ABSTRACT
PURPOSE: Breast cancer (BC) is considered a heterogeneous disease composed of distinct subtypes with diverse clinical outcomes. Luminal subtype tumors have the best prognosis, and patients benefit from endocrine therapy. However, resistance to endocrine therapies in BC is an obstacle to successful treatment, and novel biomarkers are needed to understand and overcome this mechanism. The RET, BCAR1, and BCAR3 genes may be associated with BC progression and endocrine resistance. METHODS: Aiming to evaluate the expression profile and prognostic value of RET, BCAR1, and BCAR3, we performed immunohistochemistry on tissue microarrays (TMAs) containing a cohort of 361 Luminal subtype BC. RESULTS: Low expression levels of these three proteins were predominantly observed. BCAR1 expression was correlated with nuclear grade (p = 0.057), and BCAR3 expression was correlated with lymph node status (p = 0.011) and response to hormonal therapy (p = 0.021). Further, low expression of either BCAR1 or BCAR3 was significantly associated with poor prognosis (p = 0.005; p = 0.042). Pairwise analysis showed that patients with tumors with low BCAR1/low BCAR3 expression had a poorer overall survival (p = 0.013), and the low BCAR3 expression had the worst prognosis with RET high expression stratifying these patients into two different groups. Regarding the response to hormonal therapy, non-responder patients presented lower expression of RET in comparison to the responder group (p = 0.035). Additionally, the low BCAR1 expression patients had poorer outcomes than BCAR1 high (p = 0.015). CONCLUSION: Our findings suggest RET, BCAR1, and BCAR3 as potential candidate markers for endocrine therapy resistance in Luminal BC.
Subject(s)
Breast Neoplasms , Adaptor Proteins, Signal Transducing/metabolism , Biomarkers, Tumor/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Crk-Associated Substrate Protein , Female , Guanine Nucleotide Exchange Factors , Humans , Immunohistochemistry , Prognosis , Proto-Oncogene Proteins c-retABSTRACT
AIM: To show additional prognostic information about the mutational profile and new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of adenocarcinoma (ADC) in patients without epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatments. METHODS: In human lung ADC patients (n = 125), including 24 lepidic, 67 acinar, 23 papillary, and 11 solid predominant subtypes, EGFR and KRAS were sequenced, and anaplastic lymphoma kinase (ALK) rearrangements were screened using fluorescence in situ hybridization (FISH). RESULTS: EGFR was mutated in 21.6% of patients with 19.57% showing a mean expression. The most frequent EGFR mutation was a deletion in exon 19, followed by an L858R amino acid substitution in exon 21. KRAS was mutated in 26.4% of patients with 50% displaying mean expression. ALK rearrangement was detected in 6 patients (4.8%). Predominant acinar ADC was strongly associated with EGFR and KRAS mutation. Clinical stage, lymph node metastases, and EGFR mutation in exon 18 showed a significant difference in disease-free and overall survival, but only a trend significance for EGFR and KRAS mutations. Multivariate analysis revealed that men aged >71 years, with a history of smoking (<72 packs/year), clinical stage I/II, and acinar histologic subtype presented better survival than women aged ≤ 71 years, with a history of smoking (>72 packs/year), and having a predominant solid ADC and EGFR mutation in exon 18. CONCLUSIONS: These results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.
Subject(s)
Adenocarcinoma/classification , Adenocarcinoma/genetics , ErbB Receptors/genetics , Gene Rearrangement , Lung Neoplasms/classification , Lung Neoplasms/genetics , Mutation , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Transcriptome , ras Proteins/genetics , Adenocarcinoma/etiology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adenocarcinoma, Papillary/genetics , Aged , Aged, 80 and over , Amino Acid Substitution , Anaplastic Lymphoma Kinase , Brazil , Carcinoma, Acinar Cell/genetics , Disease-Free Survival , Female , Gene Deletion , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/etiology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymphatic Metastasis , Male , Middle Aged , Mutation Rate , Neoplasm Staging , Predictive Value of Tests , Prognosis , Proto-Oncogene Proteins p21(ras) , Risk Factors , Smoking/adverse effects , Survival AnalysisABSTRACT
HAT is the main cause of graft loss in pediatric living-related LTx. Revascularization of the graft by thrombectomy and re-anastomosis has been reported to be effective for graft salvage in cases of HAT and should be attempted when potential donors are not available for emergency re-transplantation. Immediate complications secondary to revascularization attempts in cases of HAT are not described. Late complications are mainly related to biliary tree ischemia. We report a case of child who experienced intimal hepatic artery dissection, which extended into intra-hepatic branches of the artery after a thrombectomy with a Fogarty balloon catheter in an attempt to restore arterial flow after HAT. This complication led to acute deterioration of the graft and the need for emergency re-transplantation.
Subject(s)
Graft Survival , Hepatic Artery/pathology , Liver Transplantation/adverse effects , Thrombosis/surgery , Tunica Intima/pathology , Biliary Atresia , Catheterization , Child , Humans , Liver Circulation , Liver Transplantation/methods , Living Donors , Reoperation , Salvage Therapy , Thrombectomy , Thrombosis/etiologyABSTRACT
BACKGROUND/AIMS: To understand the molecular mechanisms underlying non-alcoholic steatohepatitis (NASH) prevention by S-nitroso-N-acetylcysteine (SNAC), an NO donor that inhibits lipid peroxidation, we examined hepatic differentially expressed genes between ob/ob mice receiving or not SNAC treatment concomitantly with a methionine-choline deficient (MCD) diet. METHODS: Ob/ob mice were assigned to receive oral SNAC fed solution (MCD+SNAC group) or vehicle (MCD group) by gavage. After four weeks, histopathological analysis and microarray hybridizations were conducted in liver tissues from groups. GeneSifter system was used to identify differentially expressed genes and pathways according to Gene Ontology. RESULTS: NASH was absent in the MCD+SNAC group and no significant changes in food intake or body weight were observed in comparison to MCD group. After SNAC treatment, several genes belonging to oxidative phosphorylation, fatty acid biosynthesis, fatty acid metabolism and glutathione metabolism pathways were down-regulated in comparison to the MCD group. CONCLUSIONS: SNAC treatment promotes down regulation of several genes from fatty acid (FA) metabolism related pathways, possibly through abrogation of the cytotoxic effects of reactive oxygen species and lipid peroxides with consequent prevention of mitochondrial overload. Further studies are required to investigate the clinical implications of these findings, in attempt to develop novel therapeutic strategies for NAFLD treatment.