Biomedical subjects

Toshihiko Torigoe

Publications and source records attributed to Toshihiko Torigoe.

At least 19 recordsLinked to original sources

PubMed2007

Plasma neuropeptides in patients undergoing lumbar discectomy.

STUDY DESIGN: A prospective analysis of patients with lumbar disc herniation (LDH). OBJECTIVES: To determine the role of neuropeptides as a biochemical signature of pain states in patients with LDH. SUMMARY OF BACKGROUND DATA: Increases in the plasma level of neuropeptides have been reported in patients suffering from a variety of painful conditions. However, there is no such report on patients with LDH. METHODS: From a total of 27 patients with a single-level LDH, blood samples were collected before and 3 weeks after lumbar discectomy. Plasma levels of alpha calcitonin gene-related peptide (CGRP), galanin, neuropeptide Y, and substance P were determined by using enzyme-linked immunosorbent assay. The association or correlation between preoperative concentration of plasma neuropeptides and gender, patients' age, and VAS were analyzed statistically. Also, the concentration of plasma neuropeptides was compared before and after lumbar discectomy. RESULTS: Preoperative plasma levels of CGRP were correlated significantly with the extent of sciatica as determined by VAS. In addition, plasma levels of CGRP and galanin significantly decreased after lumbar discectomy in line with the disappearance of pain symptoms. CONCLUSIONS: These findings indicate the role of plasma CGRP and possibly galanin as a systemic neurochemical signature of pain states in patients with LDH.

Adolescent↗

PubMed2006

Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5.

With the goal of establishing efficacious peptide-based immunotherapy for patients with bone and soft tissue sarcomas, we previously identified the cytotoxic T lymphocyte-defined osteosarcoma antigenic gene Papillomavirus binding factor. The present study was designed to determine the status of HLA class I expression in osteosarcoma and other bone and soft tissue sarcomas. Seventy-four formalin-fixed paraffin-embedded specimens of various bone and soft tissue sarcomas, including 33 osteosarcomas, were stained with the anti-HLA class I monoclonal antibody EMR8-5, which we recently generated. The expression of HLA class I was lost or downregulated in 46 of these specimens (62%). With respect to osteosarcoma, loss or downregulation of HLA class I expression was seen in 13 (52%) of 25 primary tumors and seven (88%) of eight metastatic tumors. In six of 11 HLA class I-negative osteosarcoma specimens, the expression of beta-2 microglobulin was also lost. Subsequently the prognostic significance of HLA class I expression was analyzed in 21 patients with osteosarcoma who had completed multidrug neoadjuvant chemotherapy and undergone adequate surgery. Patients with osteosarcoma highly expressing HLA class I showed significantly better overall and event-free survival than those with HLA class I-negative osteosarcoma. In contrast, such prognostic significance of HLA class I expression was not found in 15 patients with malignant fibrous histiocytoma of soft tissue. These findings suggest that the class I-restricted cytotoxic T lymphocyte pathway plays a major role in immune surveillance of patients with osteosarcoma.

Adolescent↗

PubMed2006

Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instillation of bacillus calmette-guerin immunotherapy for bladder cancer.

PURPOSE: Various immune systems play important roles in the clinical efficacy of intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer. However, human leukocyte antigen (HLA) class I molecules on tumor cells and various immune system cells infiltrating to/around the tumor have not been evaluated, although many prognostic factors, including clinical, pathologic, and molecular ones, have been investigated. The aim of this study was to determine immunologic prognostic factors of BCG immunotherapy for bladder cancer. EXPERIMENTAL DESIGN: Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained. We did univariate and multivariate analyses of factors affecting recurrence-free survival. The positive, weakly positive, and negative groups of cells that infiltrated to/around the tumor were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test. RESULTS: HLA class I was a significant prognostic factor both in univariate and multivariate analyses. The 5-year recurrence-free survivals of the patients with HLA class I-positive tumors and those with HLA class I-negative tumors were 55.7% and 19.1%, respectively (P = 0.019). There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects. CONCLUSIONS: Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.

Adjuvants, Immunologic↗

PubMed2006

Identification of HLA-A2- or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma.

PURPOSE AND EXPERIMENTAL DESIGN: We previously reported that glypican-3 (GPC3) was overexpressed, specifically in hepatocellular carcinoma (HCC) and melanoma in humans, and it was useful as a novel tumor marker. We also reported that the preimmunization of BALB/c mice with dendritic cells pulsed with the H-2K(d)-restricted mouse GPC3(298-306) (EYILSLEEL) peptide prevented the growth of tumor-expressing mouse GPC3. Because of similarities in the peptide binding motifs between H-2K(d) and HLA-A24 (A*2402), the GPC3(298-306) peptide therefore seemed to be useful for the immunotherapy of HLA-A24+ patients with HCC and melanoma. In this report, we investigated whether the GPC3(298-306) peptide could induce GPC3-reactive CTLs from the peripheral blood mononuclear cells (PBMC) of HLA-A24 (A*2402)+ HCC patients. In addition, we used HLA-A2.1 (HHD) transgenic mice to identify the HLA-A2 (A*0201)-restricted GPC3 epitopes to expand the applications of GPC3-based immunotherapy to the HLA-A2+ HCC patients. RESULTS: We found that the GPC3(144-152) (FVGEFFTDV) peptide could induce peptide-reactive CTLs in HLA-A2.1 (HHD) transgenic mice without inducing autoimmunity. In five out of eight HLA-A2+ GPC3+ HCC patients, the GPC3(144-152) peptide-reactive CTLs were generated from PBMCs by in vitro stimulation with the peptide and the GPC3(298-306) peptide-reactive CTLs were also generated from PBMCs in four of six HLA-A24+ GPC3+ HCC patients. The inoculation of these CTLs reduced the human HCC tumor mass implanted into nonobese diabetic/severe combined immunodeficiency mice. CONCLUSION: Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for a large number of HCC patients.

Amino Acid Sequence↗

PubMed2006

Expression and antigenicity of survivin, an inhibitor of apoptosis family member, in bladder cancer: implications for specific immunotherapy.

OBJECTIVES: To assess the expression of survivin in transitional cell carcinoma of the bladder and to study whether survivin is a transitional cell carcinoma-specific antigen that could be a target for immunotherapy. Survivin, an inhibitor of apoptosis family member, has been reported to be expressed in various cancers but not in normal adult tissues. METHODS: Immunohistochemical staining for survivin and human leukocyte antigen (HLA) class I was performed on specimens from 88 patients who underwent transurethral resection and radical cystectomy. To determine whether survivin was recognized as a tumor antigen by the host immune system, we assessed anti-survivin antibodies in the sera of 52 patients and 18 healthy volunteers with an enzyme-linked immunosorbent assay using recombinant survivin. RESULTS: Survivin and HLA class I were expressed in 77 (87.5%) and 59 (67.0%) of the 88 bladder cancer specimens, respectively, and 56 (63.6%) expressed both survivin and HLA class I. The absorbance values of anti-survivin antibodies in patients with bladder cancer were significantly greater than those in the healthy volunteers. A relationship was found between the level of serum anti-survivin antibodies and the staining intensity of survivin in the specimen. CONCLUSIONS: Survivin is expressed in carcinoma of the bladder with high sensitivity. It is suggested that survivin is presented on HLA class I molecules of antigen-presenting cells in 64% of patients with bladder cancer. Therapeutic targeting of survivin in bladder cancer is a future possibility.

Adult↗

PubMed2006

HLA-restricted specific tumor cytolysis by autologous T-lymphocytes infiltrating metastatic bone malignant fibrous histiocytoma of lymph node.

Malignant fibrous histiocytoma (MFH) of the bone is a high-grade sarcoma characterized histologically by the composition of fibroblasts and pleomorphic cells with a prominent storiform pattern. Despite institution of multi-modality treatments, the prognosis for patients with this tumor remains unsatisfactory. In the present study, towards the goal of developing active immunotherapy for those affected, we established four cell lines from a 53-year-old woman who suffered from MFH of the humerus with lymph node metastases. MFH2003 and MFH2003-B7.1 were the primary lesion-derived cell line and its B7.1-transfectant, respectively. B2003-EBV and TIL2003 were a B cell line established from peripheral blood lymphocytes and a T cell line established from tumor-invaded lymph nodes, respectively. MFH2003 cells could be maintained over a period of 1 year in vitro, and could be xenotransplanted into nude mice. The phenotype of cells analyzed by immunostaining was similar to the original tumor. TIL2003 cells were all CD8+ and specifically recognized MFH2003 cells and MFH2003-B7.1 cells, but not B2003-EBV cells. An anti-HLA-class I monoclonal antibody completely blocked the anti-MFH2003 response of TILs2003. These findings indicate the existence of an anti-MFH specific immune response in the microenvironment of metastatic lymph nodes. The present autologous cell lines provide the basis for identification of novel tumor-associated antigens and may be helpful in the establishment of immunotherapy for patients with MFH of the bone.

Animals↗

PubMed2006

Basaloid carcinoma of the thymus: report of a case.

We report a case of basaloid carcinoma of the thymus, confirmed by histopathological examination, in a 52-year-old man who underwent complete resection. Local recurrence and lung metastases developed, which were obliterated by radiation therapy. The patient survived for 81 months after surgery. We reviewed the 13 other cases of basaloid carcinoma of the thymus reported in the literature. Presumably, this tumor is radiosensitive and its metastatic route is blood-borne.

Carcinoma, Basosquamous↗

PubMed2006

Induction of autologous CD4- and CD8-mediated T-cell responses against acute lymphocytic leukemia cell line using apoptotic tumor cell-loaded dendritic cells.

OBJECTIVE: Several studies have demonstrated that dendritic cells (DCs) pulsed with tumor lysate or apoptotic tumor cells can elicit effective T-cell responses. This technique does not require the identification of the tumor antigen or HLA haplotype of the patient. We applied this approach to induce HLA class I- and class II-restricted T-cell responses directed against autologous acute lymphocytic leukemia (B-ALL) cell line NH-1. METHODS: Autologous T cells were stimulated by apoptotic tumor cell-loaded DCs generated from a patient with ALL. The stimulated and expanded T cells were isolated into CD8(+) T-cell line and CD4(+) T-cell line, and each of them was examined as to their functions. RESULTS: Both CD8(+) and CD4(+) T-cell lines demonstrated cytotoxicity against NH-1 in an major histocompatibility complex-dependent manner. Finally, we established two independent CD4(+) T-cell clones restricted to HLA-DR. The CD4(+) T-cell line responded strongly to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL) but not to autologous normal cells. Furthermore, the T-cell clones also responded to allogeneic EBV-LCLs and B-ALL cell lines in the context of the HLA-DRB1( *)04051 molecule. Interestingly, 293T and COS-7 cells, which had been transfected with the HLA-DRB1( *)04051, were also recognized by T-cell clones. CONCLUSION: These findings indicate that B-ALL has shared and strong immunogenic epitopes expressed on HLA class II molecules, the expression of which is limited to immortalized cells. These data suggest that vaccinations using DCs loaded with apoptotic tumor cells might be a potent strategy in the treatment of B-ALL.

Apoptosis↗

PubMed2005

Survivin expression is regulated by coexpression of human epidermal growth factor receptor 2 and epidermal growth factor receptor via phosphatidylinositol 3-kinase/AKT signaling pathway in breast cancer cells.

Survivin, a member of the inhibitor of apoptosis protein family, is widely expressed in a variety of human cancer tissues. Survivin inhibits activation of caspases, and its overexpression can lead to resistance to apoptotic stimuli. In this study, survivin protein expression was assessed by immunohistochemical staining of 195 invasive breast cancer specimens. Overall, 79.5% of the tumors were positive for survivin. The expression of epidermal growth factor receptor (EGFR) family, human epidermal growth factor receptor 2 (HER2) and EGFR, was also examined in 53 cases, and consequently, it was indicated that survivin positivity might be correlated with the coexpression of HER2 and EGFR. To clarify the regulatory mechanism of survivin expression in breast cancer cells, the effect of HER2 and/or EGFR expression on the survivin levels was examined. It was revealed that the survivin protein level was up-regulated by the coexpression of HER2 and EGFR, leading to the increased resistance against etoposide-induced apoptosis in breast cancer cells. Conversely, survivin levels and apoptosis resistance were decreased when cells were treated with HER2-specific inhibitor, Herceptin. Although Herceptin could down-regulate both phosphatidylinositol 3-kinase (PI3K)/AKT signal and mitogen-activated protein/extracellular signal-related kinase (ERK) kinase 1 (MEK1)/ERK signal in HER2-positive breast cancer cells, PI3K-specific inhibitor but not MEK1-specific inhibitor could decrease the survivin levels. The present study clarified the regulatory mechanism of HER2 in the expression of survivin protein in breast cancer cells.

Antibodies, Monoclonal↗

PubMed2005

A novel isoform of TUCAN is overexpressed in human cancer tissues and suppresses both caspase-8- and caspase-9-mediated apoptosis.

Caspase-associated recruitment domains (CARD) are protein-protein interaction modules found extensively in proteins that play important roles in apoptosis. One of the CARD-containing proteins, TUCAN (CARD8), was reported previously as an antiapoptotic protein with a molecular weight of 48 kDa, which was up-regulated in colon cancer cells. We identified a novel isoform of TUCAN with a molecular weight of 54 kDa. The new variant of TUCAN, termed TUCAN-54, was expressed in gastric, colon, and breast cancer tissues but was barely detected in normal noncancerous tissues, whereas 48-kDa TUCAN was detected in tumor tissues and noncancerous tissues. To know the function of TUCAN-54 in the apoptosis of cancer cells, TUCAN-54 was overexpressed in tumor cells by gene transfection. Its overexpression inhibited pro-caspase-9 activation, leading to the suppression of the cell death induced by a protein kinase inhibitor, staurosporine, or a chemotherapeutic reagent, etoposide (VP-16). In contrast, specific small interfering RNA-mediated suppression of TUCAN-54 expression in tumor cells increased the VP-16-induced cell death rate, indicating that expression of TUCAN-54 might be associated with chemoresistance of tumor cells. In addition, it inhibited caspase-8 activation as well, thereby suppressing Fas-induced cell death. It was revealed that Fas-associated death domain was physically associated with TUCAN-54 but not with 48-kDa TUCAN. Thus, TUCAN-54 might be a novel tumor-specific antiapoptotic molecule expressed in a variety of human cancer tissues, which might aggravate malignant potential of cancer cells, such as chemoresistance and immunoresistance.

Adaptor Proteins, Signal Transducing↗

PubMed2005

A quest for therapeutic antigens in bone and soft tissue sarcoma.

Over the past three decades, there have been remarkable advances in the treatment of bone and soft tissue sarcomas. These include the introduction of adjuvant chemotherapy, establishment of guidelines for adequate surgical margins, and the development of post-excision reconstruction. There have also been advances in the field of immunotherapy against bone and soft tissue sarcomas, which, unfortunately, have received less attention. However, lack of progress in chemotherapy-based treatments for bone and soft tissue sarcomas has reignited interest in immunotherapeutic approaches. Here we summarize current progress in the immunotherapy of bone and soft tissue sarcomas including the strategies utilized to identify tumor-associated antigens, and the design of clinical trials.

Journal Article↗

PubMed2005

Detection of autoantibodies to survivin and livin in sera from patients with breast cancer.

BACKGROUND: Survivin and livin are highly expressed in cancer cells and transformed cells, but show little or no expression in normal differentiated tissues. Human antibody responses to tumor-associated antigens have been detected, but little is known about the response to survivin and livin in breast cancer patients. METHODS: We examined the prevalence of anti-survivin and livin antibodies in breast cancer patients with a specific enzyme-linked immunosorbent assay (ELISA) using recombinant protein. RESULTS: Using a cutoff value for positivity determined as the mean absorbance +2SD for healthy control samples, sera from 11 of 46 breast cancer patients (23.9%) were positive by the ELISA using recombinant survivin protein. Of 46 samples from the same breast cancer patients, 15 (32.6%) were positive for anti-livin antibodies. In addition, 24 (52.2%) were positive for 1 or both ELISAs using the respective proteins. Intensity of anti-livin antibody responses did not correlate with intensity of anti-survivin responses. CONCLUSIONS: Anti-livin antibodies were detected in sera from breast cancer patients by an anti-livin ELISA using full-length recombinant livin protein. Like survivin, livin may act as a major cancer antigen in breast cancer patients.

Absorption↗

PubMed2005

A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins.

We reported previously a HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8(+) CTL. This peptide was derived from survivin protein, an inhibitor of apoptosis proteins, expressed in a variety of tumors, such as adenocarcinoma, squamous cell carcinoma, and malignant melanoma. In this report, we provide further evidence that survivin-2B80-88 peptide might serve as a potent immunogenic cancer vaccine for various cancer patients. Overexpression of survivin was detected in surgically resected primary tumor specimens of most breast and colorectal cancers and some gastric cancers as assessed by immunohistochemical study. HLA-A24/survivin-2B80-88 tetramer analysis revealed that there existed an increased number of CTL precursors in peripheral blood mononuclear cells (PBMC) of HLA-A24(+) cancer patients, and in vitro stimulation of PBMCs from six breast cancer patients with survivin-2B80-88 peptide could lead to increases of the CTL precursor frequency. Furthermore, CTLs specific for this peptide were successfully induced from PBMCs in all 7 (100%) patients with breast cancers, 6 of 7 (83%) patients with colorectal cancers, and 4 of 7 (57%) patients with gastric cancers. These data indicate that survivin expressed in tumor tissues is antigenic in cancer patients, and survivin-2B80-88-specific CTLs are present in PBMCs of various cancer patients. Our study raises the possibility that this peptide may be applicable as a general cancer vaccine to a large proportion of HLA-A24(+) cancer patients.

Adenocarcinoma↗

PubMed2005

Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin/ML-IAP in lung cancer.

CD8(+) CTLs have an essential role in immune response against tumor. Although an increasing number of tumor-associated antigens that can be recognized by CTLs have been identified from human tumors, a limited number of tumor-associated antigens is known in lung cancer. In addition, because some of them are expressed in noncancerous tissues, there exist limitations in their application to tumor immunotherapy. Livin/ML-IAP is one of recently identified inhibitor of apoptosis protein (IAP) family, which is overexpressed in melanoma cells. In this report, we show that Livin/ML-IAP is aberrantly expressed in many lung cancer cell lines and primary lung cancer tissues, whereas it is not detectable in normal tissues, including lung by reverse transcription-PCR methods. To identify HLA-A24-restricted T-cell epitopes of Livin/ML-IAP, eight peptides were selected from the amino acid sequence of this protein and screened for their binding affinity to HLA-A24. It was revealed that Livin7 peptide (amino acid sequence, KWFPSCQFLL) had the highest affinity to HLA-A24. By stimulating peripheral blood lymphocytes of HLA-A24-positive lung cancer patients with Livin7 peptide in vitro, the peptide-specific CTLs were successfully induced from four of five patients with Livin/ML-IAP-positive lung cancer but not from any of four patients without Livin/ML-IAP expression in their cancer tissues. Furthermore, the CTLs induced by Livin7 peptide showed cytotoxicity against Livin/ML-IAP(+) lung cancer cell lines in an HLA-A24-restricted manner. Our data suggest that Livin/ML-IAP may be an excellent target antigen in immunotherapy for lung cancer and Livin7 peptide may serve as a potent peptide vaccine for HLA-A*2402(+)/Livin(+) lung cancer patients.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Phase I vaccination trial of SYT-SSX junction peptide in patients with disseminated synovial sarcoma.

BACKGROUND: Synovial sarcoma is a high-grade malignant tumor of soft tissue, characterized by the specific chromosomal translocation t(X;18), and its resultant SYT-SSX fusion gene. Despite intensive multimodality therapy, the majority of metastatic or relapsed diseases still remain incurable, thus suggesting a need for new therapeutic options. We previously demonstrated the antigenicity of SYT-SSX gene-derived peptides by in vitro analyses. The present study was designed to evaluate in vivo immunological property of a SYT-SSX junction peptide in selected patients with synovial sarcoma. METHODS: A 9-mer peptide (SYT-SSX B: GYDQIMPKK) spanning the SYT-SSX fusion region was synthesized. Eligible patients were those (i) who have histologically and genetically confirmed, unresectable synovial sarcoma (SYT-SSX1 or SYT-SSX2 positive), (ii) HLA-A*2402 positive, (iii) between 20 and 70 years old, (iv) ECOG performance status between 0 and 3, and (v) who gave informed consent. Vaccinations with SYT-SSX B peptide (0.1 mg or 1.0 mg) were given subcutaneously six times at 14-day intervals. These patients were evaluated for DTH skin test, adverse events, tumor size, tetramer staining, and peptide-specific CTL induction. RESULTS: A total of 16 vaccinations were carried out in six patients. The results were (i) no serious adverse effects or DTH reactions, (ii) suppression of tumor progression in one patient, (iii) increases in the frequency of peptide-specific CTLs in three patients and a decrease in one patient, and (iv) successful induction of peptide-specific CTLs from four patients. CONCLUSIONS: Our findings indicate the safety of the SYT-SSX junction peptide in the use of vaccination and also give support to the property of the peptide to evoke in vivo immunological responses. Modification of both the peptide itself and the related protocol is required to further improve the therapeutic efficacy.

Journal Article↗

PubMed2005

Detection of autoantibodies to livin and survivin in Sera from lung cancer patients.

Survivin and livin are highly expressed in cancer cells and transformed cells, but show little or no expression in normal differentiated tissues. Although human antibody responses to cancer-associated antigens have been detected, the response to livin has not yet been described in lung cancer patients. We examined prevalence of anti-livin antibodies in such patients with a specific enzyme-linked immunosorbent assay (ELISA) using recombinant protein. Using a cutoff value for positivity determined as the mean absorbance +2S.D. for healthy control samples, 19 of 37 lung cancer patients (51.3%) were positive for anti-livin antibodies. Of 31 samples from the same lung cancer patients, 18 (58.1%) were positive for anti-survivin antibodies. When sera from 31 lung cancer patients were assessed simultaneously by anti-survivin and anti-livin ELISAs. Twenty-one patients (71%) were positive for survivin, livin, or both. Intensity of anti-livin antibody responses did not correlate with intensity of anti-survivin responses. Like anti-survivin antibodies, anti-livin antibodies, thus, can be detected in many lung cancer patients. Testing for both antibodies together may prove useful in detecting lung cancer, but more extensive studies are needed to establish the clinical significance of anti-livin antibodies.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Autoantibodies to survivin in patients with chronic hepatitis and hepatocellular carcinoma.

OBJECTIVES: Autoantibodies to tumor-associated antigens including survivin have been detected in sera from patients with hepatocellular carcinoma (HCC). However, little is known about autoantibody responses to tumor-associated antigens in patients with chronic hepatitis, which strongly predisposes to development of HCC. METHODS: We subjected sera from 57 patients with chronic hepatitis and 29 patients with HCC to an enzyme-linked immunosorbent assay (ELISA) using a full-length recombinant survivin protein. A cutoff value for positivity was determined as the mean absorbance +2SD for sera from healthy volunteers. RESULTS: In patients with chronic viral hepatitis, elevated anti-survivin antibodies were detected in 10 of 57 sera (17.5%); in HCC patients, such elevation were detected in 7 of 29 sera (24.1%). The levels of anti-survivin antibodies in HCC patients with HCV infection were significantly higher than those in the healthy control and HCC patients with HBV infection. However, there were no significant differences in the levels of anti-survivin antibodies between HCV and HCC patients with HCV infection. CONCLUSIONS: We demonstrated that elevated anti-survivin antibodies were detected for the first time in patients with chronic viral hepatitis. The results suggest that the levels of anti-survivin antibodies have no association with the progression of HCV or HBV to HCC.

Autoantibodies↗

PubMed2005

A calcium binding protein, S100A4, mediates T cell dependent cytotoxicity as a transformation-associated antigen.

The nature of the target molecule of TCR gamma delta T cell-mediated lysis remains to be determined. As we previously reported, #067 monoclonal antibody (mAb) recognizes one of the transformation-associated antigens, designated as #067 antigen. This antigen is expressed on the cell surface of rat fibrosarcoma W31 cells, which are established by transformation of fetal fibroblastic WFB cells with H-ras oncogene. It has been suggested that the #067 antigen is a target molecule for TCR gamma delta T cells since #067 mAb inhibited TCR gamma delta T cell-mediated lysis against #067 positive cells. In this study we attempted to identify the protein sequence of the #067 antigen. By using molecular cloning techniques, we demonstrated that a calcium binding protein, S100A4, was possibly one and the same molecule as the #067 antigen. It was shown that the expression of S100A4 was higher in W31 cells than in WFB cells at transcription and protein level. Flow cytometry and immunocytochemical studies showed that #067 antigen partially co-localized with S100A4 on the cell surface as well as the cytoplasm of W31 cells. Moreover, rabbit anti-S100A4 polyclonal antibodies (pAb) inhibited TCR gamma delta T cell-mediated lysis against #067 positive cells. Our results indicated that S100A4 may play a role as a possible target molecule for TCR gamma delta T cell-mediated lysis although how S100A4 is involved in TCR gamma delta T cell-mediated lysis remains to be determined.

Animals↗