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Background: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Methods: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. Results: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (&gt, 0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031–2.927), 5.497 (95% CI: 1.818–16.615), and 0.176 (95% CI: 0.056–0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102–0.852). Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies.

Simple Summary Liver cancer has a high mortality rate. Here, we retrospectively discuss the current progress and dilemmas in the clinical research and treatment of liver cancer. We primarily focus on microRNAs because of their extremely high value in applications and research. We discuss whether microRNAs can be used for the development of better biomarkers and/or therapeutic drugs, and address the difficulties, requirements for improved diagnostic technologies, and side effects related to microRNA-based drugs. Abstract Liver cancer is the leading cause of cancer-related mortality in the world. This mainly reflects the lack of early diagnosis tools and effective treatment methods. MicroRNAs (miRNAs) are a class of non-transcribed RNAs, some of which play important regulatory roles in liver cancer. Here, we discuss microRNAs with key impacts on liver cancer, such as miR-122, miR-21, miR-214, and miR-199. These microRNAs participate in various physiological regulatory pathways of liver cancer cells, and their modulation can have non-negligible effects in the treatment of liver cancer. We discuss whether these microRNAs can be used for better clinical diagnosis and/or drug development. With the advent of novel technologies, fast, inexpensive, and non-invasive RNA-based biomarker research has become a new mainstream approach. However, the clinical application of microRNA-based markers has been limited by the high sequence similarity among them and the potential for off-target problems. Therefore, researchers particularly value microRNAs that are specific to or have special functions in liver cancer. These include miR-122, which is specifically expressed in the liver, and miR-34, which is necessary for the replication of the hepatitis C virus in liver cancer. Clinical treatment drugs have been developed based on miR-34 and miR-122 (MRX34 and Miravirsen, respectively), but their side effects have not yet been overcome. Future research is needed to address these weaknesses and establish a feasible microRNA-based treatment strategy for liver cancer.

Objective Hypoglycaemia is a common complication of diabetes mellitus. Previous studies suggest that hypoglycaemic episodes may occur with other comorbidities, influencing the outcome of recovery. Recognising the predisposing factors for hypoglycaemic episodes in the emergency department is important. Therefore, we investigated the characteristics of and predisposing factors for hypoglycaemia in the emergency department. Methods Data from 186 patients were retrospectively collected from a medical centre in northern Taiwan. We divided the patients into the advanced-age group (132 patients) and the younger group (54 patients). Associated data collected for statistical analysis included vital signs on arrival, first measured blood glucose level, laboratory results, related comorbidities, length of hospital stay, and survival to discharge. Results Hypoglycaemia was more frequently observed in women in the advanced-age group than in the younger group. Tachycardia and elevated systolic blood pressure were less predominant in the advanced-age group than younger group. More patients in the advanced-age group had concurrent infection, and more patients in the younger group had liver dysfunction, elevated liver enzymes, liver cirrhosis, and concurrent stroke. Conclusions Closer attention should be paid to the possibility of infection in patients of advanced age. Liver disease and stroke need to be ruled out in younger patients.

Objective To study the epidemiology, etiologies and prognostic factors of hypoglycemia. Methods A retrospective chart review of hypoglycemic cases from December, 2009 to February, 2012 was conducted to gather the following patient data: age, gender, vital signs at triage, white blood cell count, serum glucose, C-reactive protein, glutamic oxaloacetic transaminase, creatinine, sodium, potassium, past history of liver cirrhosis, uremia, concomitant infection, concomitant cancer/malignancy, length of stay, lack of recent meal, status of acute renal failure and concomitant stroke. A total of 186 cases were enrolled in our study. We analyzed the data using commercial statistics software (SPSS for Windows, version 11.0, SPSS Inc., Chicago, IL). We used the Student's t-test and χ2 test for the statistical analyses, and significance was set at a P value less than 0.05. Results Hypoglycemia is related to several co-morbidities. In total, 10.2% of the patients had liver cirrhosis and 7.0% had uremia. More than half (55.4%) were bacterial infection during hospitalization. Acute renal failure accounted for 26.3% of the hypoglycemic episodes. In addition to the etiology of infection, the lack of a recent meal accounted for 44.6% hypoglycemic episodes. A total of 2.2% of the cases resulted from an acute cerebrovascular accident. Approximately 8.6% were concomitant with malignancy. Conclusions When hypoglycemic patients present in the emergency department, physicians should pay attention to the presence of infection, malignancy, liver diseases (liver cirrhosis and biliary tract infection), and acute renal failure.

Magnetic microbeads are widely utilized in microfluidic systems for various applications. For these tasks, the effective and efficient manipulation of magnetic microbeads is important. Among the techniques for microparticle manipulation, the optically induced electrokinetic (OEK) [e.g., optically induced dielectrophoresis (ODEP) or light-actuated AC electroosmosis (LACE)]-based technique is promising. However, its utilization for magnetic microbead manipulation in a microfluidic system has not yet been fundamentally studied. To address this issue, the effect of operating conditions on the OEK-based magnetic microbead manipulation investigated. The results showed that the maximum terminal velocity (Vterminal) of a light image that can manipulate microbeads decreased significantly with increasing AC frequency. In addition, the results revealed that the Vterminal increased with increasing intrinsic a-Si:H layer thickness (Ta-Si) when the AC frequency was higher than 30 kHz, whereas the results completely reversed when the frequency was lower than 30 kHz. Additionally, the Vterminal of larger magnetic microbeads was higher than that of smaller microbeads when the AC frequency was higher than 50 kHz; conversely, the results significantly reversed when the frequency was lower than 30 kHz. Moreover, microbead manipulation under high conductivity conditions could significantly affect the magnitude of the Vterminal. Based on the fast manipulation velocity in LACE-based microbead manipulation, its application for basic unit operations in a microfluidic system was demonstrated. Overall, this study has provided some fundamental information for the selection of optimum operating conditions for OEK-based magnetic microbead manipulation in a microfluidic system.

Conventional positive and negative selection-based circulating tumor cell (CTC) isolation methods might generally ignore metastasis-relevant CTCs that underwent epithelial-to- mesenchymal transition and suffer from a low CTC purity problem, respectively. To address these issues, we previously proposed a 2-step CTC isolation method integrating a negative selection CTC isolation and subsequent spheroid cell culture. In addition to its ability to isolate CTCs, more importantly, the spheroid cell culture used could serve as a cell culture model mimicking the process of new tumor tissue formation during cancer metastasis. Therefore, it is promising not only to selectively isolate metastasis-relevant CTCs but also to test the potential of cancer metastasis and thus the prognosis of disease. To explore these issues, experiments were performed. The key findings of this study demonstrated that the method was able to harvest both epithelial (E)- and mesenchymal (M)-type CTCs without selection bias. Moreover, both the M-type CTC count and the information obtained from the multidrug resistance-associated protein 2 (MRP2) and MRP5 gene expression analysis of the CTCs isolated via the 2-step CTC isolation method might be able to serve as prognostic factors for progression-free survival in head and neck squamous cell carcinoma.

Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited.A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer.The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2-fold compared with that of healthy control subjects (P0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P=0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off=115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation.These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis.

Cervical carcinoma is the third-most common cause of cancer-related deaths in women worldwide. However, the molecular mechanisms underlying the metastasis of cervical cancer are still unclear. Oligonucleotide microarrays coupled with bioinformatics analysis show that cytoskeletal remodeling and epithelial-to- mesenchymal transition (EMT) are significant pathways in clinical specimens of cervical cancer. In accord with clinical observations demonstrating ectopic expression of lipocalin 2 (LCN2), an oncogenic protein associated with EMT, in malignant tumors, was significantly upregulated in cervical cancer and correlated with lymph node metastasis. Overexpression of LCN2 enhanced tumor cell migration and invasion both in vitro and in vivo. Conversely, knockdown or neutralization of LCN2 reduced tumor cell migration and invasion. LCN2-induced migration was stimulated by activation of the EMT-associated proteins, Snail, Twist, N-cadherin, fibronectin, and MMP-9. Our findings collectively support a potential role of LCN2 in cancer cell invasion through the EMT pathway and suggest that LCN2 could be effectively utilized as a lymph node metastasis marker in cervical cancer.

A second corresponding author, Chia-Siu Wang, was not signified. The author Chia-Siu Wang can be contacted at wangcs@adm.cgmh.org.tw Also, there is an error in Figure 3. The correct Figure 3 can be seen here: [^]

Introduction: With unique geographic features, mountain climbing has been a popular outdoor activity in Taiwan. Related conferences on safety issues were held by Ministry of Education. It is found that mortality and morbidity of high mountain syndrome (HMS) is highly reverse related to timely diagnosis and management. Generally, it is not easy for mountain climbers to manage this condition without an expert on site. Several climbers died from HMS every year. In 2005, wireless internet service was provided in Yushan National Park (YSNP), the highest national parkin Northeast Asia. We therefore began this project - building an emergent HMS consulting system based on this service.

Cervical cancer is still a serious problem threatening to women health worldwide. The incidence of cervical adenocarcinoma (AD) is rising in more developed countries. Previously we have identified that glucose-regulated protein 58 (Grp58) serves as a poor independent prognostic factor for cervical AD. The molecular mechanism underlying Grp58 involved cervical AD carcinogenesis is unknown. The DNA microarray and enrichment analysis were used to identify pathway maps perturbed by knockdown of Grp58 expression. The WNT singling map is one of the significant enriched pathways. The β-catenin, vital effector of WNT signaling, was stably accumulated in Grp58 knockdown stable cells. A membrane fashion of β-catenin was observed in Grp58 knockdown but not control cells. By using transwell assay, we have demonstrated that accumulation of β-catenin, which was induced by Grp58 knockdown or lithium chloride treatment, inhibited the migration ability of HeLa cell. Furthermore, an exclusive expression pattern of Grp58 and β-catenin was observed in cervix tissues. In sum, we have demonstrated that β-catenin stability is negatively regulated by Grp58. Overpression of Grp58 might result in lost or decreased of membranous β-catenin in cervical cancer to promote cancer progression. Citation Format: Chia-Jung Liao, Syuan-ling Lin, Tzu-Hao Wang, Kwang-Huei Lin. Glucose-regulated protein 58 modulates β-catenin protein stability in cervical adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3290. doi:10.1158/1538-7445.AM2014-3290

Cervical cancer is the second most common cancer in women worldwide. Human papilloma virus infection is the primary cause of cervical cancer, although it cannot cause cancer by itself. Molecular markers involved in cervical carcinogenesis are needed. A two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomic strategy was used to discover genes with exceptional expression from four paired cervical cancer tissues. Immunoblotting and immunohistochemical analysis with 52 paired specimens and 107 sections were used to confirm the results of 2-DE, and the clinical significance was estimated. The molecular functions of ER-60 were investigated in vitro and in vivo. We identified ER-60 was upregulated in 71.2% of cancerous tissues. ER-60 expression differed significantly between patients with different histological types and differentiation grades (P = 0.013 and 0.045, respectively). Patients with high ER-60 expression had a lower 5-year overall survival (OS) and recurrence-free survival (RFS) rate (P = 0.038 and 0.017, respectively). High ER-60 expression was an independent prognostic factor of poor RFS (P = 0.019). Knockdown of ER-60 expression in HeLa cell decreased cell motility. The lung metastasis was inhibited when introduced ER-60-knockdown cells into severe combined immunodeficiency mice. We observed accumulation of b-catenin and regulation of b-catenin downstream CD44 and S100A4 expression in ER-60-knockdown cell were responsible for this migration inhibition. Taken together, ER-60 overexpression is a potential prognostic factor of poor OS and an independent factor of poor RFS in cervical cancer. ER-60 may be involved in cervical cancer invasion by modulating b-catenin protein stability and signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3807. doi:10.1158/1538-7445.AM2011-3807

Introduction: The global yearly incidence and mortality of cervical cancer are 471,000 annual new cases and 233,000 deaths. Almost 80% cases occur in less developed countries, where it accounts for 15% of cancer in women. Cervical carcinoma ranks as the leading malignancy of genital tract malignancy in the developing countries. The recurrence indicate poor prognosis while the clinicopathological risk factors exist. In order to identify the potential molecular biomarker, proteomic analysis was performed and gesolin protein was selected. Materials and Methods: The plasma from normal healthy and cervical cancer, and tissue of cervical cancer plus adjacent normal tissue were collected for Western blotting assay, enzyme-linked immunosorbent assay (ELISA) or immunohistochemical stain (IHC). One hundred and twenty four patients with cervical cancers underwent surgical management were enrolled to evaluate IHC Histoscore of gesolin according to the multiply of immunoreactivity and involved percentage. The Transwell assay was conducted for cell migration analysis in HeLa cell line. The statistical analysis include independent t tests, Kaplan-Meier method using the log-rank test and the Cox proportional hazard model Receiver operating characteristics (ROC) curve analysis was used to determine cut-off points of the predictive parameters in univariate analysis. Results: The Western blot and ELISA assay both demonstrated the overexpression of plasma gelsolin in cases with cervical cancer rather than normal population, and with staged III/IV rather than stage I/II cases, In addition, gelsolin protein level also increased in conditional medium of cultured HeLa cell. Thus in vitro cell migration assay revealed decreased cell numbers while adding the gelsolin neutralizing antibody or small interference RNA compared with adding mock, non-specific antibody or Luciferase-shRNA. The other clinical parameters including stage, tumor size and lymph node status also put into consideration. The best cut-off point of gesolin Histosore to clarify the recurrence by ROC curve analysis is 115. The gelsolin Histosore (≤ 115 vs > 115, P= 0.018) and lymph node metastasis (no vs yes, P Conclusion: Overexpression of plasma and cytoplasmic gelsolin protein in cervical cancer promote cell migration by binding to actin cytoskeleton for rearrangement and cell motility. Among the clinicopathological parameters, the gelsolin overexpression and lymph node metastasis disclosed the recurrence-free survival impact by multivariate analysis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1740.