MiR-199a-5p represses the stemness of cutaneous squamous cell carcinoma stem cells by targeting Sirt1 and CD44ICD cleavage signaling.

Tumorigenic cancer stem cells (CSCs) exist in various tumors including the cutaneous squamous cell carcinoma (cSCC) as a minor subpopulation and are tightly associated with metastasis and therapeutic resistance. Better understanding of CSCs properties is essential for the novel therapeutic strategy targeted toward these cancers. The cSCC stem cells (cSCCSCs) were enriched from a cSCC cell line A431 by repeated sphere culture, and identified via the expression analysis of stemness marker genes and CD44 proteolysis. MiR-199a-5p was previously reported to be related with the proteolysis modulation of CD44, so the specific regulation mechanisms were verified by overexpression in vitro and in vivo. MiR-199a-5p is under-expressed in cSCCSCs and functions as a tumor suppressive molecule. Overexpression of miR-199a-5p reduced the stemness of cSCCSCs and inhibited cell proliferation. By targeting the deacetylase Sirt1, miR-199a-5p inhibited cellular proteolysis of CD44 and reduced the CD44 intracellular domain (CD44ICD) release and nuclear translocation. Overexpression of CD44ICD reversed the effects of miR-199a-5p overexpression or Sirt1 silencing, and increased the transcriptional expression of stemness genes. Our results revealed that the miR-199a-5p/Sirt1/CD44ICD signaling pathway regulates cSCCSCs progression by affecting its migration ability and tumorigenicity, therefore can be utilized to develop a curative approach for cSCC.Abbreviations: CSCs: cancer stem cells; cSCC cutaneous squamous cell carcinoma; cSCCSCs: cSCC stem cells; CD44ICD: CD44 intracellular domain; HA: hyaluronic acid; HNSCC: hand and neck squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma;MMPs: matrix metalloproteinases; SFM: sphere formation medium; EGF: epidermal growth factor; bFGF: basic fibroblast growth factor; BSA: bovine serum albumin; CCK-8: cell counting kit-8.

Trend Analysis of Betel Nut-associated Oral Cancer and Health Burden in China.

OBJECTIVE: To forecast the future trend of betel nut-associated oral cancer and the resulting burden on health based on historical oral cancer patient data in Hunan province, China. METHODS: Oral cancer patient data in five hospitals in Changsha (the capital city of Hunan province) were collected for the past 12 years. Three methods were used to analyse the data; Microsoft Excel Forecast Sheet, Excel Trendline, and the Logistic growth model. A combination of these three methods was used to forecast the future trend of betel nut-associated oral cancer and the resulting burden on health. RESULTS: Betel nut-associated oral cancer cases have been increasing rapidly in the past 12 years in Changsha. As of 2016, betel nuts had caused 8,222 cases of oral cancer in Changsha and close to 25,000 cases in Hunan, resulting in about ¥5 billion in accumulated financial loss. The combined trend analysis predicts that by 2030, betel nuts will cause more than 100,000 cases of oral cancer in Changsha and more than 300,000 cases in Hunan, and more than ¥64 billion in accumulated financial loss in medical expenses. CONCLUSION: The trend analysis of oral cancer patient data predicts that the growing betel nut industry in Hunan province will cause a humanitarian catastrophe with massive loss of human life and national resources. To prevent this catastrophe, China should ban betel nuts and provide early oral cancer screening for betel nut consumers as soon as possible.

Pretreatment of Shaoyao Gancao Decoction () alters pharmacokinetics of intravenous paclitaxel in rats.

OBJECTIVE: To investigate the effect of Shaoyao Gancao Decoction (, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats. METHODS: Paclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0. RESULTS: The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC0-t, from 4 820±197 to 4 205±186 ng·mL-1·-1) and AUC0-∞ (from 5 237±280 to 4 514±210 ng·mL-1·-1) significantly decreased in response to the 14-day pretreatment with SGD. The values of Vdss (L/kg) were 10.74±1.08 and 9.35±0.49, those of CL (L/kg) were 0.67±0.03 and 0.57±0.03 and the t1/2 (h) values were 11.17±0.84 and 11.32±0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUC0-t and AUC0-∞ values decreased by 13% and 14% (P<0.01), respectively. The area under the curve decreased signifificantly (P<0.01), and the total clearance increased by 1.2-fold (P<0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel. CONCLUSIONS: SGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.

[Myoepithelial carcinoma of salivary glands: a clinical analysis of 13 cases].

PURPOSE: This study retrospectively analyzed the clinical data of 13 patients with myoepithelial carcinoma of salivary glands for improving the accuracy of diagnosis and treatment outcome. METHODS: Thirteen cases with myoepithelial carcinoma of the salivary glands in Xiangya Hospital from January 1992 to September 2010 were reviewed, including the clinical biological behavior, diagnosis,treatment and prognosis. RESULTS: Thirteen patients included 6 men and 7 women, aged from 14 to 71 years (median 40 years).The tumor occurred predominantly in the parotid gland (53.8%).Among the 13 cases,7 were clinically misdiagnosed as benign tumors and 2 were misdiagnosed pathologically. All cases underwent operation. Two cases received surgery plus adjuvant chemotherapy; five cases underwent surgery plus adjuvant radiotherapy. 4(30.8%) had cervical lymph node metastasis and 2 cases(15.4%) developed distant metastasis. Follow-up time ranged from 3 months to 6 years. Six cases died of local recurrence or distal metastasis. CONCLUSIONS: Myoepithelial carcinoma of the salivary glands is a rare tumor. The diagnosis is depended on histology and immunohistochemistry. The tumor has a high rate of distant metastasis and high rate of lymph node metastasis in T3 to T4 cases. Radical surgery is the treatment of choice. Elective neck dissection should be considered in T3 to T4 cN0 cases. The effect of chemotherapy and radiotherapy needs to be investigated.