Performance evaluation of predictive models for detecting MMR gene mutations associated with Lynch syndrome in cancer patients in a Chinese cohort in Taiwan.

Identifying Lynch syndrome significantly impacts cancer risk management, treatment, and prognosis. Validation of mutation risk predictive models for mismatch repair (MMR) genes is crucial for guiding genetic counseling and testing, particularly in the understudied Asian population. We evaluated the performance of four MMR mutation risk predictive models in a Chinese cohort of 604 patients with colorectal cancer (CRC), endometrial cancer (EC), or ovarian cancer (OC) in Taiwan.

Mismatch Repair (MMR) Gene Mutation Carriers Have Favorable Outcome in Colorectal and Endometrial Cancer: A Prospective Cohort Study.

Germline (Lynch syndrome, LS) and somatic deficiencies of mismatch repair proteins (MMRd) are linked to colorectal and endometrial cancer; however, their prognostic impact in Asian populations remains unclear. This prospective cohort study aimed to determine the prevalence and outcome of germline and somatic MMRd in cancer patients suspected of LS. Patients with colorectal or endometrial cancer suspected of LS were enrolled and underwent gene sequencing for germline MMRd (gMMRd) and immunohistochemistry staining of MMR proteins in a subset of the pathological samples (pMMRd).

Imipramine Suppresses Tumor Growth and Induces Apoptosis in Oral Squamous Cell Carcinoma: Targeting Multiple Processes and Signaling Pathways.

Background/aim: Oral squamous cell carcinoma (OSCC) has limited treatment options. This study investigated imipramine, a tricyclic antidepressant, as a potential therapy for OSCC using a SAS-bearing xenograft animal model.

Materials And Methods: The SAS-bearing xenograft model evaluated imipramine's impact on tumor growth.

Uptake of genetic testing among patients seeking cancer genetic counseling in Taiwan.

Genetic testing is becoming increasingly available and affordable. Understanding the reasons for individual decisions about genetic testing may assist in the identification of clinically appropriate use of genetic counseling and genetic testing resources. With the ongoing development of cancer genetic counseling services in Taiwan, we conducted this study to understand the characteristics of those seeking cancer genetic counseling and genetic testing and the predictors for undergoing genetic testing after counseling.

Attitude towards hereditary cancer risk management among women with cancer in Taiwan.

Background: Risk management intentions prior to genetic counseling predict risk management uptake following genetic testing. Limited studies examined the attitude and understanding towards genetic counseling/testing in underserved countries. The purposes of this study were to explore knowledge and attitude towards genetic counseling, testing, and risk management for breast and ovarian cancer, and to understand the factors influencing risk management intentions in women with cancer in Taiwan.

Engaging consumers in wise use of over-the-counter medications in Taiwan: Development and evaluation of a structured medication counseling approach.

Objective: To evaluate the impact of a tailored Symptom Allergy Indication Direction Self-care (SAIDS) counseling by pharmacists on consumers' correct understanding of over-the-counter (OTC) medication use.

Methods: This study used a time-based sampling of two independent cohorts at a single community pharmacy in Taiwan for two years beginning in December 2018. In the control cohort, participants received conventional counseling for the OTCs they selected.

Evaluation of use, comprehensibility and clarity of over-the-counter medicine labels: Consumers' perspectives and needs in Taiwan.

An estimate of one third of preventable medication errors occurred annually due to patients' misunderstanding of use instructions. To safeguard consumers' over-the-counter (OTC) medicine use and to develop future initiatives, this study evaluated the use, comprehensibility and clarity of the information labels on OTC packages from consumers' perspectives in Taiwan. This cross-sectional study was conducted at 29 community pharmacies; 50 pharmacy clerkship students helped participant enrolment from June to September 2017.

Evaluating BRCA mutation risk predictive models in a Chinese cohort in Taiwan.

Accurate estimation of carrier probabilities of cancer susceptibility gene mutations is an important part of pre-test genetic counselling. Many predictive models are available but their applicability in the Asian population is uncertain. We evaluated the performance of five BRCA mutation risk predictive models in a Chinese cohort of 647 women, who underwent germline DNA sequencing of a cancer susceptibility gene panel.

Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21.

Medulloblastoma (MB) is the most common type of malignant childhood brain tumor. We previously showed that inhibitors of apoptosis proteins (IAP) small-molecule inhibitors (LCL161 or LBW242) combined with chemotherapy have synergistic antiproliferative effects on MB cells. The synergistic antitumor effects of combination treatments happen through induction of autophagy and caspase-3/7-activated apoptosis.

Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome.

Background: DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1, APEX1, MUTYH, OGG1, NUDT1, XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in Chinese population with Lynch syndrome.

Methods: From Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome.

Polymer gel dosimeters for pretreatment radiotherapy verification using the three-dimensional gamma evaluation and pass rate maps.

Polymer gel dosimeters (PGDs) have been widely studied for use in the pretreatment verification of clinical radiation therapy. However, the readability of PGDs in three-dimensional (3D) dosimetry remain unclear. In this study, the pretreatment verifications of clinical radiation therapy were performed using an N-isopropyl-acrylamide (NIPAM) PGD, and the results were used to evaluate the performance of the NIPAM PGD on 3D dose measurement.

Polymorphisms of MTHFR C677T and A1298C associated with survival in patients with colorectal cancer treated with 5-fluorouracil-based chemotherapy.

Background: This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan.

Methods: We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRC patients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan-Meier curve.

DNA Methylation Identifies Loci Distinguishing Hereditary Nonpolyposis Colorectal Cancer Without Germ-Line MLH1/MSH2 Mutation from Sporadic Colorectal Cancer.

Objectives: Roughly half of hereditary nonpolyposis colorectal cancer (HNPCC) cases are Lynch syndrome and exhibit germ-line mutations in DNA mismatch repair (MMR) genes; the other half are familial colorectal cancer (CRC) type X (FCCTX) and are MMR proficient. About 70% of Lynch syndrome tumors have germ-line MLH1 or MSH2 mutations. The clinical presentation, histopathological features, and carcinogenesis of FCCTX resemble those of sporadic MMR-proficient colorectal tumors.

TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study.

Background And Aim: TP53 encodes p53, which has a crucial role in modulating genes that regulate defense against cancer development. This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk.

Methods: We identified 260 MLH1 and MSH2 germline mutation carriers from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium.

Blockade of Inhibitors of Apoptosis Proteins in Combination with Conventional Chemotherapy Leads to Synergistic Antitumor Activity in Medulloblastoma and Cancer Stem-Like Cells.

Background: Medulloblastoma (MB) is the most common pediatric primary malignant brain tumor. Approximately one-third of MB patients succumb to treatment failure and some survivors suffer detrimental side effects. Hence, the purpose of this study is to explore new therapeutic regimens to overcome chemotherapeutic agent resistance or reduce chemotherapy-induced toxicity.

A Comprehensive Evaluation of NIPAM Polymer Gel Dosimeters on Three Orthogonal Planes and Temporal Stability Analysis.

Polymer gel dosimeters have been proven useful for dose evaluation in radiotherapy treatments. Previous studies have demonstrated that using a polymer gel dosimeter requires a 24 h reaction time to stabilize and further evaluate the measured dose distribution in two-dimensional dosimetry. In this study, the short-term stability within 24 h and feasibility of N-isopropylacrylamide (NIPAM) polymer gel dosimeters for use in three-dimensional dosimetry were evaluated using magnetic resonance imaging (MRI).

Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan.

Aim: To evaluate the effects of OGG1 (Ser326Cys, 11657A/G, and Arg154His) and APE1 (Asp148Glu, and T-656G) polymorphisms on colorectal cancer (CRC) risk.

Methods: We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction.

Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study.

Background: The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers.

Methods: The study population comprises 152 CRC patients and 152 controls.

Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome.

Background And Aim: Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations.

Methods: In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium.

Culture supernatants of different colon cancer cell lines induce specific phenotype switching and functional alteration of THP-1 cells.

We developed an in vitro model to evaluate the effect of products secreted from different colorectal cancer (CRC) cell lines on specific phenotypic switching and functional alterations in THP-1 cells. We co-cultured the human monocytic cell line, THP-1, or phorbol-12-myristate-13-acetate (PMA)-treated THP-1 cells, (THP-1p), with supernatants from either the HT-29 (Dukes' B), HCT-15 (Dukes' C), or Colo205 (Dukes' D) cell lines, and assessed the cells for macrophage differentiation. The surface marker and cytokine profiles suggested that secreted CRC factors differentiated THP-1 cells into a "mixed" M1/M2 phenotype, although HT-29 and Colo205 supernatants induced THP-1p cells into predominantly M1-like macrophages and M2-like macrophages, respectively.

Tumor site- and stage-specific associations between allelic variants of glutathione S-transferase and DNA-repair genes and overall survival in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy.

Introduction: Our retrospective cohort study investigated the effect of tumor site and stage on the associations between the allelic variants of glutathione S-transferase (GST) and DNA-repair genes and overall survival (OS) in CRC patients treated with 5-fluorouracil (5-FU)-based adjuvant chemotherapy.

Material And Methods: We genotyped GSTM1, GSTT1, GSTP1 Ile105Val, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln in 491 CRC patients between 1995 and 2001. A Cox proportional-hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between the allelic variants and OS.

Associations between genetic polymorphisms of epidermal growth factor receptor (EGFR) and survival of colorectal cancer (CRC) patients treated with 5-fluorouracil-based chemotherapy.

Purpose: This retrospective cohort study investigated the association between epidermal growth factor receptor (EGFR) polymorphisms and clinical outcomes in colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU)-based chemotherapy.

Methods: We genotyped 3 EGFR polymorphisms including R497K, G-216T, and the (CA)n repeat, among 499 histologically confirmed CRC patients who had received 5-FU-based chemotherapy after surgery between 1995 and 2001. Survival analyses of EGFR polymorphisms were performed by the log rank test and Kaplan-Meier curves.

Clinical significance in oral cavity squamous cell carcinoma of pathogenic somatic mitochondrial mutations.

Somatic mutations affecting the mitochondrial DNA (mtDNA) have been frequently observed in human cancers and proposed as important oncological biomarkers. However, the clinical significance of mtDNA mutations in cancer remains unclear. This study was therefore performed to explore the possible clinical use in assessing oral squamous cell carcinoma (OSCC) of pathogenic mtDNA mutations.

Association analysis of ACE and ACTN3 in elite Caucasian and East Asian swimmers.

Purpose: Polymorphic variation in the angiotensin-converting enzyme (ACE) and α-actinin-3 (ACTN3) genes has been reported to be associated with endurance and/or power-related human performance. Our aim was to investigate whether polymorphisms in ACE and ACTN3 are associated with elite swimmer status in Caucasian and East Asian populations.

Methods: ACE I/D and ACTN3 R577X genotyping was carried out for 200 elite Caucasian swimmers from European, Commonwealth, Russian, and American cohorts (short and middle distance, ≤400 m, n = 130; long distance, >400 m, n = 70) and 326 elite Japanese and Taiwanese swimmers (short distance, ≤100 m, n = 166; middle distance, 200-400 m, n = 160).