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Cancer Statistics
Population in 2008: 23.2m
People newly diagnosed with cancer (excluding NMSC) / yr: 78,000
Age-standardised rate, incidence per 100,000 people/yr: 244.1
Risk of getting cancer before age 75:23.9%
People dying from cancer /yr: 41,100
Data from IARC GlobalCan (2008)
Taiwan Cancer Organisations and Resources
Latest Research Publications Related to Taiwan

Taiwan Cancer Organisations and Resources (5 links)

Latest Research Publications Related to Taiwan

Lin NC, Chen YL, Tsai KY
Head and neck cancer in living donor liver transplant recipients: Single center retrospective study.
Medicine (Baltimore). 2019; 98(31):e16701 [PubMed] Related Publications
The purpose of this study was to investigate the incidence and risk factors of head and neck cancer in living donor liver transplant (LDLT) recipients.This is a retrospective cohort study. A case-matched (1:4) comparison between recipients with and without developed head and neck cancer after LDLT was conducted. The differences between 2 groups were analyzed.The incidence of head and neck malignancy in our cohort was 9 of 453 (1.98%). Their cumulative survival rate was below 60% at 24 months after the diagnosis of head and neck cancer, and no recipients lived for more than 2 years after being diagnosed with stage IV cancer. In the case-control study, univariate analysis revealed that alcohol consumption (odds ratio [OR] = 8.75, 95% confidence interval [CI]: 1.55-49.56) and smoking (OR = 6.71, 95% CI: 1.20- 37.44) were factors associated with the incidence of head and neck cancer after LDLT.In the conclusion, recipients with head and neck cancer after LDLT may have a rather poor prognosis, especially those who are initially diagnosed with advanced-stage disease. Alcohol consumption and smoking may be the predisposing factors to head and neck cancer in LDLT recipients.

Yue CH, Liu JY, Chi CS, et al.
Myeloid Zinc Finger 1 (MZF1) Maintains the Mesenchymal Phenotype by Down-regulating IGF1R/p38 MAPK/ERα Signaling Pathway in High-level MZF1-expressing TNBC cells.
Anticancer Res. 2019; 39(8):4149-4164 [PubMed] Related Publications
BACKGROUND/AIM: Signaling regulation of myeloid zinc finger 1 (MZF1) has been implicated in the progression of many human malignancies; however, the mechanistic action of MZF1 in triple-negative breast cancer (TNBC) progression remains elusive. In this study, the aim was to investigate the molecular mechanisms of MZF1 and its functional role in TNBC cellular migration and invasion.
MATERIALS AND METHODS: Hs578T and MDA-MB-231 cells were transfected to stably express the acidic domain of MZF1 (MZF1
RESULTS: Herein, we found that MZF1 in high-level MZF1-expressing TNBC cells is associated with cell migration, invasion, and mesenchymal phenotype. MZF1 interacted with the promoter region of insulin-like growth factor 1 receptor (IGF1R) to drive invasion and metastasis of high-level MZF1-expressing TNBC cells. Exogenous expression of the acidic domain of MZF1 repressed the binding of endogenous MZF1 to IGF1R promoter via blocking the interaction with ETS-like gene 1 (ELK1). This blockage not only caused MZF1 protein degradation, but also restrained ELK1 nuclear localization in high-level MZF1-expressing TNBC cells. MZF1, but not ELK1, was necessary for the retention of mesenchymal phenotype by repressing IGF1R promoter activity in TNBC cells expressing high levels of MZF1. Activation of the IGF1R-driven p38MAPK-ERα-slug-E-cadherin signaling axis mediated the conversion of mesenchymal cell to epithelial phenotype, caused by MZF1 destabilization. These results suggest that MZF1 is an oncogenic inducer.
CONCLUSION: Blocking of the MZF1/ELK1 interaction to reduce MZF1 protein stability by saturating the endogenous MZF1/ELK1 binding domains might be a promising therapeutic strategy for the treatment of high-level MZF1-expressing TNBC.

Huang TS, Lee JJ, Li YS, Cheng SP
Ethacridine Induces Apoptosis and Differentiation in Thyroid Cancer Cells
Anticancer Res. 2019; 39(8):4095-4100 [PubMed] Related Publications
BACKGROUND/AIM: Ethacridine is used as a topical antiseptic as well as for second-trimester abortion. Recent studies showed that ethacridine is an inhibitor of poly(ADP-ribose) glycohydrolase (PARG) and an activator of the transcriptional coactivator with PDZ-binding motif (TAZ). This study examined the effects of ethacridine on thyroid cancer cells.
MATERIALS AND METHODS: Thyroid cancer cell lines (FTC133 and SW1736) and thyroid follicular epithelial cells (Nthy-ori 3-1) were treated with ethacridine. Viability, clonogenicity, cell-cycle distribution, and apoptosis were evaluated. The expression of thyroid differentiation markers (TTF-1, PAX8, and NIS) was determined by real-time PCR.
RESULTS: Ethacridine suppressed cell growth and clonogenic ability of thyroid cancer cells in a time- and dose-dependent manner (p<0.001). No cell-cycle arrest was found, but ethacridine dose-dependently induced apoptosis of thyroid cancer cells (p<0.001). The PAX8 and NIS expressions were significantly increased in SW1736 (3.41-fold and 1.53-fold, respectively) and Nthy-ori 3-1 cells (2.73-fold and 4.12-fold, respectively).
CONCLUSION: Ethacridine elicits apoptotic cell death in thyroid cancer cells and promotes differentiation in a subset of thyroid follicular cells.

Hsu KF, Chen CY, Chu TS, et al.
Scalp melanoma with rectus abdominis metastasis: A rare case report.
Medicine (Baltimore). 2019; 98(28):e16395 [PubMed] Free Access to Full Article Related Publications
RATIONALE: The main cause of death in melanoma patients is widespread metastases as it can metastasize to almost every organ. However, melanoma skeletal muscle metastases (MSMM) are exceptional, and only a few cases of MSMM to the rectus abdominis muscles have been previously described. And our case maybe the first reported case in Asia region.
PATIENT CONCERNS: A 45-year-old man with history of right scalp melanoma, pT3aN0M0, stage IIA status post wide excision with 2 cm safe margin and right neck lymph node dissection at 5 years before. He had an almost 5 years disease-free period but presented to our clinic due to intermittent abdominal sharp pain for 1 to 2 months, with a palpable soft tissue mass over his right abdomen. Metastatic melanoma to rectus abdominis muscles was highly suspected.
INTERVENTIONS: The patient subsequently underwent radical en-block extraperitoneal 15 cm segmental resection of the right rectus abdominis muscle including tumor mass. The resected tumor was a black-gray colored solid mass, and the final histologic study showed a metastasis of melanoma.
OUTCOMES: Postoperative course of the patient was uneventful, and the right abdominal pain was improved. The patient was referred for further target therapy, but passed away half a year later due to multiple metastasis.
LESSONS: Scalp melanoma with isolated rectus muscle metastasis is extremely rare especially for a young aged patient who had an almost 5-year disease-free period. Surgery is a potentially curative therapy for patients with isolated metastatic melanoma. The goal is negative resection margins, in order to avoid local recurrences. Radical compartmental surgery should be considered for selected stage IV melanoma patients with sole rectus abdominis MSMM, whose disease could be amenable to complete resection, in preliminary procedure to prolong disease-free survival time. For oligometastatic disease, surgical resection is sometimes useful in carefully selected patients after systemic therapy; also, it could be performed as symptomatic treatment.

Sun CF, Chen CH, Ke PZ, et al.
Esophageal duplication cyst presenting with stridor in a child with congenital pulmonary airway malformation: A case report and literature review.
Medicine (Baltimore). 2019; 98(28):e16364 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Esophageal duplication cyst (EDC) is a rare developmental aberration originated from the embryonic foregut. It may remain asymptomatic but produce local mass effect on surrounding organs if rapid enlarges. EDC may sometimes accompany with other congenital malformations. Congenital pulmonary airway malformation (CPAM) is a congenital lung malformation with an unknown chance of developing symptoms. Here we report a rare case of esophageal duplication cyst with type 2 congenital pulmonary airway malformation (CPAM).
PATIENT CONCERNS: A 16-month old boy with a prenatal diagnosis of type 2 CPAM presented progressive stridor and respiratory distress and was admitted to our hospital under the diagnosis of pneumonia. The patient responded poorly to antibiotics. A chest Xray (CXR) showed consolidation over the left upper lobe with trachea deviated to right side. A chest computed tomography (CT) revealed a cystic lesion sized 3.3 × 3.3 cm in the superior mediastinum.
DIAGNOSES: Post-operative pathological report confirmed the diagnosis of esophageal duplication cyst.
INTERVENTIONS: We pre-medicated the patient with steroids and inhaled bronchodilators for airway maintenance. Then the patient received tumor resection via median sternotomy.
OUTCOMES: The patient recovered without complication and discharged smoothly 4 days after the surgery.
LESSONS: EDC is a rare but potentially life-threatening disease owning to compression of large airways. Chest CT scan could detect the lesion non-invasively and should be considered in patients with persistent stridor, as well as CXR findings of the trachea deviated by a mass lesion in mediastinum, especially for those with CPAM.

Hung MS, Wu YF, Chen YC
Efficacy of chemoradiotherapy versus radiation alone in patients with inoperable locally advanced non-small-cell lung cancer: A meta-analysis and systematic review.
Medicine (Baltimore). 2019; 98(27):e16167 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: This meta-analysis compared radiotherapy (RT) versus concurrent chemoradiotherapy (RT+CT) in treating patients with inoperable stage III non-small-cell lung cancer (NSCLC).
METHODS: Medline, Cochrane, EMBASE, Google Scholar databases were searched until July 28, 2015 using the following keywords non-small cell lung cancer, advanced cancer, incurable/inoperable/unresectable, chemotherapy, radiotherapy, chemoradiotherapy/chemoradiation. Randomized controlled trials (RCTs) and two-armed prospective studies that compared combined RT+CT with RT alone in patients with locally advanced (stage III) nonresectable NSCLC were eligible for inclusion. Treatment effect on overall survival, progression-free survival (PFS), and objective response rate (ORR) were evaluated.
RESULTS: Ultimately, 13 RCT studies were included in the systematic review and meta-analysis. The 13 studies included a total of 1936 patients with incurable/inoperable stage III NSCLC, of which 975 received RT alone and 961 received RT+CT combination therapy. The average age ranged from 54 to 77 years. At 1 and 2 years after treatment, the pooled data reveal that patients receiving CT+RT combination therapy had higher overall survival (pooled hazard ratio (HR), 0.72; 95% CI, 0.62-0.84; P < .001; 1-yr: HR, 0.67; 95% CI, 0.54-0.84; P < .001; 2-year: HR, 0.57; 95% CI, 0.45-0.73; P < .001), higher PFS (pooled HR, 0.73, 95% CI, 0.60-0.89; P = .002; 1-year: HR, 0.36; 95% CI, 0.24-0.53; P < .001; 2-year: HR, 0.38; 95% CI, 0.23-0.63; P < .001).
CONCLUSION: Our findings show higher efficacy for concurrent CT+RT over RT alone in treating locally-advanced, unresectable stage III NSCLC.

Chang LW, Hung SC, Wang SS, et al.
Abiraterone Acetate and Enzalutamide: Similar Efficacy in Treating Post Docetaxel Metastatic Castration-resistant Prostate Cancer: Single Center Experience.
Anticancer Res. 2019; 39(7):3901-3908 [PubMed] Related Publications
BACKGROUND/AIM: Abiraterone (AA) and enzalutamide (ENZ) were introduced in Taiwan since 2012 for the treatment of patients with post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). This study aims to retrospectively compare the efficacy of the two regimens.
MATERIALS AND METHODS: The study cohort consisted of 77 mCRPC patients previously treated with docetaxel and subsequently with AA (n=63, the AA group) or ENZ (n=13, the ENZ group), all treated in our hospital. Clinical parameters of the two groups were compared to determine differences between pre-treatment variables and treatment outcomes.
RESULTS: Sixty-four patients received AA and 13 received ENZ, with a median 18.2 vs. 14.5 months follow-up (p=0.434). Prostate-specific antigen (PSA) response >50% was 31 (48.4%) in AA and 9 (69.2%) in ENZ (p=0.171), while PSA response >90% was 16 (25%) in AA and 5 (38.5%) in ENZ (p=0.32). The median progression-free survival (PFS) was 7.3 (95%CI=4.796-9.804) months in AA and 9.5 months (95%CI=5.743-13.257) in ENZ (p of log rank=0.766). The median overall survival (OS) from second-line hormone treatment was 30.2 months in AA group and 16.2 months in ENZ group (p of log rank=0.734). Neither the uni- nor the multi-variate COX-regression analysis distinguished any advantage of the two-drug regimen in terms of PFS or OS. Metastasis volume (HR=3.032, 95%CI=1.281-7.178, p=0.012) and nadir PSA (HR=1.000, 95%CI=1.000-1.001, p=0.010) were shown as independent risk factors for the survival of AA/ENZ-treated patients.
CONCLUSION: AA and ENZ had a similar efficacy in treating post-docetaxel mCRPC patients. Metastatic volume and nadir PSA were independent risk factors of these patients in predicting their disease-specific survival and overall survival.

Lin CH, Peng SF, Chueh FS, et al.
The Ethanol Crude Extraction of
Anticancer Res. 2019; 39(7):3697-3709 [PubMed] Related Publications
BACKGROUND/AIM: Cervical cancer is considered poorly chemo-sensitive in women and its treatment remains unsatisfactory. Cyperus rotundus is used in Chinese medicine as a therapeutic agent for women's disease. The effects and molecular mechanisms of the ethanol extraction of C. rotundus (CRE) on cervical cancer remain unclear. We aimed to explore the mechanisms and genetic influence of CRE on cervical cancer.
MATERIALS AND METHODS: HeLa, human cervical cancer cells were treated with various doses of CRE and changes in cell morphology and cell viability were assessed using microscopy and flow cytometry. Finally, we performed a microarray analysis to scan related genes.
RESULTS: The treatment of CRE on HeLa cells caused morphological changes and induced chromatin condensation. DNA microarray analysis showed that CRE led to up-regulation of 449 genes and down-regulation of 484 genes, which were classified in several interaction pathways.
CONCLUSION: CRE changed HeLa cell morphology and induced gene expression which associated with apoptosis and cell-cycle arrest. These results provide important information at the transcription level for targeting treatments of human cervical cancer.

Lee YJ, Chung JG, Chien YT, et al.
Suppression of ERK/NF-κB Activation Is Associated With Amentoflavone-Inhibited Osteosarcoma Progression
Anticancer Res. 2019; 39(7):3669-3675 [PubMed] Related Publications
BACKGROUND/AIM: Amentoflavone has been implicated in reducing the metastatic potential of osteosarcoma (OS) cells in vitro. The aim of the present study was to verify the antitumoral efficacy and the potential mechanism of amentoflavone osteosarcoma progression inhibition in vivo.
MATERIALS AND METHODS: A U-2 OS osteosarcoma xenograft mouse model was used in this study. Mice were treated with a vehicle control or amentoflavone (100 mg/kg/day) for 15 days. Tumor growth, signal transduction, and expression of tumor progression-associated proteins were evaluated using a digital caliper, bioluminescence imaging (BLI), animal computed tomography (CT), and ex vivo western blotting assay.
RESULTS: Amentoflavone significantly inhibits tumor growth and reduces protein levels of phospho-extracellular signal-regulated kinase (P-ERK), nuclear factor-kappaB (NF-κB) p65 (Ser536), vascular endothelial growth factor (VEGF), matrix metallopeptidase 9 (MMP-9), X-linked inhibitor of apoptosis protein (XIAP), and cyclin-D1 in osteosarcoma in vivo.
CONCLUSION: The inhibition of ERK/NF-κB activation is associated with amentoflavone-inhibited osteosarcoma progression in vivo.

Chiang CH, Yeh CY, Chung JG, et al.
Amentoflavone Induces Apoptosis and Reduces Expression of Anti-apoptotic and Metastasis-associated Proteins in Bladder Cancer.
Anticancer Res. 2019; 39(7):3641-3649 [PubMed] Related Publications
BACKGROUND/AIM: Amentoflavone has been shown to be effective against a variety of cancer cells, but its role in bladder cancer remains unclear. Thus, the aim of this study is to evaluate whether amentoflavone may induce toxicity effect of bladder cancer.
MATERIALS AND METHODS: Herein, we evaluated amentoflavone effects in a human bladder cancer cell line TSGH8301 in vitro.
RESULTS: Amentoflavone caused significant cytotoxicity in TSGH8301 cells at a concentration as low as 200 μM. FAS/FASL-dependent extrinsic apoptosis and mitochondria-dependent intrinsic apoptosis were observed in amentoflavone-treated cells in a dose-dependent manner. Levels of several proapoptotic proteins, such as FAS, FAS-ligand and BAX (B-cell lymphoma 2 associated X) were increased following amentoflavone treatment. Meanwhile, anti-apoptotic MCL-1 (myeloid cell leukemia sequence 1) and cellular FLICE-inhibitory protein (C-FLIP) protein levels were reduced. Additionally, angiogenesis and proliferation-related proteins, including matrix metalloproteinase (MMP)-2, -9, vascular endothelial growth factor (VEGF), urokinase-type plasminogen actvator (uPA) and cyclin D1 were diminished by amentoflavone.
CONCLUSION: Amentoflavone induced toxicity of bladder cancer by inhibiting tumor progression and inducing apoptosis signaling transduction.

Wu TK, Chen CH, Pan YR, et al.
Cetrimonium Bromide Inhibits Cell Migration and Invasion of Human Hepatic SK-HEP-1 Cells Through Modulating the Canonical and Non-canonical TGF-β Signaling Pathways.
Anticancer Res. 2019; 39(7):3621-3631 [PubMed] Related Publications
BACKGROUND/AIM: Cetrimonium bromide (CTAB), a quaternary ammonium surfactant, is an antiseptic agent against bacteria and fungi. However, the mechanisms by which its pharmacological actions affect epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as adenocarcinoma in SK-HEP-1 cells, have not been investigated. We, thereby, investigated whether CTAB inhibits cellular mobility and invasiveness of human hepatic adenocarcinoma in SK-HEP-1 cells.
MATERIALS AND METHODS: SK-HEP-1 cells were treated with CTAB, and subsequent migration and invasion were measured by wound healing and transwell assays. Protein expression was detected by immunoblotting analysis.
RESULTS: Our data revealed that treatment of SK-HEP-1 cells with CTAB altered their mesenchymal spindle-like morphology. CTAB exerted inhibitory effects on the migration and invasion of SK-HEP-1 cells dose-dependently, and reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, snail, slug, twist, vimentin, fibronectin, N-cadherin, Smad2, Smad3, Smad4, phosphoinositide-3-kinase (PI3K), p-PI3K, Akt, p-Akt, β-catenin, mammalian target of rapamycin (mTOR), p-mTOR, p-p70S6K, p-extracellular signal-regulated kinases (ERK)1/2, p-p38 mitogen-activated protein kinase (MAPK) and p-c-Jun N-terminal kinase (JNK), but increased protein levels of tissue inhibitor matrix metalloproteinase-1 (TIMP-1), TIMP-2, claudin-1 and p-GSK3β. Based on these observations, we suggest that CTAB not only inhibits the canonical transforming growth factor-β (TGF-β) signaling pathway though reducing SMADs (an acronym from the fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic proteins), but also restrains the non-canonical TGF-β signaling including MAPK pathways like ERK1/2, p38 MAPK, JNK and PI3K.
CONCLUSION: CTAB is involved in the suppression of TGF-β-mediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma.

Chen Y, Tsai YH, Tseng SH
Regulation of BS69 Expression in Cancers.
Anticancer Res. 2019; 39(7):3347-3351 [PubMed] Related Publications
BS69 is encoded by a gene located on chromosome 10, in a region frequently deleted in human cancers and BS69 expression is often down-regulated in human cancers. In addition, BS69 acts as a transcriptional repressor via interaction with transcriptional factors associated with tumorigenesis, such as cellular homolog of the avian myeloblastosis viral oncoprotein, v-ets erythroblastosis virus E26 oncogene homolog 2 oncoprotein, MYC-associated protein X gene-associated protein. Overexpression of BS69 can suppress proliferation of osteosarcoma, breast cancer and glioma cells in vitro; and inhibits tumor growth in xenograft models. Therefore, BS69 may act as a tumor suppressor, and may be a new target for cancer therapy. However, BS69 down-regulation has been found to be involved in cellular senescence and is associated with the reversion of the malignant phenotype of breast cancer cells. Therefore, additional studies are necessary to clarify the role of BS69 in tumor development.

Lu T, Liang WZ, Hao LJ, et al.
Action of chlorzoxazone on Ca
Chin J Physiol. 2019 May-Jun; 62(3):123-130 [PubMed] Related Publications
Chlorzoxazone is a skeletal muscle relaxant. However, the effect of chlorzoxazone on intracellular Ca

Tsyganov MM, Pevzner AM, Ibragimova MK, et al.
Human papillomavirus and lung cancer: an overview and a meta-analysis.
J Cancer Res Clin Oncol. 2019; 145(8):1919-1937 [PubMed] Related Publications
PURPOSE: This review is devoted to assessing the prevalence of human papillomavirus (HPV) in lung cancer (LC) in the world. HPV is recognized as the etiological factor of cervical cancer, however, there is widespread evidence that this virus is detected not only in gynecological carcinomas, but also in tumors of other organs, in particular the upper respiratory tract and digestive tract.
MATERIALS AND METHODS:  A search was conducted to a depth of 29 years in the PubMed, Web of Science, Scopus, databases. The review includes 95 articles.
RESULTS: Of all the analyzed studies (9195 patients), 12 works showed a complete absence of HPV in the biological material in patients with LC. The absence of a virus among lung cancer patients has been established for Canada, the Netherlands and Singapore. The highest average percent of occurrence of this virus is shown for such countries as: Brazil, Korea, Greece and Taiwan (more than 40%). But the highest percentage of HPV occurrence by region is observed in Latin America (33.5%), followed by the Asian countries (31%), in European countries the frequency is 18%. Interestingly, the highest occurrence of high oncogenic types (16 and 18) is observed in Asia (40.3%), then in Latin America (33.6%), Europe (25.6%) and North America (15.4%). Low-oncogenic types (6 and 11) are also predominantly observed in Asia (39.9%), while in Europe and North America 30% and 12.8%, respectively. A meta-analysis of the prevalence of HPV was conducted using Comprehensive Meta-Analysis 3.0. Program, which included 26 studies, the results of which revealed: the prevalence of HPV infection in tumor lung tissue was compared with normal lung tissue OR (95% CI) = 5.38 (3.21-9.00) p < 0.0001, significance was also found for Chinese studies OR = 6.3, 95% CI 3.42-11.53, p < 0.0001, I2 = 71.8% and for nine studies in Europe OR = 6.3, 95% CI 1.8-22.18, p = 0.004, I2 = 51.0%. However, given the fact that the frequency of occurrence of HPV in lung tumor tissue varies greatly, a question may arise about the real role of HPV in LC carcinogenesis, which makes further research relevant and promising.

Yang BL, Chen KC, Wu CC
Preoperative computerized tomography-guided blue dye localization for metastatic lymphadenopathy and peritoneal tumor implants during laparoscopic surgery: Two case reports.
Medicine (Baltimore). 2019; 98(25):e16159 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Computerized tomography (CT)-guided blue dye localization has been widely discussed for preoperative localization of pulmonary nodules. However, few studies have investigated this technique for intra-abdominal lesions. Although preoperative localization is not commonly required in laparotomy, it may assume importance with advancements in the field of laparoscopic surgery.
PATIENT CONCERNS: Herein, we report the cases of 2 patients diagnosed with colon cancer who underwent hemicolectomy with extended lymphadenectomy and subsequent chemotherapy.
DIAGNOSES: Follow-up CT scans showed newly developed metastatic lymphadenopathy and peritoneal tumor implants.
INTERVENTIONS: Considering the difficulty in identification of and access to the target lesions during laparoscopic surgery, preoperative CT-guided blue dye localization was performed in both cases.
OUTCOMES: All the target lesions were identified by the dye marker and removed successfully. The pathologic results revealed adenocarcinoma.
LESSONS: We established the following strategy for preoperative CT-guided dye localization of intra-abdominal lesions:Intra-abdominal lesions that are hard to identify due to their size or morphology, and difficult to approach due to their location or surrounding structures, maybe the candidates for this procedure, especially in cases of laparoscopic surgery.Operators should adjust their localization planning based on the surgery method, cutting path, and location of port sites. The target dye marker should be clearly visible in the presumed intra-operative field of view.A second dye marker should be made to ensure surgical success when the target dye marker is obscured by the surrounding structures in the presumed intra-operative field of view.

Hsiao P, Hsieh KC, Chen YS, et al.
Sorafenib with concurrent multiple-line therapies improves overall survival in advanced stage hepatocellular carcinoma.
Medicine (Baltimore). 2019; 98(25):e16074 [PubMed] Free Access to Full Article Related Publications
The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies.We analyzed the treatment and OS of 401 patients with Barcelona clinic liver cancer stage C HCC between 2012 and 2017. Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the Kaplan-Meier method.The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1-80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥5 cm, serum alpha-fetoprotein ≥200, and serum albumin ≥3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multiple-line treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan-Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib alone.Sorafenib with concurrent multiple-line therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.

Lee HJ, Li CF, Ruan D, et al.
Non-proteolytic ubiquitination of Hexokinase 2 by HectH9 controls tumor metabolism and cancer stem cell expansion.
Nat Commun. 2019; 10(1):2625 [PubMed] Free Access to Full Article Related Publications
Enormous efforts have been made to target metabolic dependencies of cancer cells for developing new therapies. However, the therapeutic efficacy of glycolysis inhibitors is limited due to their inability to elicit cell death. Hexokinase 2 (HK2), via its mitochondrial localization, functions as a central nexus integrating glycolysis activation and apoptosis resilience. Here we identify that K63-linked ubiquitination by HectH9 regulates the mitochondrial localization and function of HK2. Through stable isotope tracer approach and functional metabolic analyses, we show that HectH9 deficiency impedes tumor glucose metabolism and growth by HK2 inhibition. The HectH9/HK2 pathway regulates cancer stem cell (CSC) expansion and CSC-associated chemoresistance. Histological analyses show that HectH9 expression is upregulated and correlated with disease progression in prostate cancer. This work uncovers that HectH9 is a novel regulator of HK2 and cancer metabolism. Targeting HectH9 represents an effective strategy to achieve long-term tumor remission by concomitantly disrupting glycolysis and inducing apoptosis.

Elia R, Di Taranto G, Amorosi V, et al.
The versatility of the thoracodorsal artery based composite flaps with vascularized rib and a systematic review of the literature.
J Surg Oncol. 2019; 120(3):527-539 [PubMed] Related Publications
Pedicled and free composite flaps derived from the thoracodorsal artery system, including the latissimus dorsi-rib (LD-R) and the serratus anterior-rib (SA-R) osteo-muscular or osteo-myocutaneous flaps, are potential options to address head and neck, thorax, upper and lower extremity bone, and soft tissue defects' reconstruction. We aimed to report our series of LD/SA-R composite pedicled and free flaps, evaluating outcomes and complications, and to systematically identify all literature reporting results following LD/SA-rib reconstructions.

Lin MJ, Chen HW, Liu PH, et al.
The prescription patterns of traditional Chinese medicine for women with polycystic ovary syndrome in Taiwan: A nationwide population-based study.
Medicine (Baltimore). 2019; 98(24):e15890 [PubMed] Free Access to Full Article Related Publications
Polycystic ovary syndrome (PCOS) is a common endocrine disease of reproductive-age women, accounting for about 9% to 18% of all women in this age group. Hyperandrogenemia, oligomenorrhea, or amenorrhea or anovulation, and polycystic ovary morphology are the 3 main criteria used to diagnose PCOS currently. Substantial scientific evidence and consensus on treating Taiwanese PCOS was lacking. The aim of this study is to investigate the characteristics and utilization of traditional Chinese medicine (TCM) among Taiwanese women with PCOS.The data used in this study were derived from the Longitudinal Health Insurance Database (LHID 2000 and LHID 2005). Demographic characteristics, TCM usage, the frequency, as well as average daily dose of Chinese herbal formulas and the single herbs prescribed for patients with PCOS, were analyzed. Chinese herbal formulas and the single herbs prescribed for PCOS women during 1999 to 2013 were extracted to build up Chinese Herbal Medicine prescription database.In our study, 66.43% (n = 8205) women sought TCM treatment because of PCOS for infertility or menstrual disorders. The most commonly prescribed Chinese herbal formula was Jia-wei-xiao-yao-san (Supplemented Free Wanderer Powder). The most commonly prescribed single herb was Yi-mu-cao (Leonuri herba). Among top 20 Chinese herbal formulas, Si-wu-tang has the largest average daily dosage (9.60 g).Our study identified the characteristics and prescription patterns of TCM for patients with PCOS in Taiwan. We may need do further longitudinal research for TCM and its long-term response for improvement of pregnancy rate and reduction of metabolic disease rate.

Chen YS, Chiu YH, Li YS, et al.
Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors.
Int J Nanomedicine. 2019; 14:3601-3613 [PubMed] Free Access to Full Article Related Publications

Luo J, Wang K, Yeh S, et al.
LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling.
Nat Commun. 2019; 10(1):2571 [PubMed] Free Access to Full Article Related Publications
While the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression.

Kumar KJS, Vani MG, Hsieh HW, et al.
Antcin-A Modulates Epithelial-to-Mesenchymal Transition and Inhibits Migratory and Invasive Potentials of Human Breast Cancer Cells via p53-Mediated miR-200c Activation.
Planta Med. 2019; 85(9-10):755-765 [PubMed] Related Publications
Antcin-A (ATA) is a steroid-like phytochemical isolated from the fruiting bodies of a precious edible mushroom

Lin YC, Chen RY, Liang JA, et al.
Immunohistochemical Biomarkers of Survival in Patients With Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.
Anticancer Res. 2019; 39(6):3231-3240 [PubMed] Related Publications
BACKGROUND/AIM: To determine the prognostic effects of immunohistochemical biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma of the uterine cervix.
MATERIALS AND METHODS: This study included 42 patients receiving definitive CRT. According to the International Federation of Gynecology and Obstetrics staging system, 13, 21, and 8 patients were classified as having stage IB2, II, and III disease, respectively. Baseline immunohistochemical biomarkers, including those for hypoxia, cell proliferation, cell adhesion, immunogenicity, and evasion of apoptosis, were analyzed using tissue microarrays from biopsy specimens.
RESULTS: Myeloid cell leukemia-1 (MCL1) overexpression and the presence of pelvic lymph node metastasis were two prognostic factors for inferior cancer-specific survival. A higher H-score for c-MYC proto-oncogene, bHLH transcription factor (c-MYC) was associated with lower pelvic relapse-free survival.
CONCLUSION: For patients with adenocarcinoma of the uterine cervix requiring definitive CRT, treatment outcomes can be stratified by the immunohistochemical biomarkers MCL1 and c-MYC for cancer death and local failure, respectively.

Chen SW, Liang JA, Hung YC, et al.
Effectiveness of Image-guided Brachytherapy in Patients With Locally Advanced Cervical Squamous Cell Carcinoma Receiving Concurrent Chemoradiotherapy.
Anticancer Res. 2019; 39(6):3015-3024 [PubMed] Related Publications
AIM: To compare the advantage of image-guided brachytherapy (IGBT) over conventional two-dimensional brachytherapy (2DBT) in patients with advanced cervical squamous cell carcinoma.
PATIENTS AND METHODS: This study included 253 patients with stage IB2-IVA diseases treated with two schemes of brachytherapy. One hundred and thirty-six patients received 2DBT, whereas 117 patients received IGBT. Tumor stage, age, and tumor diameter were matched between the two groups. Local relapse-free survival, overall survival, and cumulative incidences of gastrointestinal and genitourinary complications were compared between the two groups.
RESULTS: The overall and local relapse-free survival rates were similar between the two groups. The cumulative rate of grade 2 and higher gastrointestinal complication was 21.3% for the 2DBT group, and 8.5% for the IGBT group (p=0.007), whereas that of grade 2 and higher genitourinary injury was 11.8% for the 2DBT group, and 1.7% for the IGBT group (p=0.002).
CONCLUSION: In patients with advanced cervical squamous cell carcinoma, IGBT achieves a higher therapeutic ratio compared to 2DBT technique by minimizing the late toxicities.

Huang SJ, Tseng YK, Lo YH, et al.
Association of
Anticancer Res. 2019; 39(6):2891-2902 [PubMed] Related Publications
BACKGROUND/AIM: Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC.
MATERIALS AND METHODS: This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method.
RESULTS: Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype.
CONCLUSION: We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect.

Wu MH, Hung YW, Gong CL, et al.
Contribution of Caspase-8 Genotypes to Colorectal Cancer Risk in Taiwan.
Anticancer Res. 2019; 39(6):2791-2797 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to examine the role of caspase-8 rs3834129 polymorphism on colorectal cancer (CRC) risk in Taiwanese CRC patients and healthy controls.
MATERIALS AND METHODS: The caspase-8 rs3834129 (-652 6N insertion/deletion) polymorphic genotypes were analyzed in 362 patients with CRC and the same number of age- and gender-matched healthy subjects. The interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were also examined.
RESULTS: The percentage of variants ID and DD for caspase-8 rs3834129 genotype were 37.6 and 5.8% in CRC group and 39.0 and 6.6% in the control group, respectively (p for trend=0.7987). The allelic frequency distribution analysis showed that caspase-8 rs3834129 D allele conferred a non-significant lower susceptibility for CRC compared with I allele (OR=0.92, 95%CI=0.74-1.20, p=0.5063). There was no obvious link between caspase-8 rs3834129 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No statistically significant correlation was observed between caspase-8 rs3834129 genotypic distribution and age, gender, tumor size, location or metastasis status.
CONCLUSION: Overall, caspase-8 rs3834129 genotypes may not serve as predictors for CRC risk or prognosis.

Lai HC, Lee MS, Lin C, et al.
Propofol-based total intravenous anaesthesia is associated with better survival than desflurane anaesthesia in hepatectomy for hepatocellular carcinoma: a retrospective cohort study.
Br J Anaesth. 2019; 123(2):151-160 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Previous studies have shown that anaesthetic technique can affect outcomes of cancer surgery. We investigated the association between anaesthetic technique and patient outcomes after elective hepatectomy for hepatocellular carcinoma.
METHODS: This was a retrospective single-centre cohort study of patients who received elective hepatectomy for hepatocellular carcinoma from January 2005 to December 2014. Patients were grouped according to propofol or desflurane anaesthesia. Kaplan-Meier analysis was performed and survival curves were constructed from the date of surgery to death. After propensity matching, univariable and multivariable Cox regression models were used to compare hazard ratios for death. Subgroup analyses were performed for tumour-node-metastasis staging and distant metastasis and local recurrence.
RESULTS: A total of 492 patients (369 deaths, 75.0%) with desflurane anaesthesia and 452 (139 deaths, 30.8%) with propofol anaesthesia were eligible for analysis. After propensity matching, 335 patients remained in each group. In the matched analysis, propofol anaesthesia had a better survival with hazard ratio of 0.47 (95% confidence interval, 0.38-0.59; P<0.001). Subgroup analyses also showed significantly better survival in the absence of distant metastasis (hazard ratio, 0.47; 95% confidence interval, 0.37-0.60; P<0.001) or local recurrence (hazard ratio, 0.22; 95% confidence interval, 0.14-0.34; P<0.001) in the matched groups.
CONCLUSIONS: Propofol anaesthesia was associated with better survival in hepatocellular carcinoma patients who underwent hepatectomy. Prospective studies are warranted to evaluate the effects of propofol anaesthesia on surgical outcomes in hepatocellular carcinoma patients.

Tang JY, Li LJ, Ou-Yang F, et al.
Ethyl Acetate Extract of
DNA Cell Biol. 2019; 38(8):763-772 [PubMed] Related Publications

Im SA, Lu YS, Bardia A, et al.
Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer.
N Engl J Med. 2019; 381(4):307-316 [PubMed] Related Publications
BACKGROUND: An earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival.
METHODS: We randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen). Overall survival was evaluated with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods.
RESULTS: A total of 672 patients were included in the intention-to-treat population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths among 337 patients (32.3%) in the placebo group. The addition of ribociclib to endocrine therapy resulted in significantly longer overall survival than endocrine therapy alone. The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test). The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98). The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group). The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55 to 0.87).
CONCLUSIONS: This trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor-positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up. (Funded by Novartis; MONALEESA-7 ClinicalTrials.gov number, NCT02278120.).

Hu Q, Ye Y, Chan LC, et al.
Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression.
Nat Immunol. 2019; 20(7):835-851 [PubMed] Article available free on PMC after 03/12/2019 Related Publications
How tumor cells genetically lose antigenicity and evade immune checkpoints remains largely elusive. We report that tissue-specific expression of the human long noncoding RNA LINK-A in mouse mammary glands initiates metastatic mammary gland tumors, which phenotypically resemble human triple-negative breast cancer (TNBC). LINK-A expression facilitated crosstalk between phosphatidylinositol-(3,4,5)-trisphosphate and inhibitory G-protein-coupled receptor (GPCR) pathways, attenuating protein kinase A-mediated phosphorylation of the E3 ubiquitin ligase TRIM71. Consequently, LINK-A expression enhanced K48-polyubiquitination-mediated degradation of the antigen peptide-loading complex (PLC) and intrinsic tumor suppressors Rb and p53. Treatment with LINK-A locked nucleic acids or GPCR antagonists stabilized the PLC components, Rb and p53, and sensitized mammary gland tumors to immune checkpoint blockers. Patients with programmed ccll death protein-1(PD-1) blockade-resistant TNBC exhibited elevated LINK-A levels and downregulated PLC components. Hence we demonstrate lncRNA-dependent downregulation of antigenicity and intrinsic tumor suppression, which provides the basis for developing combinational immunotherapy treatment regimens and early TNBC prevention.

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