The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumour formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervical cancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervical cancer tissues using tissue microarray slides as well as cancer cell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancer cell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervical cancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervical cancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of downstream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in HeLa and SiHa cervical cancer cell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in HeLa and SiHa cancer cell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers.
Concentrations of eight heavy metals (i.e., Fe, Mn, Cr, Ni, Cu, Zn, Cd and Pb) in the seawater, suspended particulate matter (SPM) and sediments of the Zhanjiang Bay were investigated in 2014. The concentrations of metals were generally low in the seawater and sediments of the Zhanjiang Bay in winter and summer, indicating good environmental quality in the bay. The distribution patterns of Fe and Mn in three phases indicated the influence of terrestrial inputs. The partition coefficients log(Kd) between the dissolved and particulate phases showed a general decrease in the order of Pb≈Cd>Fe≈Mn>Ni≈Cr>Zn>Cu. The concentrations of some metals in the dissolved and particulate phases showed seasonal variations. Phytoplankton production and complexation reactions may contribute to this phenomenon. The relationships among metals in different phases were different, and there were few close relationships among metals in the dissolved phase, many close relationships in the particulate phase, and more close relationships in the sedimentary phase. This finding may be related to the different mobility levels of metals in different phases.
PurposeThe aim of this paper is to explore how small and medium enterprises (SMEs) in Taiwan employ technology to participate in global supply chains so as to respond to the Fourth Industrial Revolution.Design/methodology/approachThis study chose four small to medium textile SMEs using qualitative exploratory multiple case studies to examine their participation in the global value chain (GVC) and under the context of Industry 4.0.FindingsThis study proffered a strategic model for the innovative integration of textile manufacturing companies and cultural content industry into the global market. The results identified four types of cross-disciplinary value creation strategies by Industry 4.0-driven technology and cultural content infusion: enhancing digital product display capabilities, integrating cultural content design and online marketing, creative brand marketing with cyber-physical channel integration and emotional marketing incorporated with smart services.Originality/valueThe author proposed the following cross-disciplinary value creation strategies for clothing SMEs in Taiwan: (1) enhancing digital product display capabilities, (2) integrating cultural content design and online marketing, (3) creative brand marketing with cyber-physical integration and (4) emotional marketing incorporated with smart services. Using these strategies, SMEs can incorporate cultural and lifestyle aspects into products and services and embed themselves in the global marketing links of GVCs.
To improve response rate of monotherapy of immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, it is validated that BCAT2 shapes a noninflamed TME in bladder cancer. The outcomes of multiomics indicate that BCAT2 has an inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities of proinflammatory cytokine/chemokine‐related pathways and T‐cell‐chemotaxis pathway. Immunoassays reveal that secretion of CD8+T‐cell‐related chemokines keeps a robust negative correlation with BCAT2, generating a decreasing tendency of CD8+T cells around BCAT2+ tumor cells from far to near. Cotreatment of BCAT2 deficiency and anti‐PD‐1 antibody has a synergistic effect in vivo, implying the potential of BCAT2 in combination therapy. Moreover, the value of BCAT2 in predicting efficacy of immunotherapy is validated in multiple immunotherapy cohorts. Together, as a key molecule in TME, BCAT2 is an emerging target in combination with ICB and a biomarker of guiding precision therapy.
BackgroundAndropause and psychiatric disorders are associated with various symptoms in aging males and are part of the differential diagnosis of depression and anxiety. This study was designed to investigate the relationship between symptoms of aging, anxiety, and depression, and to determine if sexual dysfunction could be a differentiating characteristic in the psychiatric outpatient clinic.MethodsOne hundred seventy-six male psychiatric outpatients participated in the study and completed self-reported measures assessing symptoms of aging, depression, and anxiety. Symptoms of aging were assessed by the Aging Males’ Symptoms scale. Anxiety and depression were measured by the Hospital Anxiety and Depression Scale. Erectile dysfunction was considered if a response to item 15 on the Aging Males’ Symptoms scale (impaired sexual potency) was rated with 4 or 5 points. Affective disturbance was assessed by the total scores of the Hospital Anxiety and Depression Scale.ResultsAge was correlated with less anxiety and more sexual symptoms. Anxiety and depression were associated with more severe symptoms of aging, and depression was associated with more sexual symptoms than was anxiety. Impaired sexual potency was the only sexual symptom not significantly associated with depression and anxiety. Depression was associated with an interspousal age gap of ≥6 years. The point prevalence of erectile dysfunction was 28.4%, and age and affective disturbance were associated with the risk of erectile dysfunction.ConclusionImpaired sexual potency should raise the suspicion of androgen deficiency rather than depression and anxiety among middle-aged or older male psychiatric outpatients.
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