No abstract

Paclitaxel, isolated from Taxus brevifolia, is considered to be an efficacious agent against a wide spectrum of human cancers, including human cervical cancer. However, dose-limiting toxicity and high cost limit its clinical application. Curcumin, a nontoxic food additive, has been reported to improve paclitaxel chemotherapy in mouse models of cervical cancer. However, the underlying mechanisms remain unclear. In this study, two human cervical cancer cell lines, CaSki [human papilloma virus (HPV)16-positive] and HeLa (HPV18-positive), were selected in which to investigate the effect of curcumin on the anticancer action of paclitaxel and further clarify the mechanisms. Flow cytometry and MTT analysis demonstrated that curcumin significantly promoted paclitaxel-induced apoptosis and cytotoxicity in the two cervical cell lines compared with that observed with paclitaxel alone (P<0.05). Reverse transcription-polymerase chain reaction indicated that the decline of HPV E6 and E7 gene expression induced by paclitaxel was also assisted by curcumin. The expression levels of p53 protein and cleaved caspase-3 were increased significantly in the curcumin plus paclitaxel-treated HeLa and CaSki cells compared with those in the cells treated with paclitaxel alone (P<0.01). Significant reductions in the levels of phosphorylation of IκBα and the p65-NF-κB subunit in CaSki cells treated with curcumin and paclitaxel were observed compared with those in cells treated with paclitaxel alone (P<0.05). This suggests that the combined effect of curcumin and paclitaxel was associated with the NF-κB-p53-caspase-3 pathway. In conclusion, curcumin has the ability to improve the paclitaxel-induced apoptosis of HPV-positive human cervical cancer cell lines via the NF-κB-p53-caspase-3 pathway. Curcumin in combination with paclitaxel may provide a superior therapeutic effect on human cervical cancer.

Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-κB-lin28B pathway. In an in vivo melanoma model, we demonstrate that miR-98 reduces melanoma metastasis and increases survival in part by reducing IL-6 levels; it also decreases Stat3 and p65 phosphorylation as well as lin28B mRNA levels. These results suggest that miR-98 inhibits melanoma metastasis in part through a novel miR-98-IL-6-negative feedback loop.

Vitiligo is a common skin disease for which immunomodulating calcineurin inhibitors have been considered reasonable treatment. We searched the MEDLINE, Embase, and Cochrane central register of controlled trials databases for articles published prior to September 2014. Thirteen studies were included in the meta-analysis. After pooling the trials, we concluded that calcineurin inhibitors showed a better therapeutic effect on vitiligo than placebo, according to lesion report (RR = 2.62, 95%CI, 1.39-4.93, p = 0.003) and patient report (RR = 1.42, 95%, 0.87-2.31, p = 0.157). Subgroup analysis was performed to determine whether the combination with phototherapy was a source of heterogeneity. The trial sequence analysis indicated that the results of combined therapy by lesion report were reliable and conclusive. However, in the patient report trials, the frequency of lesions on the hand and foot was higher, and the effect of combined therapy was still not significant. Calcineurin inhibitors showed a better therapeutic effect than placebo in the treatment of vitiligo with phototherapy. However, the typical UV-resistant sites (i.e., hand and foot) were still difficult to cure even with combined therapy. Because of concerns about photocarcinogenesis, the clinical application of combined therapy should be explored with caution.

FAHT cream is efficacious, well tolerated, and has a high margin of safety for the treatment of moderate and severe melasma in the Chinese population.

A 51‐year‐old Chinese woman (phototype III) presented to our dermatology clinic with a 3‐month history of asymptomatic pigmented maculae on the lower limbs that developed in the 11th month of amenorrhea. She had noticed no other areas of pigmentary change and denied any inflammatory episode or topical medication before their development. No personal or family history of hormonal imbalance or pigmentary demarcation lines (PDLs) was found. Physical examination revealed broad, band‐like pigmentation symmetrically distributed all over the flexor aspects of the lower limbs (Fig. 1). The medial borders of the pigmented areas were sharply demarcated, but the lateral borders merged imperceptibly into the normal skin. The patient was otherwise healthy. Laboratory examination, including full blood count, liver tests, triiodothyronine (T3), thyroxine (T4), and thyrotropic‐stimulating hormone (TSH), were normal. Hormonal investigations (Table 1) were within normal limits, except that estradiol (E2) was sharply decreased and follicle‐stimulating hormone (FSH) was highly elevated. Ultrasonic B‐mode examination showed a normal uterus and ovaries. No treatment was applied to the lesions. At a follow‐up visit, 16 months after onset, the pigmentary lines had resolved spontaneously. Moreover, the titers of hormones in serum had moved closer to normal values (Table 1). 1 Pigmentary demarcation lines on the buttocks and flexor aspect of the legs. The outer part is darker Hormone investigations on the serum of our patient with pigmentary demarcation lines (PDLs) 3 months after onset 16 months after onset Normal results Abnormal results Normal results Abnormal results 1. Prolactin1. Estradiol, 12.9 pmol/L
Normal, 40.0–100 pmol/L1. Prolactin1. Estradiol, 36.46 pmol/L
Normal, 40.0–100 pmol/L2. Luteotropic hormone2. Follicle‐stimulating hormone, 94.3 U/L
Normal, 1.5–33.4 U/L2. Luteotropic hormone2. Follicle‐stimulating hormone, 53.2 U/L
Normal, 1.5–33.4 U/L3. Progestone3. Progestone4. Total testosterone4. Total testosterone5. Free triiodothyronine5. Free triiodothyronine6. Free thyroxine6. Free thyroxine7. Thyroid‐stimulating hormone7. Thyroid‐stimulating hormone