Role of 5-HT receptors in neuropathic pain: potential therapeutic implications.

5-HT plays a crucial role in the progress and adjustment of pain both centrally and peripherally. The therapeutic action of the 5-HT receptors` agonist and antagonist in neuropathic pain have been widely reported in many studies. However, the specific roles of 5-HT subtype receptors have not been reviewed comprehensively. Therefore, we summarized the recent findings on multiple subtypes of 5-HT receptors in both central and peripheral nervous system in neuropathic pain, particularly, 5-HT1, 5-HT2, 5-HT3 and 5-HT7 receptors. In addition, 5-HT4, 5-HT5 and 5-HT6 receptors were also reviewed. Most of studies focused on the function of 5-HT subtype receptors in spinal level compared to brain areas. Based on these evidences, the pain process can be facilitated or inhibited that depending on the specific subtypes and the distribution of 5-HT receptors. Therefore, this review may provide potential therapeutic implications in treatment of neuropathic pain.

Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer.

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo.

Gastric cancer is reported as one of the leading factors resulting in tumor-related death worldwide. However, the therapies to suppress gastric cancer are still limited and the emergence of drug resistance makes it necessary to develop new and effective anticancer drugs and combinational chemotherapy schemes. Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various pharmacological activities, including anticancer. In this study, we investigated the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance. The findings suggested that LIQ, when applied in single therapy, could moderately inhibit the proliferation and migration of DDP-resistant gastric cancer cells, SGC7901/DDP. DDP and LIQ in combination induced G0/G1 cell cycle arrest to suppress the proliferation of gastric cancer cells, which were associated with the decrease of cyclin D1, cyclin A and cyclin-dependent kinase 4 (CDK4) and increase of p53 and p21. In addition, LIQ combined with DDP significantly induce apoptosis and autophagy both in vitro and in vivo through enhancing cleavage of caspase-8/-9/-3 and PARP, as well as LC3B and Beclin 1 expression. Significantly, the two drugs, when used in combination, prevented gastric cancer cell xenografts in nude mice in vivo. Together, the results revealed that application of DDP and LIQ in combination possessed a potential value against the growth of human gastric cancer with DDP resistance.

Effect of c-Met inhibitor SU11274 on human colon cancer cell growth.

BACKGROUND: Colon cancer is one of the major malignancies worldwide and it still remains resistant to much of the currently available chemotherapy. Downregulation of HGF/c-Met signaling pathway is an emerging therapy for cancer treatment. METHODS: In this study, the inhibitory effects of c-Met phosphorylation were observed with SU11274 on different colon cancer cell lines in vitro. RESULTS: The results revealed the significant inhibitory effects of SU11274 on cell proliferation and cell survival, in a time and dose-dependent manner. Furthermore, the inhibitory effects of SU11274 on different subgroups of colon cancer cells via the HGF/c-Met signaling pathway were implicated in this study. CONCLUSION: The results suggested the possible selective therapeutic effects of c-Met inhibitor on colon cancer.

Colonic polyps: application value of computer-aided detection in computed tomographic colonography.

BACKGROUND: Colonic polyps are frequently encountered in clinics. Computed tomographic colonography (CTC), as a painless and quick detection, has high values in clinics. In this study, we evaluated the application value of computer-aided detection (CAD) in CTC detection of colonic polyps in the Chinese population. METHODS: CTC was performed with a GE 64-row multidetector computed tomography (MDCT) scanner. Data of 50 CTC patients (39 patients positive for at least one polyp of ≥ 0.5 cm in size and the other 11 patients negative by endoscopic detection) were retrospectively reviewed first without computer-aided detection (CAD) and then with CAD by four radiologists (two were experienced and another two inexperienced) blinded to colonoscopy findings. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of detected colonic polyps, as well as the areas under the ROC curves (Az value) with and without CAD were calculated. RESULTS: CAD increased the overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the colonic polyps detected by experienced and inexperienced readers. The sensitivity in detecting small polyps (5 - 9 mm) with CAD in experienced and inexperienced readers increased from 82% and 44% to 93% and 82%, respectively (P > 0.05 and P < 0.001). With the use of CAD, the overall false positive rate and false negative rate for the detection of polyps by experienced and inexperienced readers decreased in different degrees. Among 13 sessile polyps not detected by CAD, two were ≥ 1.0 cm, eleven were 5 - 9 mm in diameter, and nine were flat-shaped lesions. CONCLUSIONS: The application of CAD in combination with CTC can increase the ability to detect colonic polyps, particularly for inexperienced readers. However, CAD is of limited value for the detection of flat polyps.

[Gene therapy targeting for carcinoma regulated by E2F-1 promoter].

OBJECTIVE: To study the selective effect to tumor cells mediated by a recombinant adenoviral vector carrying E2F-1 promoter. METHODS: The AdEasy-1 adenoviral vector system was used in this experiment. Several recombinant adenovirus with tumor-targeting E2F-1 promoter were constructed and then the E2F-1 promoter gene was checked by PCR and sequencing. The two adenovirus expressing GFP gene which is regulated by E2F-1 promoter or CMV promoter were used to respectively transfect tumor cells and non-proliferating normal cells, then observed and analyzed the different results caused by different promoters. Vpr gene was cloned into the targeting recombinant adenovirus. The new adenovirus named rvAdE2F-1/vpr was used to transfect tumor cells SMMC-7721, LS174T and non-proliferating normal cells H292, L-02. The surviving rate of each group was registered; the level of E2F-1 protein expressed in normal and tumor cell lines were checked by Western Blot. RESULT: E2F-1 promoter can regulate the downstream gene GFP selectively expressed in LS174T and its activity in LS174T was similar with CMV promoter's; Vpr gene regulated by E2F-1 promoter can suppress the proliferation of tumor cells and no toxicity to normal cells; In all of the tumor cells, a much higher level of E2F-1 was expressed compared with normal cell lines. E2F-1 promoter's activity correlated well with E2F-1 protein levels. CONCLUSIONS: E2F-1 promoter can control a selective cell killing to cancer cells, with no effect to normal cells. The system of E2F-1 promoter is a useful method for tumor-targeting gene therapy.