Chih-jen Huang - Academia.edu (original) (raw)

Papers by Chih-jen Huang

International Journal of Radiation Oncology Biology Physics, Nov 1, 2018

Medicine, 2017

Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and t... more Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and the prognosis in most cases of spinal PNETs appears to be poor, with a median patient survival of 1 to 2 years. We present a case with recurrent spinal PNET with brain and bone metastases that was successfully treated by multimodality treatment. A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later. Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brai...

Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines ... more Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA) is a mycotoxin that induces endoplasmic reticulum (ER) stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL) compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9) activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.

IEEE Access

This work involved human subjects or animals in its research. Approval of all ethical and experim... more This work involved human subjects or animals in its research. Approval of all ethical and experimental procedures and protocols was granted by the Institutional Review Board of Kaohsiung Medical University Hospital under Application No. KMUHIRB-EXEMPT (I)-20190216 and China Medical University Hospital under Application No. CMUH107-REC3-047, and performed in line with the Declaration of Helsinki.

Metaplastic carcinoma is a rare form of breast carcinoma. Herein we reported a breast cancer pati... more Metaplastic carcinoma is a rare form of breast carcinoma. Herein we reported a breast cancer patient with metaplastic carcinoma which mimicked infiltrating ductal carcinoma in the initial pathological diagnosis. She received modified radical mastectomy, adjuvant chemotherapy and radiotherapy to the chest wall and loco-regional lymphatic area. Eight months after radiotherapy, a 3 x 2 cm hard mass over the right upper margin of incision was noted. The pathology revealed metaplastic carcinoma. Sequentially multi-organ metastases to the bones, lung and brain developed. The survival period was only 26 months from the diagnosis of breast cancer. The pathology pictures and literature of metaplastic breast carcinoma were reviewed and discussed.

Metastatic tumors to gingival from non-oral malignancies are very uncommon. It accounts only for ... more Metastatic tumors to gingival from non-oral malignancies are very uncommon. It accounts only for less than 4% of all metastatic tumors to the oral cavity. The lung and breast are the most common distant primary sites for metastasis to oral soft tissue. Metastases from the rectal cancer to oral cavity and neck region are extremely rare, except to neck and supraclavicular lymph node. We will describe a rare case of primary adenocarcinoma of rectum with metastasis to the gingiva of the mouth. Although the prognosis of patients with gingival metastasis is felt to be poor, regional radiotherapy is effective for the palliative purpose to the local metastatic lesion of the advanced disease.

Oncogene

MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repai... more MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic ta...

Proceedings of the 3rd Clinical Natural Language Processing Workshop

A cancer registry is a critical and massive database for which various types of domain knowledge ... more A cancer registry is a critical and massive database for which various types of domain knowledge are needed and whose maintenance requires labor-intensive data curation. In order to facilitate the curation process for building a high-quality and integrated cancer registry database, we compiled a cross-hospital corpus and applied neural network methods to develop a natural language processing system for extracting cancer registry variables buried in unstructured pathology reports. The performance of the developed networks was compared with various baselines using standard micro-precision, recall and Fmeasure. Furthermore, we conducted experiments to study the feasibility of applying transfer learning to rapidly * Corresponding authors develop a well-performing system for processing reports from different sources that might be presented in different writing styles and formats. The results demonstrate that the transfer learning method enables us to develop a satisfactory system for a new hospital with only a few annotations and suggest more opportunities to reduce the burden of cancer registry curation.

Translational Cancer Research

Journal of Thoracic Disease

Background: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP rec... more Background: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP recurrence is still a major concern. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against oxidative airway diseases. The aim was to investigate the role of Nrf2 in PSP patients and its correlation with recurrence. Methods: Eighty-nine patients were enrolled and received wedge resection of lung with identifiable blebs. Nrf2 expression in resected lung tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables. The prognostic value of Nrf2 for incidence-of-recurrence was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test. Results: Nrf2 staining was predominantly observed in alveolar macrophages and type II pneumocytes of PSP patients and correlated with recurrence (P<0.001 and P=0.001, respectively) and PSP location (macrophages, P=0.013). High Nrf2 expression was correlated with better incidence-of-recurrence (macrophages, P=0.003; type II pneumocytes, P=0.003). Moreover, incidence-of-recurrence was better in patients with higher Nrf2 expression, especially those in the age ≤20, male, and non-smoking groups (macrophages, P=0.009, 0.006, and 0.012; type II pneumocytes, P=0.003, 0.011, and 0.010, respectively). Conclusions: High Nrf2 expression in alveolar macrophages and type II pneumocytes was significantly associated with the decreased recurrence risk and was the independent factor predicting a better incidenceof-recurrence in PSP. Our results suggest that Nrf2 activation in high risk patients may be a potential target for reducing PSP recurrence.

PloS one, 2016

The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacolog... more The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers. CYT-Rx20 decreased cell viability and migration through suppression of the PI3K/AKT and STAT3 pathways. Of note, the cytotoxicity and anti-migratory effect of CYT-Rx20 were enhanced by co-treatment with SC79 (AKT activator) or colivelin (STAT3 activator), suggesting the dependency of esophageal cancer cells on AKT and STAT3 for survival and migration, an o...

Head & neck, Aug 12, 2017

We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carci... more We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation with cisplatin resistance and affects the efficacy of other platinum or nonplatinum drugs is unknown. The p22phox expression in tissues and apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo chemoresistance of p22phox-overexpressing tumors was confirmed by the xenograft mouse model. The p22phox was upregulated in tumors of patients with OSCC refractory to cisplatin treatment. The p22phox overexpression markedly increased the resistance to cisplatin and carboplatin, but not oxaliplatin and 5-fluorouracil (5-FU), in OSCC cells by differentially inhibiting the drug-induced apoptosis. Furthermore, p22phox-dependent resistance to cisplatin, but not 5-FU, was demonstrated in mouse xenograft tumors. The p22phox expression may not on...

Radiation oncology (London, England), Jan 7, 2017

Patients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radic... more Patients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radical resection and adjuvant chemotherapy. This study investigated the treatment efficacy and toxicity of neoadjuvant chemoradiotherapy in patients with LACC. We retrospectively reviewed 36 patients with LACC preoperatively treated with chemotherapy and radiotherapy. Patients were administered chemoradiotherapy, which comprised radiotherapy and neoadjuvant chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Median age was 64 years (45-86 years) and median follow-up period was 23.5 months (5.0-49.1 months). Seven (19.4%) patients developed grade 3 or 4 adverse events during neoadjuvant concurrent chemoradiotherapy. Pathologic responses were not evaluated in two patients who did not undergo radical resection. Of the 34 patients who underwent surgery, nine (26.4%) achieved a pathologic complete response (pCR). The 2-year estimated overall survival and di...

Journal of Radiation Research, 2016

The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiother... more The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiotherapy (3DCRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) administered through helical tomotherapy in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy. We reviewed 144 patients with Stage II–III rectal cancer receiving preoperative fluoropyrimidine-based chemoradiotherapy followed by radical resection. Tumor responses following chemoradiotherapy were evaluated using the Dworak tumor regression grade (TRG). Of the 144 patients, 45 received IG-IMRT and 99 received 3DCRT. A significant reduction in Grade 3 or 4 acute gastrointestinal toxicity (IG-IMRT, 6.7%; 3DCRT, 15.1%; P = 0.039) was observed by IG-IMRT. The pathologic complete response (pCR) rate did not differ between the IG-IMRT and the 3DCRT group (17.8% vs 15.1%, P = 0.52). Patients in the IG-IMRT group had the trend of favorable tumor regressions (TRG 3 or 4) compared with those ...

The Kaohsiung journal of medical sciences, 2017

Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is sti... more Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found th...

Medical dosimetry : official journal of the American Association of Medical Dosimetrists, 2016

We conducted this prospective study to evaluate whether the location of the most severe acute ski... more We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the co...

Therapeutic Advances in Gastroenterology, 2016

Introduction: Patients with rectal cancer who exhibit a pathologic complete response to preoperat... more Introduction: Patients with rectal cancer who exhibit a pathologic complete response to preoperative concurrent chemoradiotherapy have excellent oncologic outcomes. In this study, we evaluated the potential advantages of adding oxaliplatin to preoperative fluoropyrimidine-based chemoradiotherapy administered in rectal cancer patients. Methods: A total of 78 patients with rectal cancer were enrolled. Patients were administered chemoradiotherapy, which comprised radiotherapy and chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Surgery was performed 10–12 weeks after radiotherapy completion. Tumor regression, adverse events, surgical complications, and short-term clinical outcomes were recorded. Results: Two patients were excluded because of incomplete radiotherapy treatment or refusal of surgery. Eventually, 76 patients underwent total mesorectal excision and no perioperative mortality was observed. Of these, 20 patients (25.6%) developed gra...

PloS one, 2016

To compare the long-term clinical outcomes of postmastectomy radiotherapy (PMRT) between breast c... more To compare the long-term clinical outcomes of postmastectomy radiotherapy (PMRT) between breast cancer patients with and without immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction. The study included 492 patients with stage II or III breast cancer who underwent modified radical mastectomy (MRM) and chemotherapy followed by PMRT between 1997 and 2011. Cox regression model and Kaplan-Meier curves were calculated, and the log-rank test was used to evaluate the differences between overall and disease-free survival rates in the 2 groups. Among 492 patients, 213 patients had immediate TRAM flap reconstruction. The mean follow-up was 7.2 years (range, 11-191 months). The 5-year and 10-year disease free survival rates were 81% and 76% for the TRAM flap group and 78% and 73% for the non-flap group. The 5-year and 10-year overall survival rates were 89% and 73% for the TRAM flap group and 83% and 74% for the non-flap group. There exists no statistically significant ...

International Journal of Radiation Oncology Biology Physics, Nov 1, 2018

Medicine, 2017

Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and t... more Primary spinal primitive neuroectodermal tumor (PNET) is relatively rare in all age groups, and the prognosis in most cases of spinal PNETs appears to be poor, with a median patient survival of 1 to 2 years. We present a case with recurrent spinal PNET with brain and bone metastases that was successfully treated by multimodality treatment. A 14-year-old teenage girl had suffered from progressive left upper back pain with bilateral lower legs weakness and numbness for 1 year. After treatment, left neck mass was noted 3 years later. Initially, magnetic resonance imaging (MRI) showed neurogenic tumor involving intradural extramedullary space of T5-T10. Pathology report showed PNET (World Health Organization grade IV) featuring lobules of neoplastic cells with round regular nuclei, high nucleus-to-cytoplasm ratio, and fibrillary cytoplasm. At the time of tumor recurrence, chest MRI then showed recurrent tumor at T2-T3 level of the epidural space with right neural foramina invasion. Brai...

Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines ... more Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA) is a mycotoxin that induces endoplasmic reticulum (ER) stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL) compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9) activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.

IEEE Access

This work involved human subjects or animals in its research. Approval of all ethical and experim... more This work involved human subjects or animals in its research. Approval of all ethical and experimental procedures and protocols was granted by the Institutional Review Board of Kaohsiung Medical University Hospital under Application No. KMUHIRB-EXEMPT (I)-20190216 and China Medical University Hospital under Application No. CMUH107-REC3-047, and performed in line with the Declaration of Helsinki.

Metaplastic carcinoma is a rare form of breast carcinoma. Herein we reported a breast cancer pati... more Metaplastic carcinoma is a rare form of breast carcinoma. Herein we reported a breast cancer patient with metaplastic carcinoma which mimicked infiltrating ductal carcinoma in the initial pathological diagnosis. She received modified radical mastectomy, adjuvant chemotherapy and radiotherapy to the chest wall and loco-regional lymphatic area. Eight months after radiotherapy, a 3 x 2 cm hard mass over the right upper margin of incision was noted. The pathology revealed metaplastic carcinoma. Sequentially multi-organ metastases to the bones, lung and brain developed. The survival period was only 26 months from the diagnosis of breast cancer. The pathology pictures and literature of metaplastic breast carcinoma were reviewed and discussed.

Metastatic tumors to gingival from non-oral malignancies are very uncommon. It accounts only for ... more Metastatic tumors to gingival from non-oral malignancies are very uncommon. It accounts only for less than 4% of all metastatic tumors to the oral cavity. The lung and breast are the most common distant primary sites for metastasis to oral soft tissue. Metastases from the rectal cancer to oral cavity and neck region are extremely rare, except to neck and supraclavicular lymph node. We will describe a rare case of primary adenocarcinoma of rectum with metastasis to the gingiva of the mouth. Although the prognosis of patients with gingival metastasis is felt to be poor, regional radiotherapy is effective for the palliative purpose to the local metastatic lesion of the advanced disease.

Oncogene

MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repai... more MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic ta...

Proceedings of the 3rd Clinical Natural Language Processing Workshop

A cancer registry is a critical and massive database for which various types of domain knowledge ... more A cancer registry is a critical and massive database for which various types of domain knowledge are needed and whose maintenance requires labor-intensive data curation. In order to facilitate the curation process for building a high-quality and integrated cancer registry database, we compiled a cross-hospital corpus and applied neural network methods to develop a natural language processing system for extracting cancer registry variables buried in unstructured pathology reports. The performance of the developed networks was compared with various baselines using standard micro-precision, recall and Fmeasure. Furthermore, we conducted experiments to study the feasibility of applying transfer learning to rapidly * Corresponding authors develop a well-performing system for processing reports from different sources that might be presented in different writing styles and formats. The results demonstrate that the transfer learning method enables us to develop a satisfactory system for a new hospital with only a few annotations and suggest more opportunities to reduce the burden of cancer registry curation.

Translational Cancer Research

Journal of Thoracic Disease

Background: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP rec... more Background: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP recurrence is still a major concern. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against oxidative airway diseases. The aim was to investigate the role of Nrf2 in PSP patients and its correlation with recurrence. Methods: Eighty-nine patients were enrolled and received wedge resection of lung with identifiable blebs. Nrf2 expression in resected lung tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables. The prognostic value of Nrf2 for incidence-of-recurrence was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test. Results: Nrf2 staining was predominantly observed in alveolar macrophages and type II pneumocytes of PSP patients and correlated with recurrence (P<0.001 and P=0.001, respectively) and PSP location (macrophages, P=0.013). High Nrf2 expression was correlated with better incidence-of-recurrence (macrophages, P=0.003; type II pneumocytes, P=0.003). Moreover, incidence-of-recurrence was better in patients with higher Nrf2 expression, especially those in the age ≤20, male, and non-smoking groups (macrophages, P=0.009, 0.006, and 0.012; type II pneumocytes, P=0.003, 0.011, and 0.010, respectively). Conclusions: High Nrf2 expression in alveolar macrophages and type II pneumocytes was significantly associated with the decreased recurrence risk and was the independent factor predicting a better incidenceof-recurrence in PSP. Our results suggest that Nrf2 activation in high risk patients may be a potential target for reducing PSP recurrence.

PloS one, 2016

The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacolog... more The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers. CYT-Rx20 decreased cell viability and migration through suppression of the PI3K/AKT and STAT3 pathways. Of note, the cytotoxicity and anti-migratory effect of CYT-Rx20 were enhanced by co-treatment with SC79 (AKT activator) or colivelin (STAT3 activator), suggesting the dependency of esophageal cancer cells on AKT and STAT3 for survival and migration, an o...

Head & neck, Aug 12, 2017

We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carci... more We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation with cisplatin resistance and affects the efficacy of other platinum or nonplatinum drugs is unknown. The p22phox expression in tissues and apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo chemoresistance of p22phox-overexpressing tumors was confirmed by the xenograft mouse model. The p22phox was upregulated in tumors of patients with OSCC refractory to cisplatin treatment. The p22phox overexpression markedly increased the resistance to cisplatin and carboplatin, but not oxaliplatin and 5-fluorouracil (5-FU), in OSCC cells by differentially inhibiting the drug-induced apoptosis. Furthermore, p22phox-dependent resistance to cisplatin, but not 5-FU, was demonstrated in mouse xenograft tumors. The p22phox expression may not on...

Radiation oncology (London, England), Jan 7, 2017

Patients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radic... more Patients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radical resection and adjuvant chemotherapy. This study investigated the treatment efficacy and toxicity of neoadjuvant chemoradiotherapy in patients with LACC. We retrospectively reviewed 36 patients with LACC preoperatively treated with chemotherapy and radiotherapy. Patients were administered chemoradiotherapy, which comprised radiotherapy and neoadjuvant chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Median age was 64 years (45-86 years) and median follow-up period was 23.5 months (5.0-49.1 months). Seven (19.4%) patients developed grade 3 or 4 adverse events during neoadjuvant concurrent chemoradiotherapy. Pathologic responses were not evaluated in two patients who did not undergo radical resection. Of the 34 patients who underwent surgery, nine (26.4%) achieved a pathologic complete response (pCR). The 2-year estimated overall survival and di...

Journal of Radiation Research, 2016

The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiother... more The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiotherapy (3DCRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) administered through helical tomotherapy in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy. We reviewed 144 patients with Stage II–III rectal cancer receiving preoperative fluoropyrimidine-based chemoradiotherapy followed by radical resection. Tumor responses following chemoradiotherapy were evaluated using the Dworak tumor regression grade (TRG). Of the 144 patients, 45 received IG-IMRT and 99 received 3DCRT. A significant reduction in Grade 3 or 4 acute gastrointestinal toxicity (IG-IMRT, 6.7%; 3DCRT, 15.1%; P = 0.039) was observed by IG-IMRT. The pathologic complete response (pCR) rate did not differ between the IG-IMRT and the 3DCRT group (17.8% vs 15.1%, P = 0.52). Patients in the IG-IMRT group had the trend of favorable tumor regressions (TRG 3 or 4) compared with those ...

The Kaohsiung journal of medical sciences, 2017

Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is sti... more Primary spontaneous pneumothorax (PSP) is a common benign problem. However, PSP recurrence is still a troublesome complication for most patients. This study intended to determine the role of matrix metalloproteinase-2 (MMP-2) and MMP-9 in type II pneumocytes of patients with PSP and its relation with recurrence. Ninety-one patients who had undergone needlescopic video-assisted thoracoscopic surgery wedge resection of lung with identifiable blebs for PSP were included in this study. Immunohistochemical (IHC) staining was used to measure the expression of MMP-2 and MMP-9 in lung tissues of PSP patients. The results were further correlated with clinicopathological parameters and recurrence rates using chi-square or Fisher's exact test. The value of MMP-2 and MMP-9 for overall recurrence was analyzed by univariate and multivariable Cox regression model. IHC data revealed that MMP-2 and MMP-9 staining was predominantly observed in type II pneumocytes of patients with PSP. We found th...

Medical dosimetry : official journal of the American Association of Medical Dosimetrists, 2016

We conducted this prospective study to evaluate whether the location of the most severe acute ski... more We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the co...

Therapeutic Advances in Gastroenterology, 2016

Introduction: Patients with rectal cancer who exhibit a pathologic complete response to preoperat... more Introduction: Patients with rectal cancer who exhibit a pathologic complete response to preoperative concurrent chemoradiotherapy have excellent oncologic outcomes. In this study, we evaluated the potential advantages of adding oxaliplatin to preoperative fluoropyrimidine-based chemoradiotherapy administered in rectal cancer patients. Methods: A total of 78 patients with rectal cancer were enrolled. Patients were administered chemoradiotherapy, which comprised radiotherapy and chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Surgery was performed 10–12 weeks after radiotherapy completion. Tumor regression, adverse events, surgical complications, and short-term clinical outcomes were recorded. Results: Two patients were excluded because of incomplete radiotherapy treatment or refusal of surgery. Eventually, 76 patients underwent total mesorectal excision and no perioperative mortality was observed. Of these, 20 patients (25.6%) developed gra...

PloS one, 2016

To compare the long-term clinical outcomes of postmastectomy radiotherapy (PMRT) between breast c... more To compare the long-term clinical outcomes of postmastectomy radiotherapy (PMRT) between breast cancer patients with and without immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction. The study included 492 patients with stage II or III breast cancer who underwent modified radical mastectomy (MRM) and chemotherapy followed by PMRT between 1997 and 2011. Cox regression model and Kaplan-Meier curves were calculated, and the log-rank test was used to evaluate the differences between overall and disease-free survival rates in the 2 groups. Among 492 patients, 213 patients had immediate TRAM flap reconstruction. The mean follow-up was 7.2 years (range, 11-191 months). The 5-year and 10-year disease free survival rates were 81% and 76% for the TRAM flap group and 78% and 73% for the non-flap group. The 5-year and 10-year overall survival rates were 89% and 73% for the TRAM flap group and 83% and 74% for the non-flap group. There exists no statistically significant ...