Diverse genetic spectrum among patients who met the criteria of hereditary breast, ovarian and pancreatic cancer syndrome

Po-Han Lin,Yun-Wen Tien,Wen-Fang Cheng,Ying-Cheng Chiang,Chien-Huei Wu,Karen Yang,Chiun-Sheng Huang 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.5

Objective: Genetic high-risk assessment combines hereditary breast, ovarian and pancreatic cancer into one syndrome. However, there is a lack of data for comparing the germline mutational spectrum of the cancer predisposing genes between these three cancers. Methods: Patients who met the criteria of the hereditary breast, ovarian and pancreatic cancer were enrolled and received multi-gene sequencing. Results: We enrolled 730 probands: 418 developed breast cancer, 185 had ovarian cancer, and 145 had pancreatic cancer. Out of the 18 patients who had two types of cancer, 16 had breast and ovarian cancer and 2 had breast and pancreatic cancer. A total of 167 (22.9%) patients had 170 mutations. Mutation frequency in breast, ovarian and pancreatic cancer was 22.3%, 33.5% and 17.2%, respectively. The mutation rate was significantly higher in patients with double cancers than those with a single cancer (p<0.001). BRCA1 and BRCA2 were the most dominant genes associated with hereditary breast and ovarian cancer, whereas ATM was the most prevalent gene related to hereditary pancreatic cancer. Genes of hereditary colon cancer such as lynch syndrome were presented in a part of patients with pancreatic or ovarian cancer but seldom in those with breast cancer. Families with a history of both ovarian and breast cancer were associated with a higher mutation rate than those with other histories. Conclusion: The mutation spectrum varies across the three cancer types and family histories. Our analysis provides guidance for physicians, counsellors, and counselees on the offer and uptake of genetic counseling.

Characteristics of Reactively Sputtered Niobium Nitride Thin Films as Diffusion Barriers for Cu Metallization

Cheng-Lin Huang,Chih-Huang Lai,Po-Hao Tsai,Hsing-An Huang,Jing-Cheng Lin,Chiapyng Lee 대한금속·재료학회 2013 ELECTRONIC MATERIALS LETTERS Vol.9 No.5

NbN films were prepared by radio frequency reactive magnetron sputtering and then employed as diffusion barriers between Cu and Si. The microstructure of the NbN films was an assembly of very small columnar crystallites with a cubic structure. To investigate the properties as diffusion barriers, we performed metallurgical reactions of Cu/NbN0.8/Si, Cu/Nb/Si and Cu/TaN0.7/Si for comparisons. The sheet resistance increased dramatically after annealing above 750°C for Cu/NbN0.80/Si, and above 500°C for both Cu/Nb/Si and Cu/TaN0.7/Si. The interfaces were deteriorated seriously and formation of Cu3Si was observed when the sheet resistance was significantly increased. The diffusion coefficient of Cu in NbN barrier films was estimated by using the change of resistance (ΔRs/Rs %). Compared with TaN0.7, NbN0.8 films possess larger grain size and lower Cu diffusion coefficient. Our results suggest that the NbN film can be used as a diffusion barrier for Cu metallization as compared to the well-known TaN film.

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis

( Po-yao Hsu ),( Yu-ju Wei ),( Jia-jung Lee ),( Sheng-wen Niu ),( Jiun-chi Huang ),( Cheng-ting Hsu ),( Tyng-yuan Jang ),( Ming-lun Yeh ),( Ching-i Huang ),( Po-cheng Liang ),( Yi-hung Lin ),( Ming-ye 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

Background/Aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs. (Clin Mol Hepatol 2021;27:186-196)

Thermal Stability, Adhesion and Electrical Studies on (Ti,Zr)Nx Thin Films as Low Resistive Diffusion Barriers between Cu and Si

Cheng-Lin Huang,Chih-Huang Lai,Po-Hao Tsai,Yu-Lin Kuo,Jing-Cheng Lin,Chiapyng Lee 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.3

In this study, we investigated the thermal stability, wettability, adhesion and reliability of (Ti,Zr)Nx films used as the diffusion barrier between Cu and Si. (Ti,Zr)Nx films were prepared by DC reactive magnetron sputtering from a Ti-5 at. % Zr alloy target in N2/Ar gas mixtures. A minimum film resistivity of 59.3 μΩ cm was obtained at an N2/Ar flow ratio of 2.75, which corresponds to the near stoichiometric composition (N/(Ti,Zr) ratio ~0.95). The sheet resistance of Cu/(Ti,Zr)N0.95/Si was not significantly increased until annealing above 750°C, indicating good thermal stability. On the other hand, the adhesion energy between Cu and the (Ti,Zr)Nx film was reduced as the N/Ti ratio was increased. To obtain reliable performance on stress-induced-voiding (SIV) and electromigration (EM) tests, we proposed to use (Ti,Zr)/(Ti,Zr)Nx/(Ti,Zr) tri-layers. We suggest that the interfacial adhesion between barrier and Cu plays an important role in reliability. The proposed tri-layer structure may be a promising candidate for a barrier, as it exhibits excellent reliability without increasing resistance.

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Predicting the surgical reparability of large-to-massive rotator cuff tears by B-mode ultrasonography: a cross-sectional study

Po-Cheng Chen,Kuan-Ting Wu,Yi-Cun Chen,Yu-Chi Huang,Ching-Di Chang,Wei-Che Lin,Wen-Yi Chou 대한초음파의학회 2022 ULTRASONOGRAPHY Vol.41 No.1

Purpose: This study aimed to compare the ability of B-mode ultrasonography and magnetic resonance imaging (MRI) to predict the repairability of large-to-massive rotator cuff tears (RCTs). Methods: This cross-sectional study included participants with large-to-massive RCTs who underwent arthroscopic repair. B-mode ultrasonography and MRI were conducted prior to arthroscopic repair. B-mode ultrasonography was used to evaluate the echogenicity of the rotator cuff muscle using the Heckmatt scale. Intra-rater and inter-rater reliabilities were examined for two independent physicians. MRI was used to evaluate the degrees of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, two experienced orthopedic surgeons performed surgery and decided whether the torn stump could be completely repaired intraoperatively. Results: Fifty participants were included, and 32 complete repairs and 18 partial repairs were performed. B-mode ultrasonography showed good intra-rater reliability and inter-rater reliability for assessment of the muscle echogenicity of the supraspinatus and infraspinatus muscles. The correlation coefficients between B-mode ultrasound findings and MRI findings showed medium to large effect sizes (r=0.4-0.8). The Goutallier classification of the infraspinatus muscles was the MRI predictor with the best discriminative power for surgical reparability (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.81 to 0.98), while the Heckmatt scale for infraspinatus muscles was the most accurate ultrasound predictor (AUC, 0.85; 95% CI, 0.74 to 0.96). No significant differences in AUCs among the MRI and ultrasound predictors were found. Conclusion: B-mode ultrasonography was a reliable examination tool and had a similar ability to predict surgical reparability to that of MRI among patients with large-to-massive RCTs. Purpose: This study aimed to compare the ability of B-mode ultrasonography and magnetic resonance imaging (MRI) to predict the repairability of large-to-massive rotator cuff tears (RCTs).Methods: This cross-sectional study included participants with large-to-massive RCTs who underwent arthroscopic repair. B-mode ultrasonography and MRI were conducted prior to arthroscopic repair. B-mode ultrasonography was used to evaluate the echogenicity of the rotator cuff muscle using the Heckmatt scale. Intra-rater and inter-rater reliabilities were examined for two independent physicians. MRI was used to evaluate the degrees of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, two experienced orthopedic surgeons performed surgery and decided whether the torn stump could be completely repaired intraoperatively.Results: Fifty participants were included, and 32 complete repairs and 18 partial repairs were performed. B-mode ultrasonography showed good intra-rater reliability and inter-rater reliability for assessment of the muscle echogenicity of the supraspinatus and infraspinatus muscles. The correlation coefficients between B-mode ultrasound findings and MRI findings showed medium to large effect sizes (r=0.4-0.8). The Goutallier classification of the infraspinatus muscles was the MRI predictor with the best discriminative power for surgical reparability (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.81 to 0.98), while the Heckmatt scale for infraspinatus muscles was the most accurate ultrasound predictor (AUC, 0.85; 95% CI, 0.74 to 0.96). No significant differences in AUCs among the MRI and ultrasound predictors were found.Conclusion: B-mode ultrasonography was a reliable examination tool and had a similar ability to predict surgical reparability to that of MRI among patients with large-to-massive RCTs.

Significance of Expression of Human METCAM/MUC18 in Nasopharyngeal Carcinomas and Metastatic Lesions

Lin, Jin-Ching,Chiang, Cheng-Feng,Wang, Shur-Wern,Wang, Wen-Yi,Kwan, Po-Cheung,Wu, Guang-Jer Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Human METCAM/MUC18, a cell adhesion molecule (CAM) in the immunoglobulin-like gene super family, plays a dual role in the progression of several epithelium cancers; however, its role in the nasopharyngeal carcinoma (NPC) remains unclear. To initiate the study we determined human METCAM/MUC18 expression in tissue samples of normal nasopharynx (NP), NPCs, and metastatic lesions, and in two established NPC cell lines. Immunoblotting analysis was used for the determination in lysates of frozen tissues, and immunohistochemistry (IHC) for expression in formalin-fixed, paraffin-embedded tissue sections of 7 normal nasopharynx specimens, 94 NPC tissue specimens, and 3 metastatic lesions. Human METCAM/MUC18 was expressed in 100% of the normal NP, not expressed in 73% of NPC specimens (or expressed at very low levels in only about 27% of NPC specimens), and expressed again in all of the metastatic lesions. The level of human METCAM/MUC18 expression in NPC tissues was about one fifth of that in the normal NP and metastatic lesions. The low level of human METCAM/MUC18 expression in NPC specimens was confirmed by a weak signal of RT-PCR amplification of the mRNA. Low expression levels of human METCAM/MUC18 in NPC tissues were also reflected in the seven established NPC cell lines. These findings provided the first evidence that diminished expression of human METCAM/MUC18 is an indicator for the emergence of NPC, but increased expression then occurs with metastatic progression, suggesting that huMETCAM/MUC18, perhaps similar to TGF-${\beta}$, may be a tumor suppressor, but a metastasis promoter for NPC.

Effect of Sm Content on the Magnetic Properties of the SmCo thin Film

Ger-Pin Lin,Po-Cheng Kuo,Hou-Chien Liu 한국자기학회 2007 한국자기학회 학술연구발표회 논문개요집 Vol.- No.-

Magnetic Properties and Microstructure of TbCo/(Co/SiN<SUB>x</SUB>)<SUB>n</SUB> Films

Pai Li Lin,Po Cheng Kuo,Sheng Chi Chen,Yen Hsiang Fang 한국자기학회 2007 한국자기학회 학술연구발표회 논문개요집 Vol.- No.-

Mesenchymal Stem Cell Secreted-Extracellular Vesicles are Involved in Chondrocyte Production and Reduce Adipogenesis during Stem Cell Differentiation

Tsai Yu-Chen,Cheng Tai-Shan,Liao Hsiu-Jung,Chuang Ming-Hsi,Chen Hui-Ting,Chen Chun-Hung,Zhang Kai-Ling,Chang Chih-Hung,Lin Po-Cheng,Huang Chi-Ying F. 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.6

BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosomespecific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. CONCLUSION: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.