Cucurbitacin E inhibits cellular proliferation and induces apoptosis in melanoma by suppressing HSDL2 expression.

BACKGROUND: Melanoma is among the most aggressive types of skin malignancy and can have an unpredictable clinical course. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma. METHODS: HSDL2 protein levels were examined by immunohistochemistry. The roles of HSDL2 in cell proliferation and apoptosis were identified by CCK-8 and colony formation assays. The function of HSDL2 in cell apoptosis was analysed by flow cytometry. Western blotting, cell proliferation and apoptosis and a xenograft tumour model were utilized to explore the inhibitory functions and mechanisms of CuE in melanoma. RESULTS: HSDL2 is overexpressed in melanoma and promotes melanoma progression by activating the ERK and AKT pathways. CuE could inhibit the ERK and AKT pathways by decreasing HSDL2 expression; therefore, CuE could inhibit melanoma growth in vitro and in vivo. CONCLUSION: HSDL2 may be a promising therapeutic target against melanoma, and CuE can inhibit melanoma by downregulating HSDL2 expression.

Inhibitory effect of kaempferol on mouse melanoma cell line B16 in vivo and in vitro.

INTRODUCTION: Melanoma is a malignant tumour and is the leading cause of death in patients with skin tumours. AIM: Kaempferol belongs to a class of flavonoids, and is associated with many biological functions such as anti-inflammatory, anti-oxidation and anti-cancer. However, the inhibitory effect of kaempferol on melanoma still remains unclear. MATERIAL AND METHODS: The effect of kaempferol on melanoma was determined by conducting both in vitro and in vivo experiments using MTT assay and flow cytometry. RESULTS: The in vitro results revealed that kaempferol obviously inhibited cell viability of melanoma B16 cells, induced cell cycle arrest and cell apoptosis. The in vivo results showed that kaempferol effectively inhibited the growth of mice xenografts. More importantly, kaempferol down-regulated the number of MDSC cells and up-regulated the number of NKT cells and CD8 T cells in the spleen. CONCLUSIONS: Taken together, these findings indicate that kaempferol might play an inhibitory role in the growth of melanoma by enhancing anti-tumour immunity of organisms.

Internal Cylinder Identification Based on Different Transmission of Longitudinal and Shear Ultrasonic Waves.

We have built a Fizeau fiber interferometer to investigate the internal cylindrical defects in an aluminum plate based on laser ultrasonic techniques. The ultrasound is excited in the plate by a Q-switched Nd:YAG laser. When the ultrasonic waves interact with the internal defects, the transmitted amplitudes of longitudinal and shear waves are different. The experimental results show that the difference in transmission amplitudes can be attributed to the high frequency damping of internal cylinders. When the scanning point is close to the internal defect, the longitudinal waves attenuate significantly in the whole defect area, and their amplitude is always smaller than that of shear waves. By comparing the transmitted amplitudes of longitudinal and shear waves at different scanning points, we can achieve a C scan image of the sample to realize the visual inspection of internal defects. Our system exhibits outstanding performance in detecting internal cylinders, which could be used not only in evaluating structure cracks but also in exploring ultrasonic transmission characteristics.

Combination of the neutrophil to lymphocyte ratio and serum toluidine red unheated serum test titer as a predictor of neurosyphilis in HIV-negative patients.

The present study explored the associations of the neutrophil to lymphocyte ratio (NLR) and the serum toluidine red unheated serum test (TRUST) titer with neurosyphilis (NS). The present retrospective study examined 87 NS patients and 80 Non-NS patients from an HIV-negative cohort and 1:1 age- and gender-matched healthy controls. The results demonstrated that the NLR was increased in both NS and Non-NS groups compared with that in the healthy controls (P<0.001 and P=0.01, respectively). The NLR and serum TRUST titer in the NS group were significantly higher than those in the Non-NS group (P=0.004 and P<0.001, respectively). The NLR was positively correlated with the serum TRUST titer (r=0.298, P<0.001). Age, elevated NLR and serum TRUST titer were distinctly associated with NS by binomial logistic regression analysis [odds ratio (OR)=1.10, P<0.001; OR=1.36, P=0.028; OR=3.07, P<0.001; respectively]. The cut-off values for the NLR and serum TRUST titer were 1.97 and 1:8, respectively. A significantly higher sensitivity of 90.8% was obtained for screening out NS with a combination of the NLR and serum TRUST titer compared with each test alone. Age, elevated NLR and serum TRUST titer were associated with NS. The combination of NLR and serum TRUST titer is a potential predictor for NS, and the reduced NLR and serum TRUST titer at the 6-month follow up suggested that the NLR and serum TRUST titer were biomarkers for monitoring the disease course.

Overexpression of CDCA8 promotes the malignant progression of cutaneous melanoma and leads to poor prognosis.

Cutaneous melanoma is very aggressive and results in high mortality rates for cancer patients. Determining molecular targets is important for developing novel therapies for cutaneous melanoma. Cell division cycle associated 8 (CDCA8) is a putative oncogene that is upregulated in multiple types of cancer. The present study aimed to examine the role of CDCA8 in cutaneous melanoma, with a focus on the association of its expression to prognosis and metastasis. First, the mRNA expression of CDCA8 in cutaneous melanoma tissues was investigated using the ONCOMINE and Gene Expression Omnibus (GEO) databases. Furthermore, the relationship between the expression of CDCA8 and cutaneous melanoma patient survival was analyzed using a Kaplan­Meier plot and Log Rank test. In addition, the effects of CDCA8 on proliferation, migration and invasion of cutaneous melanoma cell lines were investigated using reverse transcription­quantitative polymerase chain reaction (RT­qPCR), Cell Counting kit­8, colony formation assay, wound healing and Matrigel assay. Finally, the expression levels of key proteins related to the Rho­associated coiled­coil­containing protein kinase (ROCK) signaling pathway were measured by western blot assay. The results demonstrated that CDCA8 was overexpressed in cutaneous melanoma tissues and cells lines compared with normal tissues, and high expression of CDCA8 was significantly associated with poorer prognosis in patients with cutaneous melanoma. In in vitro experiments, CDCA8 knockdown inhibited A375 and MV3 cell proliferation, migration and invasion. In addition, CDCA8 knockdown reduced the phosphorylation levels of ROCK1 and myosin light chain, two downstream effector proteins of the ROCK pathway. In summary, the present findings suggested that CDCA8 may be a promising therapeutic target for the treatment of cutaneous melanoma.

Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death.

BACKGROUND: Melanoma is a leading cause of cancer death worldwide, and SMI-4a and G-Rh2 exert anti-tumor activity in multiple cancer. However, SMI-4a as well as a synergistic relationship between SMI-4a and G-Rh2 in anti-melanoma capacity are still unknown. Therefore, we investigated the effects of SMI-4a and combined SMI-4a with G-Rh2 on the viability, apoptosis and autophagy of melanoma, and to preliminarily explore the underlying mechanism of SMI-4a and combined SMI-4a with G-Rh2 in inhibiting tumor growth. METHODS: Cell viability was examined with cell counting Kit 8 assay and colony formation assay; Apoptosis was evaluated by flow cytometry and Caspase 3/7 activity assay; Western blotting was used to test proteins related to autophagy and the AKT/mammalian target of rapamycin (mTOR) signaling pathway; Tumor xenograft model in BALB/c nude mice was performed to evaluate the effects of SMI-4a and combined SMI-4a with G-Rh2 in anti-melanoma in vivo. RESULTS: SMI-4a, a pharmacological inhibitor of PIM-1, could decrease cell viability, induce apoptosis, and promote Caspase 3/7 activity in both A375 and G361 melanoma cells, and SMI-4a inhibited tumor growth by inducing autophagy via down-regulating AKT/mTOR axis in melanoma cells. Furthermore, G-Rh2 amplified the anti-tumor activity of SMI-4a in melanoma cells via strengthening autophagy. CONCLUSIONS: Our results suggested that SMI-4a could enhance autophagy-inducing apoptosis by inhibiting AKT/mTOR signaling pathway in melanoma cells, and G-Rh2 could enhance the effects of SMI-4a against melanoma cancer via amplifying autophagy induction. This study demonstrates that combined SMI-4a and G-Rh2 might be a novel alternative strategy for melanoma treatment.