Background/Aims: Intracellular calcium concentration ([Ca2+]i) homeostasis, an initial factor of cardiac hypertrophy, is regulated by the calcium-sensing receptor (CaSR) and is associated with the formation of autolysosomes. The aim of this study was to investigate the role of Calhex231, a CaSR inhibitor, on the hypertrophic response via autophagy modulation. Methods: Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in 40 male Wistar rats, while 10 rats underwent a sham operation and served as controls. Cardiac function was monitored by transthoracic echocardiography, and the hypertrophy index was calculated. Cardiac tissue was stained with hematoxylin and eosin (H&E) or Masson's trichrome reagent and examined by transmission electron microscopy. An angiotensin II (Ang II)-induced cardiomyocyte hypertrophy model was established and used to test the involvement of active molecules. Intracellular calcium concentration ([Ca2+]i) was determined by the introduction of Fluo-4/AM dye followed by confocal microscopy. The expression of various active proteins was analyzed by western blot. Results: The rats with TAC-induced hypertrophy had an increased heart size, ratio of heart weight to body weight, myocardial fibrosis, and CaSR and autophagy levels, which were suppressed by Calhex231. Experimental results using Ang II-induced hypertrophic cardiomyocytes confirmed that Calhex231 suppressed CaSR expression and downregulated autophagy by inhibiting the Ca2+/calmodulin-dependent-protein kinase-kinase-β (CaMKKβ)- AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway to ameliorate cardiomyocyte hypertrophy. Conclusions: Calhex231 ameliorates myocardial hypertrophy induced by pressure-overload or Ang II via inhibiting CaSR expression and autophagy. Our results may support the notion that Calhex231 can become a new therapeutic agent for the treatment of cardiac hypertrophy.
PurposeThe aim of this study was to identify the ultrasound features and clinicopathological characteristics of basal-like subtype of triple negative breast cancers (TNBCs).Materials and MethodsThis study was approved by the ethical board of the Second Affiliated Hospital of Harbin Medical University. The patients’ clinicopathological information was available. The ultrasound features of 62 tumors from 62 TNBC patients were interpreted. The immunohistochemical results of cytokertain5/6 (CK5/6) and Epidermal Growth Factor Receptor (EGFR) were used to classify the tumor into basal-like and normal-like groups. The association of the ultrasound features interpreted by experienced ultrasound doctors with the immunohistochemical classification was studied.ResultsOf the 62 TNBC cases, 42 (67.7%) exhibited the basal-like phenotype and 20 (32.3%) exhibited the normal-like phenotype based on the immunohistochemical CK5/6 and EGFR markers. Of all the tumors, 90.3% were invasive carcinomas. The basal-like tumors were significantly associated with a maximum diameter on ultrasound of more than 20 mm (36, 85.7%) (P = 0.0014). The normal-like tumors usually exhibited lateral shadows (15, 75%) (P = 0.0115) as well as microlobulated margins (12, 60%) (P = 0.0204) compared to the basal-like subtype. Other ultrasound features showed no significant differences between the two groups.ConclusionsAlthough ultrasound cannot yet be used to differentiate between the basal-like subtype and normal-like subtype of TNBC, ultrasound can be used to provide some useful information to the clinicians.
Asian Pac J Cancer Prev, 15 (19), 8057-8062
IntroductionDetermination of the molecular status of invasive breast cancer is useful as a prognostic and predictive factor, and it has become standard practice in the management of breast cancer because estrogen receptor (ER) and human epidermal growth factor receptor2 (HER2) positivity predict response to endocrine therapy or targeted therapy with monoclonal antibodies directed against HER2 (Bauer et al., 2007;Doreen et al., 2011). If it is possible to predict molecular status on the basis of imaging characteristics, it could assist in both pretreatment planning and prognosis, as well as add to our understanding of the biologic behavior of this disease.Breast ultrasound has gained widespread acceptance as an adjunct to mammography in diagnosis of evaluating clinical or radiological suspected abnormalities (Gordon et al., 1995;Rizzatto et al., 2001). Stavros et al. reported that it has high sensitivity (98.4%) and negative predictive (99.5%) value for diagnosing breast cancers (Stavros et al., 1995). Ultrasound (US), with its merits of safety and low cost, is becoming a preferred method for both physicians and patients. Hence, more attention is needed toward US imaging to determine whether certain type of tumor biologic factors can be predicted from imaging appearances.A few studies have looked into correlation between
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