JAK2-Mediated Phosphorylation of Stress-Induced Phosphoprotein-1 (STIP1) in Human Cells.

Stress-induced phosphoprotein-1 (STIP1)-a heat shock protein (HSP)70/HSP90 adaptor protein-is commonly overexpressed in malignant cells, where it controls proliferation via multiple signaling pathways, including JAK2/STAT3. We have previously shown that STIP1 stabilizes the protein tyrosine kinase JAK2 in cancer cells via HSP90 binding. In this study, we demonstrate that STIP1 may act as a substrate for JAK2 and that phosphorylation of tyrosine residues 134 and 152 promoted STIP1 protein stability, induced its nuclear-cytoplasmic shuttling, and promoted its secretion into the extracellular space. We also found that JAK2-mediated STIP1 phosphorylation enhanced cell viability and increased resistance to cisplatin-induced cell death. Conversely, interference STIP1 with JAK2 interaction-attained either through site-directed mutagenesis or the use of cell-penetrating peptides-decreased JAK2 protein levels, ultimately leading to cell death. On analyzing human ovarian cancer specimens, JAK2 and STIP1 expression levels were found to be positively correlated with each other. Collectively, these results indicate that JAK2-mediated phosphorylation of STIP-1 is critical for sustaining the JAK2/STAT3 signaling pathway in cancer cells.

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.

[Case-control study on therapeutic effects of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries].

OBJECTIVE: To observe the effects of Chinese herb of promoting blood circulation to dissipate blood stasis on the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum of patients with mudslide injuries, and investigate the mechanisms of Chinese herb of promoting blood circulation to dissipate blood stasis in the treatment of mudslide injuries. METHODS: Patients with mudslide injuries who were translated from Zhouqu and Chengxian to Lanzhou from 12th August 2010 were divided into two groups (group A and group B). Twenty-five patients in group A, containing 15 males and 10 females, with an average age of (39.0 +/- 3.9) years. According to AIS scoring system, 1 point in 2 cases, 2 points in 3, 3 points in 17 and 4 points in 3. No patients got 5 points. Based on ISS rating system, 16 cases got 16 points or less, 7 cases rated between 16 and 25, only 2 cases were equal to 25 points or more. Another 25 patients were in group B, including 11 males and 14 females, with a mean age of (40.1 +/- 3.6) years; AIS score showed 3 cases got 1 point, 4 got 2 points, 16 got 3 and 2 got 4 points, no patients got 5 points. Patients in group B were divided into three parts by ISS score:15 cases (16 points or less); 9 cases (range 16 to 25 points) and 1 case (25 points or more). All the patients accepted general physical checkup. Eight patients were treated by surgical treatment in group A (3 patients were treated with open reduction plate fixation, 4 patients were treated with debridement BHID, and 1 patient underwent foreign body removal) and 6 cases in group B (1 patient was treated with craniocerebral surgery,2 patients were treated with chest surgery, and 3 patients were treated with soft tissue debridement). All the patients of two groups were treated by support treatment, detumescence treatment and preventing infection, complications. A seven days course of treatment with detumescence analgesic mixture 50 ml p.o. bid, traumatologic cleansing liquid 20 ml ad us, ext 20 to 30 min qid to group A,continuous treatment of two courses. Using immunometric assay to determine serum levels of inflammatory cytokine TNF-alpha, IL-6 at the 2nd, 7th, 14th days after admission. Analysis of data were done with the help of SPSS 16.0 statistic software. RESULTS: There were no statistical differences of TNF-alpha, IL-6 between two groups at the second day after admission, and there were statistical differences at the 7th and 14th days between two groups. There were significant differences of TNF-alpha and IL-6 levels between the 7th day and the 2nd day, the 14th day and 2nd day after admission. CONCLUSION: The Chinese herb of promoting blood circulation to dissipate blood stasis can inhibit the release of inflammatory factor after traumatism.