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1.
J Acoust Soc Am ; 151(1): 434, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35105003

ABSTRACT

Static analysis is performed for fiber windings to quantitatively control the radial stress at the outer radius of the piezoelectric ceramic tube. The radial stress is verified both experimentally and theoretically, and the dependence of the resonant and material properties of the piezoelectric ceramic tubes on the radial stress is clarified. The resonance frequencies and dielectric loss remain relatively stable, but the relative permittivity and the short circuit elastic constant decrease with the radial stress. The variations of the increased bandwidth and decreased electromechanical coupling coefficient (k31), piezoelectric constant (d31 and g31), and mechanical quality factor (Qm) are associated with the height-to-radius ratio. The properties of three cylindrical transducers applied with various radial stress show similar change tendencies, and a difference of 0.34 MPa radial stress results in a variation of approximately 13 in the bandwidth, 14 in Qm, 15 in k31, d31, and g31, and 16 in the amplitude of the first pulse. These results suggest that the consistency of the radial stress is essential, and it should be relatively small. These findings guide the design and preparation of the enhanced transducer.

2.
Zhonghua Yi Xue Za Zhi ; 100(29): 2293-2296, 2020 Aug 04.
Article in Zh | MEDLINE | ID: mdl-32746601

ABSTRACT

Objective: To investigate the efficacy of percutaneous extensor tendon reconstruction in treating spastic hammery deformity. Methods: From February 2009 to July 2018, the clinicaldata of 36 patients with fresh sputum hammer fingers treated in Jinan People's Hospital were analyzed retrospectively. The tendon was percutaneously sutured with PDS Ⅱmonofilament suture and the distal end of the tendon was fixed to the base of the distal phalanx through the bone hole. Removal of the K-wire 6 weeks after the operation, the brace was used to fix the affected finger in the dorsal extension. For 8-10 weeks, only the brace was worn at night and the flexion and extension of the affected finger was gradually strengthened.The extension and flexion function of the interphalangeal joint of the finger was compared pre and post the operation with t test. Results: A total of 36 patients were enrolled but only 33 patientswere followed up for 6 to 15 months. The hammer-shaped deformity was corrected and there was no pain when moving fingers after the operation.The straightening angle of the interphalangeal joint of the finger improved from 46.2°±6.3° before surgery to 7.5°±0.6° after (t=35.12, P<0.05). The passive straightening angle decreased from 3.2°±0.3° before surgery to 0.9°±0.2° after (t=37.11, P<0.05). According to the Crawford functional assessment: excellent in 19 fingers, good in 10 fingers, can be in 4 fingers. The excellent rate was 87.9%. There was no knot exposure, skin necrosis and other complications. Conclusions: Percutaneous resection of the extensor tendon is fixed in the basal phalanx. It is a simple and feasible minimally invasive surgery for hammer-shaped deformity. It can obviously correct the hammer-shaped deformity and has fewer complications.


Subject(s)
Finger Injuries , Hand Deformities, Acquired , Humans , Muscle Spasticity , Range of Motion, Articular , Retrospective Studies , Tendons , Treatment Outcome
3.
Fa Yi Xue Za Zhi ; 36(4): 461-469, 2020 Aug.
Article in English, Zh | MEDLINE | ID: mdl-33047525

ABSTRACT

ABSTRACT: Objective To conduct bibliometric analysis of the relevant literature in the environmental field published from 1982 to 2018 collected by the Web of Science citation database and further explore the frontier research dynamics and hotspots in the environmental field. Methods The word "oil spill*" was used as the subject term for retrieval. A knowledge map of hotspots in oil spill research was built through software VOSviewer and the clustering relations between them were explored. The frequency and relevance of the keywords in the corresponding literature were obtained by the matrix of keywords built through the Thomson Data Analyzer (TDA) software. Results The four main research hotspots of marine oil spill pollution were oil spill numerical simulation and model prediction, oil spill exposure toxicity and risk assessment, oil spill component and source analysis and oil spill pollution characteristics and treatment. Conclusion The study analyzes the main content of the four research hotspots and the current research progress and provides scientific basis for further understanding of the mechanism of marine oil spill occurrence, migration and transformation, implementation of oil spill treatment and repair as well as more accurate assessment of eco-environment damage.


Subject(s)
Petroleum Pollution , Accidents , Bibliometrics , Petroleum Pollution/adverse effects , Risk Assessment , Software
5.
Zhonghua Yi Xue Za Zhi ; 97(37): 2923-2927, 2017 Oct 10.
Article in Zh | MEDLINE | ID: mdl-29050163

ABSTRACT

Objective: To investigate the percutaneously looped thread transection for treatment of stenosing tenosynovitis and evaluate its treatment outcome. Methods: From January 2014 to October 2016, Eighty-four patients with stenosing tenosynovitis were randomly divided into the open decompressionand group (42 cases) and percutaneously looped thread transection group (42 cases) in Department of Orthopedics, Affiliated Laiwu Hospital of Taishan Medical College. Incision near the digit horizontal stripes, tendon sheath were cut off in the open decompressionand group. Percutaneously looped thread transection was under the guidance of ultrasound, threading from the deep and shallow transverse tendon sheath, respectively, forming loops to cut off and decompressed the flexor tendon. Visual analog scale(VAS) was used to evaluate the extent of pain before the operation and 1 or 4 weeks after the operation, the comprehensive curative effect were evaluated 3 months after the operation. Results: In the two groups pain was alleviated. The VAS improved from (7.0±1.3)prior operation to(5.2±1.6) and (2.8±1.1)1 week and 4 weeks after the operation in the open decompressionand group , respectively. The difference before and after the operation was significant(P<0.05). The VAS improved from (7.1±1.4) prior operation to(2.7±1.3) and (0.6±0.2)1 week and 4 weeks after the operation in the percutaneously looped thread transection group, respectively. The difference before and after the operation was significant(P<0.05). The difference of VAS scores between two groups at 1 week and 4 weeks after the operation were different(P<0.05). The difference of the comprehensive curative effect between two groups at 3 months after the operation were not different(P>0.05). There were no infection, poor healing, blood vessel and nerve damage after operation in both two groups. Conclusion: Percutaneously looped thread transaction under ultrasound for the surgical treatment of stenosing tenosynovitis has less trauma and rapid recovery. It has such advantage as being effective, simple , and reach the same effects as the open decompression surgery.


Subject(s)
Tendon Entrapment , Decompression, Surgical , Humans , Tendons , Treatment Outcome
7.
Ann Oncol ; 26(5): 943-949, 2015 May.
Article in English | MEDLINE | ID: mdl-25632066

ABSTRACT

BACKGROUND: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. PATIENTS AND METHODS: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). RESULTS: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. CONCLUSIONS: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status. CLINICAL TRIALS NUMBER: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biliary Tract Neoplasms/drug therapy , Cetuximab/administration & dosage , Deoxycytidine/analogs & derivatives , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biliary Tract Neoplasms/genetics , Biliary Tract Neoplasms/mortality , Biliary Tract Neoplasms/pathology , Cetuximab/adverse effects , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Disease Progression , Disease-Free Survival , Drug Administration Schedule , Female , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Phenotype , Proportional Hazards Models , Taiwan , Time Factors , Treatment Outcome
9.
Genet Mol Res ; 13(4): 9187-95, 2014 Nov 07.
Article in English | MEDLINE | ID: mdl-25501140

ABSTRACT

An association between the sequence variants of cytokine genes and various clinical outcomes in subjects infected with the hepatitis B virus (HBV) has been demonstrated. However, the results are inconsistent and inconclusive. Further studies in other populations and the evaluation of a greater number of individuals may contribute to a better understanding of the influence of the cytokine genetic variants on the evolution of HBV infections. This study was performed to explore the relationships between the sequence variants of TNF-A-308, IFNAR1-17470, and IL-10-592 and the susceptibility to chronic hepatitis B (CHB) in a Chinese population. A total of 160 patients with CHB and 124 individuals who had spontaneously recovered (SR) from hepatitis B were enrolled in the present study. The variants at TNF-A-308, IFNAR1-17470, and IL-10-592 were determined by PCR-restriction fragment length polymorphism analysis and were confirmed by bidirectional DNA sequencing. Significant differences were found between the CHB and the SR groups in the frequency and distribution of the genotypes of both IFNAR1-17470 and IL-10-592 genes. In comparison with the CHB patients with the IFNAR1-17470 G/G variant, the odds ratio (OR) of the CHB patients with the IFNAR1-17470 C/C variant developing chronic hepatitis was 2.06 (95%CI = 1.03-4.14). In addition, the OR of the patients with CHB having the IL-10-592 C/C variant developing chronic hepatitis was 2.77 (95%CI = 1.13-4.57) when compared with that of the patients with the IL-10-592 A/A variant. In conclusion, sequence variants of both the IFNAR1-17470 and IL-10-592 genes were correlated with susceptibility to CHB.


Subject(s)
Asian People/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Hepatitis B, Chronic/genetics , Interleukin-10/genetics , Receptor, Interferon alpha-beta/genetics , Adult , Alleles , Case-Control Studies , China , Demography , Female , Gene Frequency/genetics , Humans , Male , Polymorphism, Restriction Fragment Length , Risk Factors , Tumor Necrosis Factor-alpha/genetics
11.
Eur Rev Med Pharmacol Sci ; 27(15): 6996-7004, 2023 08.
Article in English | MEDLINE | ID: mdl-37606108

ABSTRACT

OBJECTIVE: This review examined the association between red cell distribution width (RDW) and mortality after hip fracture. MATERIALS AND METHODS: PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched up to 10th January 2023 for studies comparing mortality after hip fracture based on RDW. All cut-offs of RDW were accepted. Crude and adjusted mortality ratios were pooled separately. RESULTS: Nine studies with 5,274 patients were eligible. Meta-analysis of eight studies reporting crude mortality rates showed that patients with high RDW had a significantly higher risk of mortality than those with low RDW (RR: 2.81 95% CI: 2.05, 3.86 I2=82%). The results did not change in significance on subgroup analyses based on study location, sample size, the cut-off of RDW, and follow-up. Four studies reported adjusted mortality rates. Analysis of the same showed that high RDW was an independent predictor of mortality in hip fracture patients (HR: 3.14 95% CI: 1.38, 7.14 I2=95%). CONCLUSIONS: Within the limitations of the review, RDW was found to be an indicator of mortality in hip fracture patients. High RDW was significantly associated with increased mortality despite different cut-offs among studies. Further research is needed to generate more rigorous evidence.


Subject(s)
Erythrocyte Indices , Hip Fractures , Humans
12.
Gene Ther ; 19(8): 844-51, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21918552

ABSTRACT

Antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. Baculovirus is an emerging gene delivery vector but only mediates transient expression (<7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. We first constructed plasmids featuring adeno-associated virus inverted terminal repeats (AAV ITRs), oriP/Epstein-Barr virus-expressed nuclear antigen 1 (EBNA1) or Sleeping Beauty (SB) transposon and compared their efficacies in terms of persistent expression. In human embryonic kidney (HEK293) cells, AAV ITR failed to prolong the expression while oriP/EBNA1 moderately extended the expression to 35 days. In contrast, the SB system led to stable expression beyond 77 days even without antibiotic selection. Given this finding, we constructed a hybrid SB baculovirus expressing the SB transposase and harboring the transgene cassette flanked by inverted repeat/direct-repeat (IR/DR) elements recognizable by SB. The hybrid SB baculovirus efficiently transduced mammalian cells and mediated an expression duration longer than that by conventional baculoviruses, thanks to the transgene persistence and integration. The SB baculovirus (Bac-SB-T2hEA/w) expressing the antiangiogenic fusion protein comprising endostatin and angiostatin (hEA) also enabled prolonged hEA expression. With sustained hEA expression, Bac-SB-T2hEA/w repressed the angiogenesis in vivo, hindered the growth of two different tumors (prostate tumor allografts and human ovarian tumor xenografts) in mice and extended the life span of animals. These data altogether implicated the potential of the hybrid SB-baculovirus vector for prolonged hEA expression and for the treatment of multiple types of angiogenesis-dependent tumors.


Subject(s)
Baculoviridae/genetics , Genetic Therapy , Genetic Vectors , Animals , Dependovirus/genetics , Female , Gene Expression , HEK293 Cells , Humans , Male , Mice , Ovarian Neoplasms/therapy , Prostatic Neoplasms/therapy , Recombination, Genetic , Terminal Repeat Sequences , Transduction, Genetic , Transgenes , Transposases/genetics , Xenograft Model Antitumor Assays
13.
J Viral Hepat ; 19(2): 138-46, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22239503

ABSTRACT

Earlier studies addressing the hepatitis B virus (HBV) DNA cut-off level for inactive chronic HBV infection largely involved patients with normal alanine aminotransferase (ALT) for only 1-2 years and based on a single time HBV DNA assay. This study was conducted to address this issue using serial HBV DNA assays in patients with persistently normal ALT (PNALT) over 10 years following spontaneous hepatitis B e antigen (HBeAg) seroconversion. Serial serum specimens (mean 9 samples per patient) of 62 patients with PNALT and no disease progression over 10 years (median 18.1 years) after spontaneous HBeAg seroconversion were assayed for HBV DNA. Excluding assays within 1 year after HBeAg seroconversion, 21% and 82.3% of the patients with PNALT had HBV DNA levels persistently lower than 4 log(10) and 5 log(10) copies/mL, respectively, and only 8% had a level ≥ 5 log(10) copies/mL in at least two assays. Of the 27 patients with PNALT defined by ALT <30 U/L for male and <19 U/L for female, only 33% had serum HBV DNA level persistently <4 log(10) copies/mL. There was no significant difference in the serial HBV DNA changes among patients with different gender, HBV genotype or age at HBeAg seroconversion. Liver biopsy in nine patients invariably showed minimal necroinflammation and one showed Ishak fibrosis score 4. These results suggest that 5 log(10) copies/mL (20,000 IU/mL) is a more appropriate cut-off HBV DNA level for inactive chronic HBV infection in the setting of PNALT.


Subject(s)
DNA, Viral/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/virology , Transaminases/blood , Adolescent , Adult , Biopsy , Female , Histocytochemistry , Humans , Liver/pathology , Longitudinal Studies , Male , Middle Aged , Young Adult
14.
Oral Dis ; 18(8): 809-15, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22747969

ABSTRACT

OBJECTIVE: The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. MATERIALS AND METHODS: The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests. RESULTS: Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. CONCLUSIONS: There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.


Subject(s)
Alphapapillomavirus/physiology , Carcinoma, Squamous Cell/virology , Mouth Neoplasms/virology , Neoplasms, Second Primary/virology , Papillomavirus Infections/virology , Adult , Aged , Aged, 80 and over , Alcohol Drinking , Alphapapillomavirus/classification , Areca , Disease Susceptibility , Disease-Free Survival , Female , Follow-Up Studies , Human papillomavirus 16/physiology , Human papillomavirus 18/physiology , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Retrospective Studies , Smoking , Survival Rate , Treatment Outcome
15.
Int J Oral Maxillofac Surg ; 51(6): 724-731, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34535350

ABSTRACT

Midline and paramedian mandibulotomies both have distinct anatomical and surgical strengths. A retrospective study was performed at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2019 to investigate how the osteotomy site (midline (n = 221) or paramedian (n = 44)) and type (straight, notched, or stair-stepped) affect postoperative and post-radiotherapy complications in patients undergoing wide excision of tongue cancer with flap reconstruction. Midline mandibulotomies were predominantly of the straight osteotomy type, while paramedian mandibulotomies were mostly notched type (P < 0.001). Comparably low elective tooth extraction rates were found in both approaches (P = 0.556). Paramedian mandibulotomy showed a higher osteoradionecrosis rate (P = 0.026), but there was no significance in the sub-analysis of individual types. Paramedian sites were associated with more early infection (P = 0.036) and plate exposure (P = 0.036) than midline sites with the straight osteotomy type, but complication rates did not differ significantly for the notched and stair-stepped types. Paramedian sites (P = 0.020) and notched types (P = 0.006) were associated with higher odds of osteoradionecrosis in the univariable logistic regression analysis, but only the notched type remained significant in the multivariable analysis (P = 0.048). In conclusion, paramedian sites increased the rate of osteoradionecrosis, and correlation with the osteotomy type resulted in more osteoradionecrosis in notched types and more complications in straight paramedian mandibulotomies.


Subject(s)
Osteoradionecrosis , Tongue Neoplasms , Humans , Mandible/surgery , Mandibular Osteotomy , Osteoradionecrosis/surgery , Postoperative Complications , Retrospective Studies , Tongue Neoplasms/surgery
16.
Eur Respir J ; 37(2): 376-83, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20516049

ABSTRACT

Sputum smears and culture conversion are frequently used to evaluate treatment response in pulmonary tuberculosis patients. Limited data are available on the evaluation of the correlation between under-treatment sputum smear results and culture conversion. This prospective study included sputum culture-proven pulmonary tuberculosis patients at six hospitals in Taiwan. At least two sets of sputum were collected at the completion of 8 weeks of TB treatment. The sensitivities and specificities of 2-month sputum smears were estimated based on culture conversion status. A total of 371 patients were enrolled for analysis. Factors associated with culture conversion included having a smear positive before treatment, presence of a cavity on radiography, rifampicin resistance and usage of the DOTS (directly observed therapy, short course) strategy. The sensitivities of 2-month sputum smears for culture conversion among all patients, initially smear-positive patients and initially smear-negative patients were 64.3, 71.4 and 38%, respectively, and the specificities were 81.6, 69.9 and 92.8%, respectively. In patients who were 2-month sputum smear-positive, the 2-month culture conversion rate was 80% if the patients were under DOTS and without cavitary lesions in radiograms. The predictive value of 2-month sputum smears in culture conversion was limited and highly influenced by clinical factors in pulmonary tuberculosis patients.


Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Adult , Aged , Aged, 80 and over , Ethambutol/therapeutic use , Female , Humans , Isoniazid/therapeutic use , Male , Middle Aged , Mycobacterium tuberculosis/drug effects , Pyrazinamide/therapeutic use , Radiography , Rifampin/therapeutic use , Sensitivity and Specificity , Treatment Outcome , Tuberculosis, Pulmonary/diagnostic imaging
17.
Clin Otolaryngol ; 36(2): 147-53, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21332670

ABSTRACT

OBJECTIVES: Previous studies have demonstrated a relationship between elevated serum C-reactive protein (CRP) levels and shorter survival in cancer patients. Few studies, however, have investigated the role of serum CRP levels in oral squamous cell carcinoma. The present study was conducted to analyze the relationship between preoperative CRP levels, clinicopathologic factors, and prognosis in oral squamous cell carcinoma patients. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PARTICIPANTS: Eighteen oral cavity leukoplakia and 59 oral squamous cell carcinoma patients between November 2006 and November 2009 from the Chang Gung Memorial Hospital. OUTCOME MEASURES: Clinicopathologic parameters, disease-free survival and overall survival were correlated with CRP levels. METHODS: Serum CRP levels were measured preoperatively, and all oral cavity cancer patients underwent curative intent radical surgery with or without postoperative adjuvant therapy. RESULTS: The CRP levels in leukoplakia patients were used to analyze if factors (including diabetes and liver cirrhosis, smoking, alcohol drinking and areca quid chewing) influence CRP levels, and the results demonstrated they were not associated with CRP elevation (> 5.0 mg/L) (P > 0.05). In oral cancer patients, elevated CRP levels were associated with tumor status (P = 0.005), tumor stage (P = 0.054), bone invasion (P = 0.033), lymph node metastasis (P = 0.004) and lymph node extra-capsular spread (P = 0.018). Patients with higher CRP levels showed poorer disease-free survival (log rank test, P < 0.001) and overall survival (log rank test, P = 0.013). CONCLUSIONS: Preoperative serum CRP levels are associated with advanced tumor stage, bone invasion, lymph node metastasis, lymph node extra-capsular spread and patients' survival. CRP is thus potentially a prognostic indicator, but studies with longer follow-up will be needed to confirm its reliability.


Subject(s)
Biomarkers, Tumor/analysis , C-Reactive Protein/analysis , Carcinoma, Squamous Cell/pathology , Leukoplakia, Oral/pathology , Mouth Neoplasms/pathology , Precancerous Conditions/pathology , Adult , Aged , Areca/adverse effects , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Female , Humans , Leukoplakia, Oral/mortality , Leukoplakia, Oral/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Mouth Neoplasms/mortality , Mouth Neoplasms/surgery , Neck Dissection , Neoplasm Staging , Precancerous Conditions/mortality , Precancerous Conditions/surgery , Prognosis , Retrospective Studies , Statistics as Topic , Survival Analysis , Taiwan , Tomography, X-Ray Computed
18.
Acta Radiol ; 49(9): 991-4, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18651255

ABSTRACT

BACKGROUND: Target therapy with a new class of epidermal growth factor receptor (EGFR) inhibitors shows improved clinical response in EGFR gene-mutated lung cancers. PURPOSE: To evaluate the use of computed tomography (CT)-guided core-needle biopsy specimens for the assessment of EGFR gene mutation in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: Seventeen (nine males, eight females) patients with advanced NSCLC were enrolled in this study. All patients underwent CT-guided core-needle biopsy of the lung tumor prior to treatment with the EGFR inhibitor gefitinib. There were no life-threatening complications of biopsy. The specimens were sent fresh-frozen for EGFR mutation analysis and histopathological study. RESULTS: There were 12 (70.6%) EGFR gene mutants and five (29.4%) nonmutants. The objective response rate to gefitinib therapy was 73.3% (11 of 15 patients), with 91.7% (11 of 12 mutants) for the mutant group and 0% for the nonmutant group. CONCLUSION: CT-guided core-needle biopsy of advanced NSCLC enables the acquisition of sufficient tissue for EGFR gene mutation analysis.


Subject(s)
Biopsy, Needle/methods , Carcinoma, Non-Small-Cell Lung/genetics , Genes, erbB-1/genetics , Lung Neoplasms/genetics , Tomography, X-Ray Computed , Adult , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , ErbB Receptors/antagonists & inhibitors , Female , Gefitinib , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Quinazolines/therapeutic use
19.
Oncogene ; 25(8): 1205-15, 2006 Feb 23.
Article in English | MEDLINE | ID: mdl-16205628

ABSTRACT

Mutations in the kinase domain of epidermal growth factor receptor (EGFR) are associated with clinical responsiveness to gefitinib in patients with non-small-cell lung cancers (NSCLC). Recently, we have identified many novel EGFR mutations in NSCLC tissues. In this study, we found that gefitinib could suppress the tyrosine phosphorylation of most EGFR mutants better than the wild-type receptor. However, gefitinib had quite variable growth-suppressive effects on different EGFR mutant-expressing cells. All tested EGFR mutants have high basal phosphorylation at multiple tyrosine residues. Upon EGF stimulation, the mutated EGFRs did not have apparently stronger phosphorylation at tyrosines 845, 992, 1,068, and 1,173 than the wild-type receptor. However, stronger phosphorylation at tyrosine 1,045 was observed in the S768I, L861Q, E709G, and G719S mutants. The E746-A750 deletion mutant was less responsive to EGF than the wild-type and other mutant receptors. The S768I, L861Q, E709G, and G719S mutants were refractory to EGF-induced ubiquitination and had more sustained tyrosine phosphorylation. E709G and G719S also lacked EGF-induced receptor downregulation. Our results indicate that, in addition to sensitivity to gefitinib, EGFR mutations also caused various changes in EGFR's regulatory mechanisms, which may contribute to the constitutive activation of EGFR mutants and oncogenesis in NSCLC.


Subject(s)
Antineoplastic Agents/therapeutic use , ErbB Receptors/genetics , Mutation/genetics , Quinazolines/therapeutic use , Animals , COS Cells , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Chlorocebus aethiops , Epidermal Growth Factor/pharmacology , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Gefitinib , Immunoprecipitation , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Phosphorylation/drug effects , Tumor Cells, Cultured , Tyrosine/metabolism , Ubiquitin/metabolism
20.
Oncogene ; 36(47): 6542-6554, 2017 11 23.
Article in English | MEDLINE | ID: mdl-28759046

ABSTRACT

Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers. Our data further reveal a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower trimethylation of histone H3 lysine 27 suppressive modification, relaxes chromatin, and promotes the accessibility of the transcription factor STAT1 to the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions. Down-regulation of ROS1 in highly invasive OSCC cells, nevertheless, reduces cell proliferation and inhibits metastasis to lung in the tail-vein injection and the oral cavity xenograft models. Our findings highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Finally, we demonstrate that co-targeting of ROS1 and EGFR could potentially offer an effective oral cancer therapy.


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Enhancer of Zeste Homolog 2 Protein/metabolism , Gene Expression Regulation, Neoplastic , Lung Neoplasms/secondary , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Animals , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/drug therapy , Cell Line, Tumor , Cell Proliferation , Chemokine CXCL1/metabolism , Down-Regulation , ErbB Receptors/antagonists & inhibitors , Histones/metabolism , Humans , Male , Methylation , Mice , Molecular Targeted Therapy/methods , Mouth Neoplasms/drug therapy , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , STAT1 Transcription Factor/metabolism , Up-Regulation , Xenograft Model Antitumor Assays , Zinc Finger Protein GLI1/metabolism
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