Publications by authors named "Wen-Tsung Huang"

68 Publications

Effect of diabetes mellitus comorbidity on outcomes in stages II and III colorectal cancer.

Asia Pac J Clin Oncol 2021 Nov 24. Epub 2021 Nov 24.

Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Aim: The effects of diabetes mellitus (DM) on the outcomes of colorectal cancer (CRC) are controversial. This retrospective study evaluated the effects of DM on American Joint Committee on Cancer (AJCC, 7th) Stages II and III CRC patients who received curative surgery.

Methods: We reviewed the records of CRC patients who were treated from January 2008 to December 2014 and identified the presence of DM and hypertension prior to CRC diagnosis. Cox proportional hazards analyses were used for prognostic factor determination, and survival was analyzed using the Kaplan-Meier method with the log-rank test.

Results: Total of 1066 consecutive eligible patients with stage II/III CRC were enrolled. There were 326 (30.6%) patients diagnosed with DM, and 311 (29.2%) CRC patients had recurrence. Patients with DM did not have a higher recurrence risk (p = 0.183) but had higher mortality (adjusted hazard ratio [aHR] = 1.381; 95% conference interval [CI], 1.069-1.782). In addition, HbA1c (≥7 vs. <7) was not associated with recurrence (p = 0.365). Patients with DM had more hypertension than patients without DM (69.1% vs. 37.6%, p < 0.001). A lower recurrence risk was noted in patients with hypertension (p = 0.002), but the overall survival (OS) did not reach statistical significance (aHR = 0.910; 95% CI, 0.707-1.169).

Conclusion: In our study, DM was a poor prognostic factor for survival in curative CRC patients. More studies are required to elucidate the effects that DM and other metabolic disorders, such as hypertension, have on the prognosis of patients with CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajco.13639DOI Listing
November 2021

Assessment of pegylated arginine deiminase and modified FOLFOX6 in patients with advanced hepatocellular carcinoma: Results of an international, single-arm, phase 2 study.

Cancer 2021 Aug 20. Epub 2021 Aug 20.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Arginine starvation depletes the micronutrients required for DNA synthesis and interferes with both thymidylate synthetase activity and DNA repair pathways in preclinical models of hepatocellular carcinoma (HCC). Pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, potentiates the cytotoxic activity of platinum and pyrimidine antimetabolites in HCC cellular and murine models.

Methods: This was a global, multicenter, open-label, single-arm, phase 2 trial of ADI-PEG 20 and modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients who had HCC with Child-Pugh A cirrhosis and disease progression on ≥2 prior lines of treatment. The primary objective was the objective response rate assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary objectives were to estimate progression-free survival, overall survival, safety, and tolerability. Eligible patients were treated with mFOLFOX6 intravenously biweekly at standard doses and ADI-PEG-20 intramuscularly weekly at 36 mg/m .

Results: In total, 140 patients with advanced HCC were enrolled. The median patient age was 62 years (range, 30-85 years), 83% of patients were male, 76% were of Asian race, 56% had hepatitis B viremia, 10% had hepatitis C viremia, 100% had received ≥2 prior lines of systemic therapy, and 39% had received ≥3 prior lines of systemic therapy. The objective response rate was 9.3% (95% confidence interval [CI], 5.0%-15.4%), with a median response duration of 10.2 months (95% CI, 5.8 months to not reached). The median progression-free survival was 3.8 months (95% CI, 1.8-6.3 months), and the median overall survival was 14.5 months (95% CI, 13.6-20.9 months). The most common grade ≥3 treatment-related events were neutropenia (32.9%), white blood cell count decrease (20%), platelet count decrease (19.3%), and anemia (9.3%).

Conclusions: Concurrent mFOLFOX6 plus ADI-PEG 20 exhibited limited antitumor activity in patients with treatment-refractory HCC. The study was terminated early, and no further evaluation of the combination will be pursued.

Lay Summary: Arginine is an important nutrient for hepatocellular carcinoma (HCC). The depletion of arginine with pegylated arginine deiminase (ADI-PEG 20), an arginine degrader, appeared to make chemotherapy (FOLFOX) work better in animal models of HCC and in patients with HCC on an early phase clinical trial. To formally test this hypothesis in the clinical setting, a large, global, phase 2 clinical trial was conducted of ADI-PEG 20 and FOLFOX in the treatment of patients with refractory HCC. The study showed limited activity of ADI-PEG 20 and FOLFOX in advanced HCC and was stopped early.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33870DOI Listing
August 2021

Age as a modifier of the effects of chemoradiotherapy with infusional 5-fluorouracil after D2 dissection in gastric cancer.

Aging (Albany NY) 2021 07 5;13(13):17337-17348. Epub 2021 Jul 5.

Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan.

Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, = 0.002) and gastrointestinal (46.9% vs. 14.3%, = 0.027) toxicities and death (12.5% vs. 0.0%, = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.203223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312439PMC
July 2021

Colorectal Cancer with EML4-ALK Fusion Gene Response to Alectinib: A Case Report and Review of the Literature.

Case Rep Oncol 2021 Jan-Apr;14(1):232-238. Epub 2021 Mar 1.

Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.

Anti-epithelial growth factor receptor or anti-vascular endothelial growth factor agents combined with chemotherapy were the standard of treatment for metastatic colorectal cancer (CRC). However, increasing evidence of molecularly stratified treatment makes the complexity of treatment. Anaplastic lymphoma kinase (ALK) gene alternation is one of potential target for biomarker-guided therapy for CRC. We present a case of a 56-year-old man who suffered from advanced ascending colon cancer, harboring echinoderm microtubule associated protein-like 4 (EML4)-ALK fusion gene E21; A20 variant, a rare variant in EML4-ALK fusion gene in lung cancer. We also detected this fusion gene from different tissue types including circulating tumor DNA (ctDNA) and ascites fluid. The patient was offered alectinib, an ALK inhibitor, with partial response in lung, liver, and peritoneal metastasis for 8 months. Tumor heterogeneity, especially in gastrointestinal tract cancer, raise our interest in comprehensive genetic profiling in clinical practice. Convenience and reliability of next-generation sequencing, including using ctDNA, help physicians deal with clinical dilemma. ALK-positive CRC is rare. However, advanced CRC with ALK gene alteration responds to ALK inhibitor. It is reasonable to check ALK gene alteration in clinical practice for CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000511069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983623PMC
March 2021

O6-methylguanine-DNA methyltransferase modulates cisplatin-induced DNA double-strand breaks by targeting the homologous recombination pathway in nasopharyngeal carcinoma.

J Biomed Sci 2021 Jan 4;28(1). Epub 2021 Jan 4.

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.

Background: The homologous recombination (HR) pathway is involved in DNA damage response (DDR), which is crucial to cancer cell survival after treatment with DNA damage agents. O6-methylguanine DNA methyltransferase (MGMT) is associated with cisplatin (CDDP) resistance in cancer cells; however, the underlying mechanisms remain unclear. Here, we explored the interactions between MGMT and the HR pathway in CDDP-activated DDR and their clinical implications in nasopharyngeal carcinoma (NPC).

Methods: Human NPC cells were assessed using loss-of-function approaches in vitro. The expression correlations between MGMT and major proteins of the HR pathway were analyzed through Western blotting, quantitative real-time PCR, and bioinformatic analysis by using a public database. The physical interactions between MGMT and HR proteins were studied using co-immunoprecipitation and immunofluorescence analyses. Cell comet tails and γ-H2AX expression levels were examined to evaluate double-strand break (DSB) formation. Established immunofluorescence and reporter analyses were conducted to measure HR activity. Xenograft and cell viability studies were used to assess the therapeutic potential of MGMT inhibition in combination with CDDP and poly(ADP-ribose) polymerase (PARP) inhibitor, respectively.

Results: Among major proteins of the HR pathway, MGMT suppression inhibited CDDP-induced RAD51 expression. Bioinformatic analyses showed a positive correlation between MGMT and RAD51 expression in patients with NPC. Moreover, MGMT physically interacted with BRCA1 and regulated CDDP-induced BRCA1 phosphorylation (ser 988). In functional assays, MGMT inhibition increased CDDP-induced DSB formation through attenuation of HR activity. NPC xenograft studies demonstrated that MGMT inhibition combined with CDDP treatment reduced tumor size and downregulated RAD51 expression and BRCA1 phosphorylation. Furthermore, MGMT suppression increased PARP inhibitor-induced cell death and DSB formation in NPC cells.

Conclusion: MGMT is crucial in the activation of the HR pathway and regulates DDR in NPC cells treated with CDDP and PARP inhibitor. Thus, MGMT is a promising therapeutic target for cancer treatments involving HR-associated DDR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12929-020-00699-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780675PMC
January 2021

Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model.

Int J Mol Sci 2020 Oct 31;21(21). Epub 2020 Oct 31.

Institute of Oral Medicine, Department of Dentistry, Division of Oral and Maxillofacial Surgery, Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan.

Oral carcinogenesis involves the progression of the normal mucosa into potentially malignant disorders and finally into cancer. Tumors are heterogeneous, with different clusters of cells expressing different genes and exhibiting different behaviors. 4-nitroquinoline 1-oxide (4-NQO) and arecoline were used to induce oral cancer in mice, and the main factors for gene expression influencing carcinogenesis were identified through single-cell RNA sequencing analysis. Male C57BL/6J mice were divided into two groups: a control group (receiving normal drinking water) and treatment group (receiving drinking water containing 4-NQO (200 mg/L) and arecoline (500 mg/L)) to induce the malignant development of oral cancer. Mice were sacrificed at 8, 16, 20, and 29 weeks. Except for mice sacrificed at 8 weeks, all mice were treated for 16 weeks and then either sacrificed or given normal drinking water for the remaining weeks. Tongue lesions were excised, and all cells obtained from mice in the 29- and 16-week treatment groups were clustered into 17 groups by using the Louvain algorithm. Cells in subtypes 7 (stem cells) and 9 (keratinocytes) were analyzed through gene set enrichment analysis. Results indicated that their genes were associated with the MYC_targets_v1 pathway, and this finding was confirmed by the presence of cisplatin-resistant nasopharyngeal carcinoma cell lines. These cell subtype biomarkers can be applied for the detection of patients with precancerous lesions, the identification of high-risk populations, and as a treatment target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21218171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662772PMC
October 2020

A nationwide survey of fatigue in cancer patients in Taiwan: an unmet need.

Jpn J Clin Oncol 2020 Jun;50(6):693-700

Department of Hematology and Oncology, MacKay Memorial Hospital, Taipei, Taiwan.

Background: Cancer-related fatigue (CRF) is an emerging clinical issue, although its prevalence and impact on quality of life (QOL) in cancer patients in Taiwan remain unclear. The present nationwide cross-sectional study was conducted to provide a thorough overview of the prevalence, related factors and impact of CRF in Taiwan.

Methods: In this multi-center survey, data were collected using the International Classification of Diseases 10th Revision (ICD-10) Fatigue evaluation, Brief Fatigue Inventory-Taiwan (BFI-T), the Chinese version of the Symptom Distressed Scale and a fatigue experience survey. Logistic regression was used to determine the correlations between fatigue characteristics and the factors studied.

Results: A total of 1207 cancer patients were recruited from 23 hospitals in Taiwan. Fatigue was the most distressing symptom in Taiwanese cancer patients. The distress score was higher if CRF was diagnosed using ICD-10 compared with BFI-T. Rest and nutritional supplementation were the most common non-pharmacological treatments; blood transfusion was the most common pharmacological treatment. There were 45% of patients reported not receiving a timely intervention for fatigue.

Conclusions: Fatigue is the most bothersome symptom reported by Taiwanese cancer patients. Caregivers should be aware of the impact of CRF on QOL in cancer patients, constantly measure the severity of fatigue and provide appropriate interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyaa038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284537PMC
June 2020

Low BRCA2 expression predicts poor prognoses in patients with rectal cancer receiving chemoradiotherapy.

Pathol Res Pract 2020 May 19;216(5):152922. Epub 2020 Mar 19.

Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan. Electronic address:

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is now the standard care for patients with advanced rectal cancer. Because a certain proportion of these patients have poor response to CCRT, the risk stratification of survival outcomes needs to be investigated. DNA repair responses in tumor cells can regulate malignant potential and therapy resistance. In this study, we analyzed the clinical significance of principal DNA repair effectors in patients with rectal cancer.

Methods: We applied data mining for DNA repair pathways in a published transcriptome for rectal cancer cases, and identified that tumors with BRCA2 downregulation correlated with poor response to CCRT. We next examined BRCA2 expression by using immunohistochemistry staining in tumor tissues of 172 patients with rectal cancer. The correlation between BRCA2 expression levels and clinical variables was further analyzed in this rectal cancer cohort.

Results: Among clinical and pathological factors, low BRCA2-expression was significantly correlated with higher pre-treatment (Tx) tumor status (P = .013), post-Tx tumor (P < .001) and nodal status (P = .044), vascular invasion (P = .008), and poor tumor regression grades (P < .001). In analyses of survival outcomes, patients with low BRCA2-expression were associated with shorter local recurrence-free survival (LRFS; P = .0005) and disease-specific survival (P = .0269). Multivariate analyses confirmed the independent prognostic value of low BRCA2-expression for shorter LRFS (P = .045, hazard ratio = 4.695).

Conclusion: Low BRCA2-expression is a significant predictor for tumors in advanced stages, poor response to CCRT, and shorter survivals in patients with rectal cancer. Poly (adenosine diphosphate-ribose) polymerase inhibitors targeting DNA repair response in cells have demonstrated clinical efficacy in BRCA2-mutated patients with cancer. Further studies evaluating the efficacy of CCRT combined with these inhibitors in low BRCA2-expressing rectal cancers are encouraged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.152922DOI Listing
May 2020

Induction Chemotherapy Improved Long Term Outcomes in Stage IV Locoregional Advanced Nasopharyngeal Carcinoma.

Int J Med Sci 2020 10;17(5):568-576. Epub 2020 Feb 10.

Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan.

: We aimed to determine whether adding induction chemotherapy (IC) to concurrent chemoradiation (CCRT) improved outcomes in each stage of locally advanced nasopharyngeal carcinoma (LANPC). : From 2007 to 2013, we retrospectively collected 259 histopathologically identified adult LANPC patients from two campuses in south Taiwan. Among the 238 eligibly treated cases, 156 patients received CCRT (CCRT group) upfront and 82 received IC followed by CCRT (IC group). Of these patients, 130 were stage III (92 patients that received CCRT and 38 that received IC adding CCRT) and 108 were stage IV (76 CCRT and 32 IC adding CCRT). Most chemotherapy regimens for IC are composed of cisplatin (P), 5-fluorouracil (F), and ifosfamide (I), while concurrent chemotherapy (CC) was essentially cisplatin-based. For CCRT as the upfront treatment, a P or PF regimen was usually used in CC. Survival outcomes were accessed with a Kaplan-Meier estimate and a p-value by log-rank test to compare the survival distributions of IC added to CCRT or CCRT as the upfront treatment in all LANPC stage III and LANPC IV patients. The failure free survival (FFS), overall survival (OS), local relapse free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), first failure site, and other prognostic factors were analyzed. : The median follow-up time of all treated LANPC patients was 59 months. For all LANPC patients, there was a significant difference only in the DMFS favoring IC group (91.5% vs 79.4%, p=0.013). In the subgroup study, for the stage III group, there was no significant difference between the groups for overall OS (IC group 71.3% vs CCRT group 78.7%), FFS (71.5% vs 62.4%) and RRFS (91.9% vs 90.9%). However, inferior LRLS (71.7% vs 91.5%; p = 0.03) was noted for the IC group. In contrast, for stage IV, there were significantly longer OS (75.8% vs 52.6%), FFS (66.8% vs 46.8%), and DMFS (86.0% vs 69.6%; p = 0.02, p = 0.04, and p = 0.03, respectively) rates in the IC group. : Adding PIF-based IC to CCRT for the LANPC patients resulted in better outcomes for stage IV patients, but not for stage III patients. A future properly designed study should stratify enough LANPC cases under the structure of the AJCC stage grouping system to determine which subgroups truly benefit from adding IC to CCRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijms.42005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085214PMC
December 2020

Factors associated with improvement in symptoms and quality of life for first-line EGFR-tyrosine kinase inhibitor treatment in patients with -mutated non-small-cell lung cancer - A multicenter prospective SMILE study.

J Cancer 2019 10;10(17):4151-4158. Epub 2019 Jul 10.

Department of Respiratory Therapy, China Medical University, Taichung, Taiwan.

: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard first-line treatment for advanced -mutated NSCLC patients. Factors associated with symptoms and quality of life (QOL) improvements have not been investigated. : We conducted a multicenter, prospective study to evaluate improvements in QOL and symptoms in NSCLC patients treated with first-line EGFR-TKIs. QOL was assessed using the instrument of Functional Assessment of Cancer Therapy-Lung questionnaire (FACT-L) and Treatment Outcome Index (TOI). Assessment of symptoms was evaluated using the Lung cancer subscale (LCS). : Eligible subjects included 280 patients for endpoint analyses. The mean FACT-L score increased by 4.0 ± 15.56 at Week 2 (p<0.001), 5.1 ± 18.48 at Week 4 (p<0.001), and 4.2 ± 20.27 at Week 12 (p=0.001). Similarly, a 2.3 ± 11.65 (p<0.001), 3.2 ± 13.59 (p<0.001), and 2.4 ± 14.34 (p=0.009) increase in mean TOI score were observed at Weeks 2, 4 and 12, respectively. For LCS, it was slightly increased by 1.7 ± 4.61, 2.0 ± 5.50, and 2.0 ± 5.36 at Weeks 2, 4, and 12 (all p<0.001), respectively. Subgroup analyses showed patients who were ex-smokers or with at least 3 metastatic sites were associated with symptoms improvement. Patients who were ex-smokers, with at least 3 metastatic sites, a PS of 1, or treated with gefitinib were associated with QOL improvement. : In -mutated NSCLC patients who were treated with first-line EGFR-TKIs, these ex-smokers or with 3 or more metastatic sites were associated with improvements in symptoms and QOL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.30507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692623PMC
July 2019

Subsequent thyroid disorders associated with treatment strategy in head and neck cancer patients: a nationwide cohort study.

BMC Cancer 2019 May 16;19(1):461. Epub 2019 May 16.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 138, Shengli Road, Tainan, Taiwan.

Background: We investigated the risk of thyroid disorders, namely hypothyroidism, thyrotoxicosis and thyroiditis, in head and neck cancer patients undergoing multimodal treatment.

Methods: A cohort study design using Taiwan's National Health Insurance Research Database was used to assess head and neck cancer patients over 20 years old. The cohort was divided into one group who underwent primary tumor excision only (PTE) and another with additional neck dissection (PTE + ND). The tumor sites were stratified to estimate the tumor-site-specific risk of thyroid disorders. The effect of subsequent resurgery, radiotherapy (RT), chemotherapy (CT), and concomitant (CCRT) or sequential chemoradiation therapy (sequential CT+ RT) on the risk of thyroid disorders was explored.

Results: For 1999-2012, 7460 patients who underwent PTE + ND and 3730 who underwent PTE were enrolled and followed-up until the end of 2013. There were 122 and 50 patients in the two groups, respectively, who developed thyroid disorders, with no statistical difference between the groups. Patients with hypopharyngeal, oropharyngeal, or laryngeal cancer in the PTE + ND group had a higher risk of thyroid disorders (adjusted HR: 1.50, 95% CI: 0.67-3.38) than those in the PTE group when adjusted for covariates and mortality. Patients who underwent subsequent RT (adjusted HR: 3.64, 95% CI: 1.05-2.77) and CCRT (adjusted HR: 1.70, 95% CI: 1.05-2.77) after PTE + ND had a significantly higher risk of thyroid disorders.

Conclusion: RT results in a major risk of subsequent thyroid disorders, and ND may exacerbate this effect. Physicians should monitor thyroid function from two years after treatment initiation, especially in patients who undergo ND and subsequent RT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-019-5697-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524259PMC
May 2019

The Health Promoting Mindfulness or Qigong Educational Programs for Beneficial Lifestyle Changes of Cancer Survivors.

J Cancer Educ 2020 08;35(4):743-750

Nursing Department, Fooyin University, 151 Jinxue Rd., Daliao Dist., Kaohsiung City, 83102, Taiwan.

This study used heart rate variability (HRV) to monitor levels of cancer-related fatigue (CRF) and quality of life (QOL) of cancer survivors subjected to program measures at different psychosomatic or functional levels. A longitudinal study was conducted at a cancer center in Taiwan. Fifty-two cancer survivals were randomly assigned to either the mindfulness group (n = 25) or the Qigong group (n = 27). Both groups received a 12-week mindfulness and Qigong programs, respectively. Improvements in CRF, QOL, and HRV after a 12-week program and at the 3-month follow-up point. For the long-term effects in both mindfulness and Qigong groups, CRF showed a significant downward trend (p < 0.05), but a significant upward trend was observed in HRV (p < 0.001). Mindfulness and Qigong exhibited different effectiveness in individuals, indicating that the mental and physical aspects of health are equally essential and should be addressed in a complementary combination. These findings are worthy of being shared with cancer survivors to benefit their physical and mental well-being. We suggest that healthcare professionals incorporate mindfulness and Qigong in cancer survivors' daily life as means to encourage lifestyle changes for improving their health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13187-019-01522-5DOI Listing
August 2020

Effectiveness of the Multidisciplinary Team Model in Treating Colorectal Cancer.

Gastroenterol Nurs 2018 Nov/Dec;41(6):491-496

Wen-Li Lin, MSN, Cancer Center, Chi Mei Medical Center, Liouying, Taiwan. Jia-Ling Sun, PhD, Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan. Shu-Chan Chang, MSN, Cancer Center, Chi Mei Medical Center, Liouying, Taiwan. Tsung-Chih Tsai, MD, Department of Surgery, Chi Mei Medical Center, Liouying, Taiwan. Pei-Hua Wu, MSN, Cancer Center, Chi Mei Medical Center, Liouying, Taiwan. Wen-Tsung Huang, MD, Department of Hematology and Oncology, Chi Mei Medical Center, Liouying, Taiwan. Chao-Jung Tsao, MD, Department of Hematology and Oncology, Chi Mei Medical Center, Liouying, Taiwan. Chien-Liang Lin, MD, Department of Hematology and Oncology, Chi Mei Medical Center, Liouying, Taiwan.

The multidisciplinary team (MDT) model involves multiple medical professionals providing integrated medical care. Colorectal cancer (CRC) has the highest prevalence of cancer in Taiwan. This study examines and evaluates the survival rates of CRC patients treated under the MDT model. In this retrospective and prospective study, 651 CRC patients were recruited. They were divided into 2 groups: the MDT group and the traditional care (TC) group. The MDT group comprised 326 patients who received care from a MDT. The TC group comprised 325 patients who received care from a TC. The outcome variables were survival rates, follow-up appointment compliance, and 14-day readmission rates. Adopting the MDT model for CRC care increased patient follow-up appointment compliance rates at the first week, first month, and third month (p = .032, p = .007, p = .001, respectively). The model also effectively reduced patients' 14-day readmission rates. The results indicated that the survival rates of the MDT care were superior to those of TC. The adoption of the MDT model to treat CRC effectively enhanced clinical treatment adherence, increased survival rates, and reduced the 14-day readmission rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SGA.0000000000000348DOI Listing
April 2019

Pigment epithelium-derived factor inhibits lung cancer migration and invasion by upregulating exosomal thrombospondin 1.

Cancer Lett 2019 02 12;442:287-298. Epub 2018 Nov 12.

Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address:

Exosomes are implicated in cancer cell development, migration and invasion. Pigment epithelium-derived factor (PEDF) is a secreted anticancer protein that can regulate lung cancer progression; however, the role of PEDF in non-small cell lung cancer (NSCLC), including metastasis and cancer cell-derived exosome secretion, is unclear. In this study, we analyzed the effects of PEDF on exosome-mediated migration, invasion, and tumorigenicity of cultured NSCLC cells. The results showed that PEDF overexpression significantly reduced NSCLC invasion and migration, while inducing cell aggregation, whereas PEDF knockdown had the opposite effects. Exosomes from NSCLC cells treated with recombinant PEDF had a significantly reduced ability to promote cancer cell motility, migration, and invasion compared to exosomes from untreated cells. Exosomes from PEDF-treated cells contained thrombospondin 1 (THBS1), which inhibited cytoskeletal remodeling and exosome-induced lung cancer cell motility, migration, and invasion. Furthermore, PEDF-overexpressing NSCLC cells formed smaller xenograft tumors with higher THBS1 expression compared to control tumors. Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2018.10.031DOI Listing
February 2019

CSF-ctDNA SMSEQ Analysis to Tailor the Treatment of a Patient with Brain Metastases: A Case Report.

Case Rep Oncol 2018 Jan-Apr;11(1):68-74. Epub 2018 Feb 1.

eCellMax Inc., Sunnyvale, California, USA.

Brain metastases are the most common neurological complications of adult cancers, accounting for more than half of brain tumors. The incidence of brain metastases may be increasing due to improved detection of small lesions by advanced imaging technologies. Given the fast evolution of targeted and immunotherapy regimens, it is essential to serially assess brain malignancies during the disease course for disease monitoring and tailoring of the therapeutic management. For such serial and repetitive assessment, cerebrospinal fluid (CSF) could be the biological fluid of choice to supplement cytology examination for the presence or absence of CNS malignancy, as well as provide extensive information on tumor mutational profile for personalization of treatment. The case described here emphasizes the importance of CSF-ctDNA analysis with the CellMax SMSEQ technology that led to treatment adjustment resulting in clinical remission of the patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000486568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836181PMC
February 2018

Effects of a Psychoeducational Intervention in Patients With Breast Cancer Undergoing Chemotherapy.

J Nurs Res 2018 Aug;26(4):266-279

MSN, RN, Senior Administrator, Cancer Center, Chi Mei Medical Center, Liouying.

Background: Compelling evidence has yet to be published regarding the positive effect of psychoeducational interventions (PEIs) on psychological distress in patients with breast cancer. The impact of PEIs on self-efficacy, resilience, and quality of life is also unclear.

Purpose: The aim of this study was to assess the effects of a PEI on anxiety, depression, disease-specific care knowledge, self-efficacy, resilience and quality of life in patients with breast cancer during and after chemotherapy. The intervention was administered before and during five rounds of chemotherapy treatment.

Methods: A randomized controlled trial was conducted. Patients with breast cancer (N = 40) were randomly assigned to either the experimental or control group. The experimental group participated in PEI, a brief and highly structured program consisting of two parts: (a) an educational manual that addressed depression, anxiety, disease-specific care knowledge, self-efficacy, and resilience and (b) a self-assessment of learning. The control group received only traditional pamphlet education. Data were collected at four time points: before the first chemotherapy session (T1), during the third chemotherapy session (T2), during the fifth chemotherapy session (T3), and at 2 weeks after the final chemotherapy session (T4).

Results: Anxiety, depression, resilience, and quality of life in the experimental group showed significant differences at T4. Significant differences became apparent at T2 for knowledge and at T3 for self-efficacy. The effects of knowledge, resilience, and quality of life remained significant when group and time interactions were included in the model, showing a positive relationship between PEI and the variables of knowledge, resilience, and quality of life.

Conclusions/implications For Practice: Face-to-face PEI for patients with breast cancer is potentially effective in improving knowledge, resilience, and quality of life during and after chemotherapy. In the current study, PEI significantly improved disease care techniques, reduced chemotherapy-related discomfort, and improved quality of life for participants in the experimental group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/jnr.0000000000000252DOI Listing
August 2018

HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells.

Front Pharmacol 2017 13;8:902. Epub 2017 Dec 13.

Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER) breast cancer patients. Even though dysregulations of histone deacetylases (HDACs) are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER hormone-dependent ZR-75-1 breast cancer cells . Kaplan-Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2017.00902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736991PMC
December 2017

Curcumin Inhibits LIN-28A through the Activation of miRNA-98 in the Lung Cancer Cell Line A549.

Molecules 2017 Jun 3;22(6). Epub 2017 Jun 3.

Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.

Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene as well as () and in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile, level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules22060929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152786PMC
June 2017

Associations between interventions for urolithiasis and urinary tract cancer among patients in Taiwan: The effect of early intervention.

Medicine (Baltimore) 2016 Dec;95(49):e5594

Division of Hematology and Oncology Division of Urology, Chi-Mei Medical Center, Liouying Campus Min-Hwei Junior College of Health Care Management Department of Nursing Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Biostatistics Consulting Center, National Cheng Kung University Hospital, Tainan, Taiwan.

The aim of this study was to investigate cancer risk in patients with a history of urolithiasis and to determine whether intervention for calculi attenuated the risk of subsequent urinary tract cancer (UTC).Using data from the National Health Insurance Research Database in Taiwan, we performed a nationwide cohort study enrolling participants (n = 42,732) aged > 30 years who were diagnosed with urinary tract calculi between 2000 and 2009. Age- and gender-matched insured individuals (n = 213,660) found in the health service records over the same period were recruited as the control group. The Cox proportional hazards model and competing risks regression model were used to examine the relationship between urolithiasis and UTC, as well as whether early intervention for urolithiasis decreased the subsequent cancer risk relative to late intervention.Participants with a previous diagnosis of urolithiasis (n = 695) had a 1.82-fold (95% CI: 1.66-1.99, P < 0.001) increased risk of developing UTC. Furthermore, the risk of UTC associated with urolithiasis was higher in women (adjusted HR: 2.43, 95% CI: 1.94-3.05) than in men (adjusted HR: 1.72, 95% CI: 1.55-1.90). When stratified by cancer site, the adjusted HR for bladder, renal pelvis/ureter, renal, and prostate cancers were 1.94 (95% CI: 1.62-2.33), 2.94 (95% CI: 2.24-3.87), 2.94 (95% CI: 2.29-3.77), and 1.45 (95% CI: 1.27-1.65), respectively. Patients who received interventions for urolithiasis within 3 months of detection had a decreased risk of subsequent UTC (adjusted HR: 0.53, 95% CI: 0.40-0.71, P < 0.001).The present study demonstrated that urolithiasis increased the risk of subsequent UTC, especially upper UTC. Hence, it is recommended that physicians administer the appropriate interventions as early as possible upon diagnosis of urolithiasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000005594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266053PMC
December 2016

Impact of Adjuvant Chemotherapy in Elderly Breast Patients in Taiwan, A Hospital-Based Study

Asian Pac J Cancer Prev 2016 10 1;17(10):4591-4597. Epub 2016 Oct 1.

Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang, Tainan, Taiwan, Email:

Purpose: Decisions as to whether to provide adjuvant treatment in older breast cancer patients remains challenging. Side effects of chemotherapy have to be weighed against life expectancy, comorbidities, functional status, and frailty. To aid decision-making, we retrospectively analyzed 110 women with breast cancer treated with a curative intention from 2006 to 2012. Survival data with clinical and pathological parameters were evaluated to address the role of adjuvant chemotherapy in this study population. Method: A total of 110 elderly (>70 years) patients that received mastectomy at two hospitals in Taiwan were observed retrospectively for a medium of 51 months. After mastectomy, patients received conservative treatment or adjuvant chemotherapy, or hormone therapy following clinical guidelines or physician’s preference. Data were collected from the cancer registry system. Results: Median age at diagnosis was 75.7 years. Thirty-five percent of patients received adjuvant chemotherapy, these having a significantly younger age (mean=74.0±5.3 vs 77.5±5.3, p<0.001) and higher tumor staging (p=0.003) compared with their non-chemotherapy counterparts.Five-year overall survival was non-significantly higher in patients who received adjuvant chemotherapy (with chemotherapy 64.2% vs without chemotherapy 62.6%, p=0.635), while five-year recurrence free survival was non-significantly lower (with chemotherapy 64.1% vs without chemotherapy 90.5%, p=0.80). Conclusions: In this analysis, adjuvant chemotherapy tended to be given to patients with a younger age and higher tumor staging at our institute. It was not associated with any statistically significant improvement in survival and recurrence rate. Until age specific recommendations are available, physicians must use their clinical judgment and assess the tumor biology with the patient’s comorbidities to make the best choice. Clinical trials focusing on this critical issue are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454603PMC
http://dx.doi.org/10.22034/apjcp.2016.17.10.4591DOI Listing
October 2016

[Transference in the Nurse-Patient Relationship: A Case Report on a Prostate Cancer Patient].

Hu Li Za Zhi 2015 Aug;62(4):95-102

Cancer Center, Chi Mei Medical Center, Liouying, Taiwan, ROC.

This article explores the dilemma posed with regard to a prostate cancer patient suffering from transference syndrome. Transference is generally recognized as an unconscious and inevitable part of relationships. Both nurse and patient "transfer" their past emotional and psychological needs into present situations and react accordingly. Consequently, the emotions and behaviors of nurses influence the reactions of their patients. Nurses must better understand their contributions to the nurse-patient relationship in order to better detect patient thoughts and feelings. Furthermore, nurses must recognize the needs of their patients and maintain a neutral and uncritical attitude. We developed a case management model to provide a consultation corner for cancer patients. Additionally, in an attempt to improve the quality of life of cancer patients, the developed model encouraged medical personnel to discuss sexual, belonging, and love problems with patients and to hold attitudes of professionalism, composure, caring, and solemnity. Belonging and love are basic human needs. However, for patients with prostate cancer, this basic need cannot be satisfied. Even professionally trained medical personnel have difficulty directly addressing this problem. This paper describes the meaning of transference and the importance of this concept in the therapeutic nurse-patient relationship. Finally, developing better insights into the nurse-patient relationship will help nurses use these insights to improve the quality of patient interactions and of care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6224/JN62.4.95DOI Listing
August 2015

Electrical characteristic fluctuation of 16-nm-gate trapezoidal bulk FinFET devices with fixed top-fin width induced by random discrete dopants.

Nanoscale Res Lett 2015 11;10:116. Epub 2015 Mar 11.

Parallel and Scientific Computing Laboratory, National Chiao Tung University, 1001 Ta-Hsueh Road, Hsinchu, 300 Taiwan ; Institute of Communications Engineering, National Chiao Tung University, 1001 Ta-Hsueh Road, Hsinchu, 300 Taiwan ; Department of Electrical and Computer Engineering, National Chiao Tung University, 1001 Ta-Hsueh Road, Hsinchu, 300 Taiwan.

In this work, we use an experimentally calibrated 3D quantum mechanically corrected device simulation to study the random dopant fluctuation (RDF) on DC characteristics of 16-nm-gate trapezoidal bulk fin-type field effect transistor (FinFET) devices. The fixed top-fin width, which is consistent with the realistic process by lithography, of trapezoidal bulk FinFET devices is considered in this study. For RDF on trapezoidal bulk FinFETs under the fixed top-fin width, we explore the impact of geometry and RDF on the on-/off-state current and the threshold voltage (V th) fluctuation with respect to different channel fin angles. For the same channel doping concentration, compared with an ideal FinFET (i.e., device with a right angle of channel fin), the off-state current is large in trapezoidal bulk FinFETs with a small fin angle. Furthermore, the short-channel effect and V th variation degrade as the fin angle is getting smaller. The magnitude of the normalized σV th increases 7% when the fin angle decreases from 90° to 70°.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s11671-015-0739-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398683PMC
April 2015

Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial.

J Clin Oncol 2015 Jan 8;33(2):172-9. Epub 2014 Dec 8.

Calin Cainap, Institute of Oncology, Cluj-Napoca, Romania; Shukui Qin, Chinese People's Liberation Army Cancer Center, Bayi Hospital, Beijing; Hongming Pan, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou; Ying Cheng, Tumor Hospital of Jilin Province, Changchun, People's Republic of China; Wen-Tsung Huang, Chi Mei Medical Center, Liouying; Pei-Jer Chen, National Taiwan University Hospital, Taipei, Taiwan, Republic of China; Ik Joo Chung, Chonnam National University, Hwasun Hospital, Hwasun, Jeollonam-do; Yoon-Koo Kang, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea; Masatoshi Kudo, Kinki University, Osaka, Japan; Han-Chong Toh, National Cancer Centre, Singapore, Singapore; Vera Gorbunova, Russian Academy of Medical Sciences, Moscow, Russia; Ferry A.L.M. Eskens, Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands; Jiang Qian, Mark D. McKee, Justin L. Ricker, Dawn M. Carlson, AbbVie, North Chicago, IL; Saied El-Nowiem, Alexandria University, Alexandria, Egypt.

Purpose: This open-label phase III trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy.

Patients And Methods: Patients were randomly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily. Patients were stratified by region (Outside Asia, Japan, and rest of Asia), Eastern Cooperative Oncology Group performance score (ECOG PS; 0 or 1), vascular invasion or extrahepatic spread (yes or no), and hepatitis B virus (HBV) infection (yes or no). The primary end point of the study was overall survival (OS). Secondary end points were time to progression (TTP) and objective response rate (ORR) per RECIST v1.1.

Results: We randomly assigned 1,035 patients (median age, 60 years; Asian, 66.6%; ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%). Median OS was 9.1 months on the linifanib arm (95% CI, 8.1 to 10.2) and 9.8 months on the sorafenib arm (95% CI, 8.3 to 11.0; hazard ratio [HR], 1.046; 95% CI, 0.896 to 1.221). For prespecified stratification subgroups, OS HRs ranged from 0.793 to 1.119 and the 95% CI contained 1.0. Median TTP was 5.4 months on the linifanib arm (95% CI, 4.2 to 5.6) and 4.0 months on the sorafenib arm (95% CI, 2.8 to 4.2; HR, 0.759; 95% CI, 0.643 to 0.895; P = .001). Best response rate was 13.0% on the linifanib arm versus 6.9% on the sorafenib arm. Grade 3/4 adverse events (AEs); serious AEs; and AEs leading to discontinuation, dose interruption, and reduction were more frequent with linifanib (all P < .001).

Conclusion: Linifanib and sorafenib had similar OS in advanced HCC. Predefined superiority and noninferiority OS boundaries were not met for linifanib and the study failed to meet the primary end point. TTP and ORR favored linifanib; safety results favored sorafenib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2013.54.3298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279237PMC
January 2015

Angioimmunoblastic T-cell lymphoma in Taiwan shows a frequent gain of ITK gene.

Int J Clin Exp Pathol 2014 15;7(9):6097-107. Epub 2014 Aug 15.

Department of Pathology, Chi-Mei Medical Center, Tainan, Taipei Medical University and National Taiwan University Taipei, Taiwan.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma (PTCL) of follicular helper T-cell origin and is rare in Taiwan. There are overlapping features of AITL and peripheral T-cell lymphoma with a follicular growth pattern (PTCL-F). Around one fifth of PTCL-F exhibits t(5;9)(q33;q22)/ITK-SYK chromosomal translocation, which is essentially absent in AITL. We retrospectively investigated 35 cases of AITL from Taiwan with histopathology review, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBV) and fluorescence in situ hybridization (FISH) for t(5;9)(q33;q22)/ITK-SYK and correlated the results with overall survival. Twenty-six cases of not otherwise specified PTCL (PTCL-NOS) were also examined by FISH for comparison. Most AITL patients were male (69%) and elderly (median age at 67 years) with frequent bone marrow involvement (53%), high Ann Arbor stages (77%), and elevated serum lactate dehydrogenase (68%). Most cases (80%) showed a typical CD4+/CD8- phenotype and in 90% cases there were scattered EBV-positive B-cells (less than 10% cells). None of these cases showed t(5;9)(q33;q22)/ITK-SYK translocation by FISH. Gain of ITK and SYK gene was identified in 38% and 14% tumors, respectively, but both were not associated with overall survival. Performance status < 2 was associated with a better outcome but not the other clinicopathological factors. All PTCL-NOS cases were negative for ITK-SYK translocation with similar rates (38% and 12%, respectively) of gains at ITK and SYK loci as that of AITL. In this so far the largest series of AITL from Taiwan, we reported the clinicopathological features and FISH findings on ITK and SYK genes. We confirmed the absence of t(5;9)(q33;q22)/ITK-SYK translocation, which may serve as an additional differential diagnostic tool from PTCL-F when present. PTCL-NOS shared a similar pattern of ITK and SYK gains with AITL. More studies are warranted to elucidate the roles of SYK and ITK and other genes in the lymphomagenesis of AITL in Taiwan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203228PMC
July 2015

Sprouty2 protein is downregulated in human squamous cell carcinoma of the head and neck and suppresses cell proliferation in vitro.

Mol Med Rep 2015 Jan 20;11(1):547-54. Epub 2014 Oct 20.

Department of Hematology and Oncology, Chi-Mei Medical Center, Tainan 71004, Taiwan, R.O.C.

Sprouty2 is known for its tumor-suppressing effect in various human malignant diseases. In head and neck squamous cell carcinoma (HNSCC), the role of sprouty2 in tumorigenesis and clinical implication remains elusive. The aim of the present study was to investigate the expression of sprouty2 in patients with HNSCC and its function in vitro. Quantitative analysis of mRNA expression of sprouty2 was performed on frozen tumor samples from 42 patients with HNSCC and 19 with oral verrucous hyperplasia (OVH) with paired counterparts of normal mucosa. Downregulation of sprouty2 expression was demonstrated in 79% of HNSCC samples and in 58% of OVH samples compared with paired samples of normal mucosa. Enhanced expression of sprouty2 protein suppressed the growth of HNSCC cells and signaling of the phosphorylated AKT pathway. Following transfection of the sprouty2 plasmid, HNSCC cells were more sensitive to sorafenib, a tyrosine kinase inhibitor of Raf and vascular endothelial growth factor receptor. The present study suggested that sprouty2 expression was downregulated and behaved as a tumor suppressor in HNSCC. Sprouty2 expression in tumor cells enhanced sensitivity to sorafenib. Further studies are required to define the clinical impact of sprouty2 in patients with HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2014.2700DOI Listing
January 2015

Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy.

J Clin Pathol 2014 Dec 30;67(12):1056-61. Epub 2014 Sep 30.

National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.

Aims: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is an increasingly used therapeutic strategy for advanced rectal cancer, but risk stratification and final outcomes remain suboptimal. Recently, the oncogenic role of the fibroblast growth factor/fibroblast growth factor receptor (FGFR) signalling pathway has been recognised; however, its clinical significance in rectal cancer has not been elucidated. In this study, we identify and validate targetable drivers associated with the FGFR signalling pathway in rectal cancer patients treated with CCRT.

Methods: Using a published transcriptome of rectal cancers, we found FGFR2 gene significantly predicted response to CCRT. The expression levels of FGFR2, using immunohistochemistry assays, were further evaluated in 172 rectal cancer specimens that had not received any treatment. Expression levels of FGFR2 were statistically correlated with major clinicopathological features and clinical survival in this valid cohort.

Results: High expression of FGFR2 was significantly related to advanced pretreatment tumour (p=0.022) and nodal status (p=0.026), post-treatment tumour (p<0.001) and nodal status (p=0.004), and inferior tumour regression grade (p<0.001). In survival analyses, high expression of FGFR2 was significantly associated with shorter local recurrence-free survival (p=0.0001), metastasis-free survival (MeFS; p=0.0003) and disease-specific survival (DSS; p<0.0001). Notably, high expression of FGFR2 was independently predictive of worse outcomes for MeFS (p=0.002, HR=5.387) and DSS (p=0.004, HR=4.997).

Conclusions: High expression of FGFR2 is correlated with advanced tumour stage, poor therapeutic response and worse survival in rectal cancer patients receiving neoadjuvant CCRT. These findings indicate that FGFR2 is a prognostic factor for treating rectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2014-202551DOI Listing
December 2014

The effect of yoga exercise on improving depression, anxiety, and fatigue in women with breast cancer: a randomized controlled trial.

J Nurs Res 2014 Sep;22(3):155-64

1PhD, Cancer Center, Chi Mei Medical Center 2PhD, School of Nursing, Fooyin University 3MSN, RN, Cancer Center, Chi Mei Medical Center 4PhD, RN, Assistant Professor, School of Nursing, Fooyin University 5MD, Cancer Center, Chi Mei Medical Center 6MD, Cancer Center, Chi Mei Medical Center.

Background: Depression, anxiety, and fatigue are among the most significant problems that influence the quality of life of patients with breast cancer who receive adjuvant chemotherapy. Although evidence has shown yoga to decrease anxiety, depression, and fatigue in patients with cancer, few studies on the effects of yoga have targeted patients with breast cancer. Yoga interventions should be tested to promote the psychological and physical health of women with breast cancer.

Purpose: This study examines the effectiveness of an 8-week yoga exercise program in promoting the psychological and physical health of women with breast cancer undergoing adjuvant chemotherapy in terms of depression, anxiety, and fatigue.

Methods: A sample of 60 women with nonmetastatic breast cancer was recruited. Participants were randomly assigned into either the experimental group (n = 30) or the control group (n = 30). A 60-minute, twice-per-week yoga exercise was implemented for 8 weeks as the intervention for the participants in the experimental group. The control group received standard care only.

Results: Analysis using the Johnson-Neyman procedure found that the yoga exercise reduced overall fatigue and the interference of fatigue in everyday life for the experimental group participants. Significant reductions were obtained after 4 weeks of intervention participation for those experimental group patients with relatively low starting baseline values (baseline item mean value < 3.31 and 3.22, respectively) and after 8 weeks for most patients (approximately 75%) with moderate starting baseline values (baseline item mean value < 7.30 and 5.34, respectively). The 8-week intervention did not significantly improve the levels of depression (F = 1.29, p > .05) or anxiety (F = 2.7, p > .05).

Conclusions/implications For Practice: The 8-week yoga exercise program developed in this study effectively reduced fatigue in patients with breast cancer but did not reduce depression or anxiety. Oncology nurses should strengthen their clinical health education and apply yoga to reduce the fatigue experienced by patients with breast cancer who undergo adjuvant chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/jnr.0000000000000044DOI Listing
September 2014

Factors predicting survival of patients with gastric cancer.

Asian Pac J Cancer Prev 2014 ;15(14):5835-8

Cancer Center, Chi Mei Medical Center, Liouying, Taiwan E-mail :

Background: Gastric cancer is one of the most common causes of cancer death in Taiwan. The literature has previously shown that age, tumor site, T categories, and number of metastatic nodes significantly affect prognosis. The aim of this study was to determine the long-term survival of patients with gastric cancer, as well as the effect of particular prognostic factors on survival.

Materials And Methods: This was a survival analysis study with retrospective design. We reviewed the records of 64 patients with adenocarcinoma of the stomach who had undergone gastrectomy with curative intent between 2009 and 2012 at a teaching hospital in southern Taiwan. Data extracted from patient documents included age, gender distribution, tumor location, and pathological grading.

Results: The median follow-up time was 4 years, and there were 31 deaths attributed to gastric cancer. Kaplan-Meier analysis revealed that retrieval of less than 15 lymph nodes from a patient was a significant predictor of survival. A significant predictor of poorer survival was higher pathological grading.

Conclusions: Our results indicate that the number of lymph nodes retrieved and pathological grading could be viewed as crucial prognostic factors affecting the survival of individuals with gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7314/apjcp.2014.15.14.5835DOI Listing
June 2015

Development and application of telephone counseling services for care of patients with colorectal cancer.

Asian Pac J Cancer Prev 2014 ;15(2):969-73

Cancer Center, Chi Mei Medical Center, Liouying, Taiwan E-mail :

Background: The number of colorectal cancer (CRC) patients in Taiwan has increased in recent years; therefore, the effective dissemination of information related to symptom care has become especially important. Previous studies indicated that the physical and psychological status of cancer patients can be effectively improved by telephone counseling services (TCS). Thus, determining the most effective means of establishing a TCS to support the clinical practice of oncology has become a crucial goal for nursing. The purposes of this study were to analysis the content of the TCS for CRC and explore stratification of the TCS.

Materials And Methods: The study design was retrospective. A total of 850 calls were made to CRC patients in the cancer center of Southern Taiwan during the period of January 2007- December 2011. A structure questionnaire was adopted to analysis satisfaction.

Results: Responses provided by the TCS included information regarding nutrition, side effects resulting from chemotherapy and pain. Moreover, 28.7% of CRC patients needed advanced treatment. More than 90% satisfaction with all aspects of the calls was found.

Conclusions: The TCS coulkd be shown to provide an effective means by which to expand the reach of nursing care to different times, places and patients, allowing for greater cost efficiency and more rapid service.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7314/apjcp.2014.15.2.969DOI Listing
November 2014

CDKN1A-mediated responsiveness of MLL-AF4-positive acute lymphoblastic leukemia to Aurora kinase-A inhibitors.

Int J Cancer 2014 Aug 13;135(3):751-62. Epub 2014 Jan 13.

Division of Hematology/Oncology, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Graduate Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.

Overexpression of Aurora kinases is largely observed in many cancers, including hematologic malignancies. In this study, we investigated the effects and molecular mechanisms of Aurora kinase inhibitors in acute lymphoblastic leukemia (ALL). Western blot analysis showed that both Aurora-A and Aurora-B are overexpressed in ALL cell lines and primary ALL cells. Both VE-465 and VX-680 effectively inhibited Aurora kinase activities in nine ALL cell lines, which exhibited different susceptibilities to the inhibitors. Cells sensitive to Aurora kinase inhibitors underwent apoptosis at an IC50 of ∼10-30 nM and displayed a phenotype of Aurora-A inhibition, whereas cells resistant to Aurora kinase inhibitors (with an IC50 more than 10 μM) accumulated polyploidy, which may have resulted from Aurora-B inhibition. Drug susceptibility of ALL cell lines was not correlated with the expression level or activation status of Aurora kinases. Interestingly, RS4;11 and MV4;11 cells, which contain the MLL-AF4 gene, were both sensitive to Aurora kinase-A inhibitors treatment. Complementary DNA (cDNA) microarray analysis suggested that CDKN1A might govern the drug responsiveness of ALL cell lines in a TP53-independent manner. Most importantly, primary ALL cells with MLL-AF4 and CDKN1A expression were sensitive to Aurora kinase inhibitors. Our study suggests CDKN1A could be a potential biomarker in determining the drug responsiveness of Aurora kinase inhibitors in ALL, particularly in MLL-AF4-positive patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.28708DOI Listing
August 2014
-->