here we show that both calcium and TPA activate PKC, stimulate phosphorylation of Sp1, and augment the activity of the TSG101 promoter in a manner dependent on its Sp1-binding site. Release of calcium from intracellular stores with thapsigargin, an endoplasmic reticulum Ca2+-ATPase inhibitor that elevates intracellular free Ca2+ without activating PKC, does not affect Sp1 phosphorylation and TSG101 promoter activity. Taken together, these data suggest that an intracellular calcium store independent PKC-Sp1 signaling pathway induces early keratinocyte differentiation through upregulation of TSG101.

Lower prevalence but favorable survival for human papillomavirus-related squamous cell carcinoma of tonsil in Taiwan.

Human papillomavirus (HPV) is frequently detected in squamous cell carcinoma of tonsil (TSCC) among the Western population. However, the only reported study on Chinese patients in the English literature demonstrated absence of HPV in TSCC. To evaluate the prevalence and clinical significance of HPV-related TSCC in Taiwan, we performed PCR with MY09/MY11 consensus primers and in situ hybridization to study 111 TSCC samples. The results showed that only 12.6% TSCC were HPV-positive. The favorable 5-year survival rate correlated significantly with HPV positivity (p=0.007), female (p=0.046), and early tumor (T) stage (p<0.001), but Cox's regression analysis revealed that only the status of HPV (p=0.04) and T stage (p=0.004) were independent prognostic factors for survival. In conclusion, the prevalence of HPV-related TSCC is much lower in Taiwan comparing with the Western population, and the prognosis of HPV-positive TSCC is better than that of HPV-negative TSCC.

High expression of CD105 as a prognostic predictor of early tongue cancer.

OBJECTIVES: The purpose of this article is to investigate the expressions of vascular endothelial growth factor (VEGF) and endoglin (CD105) in the biopsy tissues of squamous cell carcinoma of the tongue in early tumor stages and their relationship with the clinicopathologic features. STUDY DESIGN AND METHODS: The authors conducted retrospective clinical and biologic studies. Immunohistochemistry was used to study the expressions of VEGF and CD105 in the biopsy tissues taken from 94 patients with T1 and T2 tongue cancers. The expressions of VEGF and CD105 were analyzed and correlated to the clinicopathologic features of these patients. RESULTS: High expressions of VEGF and CD105 significantly correlated with a relatively advanced tumor stage (P=.001 and P<.001), positive nodal status (P<.001 and P<.001), presence of tumor necrosis (P=.022 and P=.01), and greater tumor thickness (P<.001 and P<.001), respectively. In addition, high expression of CD105 correlated with the presence of perineural invasion (P=.003). However, the expression of VEGF and CD105 did not significantly correlate with age, gender, vascular invasion, or histologic grading. The cumulative 5-year disease-free survival rate significantly correlated with low expression of VEGF (P=.003), CD105 (P<.001), positive nodal status (P<.001), a relatively advanced tumor stage (P=.024), greater tumor thickness (P=.023), and presence of tumor necrosis (P=.003). Nonetheless, Cox's regression analysis revealed that only the expression of CD105 was an independent prognostic predictor for survival (P<.001). CONCLUSIONS: Higher expression of either CD105 or VEGF in the tumor bed implicates a more aggressive potential for T1 and T2 tongue cancers, and the expression of CD105 is a useful predictive prognostic factor in early tongue cancer.

Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinomas.

Functional inactivation of tumor susceptibility gene tsg101 leads to cellular transformation and tumorigenesis in mice. While human TSG101 is located in a region where frequent loss of heterozygosity can be detected in a variety of cancers, no genomic deletion in TSG101 gene has been reported, casting a doubt on the role of TSG101 as a classical tumor suppressor. Some studies have revealed that TSG101 is a frequent target of splicing defects, which correlate with cellular stress and p53 status. Furthermore, recent reports have identified TSG101 as a part of the MDM2/p53 regulatory circuitry, a well-recognized circuitry that upon deregulation results in tumorigenesis. Interestingly, overexpression of tsg101 from an adventitious promoter also leads to neoplastic transformation. On the basis of this information, we have analysed TSG101 gene expression in 20 human papillary thyroid carcinomas (PTCs) by immunohistochemistry and demonstrated that the overexpression of TSG101 protein is closely associated with human PTCs. Further sequence analysis reveals no mutation in cDNA region encoding steadiness box in these PTC specimens, indicating that the upregulation of TSG101 protein is not caused by the alteration of this region. In situ hybridization analysis confirms that overexpression of TSG101 also occurs at the transcriptional level. In addition, semi-quantitative RT-PCR and subsequent Southern hybridization verify that the amounts of TSG101 transcripts are indeed lower in three normal thyroid tissues than in PTC specimens. Here we report the upregulation of TSG101 expression in PTC cells, providing the first evidence of the association of TSG101 overexpression with human tumors and suggesting that upregulation of TSG101 steady-state level might play a role in mediating tumorigenesis of human PTC.

The clinicopathological significance of p53 and p21 expression in squamous cell carcinoma of hypopharyngeal cancer.

To evaluate the roles of p53 and p21 expression in the squamous cell carcinoma of hypopharyngeal cancer, we performed the immunohistochemical studies in 58 patients with hypopharyngeal cancer. We found significant correlation between a high expression of p53 and a histological grade of well differentiation, advanced tumor (T) and TNM stage. Furthermore, low expression of p21 correlated significantly with advanced TNM stage and positive nodal status. Cox's regression analysis revealed tumor stage and nodal status were the only prognostic factors for survival. Therefore, we concluded that p53 and p21 are useful markers in predicting some clinicopathological features in hypopharyngeal cancer.

EBV-encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non-resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein-Barr virus-encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fisher's exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fisher's exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin-6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin-6 production.

Prognostic impact of p16, p53, epidermal growth factor receptor, and human papillomavirus in oropharyngeal cancer in a betel nut-chewing area.

OBJECTIVE: To evaluate the prevalence of human papillomavirus (HPV) and the prognostic significance of epidermal growth factor receptor (EGFR), p53, and p16 among patients with oropharyngeal carcinoma. DESIGN: Retrospective study. SETTING: Academic Institute of Otolaryngology, Kaohsiung, Taiwan. PATIENTS: Two hundred seventy-four patients who were diagnosed as having oropharyngeal carcinoma underwent testing for the presence of the HPV genome in the nuclei of their tumor cells from January 1, 1992, through March 31, 2008. INTERVENTIONS: The HPV genome was detected by performing polymerase chain reaction-based assays and in situ hybridization on tumor tissue from paraffin blocks. Immunohistochemistry staining for p16, p53, and EGFR was also performed. MAIN OUTCOME MEASURES: We used the Fisher exact test to evaluate the correlation between the clinicopathological variables and the presence of HPV in tumor cells. Survival analysis was based on the Kaplan-Meier method. RESULTS: We detected HPV in 45 of the 274 patients (16.4%); of these, HPV-16 and -18 were identified in 42 (93.3%) of the HPV-positive tumors. The HPV-positive oropharyngeal cancers were more likely to occur in females, nonsmoking individuals, and those who did not chew betel quid. The HPV-positive tumors significantly expressed p16 and were inversely associated with EGFR and p53 expression (all, P < .001). In addition, patients with tumor tissue that was positive for HPV (P = .008) and had negative expression of EGFR (P = .01), low expression of p53 (P = .01), and high expression of p16 (P = .04) had a better prognosis. CONCLUSION: Our results suggest that HPV, EGFR, p53, and p16 are useful biomarkers in predicting the clinical outcomes of oropharyngeal cancer.

Comprehensive study on the prognostic role of osteopontin expression in oral squamous cell carcinoma.

Osteopontin is a tumor-associated protein that promotes tumor development and metastasis. The preoperative blood samples of 94 oral squamous cell carcinoma (OSCC) patients and 28 healthy individuals were analyzed for plasma osteopontin levels, and another 256 paraffin-embedded OSCC specimens were analyzed by osteopontin immunostaining. The patients with advanced tumor (T) stage (T3/T4 vs. T1/T2) and positive nodal (N) status had significantly higher plasma levels of osteopontin (both p<0.001). Positive osteopontin immunostaining also correlated significantly with advanced T stage (p<0.001), positive N status (p<0.001), advanced TNM stage (p<0.001) and male gender (p=0.016). Unfavorable cumulative 5-year overall survival rates correlated significantly with positive osteopontin immunostaining (p<0.001), advanced T stage (p<0.001), positive N status (p<0.001) and advanced TNM stage (p<0.001). However, Cox regression analysis revealed that T stage and N status were independent prognostic factors for survival (both p<0.001) and osteopontin immunostaining was marginally significant for survival (p=0.056). The present study demonstrated that high expression level of osteopontin in either the plasma or the tumor of the patients with OSCC was associated with tumor progression, suggesting that osteopontin expression is an important prognostic factor for OSCC.

The impact of virus in N3 node dissection for head and neck cancer.

This study is to determine the impact of virus in surgical outcomes among patients of head and neck cancer with N3 lymph node metastasis. A retrospective analysis was conducted for 32 patients with operable N3 neck metastasis undergoing surgical treatment between January 1987 and October 2006. The nuclei of the tumor cells were investigated for the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNAs and were taken into account as the variable for survival analysis. The primary sites were oropharynx in 11 patients, tongue in 3, buccal mucosa in 1, hypopharynx in 8 and unknown primary in 9. The five-year cumulative overall survival rate was 40.7% and 5-year cumulative regional control rate was 55.8%. The 5-year cumulative overall survival rate of patients with unknown primary site (72.9%) and HPV or EBV positive in the tumor (77.8%) were significantly higher than those patients with known primary site (31.3%) and HPV or EBV negative in the tumor (27.4%), respectively (P = 0.0335 and P = 0.0348, log rank test). In conclusion, surgery with adjuvant therapy offers reasonable outcomes for operable N3 node in head and neck cancer in our cohort. In addition, patients with HPV or EBV positive in the tumor have a better survival.