Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.
Integrin-linked kinase (ILK), an intracellular serine-threonine kinase, has been reported to be overexpressed in multiple types of human malignancies, including colorectal cancer (CRC). The prognostic value of ILK in CRC, however, remains unknown. In the present study, expression of ILK in 25 paired primary CRC samples and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. ILK protein expression was analyzed in 102 archived, paraffin-embedded CRC samples using immunohistochemistry. The correlation between ILK expression and clinicopathological factors was evaluated by the χ(2) test. Patients' overall survival was analyzed by Kaplan-Meier method. We found that both ILK mRNA and protein expression levels were significantly up-regulated in primary CRC samples compared with their corresponding normal tissues. Immunohistochemical analysis revealed relative high expression of ILK in 43 of 102 (42.2 %) primary CRC samples. Statistical analysis showed a significant correlation of ILK expression with tumor differentiation, lymph node metastasis, tumor invasion, and tumor-node-metastasis stage. Patients with tumors displaying high-level ILK expression showed significantly shorter overall survival (P = 0.028, log-rank test). More importantly, multivariate analysis indicated that high ILK protein expression was an independent prognostic factor for CRC patients (P = 0.026). Taken together, our data suggest that ILK overexpression is associated with tumor progression and a poor prognosis in CRC patients and may represent a novel potential prognostic marker for patients with CRC.
e12617 Background: Both neoadjuvant chemotherapy and endocrine therapy only result in trivial pathological complete response rates and moderate objective response rate (ORR) in hormone receptor (HR)-positive, HER2-negative breast cancer, more promising alternatives are urgently needed. Tucidinostat is an oral subtype-selective histone deacetylase inhibitor that has shown efficacy and safety when used in combination with exemestane in patients with advanced HR+ breast cancer. This MUKDEN 05 study aimed to assess the efficacy and toxicity of the combination of tucidinostat and EC-T as a neoadjuvant strategy in patients with HR+/HER2-, stage II-III breast cancer. Methods: This study is a multicenter, single-arm, phase II study. Eligible patients received 20 mg tucidinostat orally twice a week (on days 1, 4, 8, and 11), 2 weeks on, 1 week off. The dose and administration schedule of EC-T were as follows: 4 cycles of epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100 mg/m2 every 3 weeks. The primary endpoint was the proportion of residual cancer burden (RCB) 0-I. Key secondary endpoints included pathological complete response (pCR), objective response rate (ORR), and safety. Results: Between May 2022 and August 2022, a total of 35 patients were enrolled. 27 patients were pathologically evaluable. The remaining 8 patients have completed neoadjuvant treatment and wait for operation. The ratio of RCB 0-I was 37% (95% CI, 23.2-53.7%). ORR was 86% (95% CI, 70.6-93.7%). Four (15%; 95% CI, 5.91-32.5%) patients achieved bpCR, and one (4%; 95% CI, 0.67-18.3%) patients achieved tpCR. Most adverse events (AEs) were grade 1 or 2. Grade 3/4 AEs included neutropenia (21.1%), and thrombocytopenia (15.8%). Conclusions: The combination of Tucidinostat and EC-T had an acceptable safety profile and encouraging clinical responses, offering a neoadjuvant treatment option for patients with early HR+/HER2- breast cancer. Further research is required to validate these findings. Clinical trial information: NCT05400993 .
BackgroundWe analyzed the clinical and imaging characteristics of patients with breast ductal carcinoma in situ with microinvasion (DCISM) and breast ductal carcinoma in situ (DCIS).MethodsWe analyzed the records of 40 patients diagnosed with DCISM and 61 patients with DCIS who were hospitalized at Shengjing Hospital (Shenyang, China) from January 2009 to June 2016. The size, hardness, and degree of calcification of tumors were determined by mammography and ultrasonography.ResultsIn all, 37 DCISM patients and 45 DCIS patients showed clinical palpable masses (92.5% vs 73.77%, P = 0.018). Mammography showed that the mean size of tumor was larger in DCISM patients than that of DCIS patients (3.13 ± 1.51 vs 2.68 ± 1.77, P = 0.030). Ultrasound examination revealed calcification shadows in the solid tumor mass in 17 DCISM cases and 11 DCIS patients (42.5 vs 18.03%, P = 0.007). Furthermore, estrogen receptor positivity and progesterone receptor positivity were more common in DCIS patients (32.5% vs 54.10%, P = 0.033; 22.5% vs 45.90%, P = 0.017), and the percentage of menopausal patients were higher in DCISM patients than that of DCIS patients (70.00% vs 47.54%, P = 0.026).ConclusionClinically palpable and calcified tumor masses on sonography are more commonly encountered in DCISM lesions.
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