Dupuytren’s fibroblasts, or myofibroblasts, are the primary cell type in Dupuytren’s disease. Growth factors play a role in the differentiation of fibroblasts to myofibroblasts. Myofibroblasts are ...specialized fibroblasts that display morphologic and biochemical features similar to smooth muscle cells. Cytokines, adhesion molecules, and extracellular matrix components are all thought to play a role in myofibroblast transdifferentiation. Recent research has shown that specific cytokines, such as transforming growth factor β
1 (TGF-β
1), can modulate myofibroblast expression. We hypothesize that bone morphogenetic proteins (BMPs) play a role in the modulation of Dupuytren’s fibroblasts.
Dupuytren’s fibroblasts and normal palmar fascia fibroblasts (control) were analyzed for messenger RNA expression of BMPs (BMP-1, -2, -3, -4, -5, -6, -7, -8, -9, -10 and -11), their receptors (BMPR-IA, BMPR-IB, and BMPR-II), and their antagonists (follistatin and noggin) by reverse-transcription polymerase chain reaction (PCR). Western blot analysis and immunostaining also were used to confirm the differential expression of BMP-4.
With reverse-transcription PCR the expression profile for normal palmar fascia fibroblasts versus Dupuytren’s fibroblasts was found to show similar expression of BMP-1 and -11; qualitatively decreased expression of BMP-6, BMP-8, BMPR-IA, BMPR-IB, and BMPR-II in Dupuytren’s fibroblasts; and no expression of BMP-4 in Dupuytren’s fibroblasts. There was no expression of BMP-2, -3, -5, -7, -9, and -10 in both the control fibroblasts and Dupuytren’s fibroblasts. In line with the messenger RNA expression pattern BMP-4 was detected in only the control fibroblasts and not in the Dupuytren’s fibroblasts, whereas BMP-8 (chosen for comparison purposes) was detectable in both cell populations. Immunostaining for BMP-8 and BMP-4 confirmed our findings with reverse-transcription PCR and Western blot analysis.
This study reports on the expression of BMPs in Dupuytren’s fibroblasts. We characterized the expression of BMPs in both normal palmar fascia fibroblasts and in Dupuytren’s fibroblasts through reverse-transcription PCR, Western blot analysis, and immunostaining. The most significant difference in expression profiles was in the expression of BMP-4; that is, BMP-4 was expressed in the normal fibroblasts but not in the Dupuytren’s fibroblasts. Whether BMP-4 is necessary and/or sufficient for maintaining a normal palmar fascia fibroblast phenotype is not yet known. Further studies are needed to elucidate the exact role of BMPs, and especially BMP-4, in Dupuytren’s fibroblasts.
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Background: Triple-negative breast cancer(TNBC) is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted ...medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible. Methods: Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated with oligonucleotide microarrays. A prognostic 45-gene signature for triple-negative breast cancer was identified using Student’s t test and receiver operating characteristic analysis. Results: Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A novel 45-gene signature giving 98% predictive accuracy in distant metastasis recurrence was identified in our triple-negative patient cohort. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% CI 1.04-5.06, Cox P = 0.04), outperforming five other published breast cancer prognostic signatures. The prognostic signature was statistically predictive with the node-negative triple-negative patients in the validation cohort. Conclusions: The 45-gene prognostic signature identified in this study revealed that TGF-β signaling in immune/inflammatory regulation may be critically involved in distant metastatic invasion of TNBC. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of metastasis recurrence for early-stage triple-negative patients.
Papillary thyroid carcinoma (PTC) variants exhibit different prognosis, but critical characteristics of PTC variants that contribute to differences in pathogenesis are not well-known. This study aims ...to characterize dysregulated immune-associated and cancer-associated genes in three PTC subtypes to explore how the interplay between cancer and immune processes causes differential prognosis. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to identify dysregulated genes in each variant. The dysregulation profiles of the subtypes were compared using functional pathways clustering and correlations to relevant clinical variables, genomic alterations, and microRNA regulation. We discovered that the dysregulation profiles of classical PTC (CPTC) and the tall cell variant (TCPTC) are similar and are distinct from that of the follicular variant (FVPTC). However, unique cancer or immune-associated genes are associated with clinical variables for each subtype. Cancer-related genes MUC1, FN1, and S100-family members were the most clinically relevant in CPTC, while APLN and IL16, both immune-related, were clinically relevant in FVPTC. RAET-family members, also immune-related, were clinically relevant in TCPTC. Collectively, our data suggest that dysregulation of both cancer and immune associated genes defines the gene expression landscapes of PTC variants, but different cancer or immune related genes may drive the phenotype of each variant.
Abstract
Exogenous agents and endogenous processes, such as reactive oxygen species (ROS) can induce base oxidation and DNA lesions. One of the most severe DNA lesions is the double-strand break ...(DSB). There are several repair systems to fix the resulting DNA lesions to prevent error copies of genetic information to be carried to daughter cells. Oxidative stress is an important factor to induce DNA damage during normal cellular metabolism. In this study, we wanted to use lung cancer cells, CL1-0 and CL1-5 cells, which have differential invasiveness ability to characterize DNA repair function. Hydrogen peroxide (H2O2) was treated in lung adenocarcinoma cells to induced DNA DSB. By using immunoflurecence microscope, we found that CL1-5 had more gamma-H2AX foci (DNA DSB marker) and ROS accumulation than CL1-0 post both 1 mM and 5 mM H2O2 treatment. Moreover, CL1-0 had a tight G2/M checkpoint and has a longer G2 arrest after H2O2 treatment, but not found in CL1-5. In addition, increasing sub-G1 population (apoptotic cells) was found in H2O2-treated CL1-5 but less in CL1-0. Furthermore, phosphorylated-Akt (S473) was decreased in CL1-5, In contrast, phosphorylated-ATM (S1981) and Chk2 were increased after 5 mM H2O2 treatment for 90 min. In addition, the level of GSH was persistently lower at the steady state and post H2O2 treatment in CL1-5 by LC-MS/MS analysis. Besides, the apoptotic cells were decreased but no differences in CL1-0 while supplement reduced-GSH before H2O2 treatment. We therefore hypothesize that there are different processes on dealing with ROS scavenging post oxidative stress between CL1-0 and CL1-5. Taken together, using hydrogen peroxide for treating two lung cancer cell lines seem to have different DNA repair function to regulate cellular function. In the following experiments, the activities of antioxidant enzymes, superoxide dismutase (SOD), catalase as well as glutathione peroxidase (GPx) post oxidative stress in CL1-0 and CL1-5 will be determined. Moreover, we will examine the level of GSH in different tumor cell lines to investigate whether GSH involved in tumor invasion ability.
Citation Format: Feng- Chang Wu, Yu-Fen Lin, Liang-Chuan Lai, Eric Y Chuang, Mong-Hsun Tsai. To study DNA repair function of two closely related human lung adenocarcinoma cell lines, CL1-0 and CL1-5. abstract. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2914. doi:10.1158/1538-7445.AM2013-2914
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Objective: The aim of the study was to determine whether quantitative ultrashort echo time (UTE) -T1rho magnetic resonance (MR) measurements are sensitive to proteoglycan degradation in human menisci ...by trypsin digestion. Methods: Conventional and quantitative UTE-T1rho MR sequences were performed on 4 meniscal samples using a 3T scanner. Magnetic resonance imaging was performed before and after 4, 8, and 12 hours of trypsin solution immersion, inducing proteoglycan loss. One sample was used as a control. Digest solutions were analyzed for glycosaminoglycan (GAG) content. The UTE-T1rho studies were analyzed for quantitative changes. Results: Images showed progressive tissue swelling, fiber disorganization, and increase in signal intensity after GAG depletion. The UTE-T1rho values tended to increase with time after trypsin treatment (P= 0.06). Cumulative GAG loss into the bath showed a trend of increased values for trypsin-treated samples (P= 0.1). Conclusions: Ultrashort echo time T1rho measurements can noninvasively detect and quantify severity of meniscal degeneration, which has been correlated with progression of osteoarthritis.
Anti-N-methyl-D-aspartate receptor encephalitis is characterised by psychiatric and neurological abnormalities and occurs in frequent association with ovarian teratoma. We report the first confirmed ...case of teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis in Hong Kong in a young woman presenting with confusion and prominent dyskinesia, followed by a review of the current literature.
Abstract
Background
Dysfunction in risky decision-making has been regarded as one potential contributing factor to functional impairment exhibited in patients with schizophrenia. Literature has ...revealed suboptimal risky decision-making in chronic schizophrenia patients. However, abnormality in risky decision-making has not been investigated in the early stage of illness. This study aimed to examine whether early schizophrenia patients displayed aberrant risky decision-making using two well-validated paradigms including Balloon Analogue Risk Task (BART; Lejuez et al., 2002) and Risky-Gains Task (RGT; Paulus et al., 2003).
Methods
Thirty-three clinically-stable patients diagnosed with DSM-V schizophrenia-spectrum disorder (including schizophrenia, schizoaffective disorder or schizophreniform disorder) were recruited from specialized early intervention service for psychosis in Hong Kong. A group of healthy controls (n=32), matched with age, gender and educational levels, was enrolled for comparison. All participants were evaluated with a brief battery of cognitive assessment and two computerized risky decision-making tasks. Symptom assessment was also conducted for patients.
Results
In both BART and RGT, patients with early schizophrenia-spectrum disorder performed worse than healthy controls regarding total points gained and reaction time. In BART, patients had significantly lower adjusted scores (F(1,63)=7.8, p<0.05) and lower balloon exploration rates than controls (F(1,63)=11.5, p<0.001), indicating that patients exhibited a tendency toward risk-aversion. In GRT, three-way analysis of variance revealed significant group x response interaction (F(1,63)=7.8, p<0.05), with post-hoc independent t-test showing that patients significantly preferred safe over risky options than controls (t=2.6, p<0.05). There were no significant correlations of risky decision-making parameters with symptom ratings and cognitive functions.
Discussion
We extend previous findings of chronic samples to patients with early schizophrenia-spectrum disorder and indicate that suboptimal risky decision-making with risk-aversion preference has also been observed in the early course of illness. Further research is warranted to clarify the longitudinal change of aberrant risk-aversive behavioral patterns and its relationship with prospective functional and symptom outcomes.
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