ABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of antigen-processing machinery (APM) component defects in HLA class I antigen down-regulation in laryngeal squamous cell carcinoma (SCC) and to assess the clinical significance of these defects.</p><p><b>METHODS</b>Fifty-one formalin-fixed, paraffin-embedded SCC specimens were examined for the expressions of APM component transporter associated with antigen processing (TAP1) and low molecular weight polypeptide (LMP-7) and HLA class I antigen by immunohistochemistry.</p><p><b>RESULTS</b>HLA class I antigens, TAP-1 and LMP-7 expressions were down-regulated in 56.9% (29/51), 39.2% (20/51) and 45.1% (23/51) of the tested specimens respectively, whereas HLA class I antigens, TAP-1 and LMP-7 expressions lost in 21.6% (11/51), 33.3% (17/51) and 27.5% (14/51) of the tested specimens respectively. TAP-1 and LMP-7 expressions were significantly correlated with HLA class I antigen expression (r=0.460, P<0.05 and r=0.685, P<0.05, respectively). HLA class I antigens down-regulation was significantly correlated with T stage (χ2=8.61, P<0.05). Both TAP-1 and LMP-7 down-regulations were significantly correlated with T stage (χ2 values were 9.72 and 8.97 respectively, P<0.05) and TNM stage (χ2 values were 9.18 and 7.70 respectively, P<0.05). TAP-1, LMP-7 and HLA class I antigen down-regulations were significantly associated with reduced patients' overall survival (P<0.05) and disease-free survival (P<0.05). Multivariate analysis showed lymph node metastasis, recurrence and HLA class I antigen down-regulation were unfavorable prognostic factors (P<0.05).</p><p><b>CONCLUSIONS</b>Down-regulated expressions of HLA class I antigen and APM component TAP-1 and LMP-7 occur frequently in laryngeal squamous cell carcinoma, by which cancer cells could avoid immune surveillance, while HLA class I antigen down-regulation is a major contributing factor to tumour progression and mortality.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , ATP Binding Cassette Transporter, Subfamily B, Member 2 , ATP-Binding Cassette Transporters , Metabolism , Antigen Presentation , Carcinoma, Squamous Cell , Allergy and Immunology , Metabolism , Pathology , Gene Expression Regulation, Neoplastic , Histocompatibility Antigens Class I , Metabolism , Laryngeal Neoplasms , Allergy and Immunology , Metabolism , Pathology , Proteasome Endopeptidase Complex , MetabolismABSTRACT
Human papillomavirus (HPV) infection is very common but with limited therapies available. Although the prophylactic vaccination will be promoted worldwide soon, it can only show its benefits decades later. For individuals who already have established infections and dysplasias, it has little efficacy. In contrast, the therapeutic vaccines bridge the temporal deficit by fighting against the established HPV infections and HPV-related diseases. HPV oncogenes may be delivered in viral and bacterial vectors, in peptides or protein, in nucleic acid form, or in cell-based vaccines. This review summarizes the clinical trials of HPV therapeutic vaccines under the way and the different preclinical research strategies that are under investigations.
Subject(s)
Animals , Female , Humans , Cancer Vaccines , Therapeutic Uses , Uterine Cervical Dysplasia , Therapeutics , Virology , Condylomata Acuminata , Therapeutics , Virology , Papillomavirus Infections , Therapeutics , Papillomavirus Vaccines , Therapeutic Uses , Uterine Cervical Diseases , Therapeutics , Virology , Uterine Cervical Neoplasms , Therapeutics , VirologyABSTRACT
<p><b>OBJECTIVE</b>To study the specific protection of myeloid cells from chemotherapeutic agents and radiation.</p><p><b>METHODS</b>The recombinant retroviral vectors containing MDR1 gene and MnSOD gene regulated by APN myeloid promoter were constructed and introduced into myeloblastic cell line KG1a and hepatoma cell line BEL7402. The resistance of the cells to antitumor drugs and radiation were analyzed by cell survival assay. In vivo, the murine bone marrow cells were isolated and infected by the retroviral particles, which were transplanted into recipient mouse treated with paclitaxel or X-ray. The murine white blood cell (WBC) was counted in order to assay the effects of MDR1 or MnSOD gene on hematopoiesis in the course of chemotherapy and radiotherapy.</p><p><b>RESULTS</b>The resistance to chemotherapeutic agents such as cochicine, Vp-16, vincristine, doxorubcin and paclitaxel were elevated markedly by 10.6, 10.4, 11.2, 4.2 and 14.2 folds in KG1a cell line transduced with MDR1 gene. The resistance to radiation increased 3.7 folds at the dose of 10 Gy compared with parental cells in KGla cell line transduced with MnSOD gene derived by APN promoter. In contrast, the chemosensitivity and the radiosensitivity showed no significant change in BEL 7402 cell line transduced with MDR1 gene and MnSOD gene. In vivo, the WBC counts in the mouse introduced with MDR1 gene or MnSOD gene were higher than those in the control mouse (P < 0.01).</p><p><b>CONCLUSION</b>The expression of MDR1 gene and MnSOD gene regulated by APN myeloid promoter is effective on myelo-specific protection without enhancing the resistance of tumor cells in vitro. The hematopoiesis can be reconstituted in vivo during anticancer drug or radiation treatment. This study may provide experimental evidence and new clues for myeloprotection of cancer patients being treated with chemotherapy and/or radiotherapy.</p>