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1.
Malays J Pathol ; 45(3): 405-416, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38155382

ABSTRACT

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis and cytopenia. Studies have reported differences in MDS between Asian and Western countries, but data from Taiwan are scarce. MATERIALS AND METHODS: In this study we analysed the clinical and pathological features of 32 Taiwanese MDS patients with del(5q) (ie, del(5q) alone [Group A, n = 11], del(5q) with one additional cytogenetic abnormality other than monosomy 7 or del(7q) [Group B, del(5q)+1; n = 6], and del(5q) with ≥2 additional cytogenetic abnormalities [Group C, n = 15]). RESULTS: Progression-free survival (PFS) and overall survival (OS) were more favourable for Group A than for Groups B (p < 0.05) and C (p ≤ 0.001). Multivariate analysis showed that age >70 years, thrombocytopenia, and karyotype other than del(5q) alone were poor prognostic factors. Among the patients that had World Health Organization (WHO)-defined MDS with isolated del(5q), one patient (9%) had a typical marrow morphology of 5q minus syndrome with erythroid hypoplasia and four patients (36%) had hypolobated megakaryocytes. In addition, PFS and OS were significantly more favorable for the patients with del(5q) alone than for those with del(5q)+1 (p < 0.05). CONCLUSION: The bone marrow morphology, clinical features, and prognosis of Taiwanese MDS patients with del(5q) were different from those associated with MDS with isolated del(5q) as defined in the current WHO classification. Researchers should compare different geographic regions and racial populations to determine whether geographic and racial differences exist with respect to MDS with del(5q).


Subject(s)
Myelodysplastic Syndromes , Humans , Aged , Taiwan , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/pathology , Chromosome Deletion , Bone Marrow , Karyotyping
3.
Neuromuscul Disord ; 33(6): 531-538, 2023 06.
Article in English | MEDLINE | ID: mdl-37290230

ABSTRACT

It is unclear how improvements in peripheral motor function in children with spinal muscular atrophy (SMA), treated with nusinersen, translate into clinically significant respiratory/sleep outcomes. A retrospective chart review of SMA children at the Sydney Children's Hospital Network was undertaken looking at 2 years before and after receiving their first dose of nusinersen. Polysomnography (PSG), spirometry and clinical data were collected and analysed using paired and unpaired t-tests for PSG parameters and generalised estimating equations for longitudinal lung function data. Forty-eight children (10 Type 1, 23 Type 2, 15 Type 3) at mean age 6.98 yrs (SD 5.25) for nusinersen initiation were included. There was a statistically significant improvement in oxygen nadir during sleep in individuals post nusinersen (mean of 87.9% to 92.3% (95%CI 1.24 - 7.63, p = 0.01)). Based on clinical and PSG findings, 6/21 patients (5 Type 2, 1 Type 3) ceased nocturnal NIV post nusinersen. Non-significant improvements were demonstrated in mean slope for FVC% predicted, FVC Z-score and mean FVC% predicted. Within 2 years of commencing nusinersen, stabilisation of respiratory outcomes occurred. Whilst some of the SMA type 2/3 cohort ceased NIV, there were no statistically significant improvements lung function and most PSG parameters.


Subject(s)
Muscular Atrophy, Spinal , Spinal Muscular Atrophies of Childhood , Humans , Child , Retrospective Studies , Muscular Atrophy, Spinal/drug therapy , Oligonucleotides/therapeutic use , Spinal Muscular Atrophies of Childhood/complications , Spinal Muscular Atrophies of Childhood/drug therapy , Sleep
4.
Malays J Pathol ; 44(1): 61-66, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35484887

ABSTRACT

Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour affecting mainly elderly patients and is more common in the West than in Asia. It is associated with Merkel cell polyomavirus (MCPyV), immunosuppression, and ultraviolet light. In this study, we retrospectively investigated the first series of MCC from Taiwan and identified 19 cases from three tertiary centres. All patients were males with a median age of 67.5. Twelve (63%) cases occurred in the extremities, with one unique case presenting initially as nodal metastasis of unknown primary. Immunohistochemically, the great majority of tumours expressed CK20 (89%), synaptophysin (89%), and INSM1 (84%), with none positive for TTF1. Eleven (58%) cases were positive for MCPyV by immunohistochemistry (clone CM2B4). All patients were treated with excision, including four with additional radiotherapy and one with radiotherapy and chemotherapy. Nodal status and treatment modalities significantly affected survival. The median survival time of MCPyV-positive cases was much longer than the negative cases (median 40 vs. 10 months). In summary, we presented the first report on the clinicopathological features of MCC in Taiwan, with 58% cases associated with MCPyV. The prognosis of patients with MCPyV-positive tumours was better than those negative for MCPyV.


Subject(s)
Carcinoma, Merkel Cell , Merkel cell polyomavirus , Polyomavirus Infections , Skin Neoplasms , Aged , Carcinoma, Merkel Cell/pathology , Female , Humans , Male , Polyomavirus Infections/complications , Polyomavirus Infections/pathology , Prognosis , Repressor Proteins , Retrospective Studies , Skin Neoplasms/pathology , Taiwan
5.
Diabetes Metab ; 47(3): 101184, 2021 05.
Article in English | MEDLINE | ID: mdl-32827752

ABSTRACT

AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase (DPP)-4 inhibitors added to insulin regimens in patients with type 2 diabetes mellitus (T2DM) can improve glycaemic control. This study compared the efficacy and safety of empagliflozin and linagliptin added to premixed insulin therapy in patients with poorly controlled T2DM. METHODS: In this 24-week, open-label, parallel-design randomized controlled trial, patients with poorly controlled T2DM despite a premixed insulin regimen were randomized to receive 5mg of linagliptin (n=53) or 25mg of empagliflozin (n=53) for 24 weeks. RESULTS: At week 24, changes in glycated haemoglobin (HbA1c) from baseline were -0.06±0.17% and -1.01±0.16% in the linagliptin and empagliflozin groups, respectively, and the mean treatment HbA1c difference was -0.88% (95% CI: -1.33, -0.43). At week 24, the empagliflozin group showed significant reductions, compared with the linagliptin group, in fasting plasma glucose (P<0.001), body weight (P<0.001), systolic blood pressure (P=0.003) and total daily insulin dose (P=0.042). Hypoglycaemia was reported to be slightly, and not significantly, higher in the empagliflozin group vs linagliptin group (30.2% vs 22.6%, respectively; P=0.51). Similar percentages of patients (1.9%) had urinary tract infections in the two groups. CONCLUSION: In Asian patients with inadequately controlled T2DM while taking premixed insulin, the addition of empagliflozin for 24 weeks provided better glycaemic control and greater reductions in body weight and systolic blood pressure than the addition of linagliptin. Clinical Trial Registration #: NCT03458715.


Subject(s)
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucosides , Insulin , Linagliptin , Benzhydryl Compounds/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Drug Therapy, Combination/adverse effects , Glucosides/adverse effects , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Linagliptin/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Treatment Outcome
6.
Diabet Med ; 38(5): e14436, 2021 05.
Article in English | MEDLINE | ID: mdl-33095935

ABSTRACT

AIMS: Microalbuminuria is an indicator of adverse cardiovascular events and chronic kidney disease. Studies have described an elevated resting heart rate as a risk factor for microalbuminuria in people with cardiovascular disease, but none have clarified its role in microalbuminuria development in people with type 2 diabetes. Therefore, this study investigated the relationship between resting heart rate and new-onset microalbuminuria in type 2 diabetes. METHODS: A total of 788 people from a glycaemic control trial in Taiwan were enrolled. Microalbuminuria was defined as a fasting urine albumin-to-creatinine ratio ≥30 mg/g in two consecutive urine tests. Resting heart rate and other covariates were measured at baseline. The quartile of resting heart rates, categorized as <70, 70-74, 75-80 and >80 beats/min, was used for analysis. Cox proportional hazard models were used to evaluate the association between resting heart rate and risk of microalbuminuria. RESULTS: During the follow-up period, 244 people (31%) developed microalbuminuria. Those who developed microalbuminuria had a longer diabetes duration (median = 3.0 vs. 2.0 years, p < 0.001), higher rate of hypertension (77% vs. 66%, p = 0.003), higher rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment (50% vs. 38%, p = 0.001) and higher baseline HbA1c level (70 vs. 64 mmol/mol, 8.6 vs. 8.0%, p < 0.001). After adjusting for demographics, metabolic profiles and inflammatory markers, developing microalbuminuria was significantly associated with baseline resting heart rate of 70-74, 75-80 and >80 beats/min (with hazard ratios [95% CI] of 2.05 [1.32, 3.18], 2.10 [1.32, 3.32] and 1.62 [1.01, 2.59], respectively) compared to resting heart rates <70 beats/min. An average increased risk of microalbuminuria for increment of 10 beats/min was about 24% among those with hypertension (with hazard ratios of 1.24 [1.05, 1.47] in the multivariable Cox model). CONCLUSIONS: This prospective cohort study showed that resting heart rate may be an associative risk factor for developing microalbuminuria in type 2 diabetes.


Subject(s)
Albuminuria/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/physiopathology , Adult , Aged , Albuminuria/epidemiology , Albuminuria/etiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/etiology , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Female , Follow-Up Studies , Heart Rate , Humans , Hypertension/complications , Hypertension/epidemiology , Hypertension/physiopathology , Male , Middle Aged , Randomized Controlled Trials as Topic , Risk Factors , Taiwan/epidemiology
7.
Malays J Pathol ; 42(2): 237-243, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32860376

ABSTRACT

INTRODUCTION: Follicular lymphoma (FL) is usually a nodal lymphoma expressing CD10, rarely with leukaemic presentation (FL-LP). MATERIALS AND METHODS: We searched for FL-LP in our institution from 2000 to 2018 and characterised the neoplastic cells by flow cytometry, immunohistochemistry and fluorescence in situ hybridization. Thirteen (6.1%) of 212 FL cases were FL-LP, all de novo neoplasms. The leukaemic cells were small in 12 cases and large in one. All had concurrent FL, mostly (92%; 12/13) low-grade. The single case with large leukaemic cells had a concurrent primary splenic low-grade FL and a double-hit large B-cell lymphoma in the marrow. RESULTS: CD10 was expressed in the leukaemic cells in 38% (5/13) cases by flow cytometry and in 77% (10/13) cases in tumours (p= 0.0471). IGH/BCL2 reciprocal translocation was identified in 85% (11/13) cases. Most patients were treated with chemotherapy. In a median follow-up time of 36 months, nine patients were in complete remission. The 2- and 5-year survival rates were at 100% and 83%, respectively. In this study, we characterised a series of de novo FL-LP in Taiwan. All patients had concurrent nodal and/or tissue tumours, which might suggest that these patients seek medical help too late. CONCLUSION: The lower CD10 expression rate by flow cytometry than by immunohistochemistry might be due to different epitopes for these assays. Alternatively, loss of CD10 expression might play a role in the pathogenesis of leukaemic change. The clinical course of FL-LP could be aggressive, but a significant proportion of the patients obtained complete remission with chemotherapy.


Subject(s)
Leukemia, B-Cell , Lymphoma, Follicular , Neprilysin/metabolism , Adult , Aged , Female , Flow Cytometry , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Leukemia, B-Cell/metabolism , Leukemia, B-Cell/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Lymphoma, Follicular/metabolism , Lymphoma, Follicular/pathology , Male , Middle Aged , Prognosis , Survival Rate
8.
Vet J ; 257: 105449, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32546356

ABSTRACT

Infection with bovine leukaemia virus (BLV), a retrovirus, causes dysfunction of the immune system and can have a marked economic impact on dairy industries due to decreased milk production and reduced lifespan in affected dairy cattle. The presence of proviral DNA has been the major diagnostic indicator of BLV infection. However in the course of BLV infection, the viral genome can be dormant, without detectable gene expression, resulting in limited impact on infected animals. At present, there is limited knowledge regarding haematological indices in dairy cattle that could indicate activation of the BLV genome and suggest reactivated BLV infection. In this study, BLV infection and BLV genome reactivation were evaluated based on the presence of BLV DNA and BLV env gene transcripts, respectively. BLV RNA transcription was confirmed. Among 93 whole blood samples obtained from asymptomatic dairy cattle, the prevalence of BLV proviral DNA and transcripts was 93.5% (n = 87/93) and 83.9% (n = 78/93), respectively. Between groups with and without BLV, the mean counts of white blood cells and lymphocytes in whole blood were significantly associated with the presence of BLV RNA (P < 0.05), but not with BLV proviral DNA. These results shed light on the activation status of the BLV genome and should be taken into account when evaluating the possible impact of BLV on cattle.


Subject(s)
Enzootic Bovine Leukosis/epidemiology , Leukemia Virus, Bovine/physiology , Leukocyte Count/veterinary , RNA, Viral/analysis , Reinfection/veterinary , Animals , Cattle , Dairying , Enzootic Bovine Leukosis/virology , Female , Reinfection/epidemiology , Reinfection/virology , Viral Load/veterinary
9.
Nutr Metab Cardiovasc Dis ; 29(4): 390-397, 2019 04.
Article in English | MEDLINE | ID: mdl-30782508

ABSTRACT

BACKGROUND AND AIMS: This study examined the association between macronutrient intake at different times of the day and blood lipid levels. METHODS AND RESULTS: The study was based on the Nutrition and Health Survey in Taiwan, a cross-sectional study of non-institutionalized and non-pregnant healthy adults (≥19-years-old). A one-day (24 h) dietary recall assessed participants' food intake. Fasting plasma triglycerides, total cholesterol, and high-density lipoprotein (HDL) cholesterol were determined. Low-density lipoprotein (LDL) cholesterol was estimated based on the Friedewald formula. According to the data of eligible subjects (n = 1283), the time of energy intake was categorized into three meal times 0500-0929 (morning), 1130-1329 (noon), and 1730-2029 (evening), along with three snack times 0930-1129 (mid-morning), 1330-1729 (afternoon), and 2030-0459 (night). Energy and macronutrient intake were calculated for the 6 time periods, based on 24 h recall data. An adjusted regression model showed that by transferring 100 kcal intake at night to the morning or noon, LDL cholesterol would be lower by 1.46 (95% CI: 2.42-0.50) and 1.27 mg/dL (95% CI: 2.24-0.30), respectively. Transferring 100 kcal of fat intake at night to earlier periods was associated with a lower LDL cholesterol level, especially transferring to noontime (significantly lower by 5.21 mg/dL, 95% CI: [7.42-2.99]) and evening (significantly lower by 3.19 mg/dL, 95% CI: [6.29-0.08]). CONCLUSIONS: Total cholesterol and LDL cholesterol had the same pattern of association with the timing of energy intake. The study showed that elevated total and LDL cholesterol were positively associated with nighttime energy and fat intake.


Subject(s)
Cholesterol, LDL/blood , Cholesterol/blood , Energy Intake , Energy Metabolism , Feeding Behavior , Meals , Adult , Aged , Biomarkers/blood , Cross-Sectional Studies , Humans , Middle Aged , Nutrition Surveys , Taiwan , Time Factors , Young Adult
10.
Ann Oncol ; 29(1): 256-263, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29077846

ABSTRACT

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Extranodal NK-T-Cell/drug therapy , Lymphoma, Extranodal NK-T-Cell/radiotherapy , Adolescent , Adult , Aged, 80 and over , Chemoradiotherapy , Cohort Studies , Drug Administration Schedule , Female , Humans , Lymphoma, Extranodal NK-T-Cell/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Young Adult
11.
Sci Rep ; 7(1): 12652, 2017 10 04.
Article in English | MEDLINE | ID: mdl-28978911

ABSTRACT

The mortality prediction models for the general diabetic population have been well established, but the corresponding elderly-specific model is still lacking. This study aims to develop a mortality prediction model for the elderly with diabetes. The data used for model establishment were derived from the nationwide adult health screening program in Taiwan in 2007-2010, from which we applied a 10-fold cross-validation method for model construction and internal validation. The external validation was tested on the MJ health screening database collected in 2004-2007. Multivariable Cox proportional hazards models were used to predict five-year mortality for diabetic patients ≥65 years. A total of 220,832 older subjects with diabetes were selected for model construction, of whom 23,241 (10.5%) died by the end of follow-up (December 31, 2011). The significant predictors retained in the final model included age, gender, smoking status, body mass index (BMI), fasting glucose, systolic and diastolic blood pressure, leukocyte count, liver and renal function, total cholesterol, hemoglobin, albumin, and uric acid. The Harrell's C in the development, internal-, and external-validation datasets were 0.737, 0.746, and 0.685, respectively. We established an easy-to-use point-based model that could accurately predict five-year mortality risk in older adults with diabetes.


Subject(s)
Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/mortality , Liver/metabolism , Models, Cardiovascular , Aged , Blood Pressure , Body Mass Index , Cardiovascular Diseases/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Fasting , Female , Humans , Liver/physiopathology , Male , Middle Aged , Proportional Hazards Models , Risk Assessment , Risk Factors , Smoking/adverse effects , Taiwan/epidemiology , Uric Acid/metabolism
12.
Clin Genet ; 92(4): 397-404, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28170089

ABSTRACT

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing. RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene. DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.


Subject(s)
Epilepsies, Partial/genetics , Genetic Predisposition to Disease , Repressor Proteins/genetics , TOR Serine-Threonine Kinases/genetics , Adolescent , Child , Child, Preschool , Epilepsies, Partial/pathology , Female , GTPase-Activating Proteins , Humans , Male , Mechanistic Target of Rapamycin Complex 1/genetics , Mutation , Pedigree , RNA Splicing/genetics , Exome Sequencing
13.
Int J Oral Maxillofac Surg ; 46(3): 363-372, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27600798

ABSTRACT

The extraction of an impacted third molar violates the surrounding soft and bony tissues. The surgeon's access to the tooth, for which there are various surgical approaches, has an important impact on the periodontium of the adjacent second molar. The aim of this review was to analyze the relationships between the different flap techniques and postoperative periodontal outcomes for the mandibular second molars (LM2) adjacent to the impacted mandibular third molars (LM3). An electronic search of MEDLINE and other databases was conducted to identify randomized controlled trials fulfilling the eligibility criteria. To assess the impact of flap design on the periodontal condition, the weighted mean difference of the probing depth reduction (WDPDR) and the weighted mean difference of the clinical attachment level gain (WDCAG) at the distal surface of LM2 were used as the primary outcomes. The results showed that, overall, the different flap techniques had no significant impact on the probing depth reduction (WDPDR -0.14mm, 95% confidence interval -0.44 to 0.17), or on the clinical attachment level gain (WDCAG 0.05mm, 95% confidence interval -0.84 to 0.94). However, a subgroup analysis revealed that the Szmyd and paramarginal flap designs may be the most effective in reducing the probing depth in impacted LM3 extraction, and the envelope flap may be the least effective.


Subject(s)
Molar, Third/surgery , Surgical Flaps , Tooth Extraction , Tooth, Impacted/surgery , Wound Healing , Humans , Periodontal Attachment Loss , Periodontal Index , Periodontal Pocket , Postoperative Complications
14.
Niger J Clin Pract ; 19(2): 301-2, 2016.
Article in English | MEDLINE | ID: mdl-26856300

ABSTRACT

Isolated traumatic gallbladder rupture subsequent to blunt abdominal injury is rare. Most literatures on the subjects consist of case reports. We reported a rare case of isolated gallbladder rupture and discussed the possible predisposing factors to gallbladder rupture.


Subject(s)
Abdominal Injuries/complications , Gallbladder/injuries , Wounds, Nonpenetrating/complications , Abdominal Injuries/diagnostic imaging , Adult , Cholecystectomy , Gallbladder/diagnostic imaging , Gallbladder/surgery , Humans , Male , Rupture/etiology , Rupture/surgery , Tomography, X-Ray Computed , Treatment Outcome
15.
Leukemia ; 30(6): 1311-9, 2016 06.
Article in English | MEDLINE | ID: mdl-26854024

ABSTRACT

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.


Subject(s)
Enteropathy-Associated T-Cell Lymphoma/metabolism , Janus Kinases/metabolism , Receptors, G-Protein-Coupled/metabolism , STAT Transcription Factors/metabolism , Signal Transduction , Adult , Aged , Aged, 80 and over , Cell Survival/drug effects , Cells, Cultured , Enteropathy-Associated T-Cell Lymphoma/pathology , Female , GTP-Binding Protein alpha Subunit, Gi2/genetics , Gene Expression Profiling , Humans , Janus Kinase 3/genetics , Male , Middle Aged , Mutation , Protein Kinase Inhibitors/pharmacology , STAT5 Transcription Factor/genetics , Signal Transduction/drug effects , Young Adult
16.
Oncogene ; 35(17): 2156-65, 2016 04 28.
Article in English | MEDLINE | ID: mdl-26257061

ABSTRACT

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour. The neoplasms are difficult to resect entirely because of their highly infiltration property and leading to the tumour edge is unclear. Gliadel wafer has been used as an intracerebral drug delivery system to eliminate the residual tumour. However, because of its local low concentration and short diffusion distance, patient survival improves non-significantly. Axl is an essential regulator in cancer metastasis and patient survival. In this study, we developed a controlled-release polyanhydride polymer loading a novel small molecule, n-butylidenephthalide (BP), which is not only increasing local drug concentration and extending its diffusion distance but also reducing tumour invasion, mediated by reducing Axl expression. First, we determined that BP inhibited the expression of Axl in a dose- and time-dependent manner and reduced the migratory and invasive capabilities of GBM cells. In addition, BP downregulated matrix metalloproteinase activity, which is involved in cancer cell invasion. Furthermore, we demonstrated that BP regulated Axl via the extracellular signal-regulated kinases pathway. Epithelial-to-mesenchymal transition (EMT) is related to epithelial cells in the invasive migratory mesenchymal cells that underlie cancer progression; we demonstrated that BP reduced the expression of EMT-related genes. Furthermore, we used the overexpression of Axl in GBM cells to prove that Axl is a crucial target in the inhibition of GBM EMT, migration and invasion. In an in vivo study, we demonstrated that BP inhibited tumour growth and suppressed Axl expression in a dose-dependent manner according to a subcutaneous tumour model. Most importantly, in an intracranial tumour model with BP wafer in situ treatment, we demonstrated that the BP wafer not only significantly increased the survival rate but also decreased Axl expression, and inhibited tumour invasion. These results contribute to the development of a BP wafer for a novel therapeutic strategy for treating GBM invasion and increasing survival in clinical subjects.


Subject(s)
Glioblastoma/drug therapy , Glioblastoma/genetics , Phthalic Anhydrides/administration & dosage , Proto-Oncogene Proteins/biosynthesis , Receptor Protein-Tyrosine Kinases/biosynthesis , Animals , Cell Line, Tumor , Cell Movement/drug effects , Drug Delivery Systems , Epithelial-Mesenchymal Transition/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/pathology , Humans , Mice , Neoplasm Invasiveness/genetics , Neoplasm Metastasis , Phthalic Anhydrides/chemistry , Polymers/administration & dosage , Polymers/chemistry , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Xenograft Model Antitumor Assays , Axl Receptor Tyrosine Kinase
17.
Genet Mol Res ; 14(3): 11362-70, 2015 Sep 25.
Article in English | MEDLINE | ID: mdl-26436377

ABSTRACT

Recent studies have revealed that the inflammatory process plays a role in the pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced glycation end products (RAGE) participate in regulating inflammation, even in the production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1 have a marked effect on ligand binding and transcription regulating. In this study, we investigated the potential genetic contribution of the RAGE, S100A8, and MMP-1 genes to OA. We performed a matched case-control association study and genotyped OA patients and healthy controls, who were analyzed by polymerase chain reaction-restriction fragment length polymorphism assays. A total of 207 patients were diagnosed with knee OA and underwent total knee replacement. The control group included 207 individuals who had standard X-rays of the knee joints to confirm K/L < 2 and were matched by age and gender. Single-nucleotide polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8 rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant difference between OA patients and healthy controls. RAGE -429T/C and 557G/A showed a significant association between OA patients and healthy controls (P = 0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1 haplotypes showed associations with OA. Our results suggest that the investigated polymorphism in the RAGE gene play a role in OA in the Han Chinese population.


Subject(s)
Asian People/genetics , Ethnicity/genetics , Genetic Predisposition to Disease , Osteoarthritis, Knee/genetics , Polymorphism, Single Nucleotide/genetics , Receptor for Advanced Glycation End Products/genetics , Severity of Illness Index , Aged , Calgranulin A/genetics , Case-Control Studies , Female , Genetic Association Studies , Haplotypes/genetics , Humans , Male , Matrix Metalloproteinase 1/genetics
18.
Br J Cancer ; 113(1): 182-92, 2015 Jun 30.
Article in English | MEDLINE | ID: mdl-25989276

ABSTRACT

BACKGROUND: Evidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited. METHODS: We used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake. RESULTS: Intake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend <0.001) and to laryngeal cancer (OR=0.67, 95% CI: 0.54-0.83, P for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral/pharyngeal cancer. Inverse associations were generally observed for the anatomical subsites of oral and pharyngeal cancer and within covariate strata for both sites. CONCLUSION: Our findings suggest that greater vitamin E intake from foods may lower HNC risk, although we were not able to explain the heterogeneity observed across studies or rule out certain sources of bias.


Subject(s)
Head and Neck Neoplasms/epidemiology , Vitamin E/administration & dosage , Adult , Aged , Female , Humans , Male
19.
Int J Oral Maxillofac Surg ; 44(8): 1018-26, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25920597

ABSTRACT

The objective of this study was to undertake a systematic review to assess the efficacy of botulinum toxin therapy (BTX) for temporomandibular joint disorders (TMDs). A comprehensive search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was conducted to locate all relevant articles published from inception to October 2014. Eligible studies were selected based on inclusion criteria and included English language, peer-reviewed publications of randomized controlled trials comparing BTX versus any alternative intervention or placebo. Quality assessment and data extraction were done according to the Cochrane risk of bias tool and recommendations. The entire systematic search and selection process was done independently by two reviewers. Five relevant study trials were identified, involving 117 participants. Two trials revealed a significant between-group difference in myofascial pain reduction, another trial that compared BTX with fascial manipulation showed equal efficacy of pain relief on TMDs, while the remaining two trials showed no significant difference between the BTX and placebo groups. Because of considerable variations in study methods and evaluation of results, a meta-analysis could not be performed. Based on this review, no consensus could be reached on the therapeutic benefits of BTX on TMDs. A more rigorous design of trials should be carried out in future studies.


Subject(s)
Botulinum Toxins, Type A/therapeutic use , Myofascial Pain Syndromes/drug therapy , Neuromuscular Agents/therapeutic use , Temporomandibular Joint Disorders/drug therapy , Humans , Randomized Controlled Trials as Topic
20.
Int J Oral Maxillofac Surg ; 44(3): 395-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25480009

ABSTRACT

A retrospective cohort study was performed to evaluate the use of panoramic radiographs as a screening tool for low bone mass in postmenopausal women. Female subjects aged ≥50 years were included. The predictor variables were gonial angle, antegonial angle, mandibular cortical bone integrity, periodontal disease status, and number of remaining teeth. The primary outcome variable was bone mineral density status. Descriptive and logistic regression statistics were computed; P<0.05 was considered significant. The sample was composed of 273 subjects, aged 50-89 years. Visual assessment of mandibular cortical bone integrity demonstrated a statistically significant correlation with low bone mass diagnosis on univariate logistic regression (P=0.019), but lost significance on multivariate analysis with age, body mass index, and number of remaining teeth (P=0.6). A visual estimation of the mandibular cortical bone integrity from panoramic radiographs may be useful for identifying postmenopausal women at high risk for osteoporosis.


Subject(s)
Bone Density , Mandible/diagnostic imaging , Osteoporosis, Postmenopausal/diagnostic imaging , Radiography, Panoramic , Absorptiometry, Photon , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Retrospective Studies , Risk Assessment
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