Honokiol attenuate the arsenic trioxide-induced cardiotoxicity by reducing the myocardial apoptosis.

Despite advantages of arsenic trioxide (ATO) in oncological practice, its clinical applications have been hampered by severe cardiotoxicity. The general mechanism of ATO-induced cardiotoxicity has been attributed to its damage to mitochondria, resulting in cardiac remodeling. Honokiol (HKL) is a naturally occurring compound derived from Magnolia bark. Previous studies have demonstrated that HKL exerts cardio-protective effects on ischemia/reperfusion (I/R) or chemical-induced cardiotoxicity by counteracting the toxic effects on mitochondria. The present study was conducted to investigate whether HKL pretreatment protects against ATO-induced cardiac oxidative damage and cell death. For the in vitro study, we evaluated the effects of ATO and/or Honokiol on reactive oxygen species (ROS) production and apoptosis induction in primary cultured cardiomyocytes; for the in vivo study, BALB/c mice were administrated with ATO and/or HKL for a period of 4 weeks, myocardial apoptosis, cardiac function, and cardiac remodeling (cardiac hypertrophy and cardiac fibrosis) were assessed at the end of administration. Our results demonstrated Honokiol pretreatment alleviated the ATO-induced boost in ROS concentration and the following apoptosis induction in primary cultured cardiomyocytes. In the mouse model, Honokiol pretreatment ameliorated ATO-induced myocardial apoptosis, cardiac dysfunction, and cardiac remodeling. Collectively, these results indicated that Honokiol provide a protection against ATO-induced cardiotoxicity by reducing mitochondrial damage. In addition, given that Honokiol has shown considerable suppressive effects on leukemia cells, our data also imply that ATO and Honokiol combination may possibly be a superior avenue in leukemia therapy.

Adenoid cystic carcinoma of the vagina: A case report.

RATIONALE: Squamous carcinoma is the most common malignancy of vagina. Adenoid cystic carcinoma (ACC) in the vagina is very rare. PATIENT CONCERNS: In the present study, we present a 45-year-old woman with a palpable swelling in the vagina. The patient reported body paresthesia, chest congestion, expiratory dyspnea, and itching in the thigh root. DIAGNOSIS: The ultrasound results revealed inhomogeneous echoes of the muscular layer in the middle and distal of the vagina, and probed a slightly richer blood flow signal. Then biopsy was performed. On microscopic examination, it was observed that tumor cells were arranged in a tubular or cribriform pattern, and exhibited a consistent size, small nuclei, and nuclear fission. The myoepithelium was lined around the glandular cavity, but the myoepithelium was tumorous. Immunohistochemistry was performed for further verification. Vimentin was positive in mesenchyme and CK-P was positive in epithelial cells. P63 and calponin were spotted, which were focal positive around the glandular cavity. Finally, the patient was diagnosed as ACC. INTERVENTIONS: At last, the patient chose chemoradiotherapy, not surgical excision. OUTCOMES: The patient is alive and well 13 months after the initial diagnosis. LESSONS: ACC in the vagina is extremely rare. To our knowledge, this report is the first case of ACC arising from the vagina in English-language literature. Extensive surgical section of the tumour and chemoradiotherapy are recommended for therapy. Because of rarity, the prognosis of ACC in vagina is not known.

CRIP1 promotes cell migration, invasion and epithelial-mesenchymal transition of cervical cancer by activating the Wnt/ß­catenin signaling pathway.

Cervical cancer (CC) is the third most common cancer and the fourth leading cause of malignancy-related mortality in women worldwide. In addition, epithelial-mesenchymal transition (EMT) has been generally studied in tumor metastasis researches in recent years. Cysteine-rich intestinal protein 1 (CRIP1) is differently expressed in human cancer cells. However, the role it plays in CC has not been revealed at present. Preliminary experiments have shown that CRIP1 had a higher expression in CC tissues, compared with adjacent noncancerous tissues. Real-time PCR and western blot were performed to analyze CRIP1 expression in CC cell lines. CRIP1 transient transfection vector and siRNA were constructed. Further analysis revealed the promotion effects of CRIP1 on the cell migration and invasion of CC in vitro (P < 0.01). In addition, western blot was performed to show that CRIP1 mediates EMT by means of EMT marker detection. The expression of CRIP1 and ߭catenin in CC tissues was analyzed by immunohistochemistry (IHC). Interestingly, CRIP1 and ߭catenin were both highly expressed in CC tissues (P < 0.01). Furthermore, CRIP1 increased the protein expression level of c-myc, cyclinD-1 and cytoplasmic ߭catenin, which are indicators for activating the Wnt/߭catenin signaling pathway. In conclusion, CRIP1 promotes cell migration and invasion, mediates EMT and activates the Wnt/߭catenin signaling pathway in CC.

Suppression of human MDA-MB-435S tumor by U6 promoter-driven short hairpin RNAs targeting focal adhesion kinase.

PURPOSE: Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase implicated in cancer cell survival, proliferation, and in various steps in the metastatic cascade. In the present study, we took advantage of a cationic liposome as gene carrier and targeted FAK function through both in vitro and in vivo approaches. METHODS: We utilized a plasmid-encoded hairpin RNA targeting the human FAK mRNA (pGensil2-shRNA/FAK), as a means to inhibit FAK expression for evaluating its anti-tumor effect in vitro and in vivo. Human MDA-MB-435S breast cancer cells were transfected with pGensil2-shRNA/FAK and examined for apoptosis by propidium iodide staining, DNA ladder, and flow cytometric analysis. For in vivo study, subcutaneous breast carcinomatosis models in nude mice were established to evaluate the therapeutic potential of pGensil2-shRNA/FAK. Assessments of proliferation (Ki-67), apoptosis (TUNEL) and angiogenesis (CD31) were done using immunohistochemical analysis. RESULTS: Transcripts expressed from plasmid both in vitro and in vivo were identified by northern blot analysis. pGensil2-shRNA/FAK effectively down-regulated the expression of FAK as demonstrated in vitro by real time RT-PCR and western blot analysis, whereas by real time RT-PCR and IHC staining of MDA-MB-435S tumors growing subcutaneously. Breast cancer cells lacking FAK expression undergo apoptosis in vitro. Systemic delivery of cationic liposome-complexed plasmids targeting FAK, resulted in the diminishment of subcutaneous tumor growth beyond the effects observed with liposomes carrying a non-specific shRNA. This diminishment in growth was associated with elevated levels of apoptosis (TUNEL staining), decreased cell proliferation (Ki-67 staining) and diminished endothelial cell density (CD31 staining). CONCLUSION: These results indicate that the systemic delivery of plasmid DNA targeting FAK function using cationic liposome as a gene carrier, represents a promising avenue for breast cancer therapy.