[Show abstract][Hide abstract] ABSTRACT: Special AT-rich sequence binding protein 1 (SATB1) is a master chromatin organizer that has recently been reported to directly upregulate metastasis-associated genes and downregulate tumor suppressor genes. However, its clinical significance in the case of ovarian cancer remains unclear. In the current study, we assessed the expression levels of SATB1 in ovarian cancer and aimed to show whether it may be a conventional clinicopathological parameter. Epithelial ovarian cancer (n=91), borderline cystadenoma (n=13) and normal ovarian background tissues (n=8) were collected immediately following excision during surgery. The mRNA expression levels of SATB1, VEGF-A and MMP-9 were determined using real-time quantitative PCR. Western blotting and immunohistochemical staining were carried out to detect the protein expression levels of SATB1. Expression levels within the ovarian cancer specimens were compared to the normal background tissues and analyzed against FIGO stage, lymph node involvement and histological type. SATB1 mRNA in malignant and borderline ovarian cystadenoma tissues was 6.74- and 5.70-fold higher compared with normal ovarian tissue, respectively (P<0.01). Western blot analysis revealed that a strong positive band of SATB1 expression was present in ovarian cancer tissues. Immunohistochemical staining showed that the positive expression rates of SATB1 in ovarian cancer, borderline ovarian cystadenoma and normal ovarian tissues were 69.2, 61.5 and 0% (P<0.01), respectively. SATB1 expression increased concomitantly with increasing FIGO stage and lymph node involvement. Survival curves showed that a higher SATB1 expression was correlated with shorter survival. Our results provide evidence that SATB1 expression is significantly associated with progression, metastasis and prognosis of epithelial ovarian cancer. SATB1 may therefore serve as a conventional clinicopathological parameter of ovarian cancer.
[Show abstract][Hide abstract] ABSTRACT: Doxorubicin (Dox) is one of the most commonly used and highly effective antineoplastic agents, but the clinical application of this broad spectrum drug is largely hampered by its poor stability and serious toxicity to normal tissues. Hence, it is essential to improve the therapeutic effect and decrease the systematic toxicity for the administration of doxorubicin. In our study, doxorubicin was incorporated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelle by a self-assembly method. The cytotoxicity and cellular uptake efficiency of Dox-loaded MPEG-PCL (Dox/MPEG-PCL) micelle against B16-F10 murine melanoma cells was examined by the methylthiazoltetrazolium (MTT) test and flow cytometry. The antitumor activity of Dox/MPEG-PCL was evaluated in C57BL/6 mice injected subcutaneously with B16-F10 cells. Toxicity was evaluated in tumor-free mice. Meanwhile, tumor proliferation, intratumoal angiogenesis and apoptotic cells were evaluated by PCNA, CD31 staining and TUNEL assay, respectively. Encapsulation of doxorubicin in MPEG-PCL micelle improved the cytotoxicity of doxorubicin and enhanced its cellular uptake on B16-F10 cell in vitro. Administration of Dox/MPEG-PCL micelle resulted in significant inhibition (75% maximum inhibition relative to controls) in the growth of B16-F10 tumor xenografts and prolonged the survival of the treated mice (P<0.05). These anti-tumor responses were associated with marked increase of tumor apoptosis and notable reduction of cell proliferation and intratumoral microvessel density (P<0.05). The system toxicity also decreased in the Dox/MPEG-PCL group compared with free doxorubicin group. Our data indicate that the encapsulation of doxorubicin in MPEG-PCL micelle improved the anti-tumor activity in vivo without conspicuous systemic toxic effects.
[Show abstract][Hide abstract] ABSTRACT: Application of camptothecin (CPT) is hampered due to its extreme water insolubility and unpredictable side effects. Therefore, it is essential to establish an efficient and safe protocol for the administration of camptothecin against tumor growth and metastasis. Here, we encapsulated camptothecin with N-trimethyl chitosan (CPT-TMC) and tested it on BALB/c mice subcutaneously injected with murine hepatocellular carcinoma cells at the hindlimb feet pad. CPT-TMC effectively inhibited tumor growth and lymphatic metastasis, prolonged survival time, yet without apparent toxic effects. Thus, CPT-TMC may provide a novel and effective therapeutic strategy against human advanced hepatic cancer without conspicuous systemic toxic effects.
Cancer letters 11/2010; 297(1):56-64. · 5.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphatic metastasis plays a critical role in ovarian cancer, indicates poor prognoses and correlates to the majority of cancer deaths. Camptothecin derivatives exhibit promising activity for the treatment of solid tumors because of its specific inhibition of eukaryotic DNA topoisomerase I. Yet, its application is hindered due to extreme water insolubility and severe side effects. It is essential to establish an efficient and safe protocol for the administration of camptothecin versus tumor metastasis and growth. In the current research, we encapsulated camptothecin with N-trimethyl chitosan (CPT-TMC) to increase its water-solubility and lower its side effects, and tested it on a high potential lymphogenous metastatic model of human ovarian cancer. In the prophase study, we successfully transfected SKOV3 cells with VEGF-D recombinant plasmid DNA (pcDNA3.1(+)/VEGF-D) to construct a cell line named SKOV3/VEGF-D and establish a feasible lymphogenous metastatic model. The antitumor and antimetastatic activities of CPT-TMC were evaluated in nude mice subcutaneously inoculated with SKOV3/VEGF-D cells at the left hindlimb claw pad. The tumor-bearing mice were divided randomly into four groups and treated twice per week for three weeks. Evan's Blue Dye was used to delineate functional lymphatic vessels. Lymphatic metastasis rates were detected by hematoxylin and eosin (HE) staining. Expression of VEGF-D and MMP-9 were investigated by immunohistochemistry. In contrast to controls, administration of CPT-TMC achieved effective inhibition in primary tumor volume and lymphogenous metastasis, yet without apparent systemic toxic effects. These effects were associated with simultaneously down-regulated VEGF-D and MMP-9 expression, significantly decreased tumor-associated lymphatic and blood sprouts, tremendously reduced systemic toxic effects, dramatically increased tumor apoptotic index. Our data indicate that CPT-TMC is superior to CPT by maximizing its anticancer and antimetastatic activities with minimal toxicity on hosts. CPT-TMC may become a potentially therapeutic strategy against human advanced ovarian cancer.
[Show abstract][Hide abstract] ABSTRACT: Cancer-related deaths are still the most fearsome threaten to human health. It is necessary to develop an innovative and active strategy for the prophylactic immunization against tumorigenesis. Multiple lines of evidence have demonstrated that cancer stem cells (CSCs) are the initiating cells of tumor formation, as well as the source of local recurrence and distant metastases. Mesenchymal stem cells (MSCs), the adult pluripotent progenitors of multiple mesenchymal lineages, have an unusual tropism to preclinical tumor lesions. Both MSCs and CSCs or populations of tumor-initiating cells may also have similar reactogenicity or immunogenicity. Based on the information given above, a hypothesis is generated that MSCs may possess a potential of cellular vaccine for bio-prevention against tumorigenesis via eliciting cross-immunity and inducing active antibodies.
Medical Hypotheses 10/2010; 76(2):206-7. · 1.18 Impact Factor