Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, p...Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-ceU infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.展开更多
Objective:Previous reports have shown that the gene promoter region of retinoic acid receptor β(RARβ) was hypermethylated in cervical carcinoma,implying the inhibition of gene transcription.The aim of this study was...Objective:Previous reports have shown that the gene promoter region of retinoic acid receptor β(RARβ) was hypermethylated in cervical carcinoma,implying the inhibition of gene transcription.The aim of this study was to investigate the association of cervical cancer development with the RARβ gene expression at the mRNA and protein level to assess the impact of RARβ as a marker for early detection of the cancer.Methods:We collected 126 cases of formalin fixed and paraffin embedded cervical tissue specimens as well as 37 cases of fresh tissue samples from women with cervicitis,cervical intraepithelial neoplasia(CIN) and cervical squamous cell carcinoma(CSCC).The RARβ mRNA and protein expression was detected by quantitative RT-PCR and immunohistochemistry,respectively.Results:(1) The mRNA expression of RARβ in CIN and cervical cancer was markedly decreased compared to cervicitis with a statistically very significant difference,but no difference was found between CIN and cervical cancer.(2) RARβ protein was normally expressed in the epithelial cells of cervicitis and partially lost in a few cases,but with the development of cervical lesion pathogenesis and cancer,a significant loss of protein expression was detected in CIN(38%) and CSCC(57%) compared to cervicitis(P < 0.01).Conclusion:The downregulation of RARβ transcription or loss of protein expression is an important indicator of cervical cancer and its precursur lesions.The detection of RARβ expression coupled with aberrant methylation of the gene may become a biomarker for the early prognosis or diagnosis of the cancer.展开更多
Objective: To study the role of Th1/Th2 cytokines in thepathogenesis of recurrent genital herpes (RGH), and tobetter understand the relationship between them. Methods: A two-color immunofluorescent staining of cellsur...Objective: To study the role of Th1/Th2 cytokines in thepathogenesis of recurrent genital herpes (RGH), and tobetter understand the relationship between them. Methods: A two-color immunofluorescent staining of cellsurface antigen and intracellular cytokines for flowcytometric analysis was used for CD_3, IL-2, IL-10, IL-12,IFN-γ and TNF-α in CD_3^+ T-lymphocytes in activatedperipheral blood mononuclear cells of patients with RGH. Results: Compared to controls, patients with RGHshowed fewer CD_3^+ T cells (P<0.05) and IL-2 producing andIFN-γ producing T cells (P<0.02 and P<0.001, respectively)after in vitro stimulation with PMA and ionomycin in thepresence of a protein transport inhibitor. More IL-10producing and IL-12 producing T cells were found inpatients with RGH (P<0.01). There was no significantdifference in the number of TNF-α producing cells betweenRGH patients and controls (P<0.05). Conclusion: RGH patients showed relatively more Th2cytokines. The imbalance between Th1 and Th2 cytokinesresults in inhibitory effects on a series of cell-immuneresponses, which may play an important role in thepathogenesis of RGH.展开更多
基金supported by the Viragh Foundation(L.Z.)National Institutes of Health(NIH)(Grant No.K23 CA148964,L.Z.)the NCI SPORE in Gastrointestinal Cancers(Grant No.P50 CA062924,L.Z.)
文摘Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-infiltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-ceU infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.
基金Supported by a grant from the Natural Science Foundation of China (No. 30760279)
文摘Objective:Previous reports have shown that the gene promoter region of retinoic acid receptor β(RARβ) was hypermethylated in cervical carcinoma,implying the inhibition of gene transcription.The aim of this study was to investigate the association of cervical cancer development with the RARβ gene expression at the mRNA and protein level to assess the impact of RARβ as a marker for early detection of the cancer.Methods:We collected 126 cases of formalin fixed and paraffin embedded cervical tissue specimens as well as 37 cases of fresh tissue samples from women with cervicitis,cervical intraepithelial neoplasia(CIN) and cervical squamous cell carcinoma(CSCC).The RARβ mRNA and protein expression was detected by quantitative RT-PCR and immunohistochemistry,respectively.Results:(1) The mRNA expression of RARβ in CIN and cervical cancer was markedly decreased compared to cervicitis with a statistically very significant difference,but no difference was found between CIN and cervical cancer.(2) RARβ protein was normally expressed in the epithelial cells of cervicitis and partially lost in a few cases,but with the development of cervical lesion pathogenesis and cancer,a significant loss of protein expression was detected in CIN(38%) and CSCC(57%) compared to cervicitis(P < 0.01).Conclusion:The downregulation of RARβ transcription or loss of protein expression is an important indicator of cervical cancer and its precursur lesions.The detection of RARβ expression coupled with aberrant methylation of the gene may become a biomarker for the early prognosis or diagnosis of the cancer.
文摘Objective: To study the role of Th1/Th2 cytokines in thepathogenesis of recurrent genital herpes (RGH), and tobetter understand the relationship between them. Methods: A two-color immunofluorescent staining of cellsurface antigen and intracellular cytokines for flowcytometric analysis was used for CD_3, IL-2, IL-10, IL-12,IFN-γ and TNF-α in CD_3^+ T-lymphocytes in activatedperipheral blood mononuclear cells of patients with RGH. Results: Compared to controls, patients with RGHshowed fewer CD_3^+ T cells (P<0.05) and IL-2 producing andIFN-γ producing T cells (P<0.02 and P<0.001, respectively)after in vitro stimulation with PMA and ionomycin in thepresence of a protein transport inhibitor. More IL-10producing and IL-12 producing T cells were found inpatients with RGH (P<0.01). There was no significantdifference in the number of TNF-α producing cells betweenRGH patients and controls (P<0.05). Conclusion: RGH patients showed relatively more Th2cytokines. The imbalance between Th1 and Th2 cytokinesresults in inhibitory effects on a series of cell-immuneresponses, which may play an important role in thepathogenesis of RGH.
