Malignancy In Taiwan Research Articles

SERPING1 Reduces Cell Migration via ERK-MMP2-MMP-9 Cascade in Sorafenib- Resistant Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignant tumor, and it ranks 2nd in terms of mortality rate among all malignancies in Taiwan. Sorafenib is a multiple tyrosine kinase inhibitor that suppresses tumor cell proliferation and angiogenesis around tumors via different pathways. However, the survival outcome of advanced HCC patients treated with sorafenib is still unsatisfactory. Unfortunately, there are no clinically applicable biomarkers to predict sorafenib therapeutic efficiency in HCC thus far. We found that serpin peptidase inhibitor, clade G, member 1 (SERPING1) is highly associated with overall and recurrence-free survival rates in HCC patients and is also highly correlated with several clinical parameters. SERPING1 expression was increased with sorafenib in both the HCC cell extract and conditioned medium, which was also observed in sorafenib-resistant HepG2 and Huh7 cells. Sorafenib decreased cell viability and migration, which was similar to the effect of SERPING1 in HCC progression. Moreover, sorafenib inhibited both MMP-2 and MMP-9 activity and enhanced the expression of p-ERK in HCC cells. In summary, sorafenib reduces HCC cancer progression might through the p-ERK-MMP-2-MMP-9 cascade via upregulation of SERPING1. In the present study, the roles and molecular mechanisms of SERPING1 and its value as a marker for predicting sorafenib resistance and progression in HCC patients were examined. The results of the present study provide a deep understanding of the roles of SERPING1 in HCC sorafenib resistance, which can be applied to develop early diagnosis and prognosis evaluation methods and establish novel therapeutic targets for specifically treating HCC.

Plumbagin Induces Reactive Oxygen Species and Endoplasmic Reticulum Stress-related Cell Apoptosis in Human Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC), a major malignancy in Taiwan, is an invasive epithelial neoplasm resulting in a low survival rate. Current treatments do not prevent OSCC progression, and antitumor therapies should be improved. Plumbagin, a natural compound extracted from Plumbago zeylanica L., appears to have antitumor effects in various tumors. The antitumor mechanism of plumbagin in OSCC is still unclear. This study investigated the molecular mechanism through which plumbagin induces apoptosis. To investigate the antiproliferative and pro-apoptotic effects of Plumbagin on OSCC cells and explore its underlying mechanism, cell counting kit-8, cell cycle analysis, and annexin V/PI assay were conducted. The functions of plumbagin on endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) deficiency were analyzed using flow cytometric analysis. Plumbagin-induced apoptosis-associated proteins were detected using western blotting. Plumbagin induced apoptosis in OSCC cells by suppressing tumor cell proliferation through ROS production, ER stress, mitochondrial dysfunction, and caspases activation. Plumbagin is a promising antitumor candidate targeting human OSCC.

From Infection to Malignancy: Tracing the Impact of Human Papillomavirus on Uterine Endometrial Cancer in a Nationwide Population-Based Cohort Study.

Uterine endometrial cancer (EC) is the most common gynecological malignancy in Taiwan. This study aimed to investigate the association between human papillomavirus (HPV) infection and the development of uterine EC among Taiwanese women. A nationwide population cohort research approach was employed, leveraging longitudinal health insurance databases (LHID 2007 and 2015) from the National Health Insurance Research Database alongside data from the Taiwan Cancer Registry datasets. A comparative analysis examined 472,420 female patients with HPV infection and 944,840 without HPV infection. The results demonstrated that the HPV cohort exhibited a significantly elevated risk of uterine EC, as evidenced by an adjusted hazard ratio (aHR) of 1.588 (95% CI: 1.335-1.888). Furthermore, this elevated risk extended to type 1 EC with an aHR of 1.671 (95% CI: 1.376-2.029), specifically the endometrioid adenocarcinoma subtype with an aHR 1.686 (95% CI: 1.377-2.065). Importantly, these findings were statistically significant (p < 0.001). In conclusion, this research unveils a potential association between HPV infection and an increased risk of uterine EC, particularly the type 1 endometrial cancer subtype, within the Taiwanese female population. These findings have implications for preventive measures and screening programs targeting HPV infection to reduce the risk of this prevalent gynecological malignancy in Taiwan.

Cytologically proven leptomeningeal carcinomatosis in gastric cancer patients: Experience in a tertiary referral center

AbstractLeptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. The reported incidence may be underestimated because of the non‐specific clinical presentation and the suboptimal accuracy of the confirmation tests. Despite advances in multidisciplinary care, the prognosis for patients with LMC remains poor. Gastric cancer (GC) ranking 9th in incidence among all kinds of malignancies in Taiwan. We aimed to review our experience with LMC in GC patients at a tertiary referral center to analyze the clinical features and survival outcomes. All patients with a malignant diagnosis of cerebrospinal fluid (CSF) cytology at the National Taiwan University Hospital were reviewed from January 2002 to December 2018. The survival analysis was calculated by the Kaplan‐Meier method. Univariate and multivariate Cox proportional hazards regression analysis were used to identify factors associated with survival. We identified 18 patients with a diagnosis of GC‐related LMC. LMC occurred in approximately 0.45% of GC patients during this period. Nine (50%) were male, and the median age was 58.5 years old. The most frequent neurological symptom of these patients was altered mental status (72.2%), followed by headache (44.4%) and nausea/vomiting (44.4%). Intracranial hypertension was noted in 87.5% with the mean opening pressure to be 385.3 mmCSF. Intrathecal (IT) chemotherapy was administered to nine patients, principally with methotrexate alone (55.6%). Fourteen patients received CSF drainage by ventriculo‐peritoneal shunt or external ventricular drainage via Ommaya reservoir for relieving intracranial hypertension. In the univariate Cox proportional hazards regression analysis, the poor ECOG performance status (&gt;2), absence of other metastases, and absence of CSF drainage were all prognostic factors of poor survival. In conclusion, LMC was a rare manifestation of GC and was associated with an extremely poor survival when the performance status was poor at presentation. CSF drainage may have some impact on the survival duration in selected cases with LMC.

UBE2C triggers HIF-1α-glycolytic flux in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy in Taiwan. Therefore, refining the diagnostic sensitivity of biomarkers for early‐stage tumours and identifying therapeutic targets are critical for improving the survival rate of HNSCC patients. Metabolic reprogramming contributes to cancer development and progression. Metabolic pathways, specifically, play a crucial role in these diverse biological and pathological processes, which include cell proliferation, differentiation, apoptosis and carcinogenesis. Here, we investigated the role and potential prognostic value of the ubiquitin‐conjugating enzyme E2 (UBE2) family in HNSCC. Gene expression database analysis followed by tumour comparison with non‐tumour tissue showed that UBE2C was upregulated in tumours and was associated with lymph node metastasis in HNSCC patients. Knockdown of UBE2C significantly reduced the invasion/migration abilities of SAS and CAL27 cells. UBE2C modulates glycolysis pathway activation and HIF‐1α expression in SAS and CAL27 cells. CoCl2 (HIF‐1α inducer) treatment restored the expression of glycolytic enzymes and the migration/invasion abilities of UBE2C knockdown cells. Based on our findings, UBE2C expression mediates HIF‐1α activation, increasing glycolysis pathway activation and the invasion/migration abilities of cancer cells. UBE2C may be an independent prognostic factor and a therapeutic target in HNSCC.

Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice.

Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research.

Breast Cancer Survival Analysis Model

(1) Background: Breast cancer (BC)—a leading cause of mortality in women globally—accounts for more than two million cases annually. BC was the most common cancer in Taiwan in 2015 and ranks among the top 10 malignancies in Taiwan. (2) Methods: We established a collection of BC survival and metastasis analyses using the Kaplan–Meier, logarithmic test, and Cox proportional hazard models to investigate the association among BC stages, different treatment modalities, and survival rate of patients with BC at various follow-up intervals. We also evaluated whether clinical prognostic factors had univariate and multivariate effects on the survival of patients with BC. Finally, we performed a metastasis analysis using the survival transition rate values of BC stages to develop a Markov chain and semi-Markov simulation model for BC and BC metastasis analysis, respectively. (3) Results: The Kaplan–Meier survival analysis revealed that the risk of BC treated with surgery was lower than that of those who did not receive surgery and the recommended treatment methods should be ranked by survival as follows: surgery, hormone therapy, chemotherapy, and radiation therapy (in descending order of risk). This is attributed to the predicted survival rate which ranges from 99.6% to 91.2%. Moreover, Cox’s treatment method considered the patient’s attributes and revealed a significant difference (p = 0.001). The Markov chain analyses determined the chance of metastasis at each stage, indicating that the lower the stage of BC, the greater the survival rate. (4) Conclusions: Patients’ treatment is influenced by different BC stages, and earlier detection presents better chances of survival and a greater probability of treatment success.

The correlation of epithelial-mesenchymal transition-related gene expression and the clinicopathologic features of colorectal cancer patients in Taiwan.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the world. It has been the most prevalent malignancy in Taiwan for consecutive thirteen years. Despite the diversity of its etiologic and pathophysiologic factors, a biological process named as epithelial-mesenchymal transition (EMT) is indispensable in the progression of epithelial cancer. Our aim is to investigate the correlation between the expression of 8 EMT-related proteins (E-cadherin, β-catenin, claudin-1, CD44, N-cadherin, fibronectin, vimentin, S100A4) and the clinicopathologic features of CRC in Taiwan, along with the DNA CpG epigenetic status of CD44 gene. In immunohistochemical assessment, decreased expression of E-cadherin is statistically associated with the progression of cancer stage, while decreased expression of claudin-1 as well as increased β-catenin nuclear translocation and N-cadherin expression is statistically associated with the progression of histopathologic grade. E-cadherin, nuclear β-catenin and claudin-1 are also associated with other important prognostic factors, including nodal metastasis, tumor deposits, and elevated serum CA 19–9 levels. In addition, the left-sided colon and rectal cancers show increased nuclear translocation of β-catenin compared to the right-sided colon cancers, while the rectal cancers show increased fibronectin expression compared to the right-sided and left-sided colon cancers. Moreover, vimentin is aberrantly expressed in one case of signet-ring cell carcinoma. The DNA methylation levels of CD44 gene promoter between the tumoral and non-tumorous tissues by NGS comparison showed statistical difference on six CpG sites. However, such difference may not be sufficient because these DNA methylation proportions are too low to inactivate CD44 gene. Our results demonstrate the expression of E-cadherin, claudin-1, and nuclear β-catenin is closely related to the clinicopathologic prognostic determinants of CRC in Taiwan. The DNA methylation level of CD44 gene and its protein expression, however, show no correlation with the clinicopathologic features in CRC.

Targeted Sequencing of Taiwanese Breast Cancer with Risk Stratification by the Concurrent Genes Signature: A Feasibility Study.

Breast cancer is the most common female malignancy in Taiwan, while conventional clinical and pathological factors fail to provide full explanation for prognostic heterogeneity. The aim of the study was to evaluate the feasibility of targeted sequencing combined with concurrent genes signature to identify somatic mutations with clinical significance. The extended concurrent genes signature was based on the coherent patterns between genomic and transcriptional alterations. Targeted sequencing of 61 Taiwanese breast cancers revealed 1036 variants, including 76 pathogenic and 545 likely pathogenic variants based on the ACMG classification. The most frequently mutated genes were NOTCH, BRCA1, AR, ERBB2, FANCA, ATM, and BRCA2 and the most common pathogenic deletions were FGFR1, ATM, and WT1, while BRCA1 (rs1799965), FGFR2 (missense), and BRCA1 (rs1799949) were recurrent pathogenic SNPs. In addition, 38 breast cancers were predicted into 12 high-risk and 26 low-risk cases based on the extended concurrent genes signature, while the pathogenic PIK3CA variant (rs121913279) was significantly mutated between groups. Two deleterious SH3GLB2 mutations were further revealed by multivariate Cox’s regression (hazard ratios: 29.4 and 16.1). In addition, we identified several significantly mutated or pathogenic variants associated with differentially expressed signature genes. The feasibility of targeted sequencing in combination with concurrent genes risk stratification was ascertained. Future study to validate clinical applicability and evaluate potential actionability for Taiwanese breast cancers should be initiated.

Detection and prognostic significance of isolated tumor cells and micrometastases in pelvic lymph nodes of patients with early ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) accounts for approximately 18% of all epithelial ovarian malignancies in Taiwan and portends a poor prognosis. Here, we sought to investigate whether immunohistochemistry with an anti-pan-cytokeratin antibody cocktail (AE1/AE3) can be used as an adjunct to hematoxylin and eosin (H&E) staining for improving the detection of isolated tumor cells (ITCs) and micrometastasis to pelvic lymph nodes (LNs). We also assessed whether these lesions may predict disease recurrence.Pelvic lymphadenectomy specimens were obtained from 197 patients with stage 1 OCCC who had undergone surgery between 2000 and 2018 from Linkou and Kaohsiung Chang Gung Memorial Hospital. Immunohistochemical staining with AE1/AE3 was applied to a total of 1186 slides. Clusters of metastatic tumor cells, detected immunohistochemically, were classified as ITCs (clusters with diameters of ≤0.2 mm) or micrometastases (tumor cell clusters of >0.2 but ≤2.0 mm). We also assessed the diameter of metastases in patients with positive lymph nodes (stage IIIA1, n = 3, 7 positive nodes).Clusters with a positive AE1/AE3 staining were identified in five (2.53%) of the 197 patients (ITCs, n = 3; micrometastasis, n = 2). Four patients had no evidence of disease recurrence but a patient recurred at follow-up. Metastatic foci of patients with stage IIIA1 disease were all >2.0 mm in size.Immunohistochemical staining with AE1/AE3 can identify micrometastasis or ITCs in LNs missed on routine H&E staining. The role of micrometastasis in predicting recurrent OCCC and implementing on treatment strategies requires further investigation.

Ginsenoside M1 Induces Apoptosis and Inhibits the Migration of Human Oral Cancer Cells.

Oral squamous cell carcinoma (OSCC) accounts for 5.8% of all malignancies in Taiwan, and the incidence of OSCC is on the rise. OSCC is also a common malignancy worldwide, and the five-year survival rate remains poor. Therefore, new and effective treatments are needed to control OSCC. In the present study, we prepared ginsenoside M1 (20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol), a major deglycosylated metabolite of ginsenoside, through the biotransformation of Panax notoginseng leaves by the fungus SP-LSL-002. We investigated the anti-OSCC activity and associated mechanisms of ginsenoside M1 in vitro and in vivo. We demonstrated that ginsenoside M1 dose-dependently inhibited the viability of human OSCC SAS and OEC-M1 cells. To gain further insight into the mode of action of ginsenoside M1, we demonstrated that ginsenoside M1 increased the expression levels of Bak, Bad, and p53 and induced apoptotic DNA breaks, G1 phase arrest, PI/Annexin V double-positive staining, and caspase-3/9 activation. In addition, we demonstrated that ginsenoside M1 dose-dependently inhibited the colony formation and migration ability of SAS and OEC-M1 cells and reduced the expression of metastasis-related protein vimentin. Furthermore, oral administration or subcutaneous injection of ginsenoside M1 significantly reduced tumor growth in SAS xenograft mice. These results indicate that ginsenoside M1 can be translated into a potential therapeutic against OSCC.

Polysaccharide-containing fraction from Artemisia argyi inhibits tumor cell-induced platelet aggregation by blocking interaction of podoplanin with C-type lectin-like receptor 2

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Taiwan. Many risks factors induce liver chronic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Mulberry fruits containing polyphenols to remove free radicals and mitigate inflammation has been reported to not only against gastric cancer, melanoma and leukemia but also prevent liver injury induced by alcohol or CCl4 in previous researches. The aim of this study is to examine whether Mulberry could inhibit hepatocarcinogenesis. In animal experiment, diethylnitrosamine (DEN) was used to induce hepatic tumorgenesis. After injecting DEN, the rats treated with mulberry water extracts (MWE) had less and smaller tumor than others without MWE. Moreover, MWE reduced the serum ALT and AST, HCC marker, cleavage caspases, Ser-15-p53 and Ser46-p53 induced by DEN. Further, we observed that mulberry polyphenol extracts (MPE) inhibited the cell growth of HepG2 cell and Hep3B cell. By using flow cytometry and western blotting methods, MPE induced HepG2 cell apoptosis by increase subG1 cells and the elevated expression of caspase-3/8/9. Instead of apoptosis, MPE caused Hep3B cells autophagy by inhibiting Akt and mTOR phosphorylation. Comprehensively, mulberry extracts has a potential to be a health supplement to prevent hepatocarcinogenesis in the future. © 2019

The impact of home hospice care on patients with hematologic disorder in Taiwana population-based cohort study.

e19304 Background: The aim of the study is to examine the effect of home hospice care on quality of end-of-life (EOL) care for patients with hematologic malignancies in Taiwan between 2002 and 2011 by using the Taiwanese National Health Insurance Research Database. Methods: We enrolled patients with hematologic malignancies and lung cancer from the Longitudinal Cohort of Diabetes Patients database. For realizing the impact of home hospice care, those patients were divided into two groups, inpatient hospice care and home hospice care. Results: In Taiwan, 18.44 % patients with hematologic malignancies received hospice care and the ratio was similar with patients with lung cancer. Among those patients, 28.64% patient were able to receive home hospice care. The mean probability of survival was longer in the home-hospice group. Considering those indicators for the quality of hospice, blood transfusion and antibiotic use were significantly more frequent in the home hospice group. But the total cost for the last month for home hospice group was cheaper than inpatient hospice group. Conclusions: Hospice care for patients with hematologic disorder still need improvement. Receiving home hospice care in Taiwan did not decrease the survival life so to enroll the suitable patients for home hospice care are reasonable.

Abstract P4-07-12: Residual risk stratification of Taiwanese breast cancer following curative therapies with digital RNA counting and actionable mutations sequencing

Abstract Introduction: Breast cancer is the most common female malignancy in Taiwan and treatment outcomes have improved enormously with early detection and advancements in adjuvant therapy. Unfortunately, a subset of early stage breast cancer still suffers from recurrence, metastasis, or even cancer-specific death despite treatment improvement, and conventional pathological factors fail to provide sufficient explanatory power accounting for the observed prognostic discrepancy. The aim of the project is to take advantage of digital RNA counting for gene expression and targeted sequencing of actionable mutations to develop a predictive model for operable breast cancers initially treated with curative intention, and the risk of recurrence, distant metastasis, as well as breast cancer-specific mortality will be speculated. Methods: Two approaches are applied for candidate genes yield; we have identified concurrent genes from the coherent patterns between genomic and transcriptional profiles, and the synthesized signatures were prognostic. In addition, concordant genes from leading edge analysis of published gene expression signatures were retrieved, and the consensus of leading edge subsets could stratify breast cancer patients into groups with distinct survival patterns. With bioinformatics tools, the harvested genes will be used to build a risk stratification model, and the residual risk after surgery and adjuvant therapy will be evaluated from archived formalin-fixed paraffin embedded (FFPE) cancer tissues, augmenting the clinical significance of the proposed signature. And finally, actionable mutations will be identified for relapsing patients through targeted sequencing. Results: There were 1584 extended concurrent genes with the threshold MAD (medium absolute deviation) of 0.9, constituting 15.89% of common genes across copy number variation and gene expression arrays. We also constructed breast cancer risk prediction using concordance of genes from leading edge analysis of various prognostic signatures; enrolled signatures were split into either the up-regulated or down-regulated gene sets within each study, and leading edge analysis of filtered up-/down-regulated gene sets from all training data sets were performed, followed by the PLS (partial least square) risk predictive model composed of consensus of leading edge subsets among all assayed subjects. The 145-gene BCeC Sig platform designated for the current study has been established, and was prognostic in 96 Taiwanese breast cancers (log-rank test: P&amp;lt;0.01). Among 37 breast cancers categorized into the high-risk group, there were 383 SNPs, 23 deletes, and 11 insertions. Variations per breast cancer were between 91 and 162 (average: 120). When collapsed into genes, the most altered genes were: BRCA1/2 (30 variants), FANCA(27), NOTCH(21), ALK, AR (20), ATM, BSG(14), FGFR, MET(12), JAK2, PDFGR, RET(11), CSF1R, DAB2I, and TP53(10). Discussion and conclusions: Archived pathological specimens provide an invaluable source to validate the residual risk prediction model for breast cancer patients managed with contemporary multi-modality treatment including surgery, chemo-, endocrine, and targeted therapy. Degraded nucleic acid from FFPE samples could be tackled by the latest NanoString digital RNA counting. This breast cancer residual risk model, composed of concurrent genes and consensual leading edge subset of published gene expression signatures, is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients in terms of personalized medicine Citation Format: Chi-Cheng Huang, Ching-Shui Huang. Residual risk stratification of Taiwanese breast cancer following curative therapies with digital RNA counting and actionable mutations sequencing [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-12.

Aspirin use is associated with reduced risk for recurrence of pyogenic liver abscess: a propensity score analysis

Aspirin possesses anti-bacterial activity that may prevent recurrence of Klebsiella pneumoniae pyogenic liver abscess (KP-PLA). In ex-vivo study, aspirin was administered before bactericidal assay against serotype K1 K. pneumoniae. We identified 5,912 patients with PLA who had no known pre-existing hepatobiliary diseases or malignancy in Taiwan from 1999 to 2013 from nationwide cohort study. Multivariate Cox proportional hazards regression models was used to estimate the hazard ratios [HR] for the association between aspirin use and recurrent PLA. The PLA recurrence rate in patients taking aspirin daily for 30 or more days, from 90 days before to 90 days after the first PLA episode (aspirin users), and aspirin non-users was 42.5 and 74.6 per 1,000 person-years of follow-up, respectively. The population-based study showed a HR for PLA recurrence in aspirin users of 0.50 (95% confidence interval, 0.35–0.69), relative to that in non-users, after adjustments for confounders. An ex-vivo study indicated that aspirin was able to significantly enhance bacterial killing by leukocytes, whether collected from diabetic patients with KP-PLA recurrence or from healthy volunteers. Our results suggest that aspirin is associated with reduced risk for PLA recurrence among Taiwanese with PLA who had no preexisting hepatobiliary diseases or malignancy.

Mulberry fruits extracts induce apoptosis and autophagy of liver cancer cell and prevent hepatocarcinogenesis in vivo

Hepatocellular carcinoma (HCC) is one of the most common malignancies in Taiwan. Many risks factors induce liver chronic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Mulberry fruits containing polyphenols to remove free radicals and mitigate inflammation has been reported to not only against gastric cancer, melanoma and leukemia but also prevent liver injury induced by alcohol or CCl4 in previous researches. The aim of this study is to examine whether Mulberry could inhibit hepatocarcinogenesis. In animal experiment, diethylnitrosamine (DEN) was used to induce hepatic tumorgenesis. After injecting DEN, the rats treated with mulberry water extracts (MWE) had less and smaller tumor than others without MWE. Moreover, MWE reduced the serum ALT and AST, HCC marker, cleavage caspases, Ser-15-p53 and Ser46-p53 induced by DEN. Further, we observed that mulberry polyphenol extracts (MPE) inhibited the cell growth of HepG2 cell and Hep3B cell. By using flow cytometry and western blotting methods, MPE induced HepG2 cell apoptosis by increase subG1 cells and the elevated expression of caspase-3/8/9. Instead of apoptosis, MPE caused Hep3B cells autophagy by inhibiting Akt and mTOR phosphorylation. Comprehensively, mulberry extracts has a potential to be a health supplement to prevent hepatocarcinogenesis in the future.

YWHAE promotes proliferation, metastasis, and chemoresistance in breast cancer cells.

Breast cancer is the most common female-specific malignancy in Taiwan and developed countries worldwide, and its incidence continues to grow. 14-3-3ε (YWHAE), which belong to 14-3-3 family, it has been reported up-regulated in breast cancer tissues. However, the clinical implication and function of YWHAE in breast cancer remains unclear. In this study, we investigated the prognostic value of the YWHAE in human breast cancer. Immunohistochemistry was used to analyze YWHAE expression in breast cancer tissues. Cell model was applied to examine the functions of YWHAE. The chemotherapeutic agents were used to evaluate the effect of YWHAE in breast cancer cell lines. YWHAE expression was associated with tumor size, lymph node metastasis, and poor patient survival in patients with breast cancer. YWHAE overexpression significantly increased the proliferation, migration, and invasion abilities of breast cancer cells. Knockdown of YWHAE expression reduced the expression of Snail and Twist in breast cancer cells. We also found that YWHAE was responsible for the resistance of breast cancer cells to chemotherapeutic agents, and knockdown of YWHAE enhanced sensitivity to multiple chemotherapeutic agents in breast cancer cells. Taken together, our findings indicated that YWHAE promoted cancer progression and chemoresistance in breast cancer cells and can be a potential therapeutic target for breast cancer.

Hepatitis B reactivation among 1962 patients with hematological malignancy in Taiwan

BackgroundThe risk of Hepatitis B virus (HBV) reactivation in patients with different hematological malignancy except lymphoma were rarely known before.MethodsA total of 1962 patients with hematological malignancy were enrolled and followed-up at the National Taiwan University Hospital between 2008 and 2013. The clinical characteristics, HBV serology, and laboratory data were retrospectively reviewed and analyzed.ResultsA total of 1962 patients comprising 1048 men and 914 women were studied. The median age of the patients was 55 years (range, 15–97 years). Chronic HBV carriage was documented at diagnosis of hematological malignancy in 286 (14.6%) patients. A total of 171 (59.8%) of the 286 HBV carriers received primary prophylaxis with anti-HBV agents. Of the HBV carriers, 97 (33.9%) developed hepatitis B reactivation during or after chemotherapy, including 59 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among patients with hematological malignancy and HBV carriage was 10.4 per 100 person–years. A multivariate analysis revealed hepatocellular carcinoma (p < 0.001) and antiviral prophylaxis use (p < 0.001) were independent risk factors of HBV reactivation in HBV carriers. Of the 1676 patients with initial negative hepatitis B surface antigen (HBsAg) counts, 41 (2.4%) experienced hepatitis B reactivation, reverse seroconversion of HBsAg, and lost their protective hepatitis B surface antibody (anti-HBs). A multivariate analysis revealed that diabetes mellitus (p = 0.005, odds ratio (OR): 0.218, 95% confidence interval (CI): 0.076–0.629), allogeneic transplantation (p = 0.013, OR: 0.182, 95% CI: 0.047–0.701), liver cirrhosis (p < 0.001, OR: 0.002, 95% CI: 0–0.047), low anti-HBs titers (p = 0.016, OR: 0.020, 95% CI: 0.001–0.480), and positive hepatitis B core antibody (p = 0.013, OR: 0.070, 95% CI: 0.009–0.571) were independent risk factors of positive seroconversion of HBsAg in patients with hematological malignancy.ConclusionsThe incidence of HBV reactivation among the patients with varying subtypes of hematological malignancy is similar. Prophylaxis with anti-HBV agents critically reduced the risk of hepatitis B reactivation.

Risk of cancer in patients with genital warts: A nationwide, population-based cohort study in Taiwan.

BackgroundCondyloma acuminata currently affects around 1% of sexually active adults, and its incidence is increasing. The coexistence of genital warts (GW) and certain cancers and an association between human papillomavirus (HPV) and various malignancies have been reported. Therefore, we conducted this large national study to analyze the risk of malignancies among men and women with GW in Taiwan.Methods and findingsBetween January 2000 and December 2013, approximately 3 million patients were reported to the National Health Insurance Research Database of Taiwan. Of these patients, 21,763 were diagnosed with GW. In the same time period, a total of 213,541 cancer cases were reported to the registry, of which 1002 were recorded among patients with GW. The age-specific incidence rates of GW and standardized incidence ratios (SIRs) of malignancies compared to the general population were calculated. Women acquired GW earlier than men, with a mean age at diagnosis of 32.63±12.78 years. The highest incidence rate for both genders peaked at 20–29 years. Of the 1002 patients with GW and malignancies, the SIR was 1.95 (95%CI 1.83–2.07). The most markedly increased risk was found for HPV-related cancers, with a SIR of 9.74 (95%CI 3.70–15.77). Significantly elevated risks were also noted for smoking-related cancers, anogenital cancers, cervix in situ, colon, rectum, lung, kidney, and prostate cancers. Most cancers developed within 10 years after the diagnosis of GW.ConclusionsPatients with GW have an increased risk of HPV-related cancers, especially anogenital malignancies in Taiwan. The elevated risk of other cancers highlights differences in exposure and risk factors among patients with GW compared to the general population. Cancer screening and HPV vaccination programs should be emphasized for at-risk patients.

US-Guide Microwave and Radiofrequency Ablation for Liver Tumors

Hepatocellular carcinoma and hepatic metastases are the common malignancy in Taiwan. Surgical resection remains the reference standard in the treatment of malignant liver tumors; however, a large number of patients have disease that is not amenable to surgical therapy. Therefore, several ablative treatment modalities have been developed for local control of liver tumors in patients with malignant hepatic tumors. Radiofrequency ablation (RFA) is the most frequently used of these methods because of its effectiveness, safety in both percutaneous and surgical settings, and relative ease of use. However, RFA is fundamentally restricted by the need to conduct electric energy into the body. The majority of tissue heating is thus due to thermal conduction, which decreases exponentially away from the source. RFA is most effective in the treatment of the hepatic tumors smaller than 3cm. Using multi-probes with switch-controller RFA system can create a larger ablated area for the malignant tumor and can enhance the therapeutic effect in the treatment of medium size (3 to 5 cm) malignant hepatic tumors. Microwave (MW) ablation offers many of the advantages of RF ablation while possibly overcoming some of the limitations. Since MW ablation does not rely on conduction of electricity into tissue, it is not limited by charring. Therefore, temperatures greater than 100°C are readily achieved, which potentially results in a larger zone of ablation, faster treatment time, and more complete tumor kill. In addition, MW ablation has a much broader power field than does RF ablation. This may allow for larger zones of thermal ablation and a more uniform tumor kill. Because the cooling effect of blood flow is most pronounced within the zone of conductive rather than active heating, a larger power field may also enhance treatment of perivascular tumors. MW ablation and multiple-probes RFA with switch controller are both promising new options in the treatment of malignant hepatic neoplasms.