ABSTRACT
OBJECTIVE: Our study aims to investigate the association of extended adjuvant endocrine therapy with disease-free survival (DFS), muscle mass, muscle strength, and visceral adipose tissue in patients with nonmetastatic breast cancer and the effect of extended endocrine therapy on body composition. Patients and Methods. Patients (N = 90) with nonmetastatic breast cancer aged between 60 and 65 years old were prospectively recruited in this study, compromising a cohort of subjects rece iving 5 years or 10 years of adjuvant endocrine therapy. Patients' DFS was compared between these two groups. Patients' body composition including muscle and fat using CT scans, muscle strength, and gait speed was evaluated in these two groups. RESULTS: Dietary behavior was recorded with the food frequency questionnaire (FFQ). Patients' age, body weight, and body mass index (BMI) did not differ between the two groups. An extended adjuvant endocrine therapy into 10 years could translate into DFS benefit (123.8 vs. 102.2 months, P=0.038). Patients receiving 10 years of adjuvant endocrine therapy had less skeletal muscle and more visceral fat compared with patients receiving 5 years of adjuvant endocrine therapy. The skeletal muscle index was 50.3 ± 1.6 cm2/m2 versus 46.5 ± 1.3 cm2/m2 in the 10 years or 5 years of adjuvant endocrine therapy group (P=0.042). The visceral fat was 28.9 ± 2.9 cm2/m2 versus 55.0 ± 3.2 cm2/m2 in the 10 years or 5 years of adjuvant endocrine therapy group (P=0.011). The muscle strength, gait speed, and FFQ results in the two groups not reaching statistical difference. CONCLUSION: In conclusion, breast cancer patients with 10 years of adjuvant endocrine therapy had DFS benefit, but with more muscle loss and adipose tissue deposits compared to patients receiving 5 years of adjuvant endocrine therapy.
ABSTRACT
BACKGROUND: TNFAIP8, also known as TIPE, is a suppressor of apoptosis. High expression of both TIPE mRNA and protein has been detected in various cancer cell lines and clinical specimens compared to healthy tissues. Many reports have shown that there is a strong correlation between TIPE overexpression and cancer progression and poor prognosis in human solid cancers. METHODS: To illustrate the functional and clinical significance of TIPE in gastric cancer, we used reverse transcription polymerase chain reaction, quantitative real-time polymerase chain reaction, and immunohistochemistry to measure TIPE expression in clinical gastric specimens. Then, TIPE expression was knocked down by using shRNA and anti-DR5ScFv, to examine different expressions of TIPE in BGC823 cell lines, while cell proliferation and apoptosis were induced. RESULTS: We found that there was a strong correlation between TIPE expression and TNM stage (P=0.044), tumor depth (P=0.016), lymph node metastasis (P=0.026), and distant metastasis (P=0.045). No significant correlation was found between TIPE expression with the patients' age (P=0.062) or sex (P=0.459). Anti-DR5ScFv induced TIPE depletion both in vitro and in vivo and resulted in apoptosis and suppression of proliferation. CONCLUSION: Our results suggested that TIPE expression was associated with gastric cancer progression, and most importantly, suppressing TIPE expression might be an effective therapeutic strategy.
ABSTRACT
Tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor-adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r=0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC.
ABSTRACT
OBJECTIVE: To prepare hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody, and study their characteristics, functions, and mechanisms of action. MATERIALS AND METHODS: The anti-human death receptor 5 single-chain antibody was constructed and expressed. Protein-loaded hydroxyethyl chitosan nanoparticles were prepared, and their size, morphology, particle-size distribution and surface zeta potential were measured by scanning electron microscopy and laser particle-size analysis. Mouse H22 hepatocellular carcinoma cells were cultured, and growth inhibition was examined using the CellTiter-Blue cell-viability assay. Flow cytometry and Hoechst 33342 were employed to measure cell apoptosis. Kunming mice with H22 tumor models were treated with protein-loaded hydroxyethyl chitosan nanoparticles, and their body weight and tumor size were measured, while hematoxylin and eosin staining was used to detect antitumor effects in vivo and side effects from tumors. RESULTS: The protein-loaded hydroxyethyl chitosan nanoparticles had good stability; the zeta potential was -24.2±0.205, and the dispersion index was 0.203. The inhibition of the protein-loaded hydroxyethyl chitosan nanoparticles on H22 growth was both time- and dose-dependent. Increased expressions of active caspase 8, active caspase 3, and BAX were detected following treatment. The average weight gain, tumor weight, and mean tumor volume of the protein and protein-loaded hydroxyethyl chitosan nanoparticle groups were significantly different (P<0.05) compared with the phosphate-buffered saline group. CONCLUSION: The protein-loaded hydroxyethyl chitosan nanoparticles effectively suppressed tumor growth, indicating that nanotechnology has the potential for broad application in cancer therapy.
