[Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer].

OBJECTIVE: To investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer. METHODS: Forty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days. RESULTS: LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05). CONCLUSIONS: The use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.

[Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: a prospective study].

OBJECTIVE: To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy. METHODS: One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study, and they were randomized into 2 groups, i.e., treatment group, which received the therapy of CIK cells transfusion, and control group, which was given regular follow-up. Meanwhile, patients with positive hormone receptor in the two groups were given endocrine therapy, and the patients with positive axillary lymph nodes were given radiotherapy to the chest wall and regional lymph nodes. The difference of quality of life between the two groups was analyzed according to the EORTC QLQ-BR53 quality of life questionnaire, and the adverse reactions were monitored. RESULTS: As regarding the functional evaluation, the physical function scores of patients of the treatment group were (83.43 ± 14.87) and (88.55 ± 11.62) at 3 and 6 months after the CIK cell therapy, respectively, significantly higher than the baseline value [(74.83 ± 13.82), P < 0.05)]. Global health status/QOL scores were (83.30 ± 19.09) and (89.68 ± 10.81), significantly higher than the baseline value [(77.72 ± 21.05), P < 0.05]. As regarding symptoms, the scores of fatigue, nausea, vomiting and loss of appetite of patients in the treatment group were higher than the baseline value, with significant differences (P < 0.05). The nausea and vomiting scores in the control group at 3 and 6 months of followed-up were (26.67 ± 22.56) and (21.47 ± 21.06), significantly lower than the baseline values [(33.31 ± 27.07), P < 0.05]. The scores of worrying about the future in the patients of treatment group were (47.56 ± 30.84) and (42.33 ± 26.95) after 3 and 6 months, significantly better than the baseline value [(57.41 ± 30.63), P < 0.05]. The systematic therapy side effects scores were (31.95 ± 27.52) and (23.72 ± 22.87), significantly better than the baseline value [(40.56 ± 26.28), P < 0.05]. The scores of arm edema were (45.26 ± 25.42) and (36.61 ± 20.51), significantly milder than the baseline value [(55.11 ± 22.82), P < 0.05]. In the control group, the scores of arm edema were (44.85 ± 28.94) and (38.64 ± 23.68), significantly lower than the baseline values [(53.26 ± 23.84) points, P < 0.05]. Alopecia scores were (29.93 ± 24.72) and (24.18 ± 22.66), significantly lower than the baseline values [(35.92 ± 22.08), P < 0.05]. In the treatment group, the patients' physical function, social function and global health status/QOL, fatigue, insomnia, and worrying about the future rates were significantly higher than that of the control group (P < 0.05 for all). Three patients after CIK reinfusion had transient fever, and 6 cases felt pain in the lower limb, but the symptoms were relieved after symptomatic treatment. CONCLUSIONS: Therapy of autologous CIK cells transfusion can significantly improve the quality of life of breast cancer patients, and the adverse reactions during the treatment can be alleviated by symptomatic treatment.

Small breast epithelial mucin promotes the invasion and metastasis of breast cancer cells via promoting epithelial­to­mesenchymal transition.

The aim of the present study was to observe the influence of the small breast epithelial mucin (MUCL1) (also known as SBEM) gene on migration and invasion ability of breast cancer cells and to explore the potentially involved mechanism. SBEM­interference plasmid and SBEM­overexpressing plasmid were constructed. SBEM­knockdown or SBEM­â€‹overexpressing MCF­7 and MDA­MB­231 breast cancer cells were established by lentivirus­mediated stable transfection method. The scratch wound­healing assay and Transwell chamber experiment were used to detect the influence of the SBEM gene on the migration and invasion abilities of MCF­7 and MDA­MB­231 cells. Real­time PCR (polymerase chain reaction) and western blotting were used to detect the expression of epithelial­to­mesenchymal transition (EMT)­related markers and regulators. The cell morphology was observed after transfection. The SBEM­knockdown or SBEM­overexpressing MCF­7 and MDA­MB­231 cells were established successfully. The migration and invasion abilities were decreased after SBEM was downregulated, and were increased after SBEM was overexpressed both in MCF­7 and MDA­MB­231 cell lines. The mRNA and protein expressions of N­cadherin, Twist and vimentin were elevated following SBEM overexpression, while the expression of E­cadherin and claudin­1 were found to be decreased following SBEM overexpression. In conclusion, SBEM has the potential to promote migration and invasion ability of breast cancer cells via promoting epithelial­to­mesenchymal transition.

[Apoptosis-inducing effect of alternol on mouse lymphocyte leukemia cells and its mechanism].

Alternol is purified from fermentation productions of microorganisms named as Alternaria alternata var. monosporus. The research is to investigate the apoptosis-inducing effect of alternol on mouse lymphocyte leukemia (L1210) cells and the possible mechanisms. MTT method was used to evaluate the viability of L1210 cells. Apoptosis of L1210 cells was detected by morphological assessment, DNA electrophoresis assay and flow cytometry. Western blotting analysis was carried out to determine the apoptosis-related proteins. Proliferation inhibition of L1210 cells by alternol was found remarkably in a dose-dependent manner. When treated with alternol, apoptotic morphological features of L1210 cells were observed by fluorescent microscopy (AO/EB) and the apoptosis rate was also elevated in a time-dependent manner. After treatments with various concentrations of alternol for 48 h, DNA laddering appeared. The increase of reactive oxygen species (ROS) production was found after cells were exposed to alternol for 6 h, while the decrease of mitochondrial transmembrane potential (delta psi m) was not found until cells were exposed to alternol for 24 h. Furthermore, the level of Bcel-2 and Bcl-2/Bax was down-regulated, while the level of caspase-3 and caspase-9 but not caspase-8 was up-regulated when alternol was added for 72 h. In summary, the results suggested that alternol could inhibit the proliferation of L1210 cells and induce apoptosis of L1210 cells, which was mediated by mitochondria-dependent pathway.

Lambert-Eaton myasthenic syndrome in a patient with small-cell lung cancer: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder characterized by fluctuating proximal limb muscle weakness, decreased deep tendon reflexes and various autonomic symptoms. LEMS is reportedly the most common neurological paraneoplastic syndrome. This is the case report of a patient with small-cell lung cancer (SCLC) who developed LEMS. A 68-year-old male patient presented with a 6-month history of progressive weakness of the proximal limbs and a 2-month history of xerostomia. The patient was admitted to the Department of Neurology of the People's Liberation Army General Hospital of Shenyang Military Region (Shenyang, China). The symptoms of the patient were not relieved with supportive therapy. Further laboratory tests, electrodiagnostic studies, chest computed tomography and immunohistochemical staining confirmed the diagnosis of LEMS in the presence of SCLC. Following administration of two cycles of rescue chemotherapy with a combination of etoposide and cisplatin, the symptoms of the patient were gradually relieved and, after six cycles of therapy, the primary malignancy completely regressed. In conclusion, a diagnosis of LEMS may lead to the timely detection of SCLC, significantly improving patient prognosis and survival.

Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer.

To investigate the potential role of small breast epithelial mucin (SBEM) as a marker for detecting hematogenous micrometastasis in breast cancer and explore its clinical significance in neoadjuvant chemotherapy. SBEM protein expression in 82 tissue specimens of primary breast cancer was detected using immunohistochemistry (IHC), and SBEM expression in peripheral blood (PB) samples of 109 primary breast cancer patients (94 cases at stage I-III, 15 cases at stage IV) was detected by flow cytometry (FCM) and reverse transcription polymerase chain reaction (RT-PCR). Moreover, SBEM mRNA expression was monitored by quantification real-time PCR (QPCR) before and after 3 cycles' neoadjuvant chemotherapy. SBEM expression correlated with tumor node metastasis (TNM) staging and lymph node metastasis at both mRNA and protein levels. SBEM expression in PB of breast cancer patients was markedly higher than that of healthy donors and other cancer patients. SBEM was found expressed in PB of 50 cases among 94 cases at stage I-III and expressed in PB of 11 cases among 15 cases at stage IV. After 3 cycles' neoadjuvant chemotherapy, SBEM expression levels were significantly down-regulated in up to 58% breast cancer patients. SBEM has the potential to be a specific marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer.

Study on relationship between angiogenesis and micrometastases of peripheral blood in breast cancer.

PURPOSE: To investigate the relationship between microvessel density, expression of vascular endothelial growth factor A (VEGF-A) and micrometastases in peripheral blood of patients with breast cancer. METHOD: Microvessel density (MVD) and expression of VEGF-A were detected by immunohistochemistry S-P. Nested RT-PCR was introduced to detect the expression of hMAM mRNA in peripheral blood of all cases. RESULT: Average MVD was 28.95 +/- 6.95 microvessels/100x and positive rate of VEGF-A was 64.0% (32/50) in 50 cases with breast cancer. MVD count and expression of VEGF-A were related to tumor size, metastasis of axillary lymph nodes and clinical stages (P < 0.05), independent of age and histological classification (P > 0.05). The positive rate of hMAM mRNA in peripheral blood was 34.0% (17/50), which correlated with lymphatic metastasis and clinical stages (P < 0.05), independent of pathological category, menopause and hormone receptor (P > 0.05). MVD count and positive rate of VEGF-A in breast cancer with positive expression of hMAM mRNA was obviously higher than those without hMAM mRNA expression (chi (2) = 5.766, P = 0.032; t = 5.37, P = 0.002). CONCLUSIONS: MVD count and positive expression of VEGF-A closely correlated to hMAM mRNA released from tumor cells in the circulation. hMAM mRNA is expected to become a valuable marker for further study on micrometastases of breast cancer.

Alternol inhibits proliferation and induces apoptosis in mouse lymphocyte leukemia (L1210) cells.

Alternol is a novel compound purified from the fermenting products by microorganisms named as Alternaria alternata var. monosporus from the bark of Yew. In this study, we tested its effect on mouse lymphocyte leukemia L1210 cells. Alternol was found to inhibit the proliferation and induce apoptosis in L1210 cells. When the cells were treated with Alternol, chromatin condensation and phosphatidylserine externalization were observed with the down-regulation of the pro-survival gene Bcl-2 and the activation of caspase-3, caspase-9, but not caspase-8. Moreover, exposure of cells to Alternol resulted in a significant increase in reactive oxygen species (ROS) and mitochondrial transmembrane potential (DeltaPsim) depolarization. Taken together, these results demonstrate that Alternol is a potent agent in inducing L1210 cells to apoptosis, which involve caspase activation and ROS generation.