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1.
J Formos Med Assoc ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32402521

RESUMO

BACKGROUND: Sorafenib has been shown to prolong the progression free survival (PFS) of advanced radioiodine (RAI) refractory differentiated thyroid cancer (DTC) and has been approved by the FDA as the result of the phase III DECISION trial. Sorafenib has been reimbursed for the treatment of RAI refractory DTC in Taiwan since Jan 2017. High percentage of adverse events (AE) was noted in DECISION trial. We conducted a study to show the real-world experience of sorafenib in Taiwan. METHODS: We retrospectively collected the clinical data, including dose, AE, and PFS of sorafenib, of the DTC patients who received sorafenib treatment in National Cheng Kung University Hospital and China Medical University Hospital by chart review from 2012 to 2018. RESULTS: Thirty-six advanced DTC patients with progression were included in this study. The starting dose of sorafenib in most patients was 200 mg twice daily and the mean daily maintenance dose was 433 mg. Five patients had partial response (13.9%) and 28 patients had stable disease (77.8%). The median PFS was 17.3 months (95% confidence interval: 11.9-33.6 months). Daily maintenance dose ≥ 600 mg was associated with better PFS (median PFS, not reached). The most common toxicity of sorafenib was hand foot skin reaction (69%), followed by diarrhea (42%), and skin rash (33%). Most of the toxicities were grade I/II. CONCLUSION: Higher maintenance dose of sorafenib is associated with longer PFS while starting from half dose is feasible to minimize the incidence of high grade toxicities in the real-world use of sorafenib.

2.
Eur J Dent Educ ; 24(1): 5-16, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31278815

RESUMO

INTRODUCTION: Virtual reality-based platforms are becoming increasingly popular in education. The aim of this study was to evaluate the performance of undergraduate dental students with the introduction of the Moog Simodont dental trainer (VR) within the pre-clinical curriculum in the direct restoration module of the operative dentistry course using manual and digital methods. METHODS: Thirty-two randomly selected year 2 undergraduate students were divided into two groups: group 1, exposed to the Moog Simodont dental trainer (VR) and group 2, no exposure to VR. All students were then evaluated in carrying out a Class I preparation in a single-blinded fashion. All preparations were evaluated by three assessors using a traditional manual approach and a digital software. Statistical analysis of the data was performed using chi-square test (alpha = 0.05). RESULTS: The number of students who performed satisfactory preparations was more in group 1 (12/16), compared to group 2 (7/16). The percentage of satisfactory domains was significantly higher in group 1, compared to group 2, both in the manual evaluation (83.9% (94/112) and 59.8% (67/112) in groups 1 and 2, respectively) and in the digital evaluation (85.7% (96/112) and 55.4% (62/112) in groups 1 and 2, respectively) (P < .05). There was no significant difference between the manual and digital methods of evaluation with regard to the percentage of satisfactory or unsatisfactory preparations (P > .05). CONCLUSIONS: The use of the Moog Simodont dental trainer (VR) significantly improved the satisfactory performance of students. The virtual reality simulator may be a valuable adjunct in the undergraduate direct restorations course and for remedial student.


Assuntos
Estudantes de Odontologia , Realidade Virtual , Competência Clínica , Simulação por Computador , Dentística Operatória , Educação em Odontologia , Humanos , Interface Usuário-Computador
3.
Cancers (Basel) ; 11(10)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652551

RESUMO

Identifying bioenergetics that facilitate the epithelial to mesenchymal transition (EMT) in breast cancer cells may uncover targets to treat incurable metastatic disease. Metastasis is the number one cause of cancer-related deaths; therefore, it is urgent to identify new treatment strategies to prevent the initiation of metastasis. To characterize the bioenergetics of EMT, we compared metabolic activities and gene expression in cells induced to differentiate into the mesenchymal state with their epithelial counterparts. We found that levels of GLS2, which encodes a glutaminase, are inversely associated with EMT. GLS2 down-regulation was correlated with reduced mitochondrial activity and glutamine independence even in low-glucose conditions. Restoration of GLS2 expression in GLS2-negative breast cancer cells rescued mitochondrial activity, enhanced glutamine utilization, and inhibited stem-cell properties. Additionally, inhibition of expression of the transcription factor FOXC2, a critical regulator of EMT in GLS2-negative cells, restored GLS2 expression and glutamine utilization. Furthermore, in breast cancer patients, high GLS2 expression is associated with improved survival. These findings suggest that epithelial cancer cells rely on glutamine and that cells induced to undergo EMT become glutamine independent. Moreover, the inhibition of EMT leads to a GLS2-directed metabolic shift in mesenchymal cancer cells, which may make these cells susceptible to chemotherapies.

4.
J Am Chem Soc ; 141(39): 15504-15508, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31533429

RESUMO

Double-bond photoisomerization in molecules such as the green fluorescent protein (GFP) chromophore can occur either via a volume-demanding one-bond-flip pathway or via a volume-conserving hula-twist pathway. Understanding the factors that determine the pathway of photoisomerization would inform the rational design of photoswitchable GFPs as improved tools for super-resolution microscopy. In this communication, we reveal the photoisomerization pathway of a photoswitchable GFP, rsEGFP2, by solving crystal structures of cis and trans rsEGFP2 containing a monochlorinated chromophore. The position of the chlorine substituent in the trans state breaks the symmetry of the phenolate ring of the chromophore and allows us to distinguish the two pathways. Surprisingly, we find that the pathway depends on the arrangement of protein monomers within the crystal lattice: in a looser packing, the one-bond-flip occurs, whereas, in a tighter packing (7% smaller unit cell size), the hula-twist occurs.

5.
J Clin Med ; 8(9)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510046

RESUMO

Despite the advancement in medical knowledge that has improved the survival rate of many cancers, the survival rate of pancreatic cancer has remained dismal with a five-year survival rate of only 9%. The poor survival of pancreatic cancer emphasizes the urgent need to identify the causes or the risk factors of pancreatic cancer in order to establish effective preventive strategies. This review summarizes the current evidence regarding the environmental (non-genetic, including lifestyle, and clinical factors) risk factors of pancreatic cancer. Based on the current evidence, the established risk factors of pancreatic cancer are cigarette smoking, chronic diabetes, and obesity. Other strong risk factors include low consumption of fruits and vegetables, excess consumption of alcohol, poor oral hygiene, and the lack of allergy history. In the future, more studies are needed to identify additional risk factors of pancreatic cancer, especially the modifiable risk factors that could be included in a public health campaign to educate the public in order to reduce the incidence of pancreatic cancer.

6.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1694-1703, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31350264

RESUMO

BACKGROUND: Helicobacter pylori eradication has been shown to decrease gastric adenocarcinoma risk. The epidemiology of gastric lymphoma, which is also associated with H. pylori, and other rare subtypes of gastric cancer is less clear. This study comprehensively evaluated the incidence trend and the survival of gastric cancer in Taiwan by histologic subtype. METHODS: The incidence trends of gastric cancer in Taiwan from 1996 and 2013 were evaluated using data from the Taiwan Cancer Registry. The life-table method and the Cox proportional hazards analysis were used to evaluate the survival of gastric cancer. RESULTS: The incidence of all gastric cancers in Taiwan decreased from 15.97 per 100,000 in 1996 to 11.57 per 100,000 in 2013. The most frequent histologic subtype of gastric cancer in Taiwan was adenocarcinoma, followed by lymphoma and sarcoma (mainly gastrointestinal stromal tumor). The best survival was in patients with sarcoma, followed by lymphoma, neuroendocrine tumor, and adenocarcinoma. Generally, women had a better survival than men. The incidence of adenocarcinoma significantly decreased from 13.56 per 100,000 in 1996 to 9.82 per 100,000 in 2013 (P < 0.0001). In contrast, the incidences of mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma did not decrease. CONCLUSIONS: The incidence of adenocarcinoma and lymphoma, both of which are associated with H. pylori, showed diverging trends. The survival of gastric cancer differed by histologic subtype and sex. IMPACT: The disparity in the incidence trends between gastric lymphoma and adenocarcinoma, both associated with H. pylori, warranted the need to search for additional risk factors of gastric lymphoma.

7.
Cancer Biol Med ; 16(1): 79-102, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31119048

RESUMO

Objective: Polycystic kidney disease (PKD) is the major cause of kidney failure and mortality in humans. It has always been suspected that the development of cystic kidney disease shares features with tumorigenesis, although the evidence is unclear. Methods: We crossed p53 mutant mice (p53N236S, p53S) with Werner syndrome mice and analyzed the pathological phenotypes. The RNA-seq, ssGSEA analysis, and real-time PCR were performed to dissect the gene signatures involved in the development of disease phenotypes. Results: We found enlarged kidneys with fluid-filled cysts in offspring mice with a genotype of G3mTerc -/- WRN -/- p53 S/S (G3TM). Pathology analysis confirmed the occurrence of PKD, and it was highly correlated with the incidence of tumorigenesis. RNA-seq data revealed the gene signatures involved in PKD development, and demonstrated that PKD and tumorigenesis shared common pathways, including complement pathways, lipid metabolism, mitochondria energy homeostasis and others. Interestingly, this G3TM PKD and the classical PKD1/2 deficient PKD shared common pathways, possibly because the mutant p53S could regulate the expression levels of PKD1/2, Pkhd1, and Hnf1b. Conclusions: We established a dual mouse model for PKD and tumorigenesis derived from abnormal cellular proliferation and telomere dysfunction. The innovative point of our study is to report PKD occurring in conjunction with tumorigenesis. The gene signatures revealed might shed new light on the pathogenesis of PKD, and provide new molecular biomarkers for clinical diagnosis and prognosis.

8.
Cancers (Basel) ; 11(5)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137625

RESUMO

Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is mostly latent in adults, can be activated under selective pressures, rendering these cancers resistant to chemo- and immunotherapies. EMT can also drive tumor metastases, which in turn also suppress the cancer-fighting activity of cytotoxic T cells that traffic into the tumor, causing immunotherapy to fail. In this review, we compare and contrast immunotherapy treatment options of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). We discuss why, despite breakthrough progress in immunotherapy, attaining predictable outcomes in the clinic is mostly an unsolved problem for these tumors. Although these two cancer types appear different based upon their tissues of origin and molecular classification, gene expression indicate that they possess many similarities. Patient tumors exhibit activation of EMT, and resulting stem cell properties in both these cancer types associate with metastasis and resistance to existing cancer therapies. In addition, the EMT transition in both these cancers plays a crucial role in immunosuppression, which exacerbates treatment resistance. To improve cancer-related survival we need to understand and circumvent, the mechanisms through which these tumors become therapy resistant. In this review, we discuss new information and complementary perspectives to inform combination treatment strategies to expand and improve the anti-tumor responses of currently available clinical immune checkpoint inhibitors.

9.
J Biomed Inform ; 94: 103192, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31048074

RESUMO

To probe the complexity of modern diseases, multidisciplinary approaches are increasingly applied. Typically underpinning such studies are collaborations between wet bench experimentalists and dry lab bioinformaticians. Despite the need, bioinformatics collaborators remain difficult to find. Therefore, we undertook a study to understand the nature of this research, so that we may better understand how to meet the needs of future multidisciplinary projects. To accomplish this, we have performed a retrospective study of data from three years of projects performed by the UTHealth Bioinformatics Service Center. Based on this, we found that the bioinformatics in these collaborative projects are extremely diverse and require a high degree of intellectual engagement, while requiring only a small amount of publishable methods development. Very few of the specific skills, the strength of a service core, could be recycled across projects, which were generally exploratory and open-ended and required cycles of biological hypothesis development and (in silico) testing. We find that biomedical research requires bioinformaticians that are highly trained, having the ability to think biologically, but investigating using computational rather than bench experiments. This is in contrast to the activities that are typically the basis for an independent career in biomedical informatics, namely developing new software and algorithms. These findings suggest that to foster team-based multidisciplinary research, institutions must adopt policies that recognize contributions to research by applied bioinformatics scientists.

10.
Alcohol Clin Exp Res ; 43(6): 1225-1233, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30977906

RESUMO

BACKGROUND: Carriers of the ALDH2*2 allele have impaired alcohol metabolism and are more susceptible to the development of alcohol-related cancers, including head and neck cancer (HNC). Screening for ALDH2*2 allele may identify high-risk individuals for alcohol health education. Although genotyping of ALDH2 is the most accurate way to identify ALDH2 deficiency, it may not be practical due to the cost and requirement for genotyping service. METHODS: This study evaluated the accuracy of the alcohol flushing questionnaire to identify ALDH2 deficiency in a case-control study of HNC conducted in Taiwan using data collected from 904 patients with HNC and 1,078 controls. RESULTS: Overall, alcohol flushing questionnaire had a high sensitivity (89%) of identifying ALDH2*2 carriers among the control subjects and a good sensitivity (79%) among the patients with HNC. The sensitivity of the alcohol flushing questionnaire in identifying ALDH2*2 carriers was affected by alcohol use, with a lower sensitivity among individuals who consumed alcohol, particularly among current regular (drinking alcohol once per week or more) alcohol drinkers. CONCLUSIONS: The current validation study showed that the alcohol flushing questionnaire may be a reasonable method to identify ALDH2-deficient individuals. However, current regular users of alcohol who reported no alcohol flushing may need to undergo genotyping of ALDH2 for a more accurate assessment of the ALDH2 status.

11.
Sci Transl Med ; 11(488)2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996079

RESUMO

Eradicating triple-negative breast cancer (TNBC) resistant to neoadjuvant chemotherapy (NACT) is a critical unmet clinical need. In this study, patient-derived xenograft (PDX) models of treatment-naïve TNBC and serial biopsies from TNBC patients undergoing NACT were used to elucidate mechanisms of chemoresistance in the neoadjuvant setting. Barcode-mediated clonal tracking and genomic sequencing of PDX tumors revealed that residual tumors remaining after treatment with standard frontline chemotherapies, doxorubicin (Adriamycin) combined with cyclophosphamide (AC), maintained the subclonal architecture of untreated tumors, yet their transcriptomes, proteomes, and histologic features were distinct from those of untreated tumors. Once treatment was halted, residual tumors gave rise to AC-sensitive tumors with similar transcriptomes, proteomes, and histological features to those of untreated tumors. Together, these results demonstrated that tumors can adopt a reversible drug-tolerant state that does not involve clonal selection as an AC resistance mechanism. Serial biopsies obtained from patients with TNBC undergoing NACT revealed similar histologic changes and maintenance of stable subclonal architecture, demonstrating that AC-treated PDXs capture molecular features characteristic of human TNBC chemoresistance. Last, pharmacologic inhibition of oxidative phosphorylation using an inhibitor currently in phase 1 clinical development delayed residual tumor regrowth. Thus, AC resistance in treatment-naïve TNBC can be mediated by nonselective mechanisms that confer a reversible chemotherapy-tolerant state with targetable vulnerabilities.

12.
BMJ Case Rep ; 12(4)2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31005876

RESUMO

Crohn's disease (CD) is a multifactorial, chronic immune-mediated disorder. The oral cavity is involved in 0.5% to 20% of the patients with CD. Oral manifestations of CD are sometimes nonspecific and can be overlooked by the clinicians. These manifestations may precede intestinal symptoms and can serve as indicators for early diagnosis. To increase awareness and to contribute to the standard intervention, here we report a paediatric case with persistent idiopathic swelling of the lower lip and perianal fistula. Microscopic examinations revealed multiple non-necrotising granulomas with chronic inflammation, oedema and lymphangiectasia. The patient was treated with metronidazole 500 mg and ciprofloxacin 500 mg twice a day for one month. The perioral lesions were managed with topical 0.03% tacrolimus and oral prednisone 10 mgtwice a day for one month, followed by a tapered regimen of 10 mg/day for another month. The patient's symptoms improved without full remission at the 6-month follow-up.


Assuntos
Doença de Crohn/complicações , Doenças Labiais/etiologia , Criança , Doença de Crohn/diagnóstico , Humanos , Masculino , Fístula Retal/complicações
13.
Cell Metab ; 29(6): 1274-1290.e9, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-30930169

RESUMO

Telomere shortening is associated with stem cell decline, fibrotic disorders, and premature aging through mechanisms that are incompletely understood. Here, we show that telomere shortening in livers of telomerase knockout mice leads to a p53-dependent repression of all seven sirtuins. P53 regulates non-mitochondrial sirtuins (Sirt1, 2, 6, and 7) post-transcriptionally through microRNAs (miR-34a, 26a, and 145), while the mitochondrial sirtuins (Sirt3, 4, and 5) are regulated in a peroxisome proliferator-activated receptor gamma co-activator 1 alpha-/beta-dependent manner at the transcriptional level. Administration of the NAD(+) precursor nicotinamide mononucleotide maintains telomere length, dampens the DNA damage response and p53, improves mitochondrial function, and, functionally, rescues liver fibrosis in a partially Sirt1-dependent manner. These studies establish sirtuins as downstream targets of dysfunctional telomeres and suggest that increasing Sirt1 activity alone or in combination with other sirtuins stabilizes telomeres and mitigates telomere-dependent disorders.

14.
Cancer Med ; 8(4): 1854-1864, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30865385

RESUMO

Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03-1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41-3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65-1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.

15.
Breast Cancer Res ; 21(1): 37, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845991

RESUMO

BACKGROUND: Triple-negative breast cancers (TNBCs), which lack receptors for estrogen, progesterone, and amplification of epidermal growth factor receptor 2, are highly aggressive. Consequently, patients diagnosed with TNBCs have reduced overall and disease-free survival rates compared to patients with other subtypes of breast cancer. TNBCs are characterized by the presence of cancer cells with mesenchymal properties, indicating that the epithelial to mesenchymal transition (EMT) plays a major role in the progression of this disease. The EMT program has also been implicated in chemoresistance, tumor recurrence, and induction of cancer stem cell (CSC) properties. Currently, there are no targeted therapies for TNBC, and hence, it is critical to identify the novel targets to treat TNBC. METHODS: A library of compounds was screened for their ability to inhibit EMT in cells with mesenchymal phenotype as assessed using the previously described Z-cad reporters. Of the several drugs tested, GSK3ß inhibitors were identified as EMT inhibitors. The effects of GSK3ß inhibitors on the properties of TNBC cells with a mesenchymal phenotype were assessed using qRT-PCR, flow cytometry, western blot, mammosphere, and migration and cell viability assays. Publicly available datasets also were analyzed to examine if the expression of GSK3ß correlates with the overall survival of breast cancer patients. RESULTS: We identified a GSK3ß inhibitor, BIO, in a drug screen as one of the most potent inhibitors of EMT. BIO and two other GSK3ß inhibitors, TWS119 and LiCl, also decreased the expression of mesenchymal markers in several different cell lines with a mesenchymal phenotype. Further, inhibition of GSK3ß reduced EMT-related migratory properties of cells with mesenchymal properties. To determine if GSK3ß inhibitors target mesenchymal-like cells by affecting the CSC population, we employed mammosphere assays and profiled the stem cell-related cell surface marker CD44+/24- in cells after exposure to GSK3ß inhibitors. We found that GSK3ß inhibitors indeed decreased the CSC properties of cell types with mesenchymal properties. We treated cells with epithelial and mesenchymal properties with GSK3ß inhibitors and found that GSK3ß inhibitors selectively kill cells with mesenchymal attributes while sparing cells with epithelial properties. We analyzed patient data to identify genes predictive of poor clinical outcome that could serve as novel therapeutic targets for TNBC. The Wnt signaling pathway is critical to EMT, but among the various factors known to be involved in Wnt signaling, only the higher expression of GSK3ß correlated with poorer overall patient survival. CONCLUSIONS: Taken together, our data demonstrate that GSK3ß is a potential target for TNBCs and suggest that GSK3ß inhibitors could serve as selective inhibitors of EMT and CSC properties for the treatment of a subset of aggressive TNBC. GSK3ß inhibitors should be tested for use in combination with standard-of-care drugs in preclinical TNBC models.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Conjuntos de Dados como Assunto , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Humanos , Concentração Inibidora 50 , Cloreto de Lítio/farmacologia , Cloreto de Lítio/uso terapêutico , Células-Tronco Neoplásicas/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/mortalidade , Via de Sinalização Wnt
16.
Prenat Diagn ; 39(5): 361-368, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30740743

RESUMO

OBJECTIVES: To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell-free DNA (cfDNA) testing. METHODS: We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate. RESULTS: The FFs were 8.8% (6.6-12.1), 8.7% (6.3-11.6), and 7.7% (5.1-9.3) among women taking 0, 1, and two or more medications, respectively (P < 0.01). Using multivariable linear mixed effects model, the mean FF was significantly lower among those taking two or more medications compared with the nonexposed group. FF was directly correlated with gestational age at the time of cfDNA testing and inversely correlated with maternal obesity. Exposure to metformin was associated with 1.8% (0.2-3.4) lower mean FF when compared with the nonexposed group (P = 0.02). Obesity and intake of two or more medications were associated with higher hazard ratio of having a low FF less than 4%. CONCLUSIONS: Exposure to metformin or two or more medications was associated with decreased FF, and obesity is associated with delay in achieving adequate FF percentage. These findings should be considered while counseling patients on test limitations.

17.
Head Neck ; 41(7): 2285-2290, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30758100

RESUMO

BACKGROUND: Frey syndrome is a common complication after parotidectomy. This study aimed to investigate the potential predictors for developing severe Frey syndrome after parotidectomy and to identify patients who may benefit from additional preventive maneuvers. METHODS: A total of 485 patients received parotidectomy because of parotid tumors at the Otolaryngology Department of the National Cheng Kung University Hospital, from July 2009 to November 2015. Only 115 of 485 patients were included in this study and to fill in a questionnaire to determine the occurrence and severity of Frey syndrome. RESULTS: A total of 115 parotidectomies were identified. 84 (73%, 84/115) patients were aware of the discomfort and were thus considered symptomatic. 39 (34%, 39/115) patients considered the symptoms apparently affected their quality of life. MSI tests showed that 56 (49%, 56/115) patients had a positive MSI test. By combining the results from symptom questionnaire and MSI test, 23 patients (20%, 23/115) had a severe form of Frey syndrome. Among all clinicopathological variables, the resected specimen size was the only significant predictor of the severe Frey syndrome group (P = 0.04). Disease pathology, tumor size, and adjuvant radiotherapy did not correlate with the severe Frey syndrome. Using receiver operating curve analysis, the best cutoff value of the resected specimen size (in largest dimension) for predicting severe Frey syndrome was 40 mm(sensitivity: 71.7%, specificity: 42.0%; area under the curve = 0.6483). The odds ratio of severe Frey syndrome with every 10 mm increase in the largest diameter of resected specimen was 1.30 (95% confidence interval, 1.01-1.68; P = 0.04). CONCLUSIONS: Resected specimen size is the only significant predictor of developing severe Frey syndrome after parotidectomy. Preventive interventions may have to be considered in high-risk patients whose resected specimen size (in largest dimension) is greater than 40 mm.

18.
Int J Cancer ; 144(11): 2795-2810, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30485433

RESUMO

Oral squamous cell carcinoma (OSCC) LN1-1 cells previously showed greater capacities for lymphangiogenesis and lymph node metastasis compared to their parental OEC-M1 cells, in addition to an ability to enhance the migration and tube formation of lymphatic endothelial cells (LECs). Purified by a series of differential centrifugations and characterized using electron microscopy, dynamic light scattering and western blot, LN1-1 cell-derived extracellular vesicles (LN1-1 EVs) were shown to promote LEC migration, tube formation and uptake by LECs more effectively than did OEC-M1 cell-derived EVs (OEC-M1 EVs). Using stable isotope labeling with amino acids in cell culture/liquid chromatography-tandem mass spectrometry-based proteomic platform, the laminin-332 proteins, including laminin α3, ß3 and γ2, were validated as highly expressed proteins in LN1-1 EVs. Clinically, a higher level of laminin-332 was detected in plasma EVs from OSCC patients with lymph node metastasis than in both healthy controls and OSCC patients without lymphatic metastasis, suggesting EV-borne laminin-332 as a novel and noninvasive biomarker for the detection of lymph node metastasis in OSCC. The knockdown of laminin γ2 and inhibition by anti-laminin-332 neutralizing antibodies impaired LN1-1 EV-mediated LEC migration, tube formation and uptake by LECs. Importantly, laminin γ2-deficient EVs showed a reduced ability to drain into lymph nodes in comparison with the control EVs. In addition, the laminin 332/γ2-mediated EV uptake was dependent on integrin α3 but not ß1, ß4 or α6. Collectively, the uptake of laminin γ2-enriched EVs by LECs enhanced in vitro lymphangiogenesis and EV-borne laminin-332 is thus a viable biomarker for OSCC.


Assuntos
Integrina alfa3/metabolismo , Laminina/metabolismo , Linfangiogênese , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Células Endoteliais/patologia , Vesículas Extracelulares/patologia , Técnicas de Silenciamento de Genes , Humanos , Laminina/genética , Linfonodos/patologia , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Vasos Linfáticos/citologia , Masculino , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Cancer Epidemiol Biomarkers Prev ; 28(2): 248-257, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30275114

RESUMO

BACKGROUND: Although alcohol drinking is an established risk factor of head and neck cancer (HNC), less is known about its role in the prognosis of HNC. The current study investigated the association between pretreatment alcohol consumption and the overall survival (OS) of HNC patients. METHODS: Cox proportional hazards models were performed to evaluate the association between prediagnosis alcohol drinking and the OS of HNC patients. In addition, the influence of the polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on this relationship was also evaluated. RESULTS: The results showed a significant positive dose-response relationship between prediagnosis alcohol use and worse OS of HNC patients. This association was more significant for oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer than for oral cancer. The association between alcohol use and the poorer OS of HNC patients was mainly through its association with a higher stage of HNC at diagnosis. The worst OS associated with alcohol use was observed among HNC patients with the fast ADH1B and the slow/nonfunctional ALDH2 genotype combination. CONCLUSIONS: Our analysis showed a significant positive dose-response relationship between prediagnosis alcohol use and a worse OS of HNC. This association was mainly due to the higher stage of HNC among alcohol drinkers. In addition, the polymorphisms of the ethanol-metabolizing genes, ADH1B and ALDH2, modified the relationship between prediagnosis alcohol use and the OS of HNC patients. IMPACT: Prediagnosis alcohol use may be a prognostic indicator of HNC.

20.
Aust Endod J ; 45(3): 407-413, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30520194

RESUMO

This systematic review assessed the effect of different root canal instrumentation systems on endotoxin reduction from the root canal system. The literature search was conducted in two electronic databases (PubMed and Scopus) using specific key words. The search strategy followed the PRISMA guidelines. Qualitative synthesis and quantitative synthesis of the data were performed and data interpretation was done based on the guidelines in the Cochrane Handbook. The risk of bias was assessed using Cochrane criteria. The initial search yielded 600 citations, of which three papers met the criteria for inclusion in this review. Studies showed a significant reduction in endotoxin following rotary and reciprocating instrumentation, with no significant differences between them. The meta-analysis showed no statistical significant difference between reciprocation and rotary files (P > 0.05). In conclusion, the instrumentation techniques compared in this review decrease endotoxin content from root canals, with no significant difference between them.


Assuntos
Cavidade Pulpar , Preparo de Canal Radicular , Endotoxinas , Tratamento do Canal Radicular
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