Biomedical subjects

Satoshi Kawaguchi

Publications and source records attributed to Satoshi Kawaguchi.

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↗

PubMed2007

Quantitative analysis of sensory functions after lumbar discectomy using current perception threshold testing.

A Neurometer device is an electrical nerve stimulator used to determine the current perception threshold (CPT) evoked by stimulating A-beta fibers at 2,000 Hz, A-delta fibers at 250 Hz and C fibers at 5 Hz. CPT evaluation is used for analyzing peripheral nerve dysfunction. In this study, the sensory disturbance of the lower-extremity was quantitatively analyzed using CPT testing before and after lumbar discectomy. In 33 patients (L4/5: 16 and L5/S: 17), as subjective evaluations, tactile sensation and leg pain were assessed before and 2 weeks after surgery. In the subjectively improved group (n = 22), significant decreases in CPT at 2,000 and 250 Hz were noted postoperatively, whereas in the unchanged group (n = 11), no significant changes in CPT at any frequencies was noted. The leg pain improved in all patients. Likewise, CPT at 5 Hz, which stimulated C fiber, decreased significantly for both improved and unchanged groups. CPT measured by a Neurometer is very useful in assessing lower-extremity sensory functions before and after surgery for lumbar disc herniation.

Adult↗

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

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↗

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

Aberrant laminin beta3 isoforms downstream of EWS-ETS fusion genes in Ewing family tumors.

Ewing family tumors (EFTs) are associated with a chromosomal translocation resulting in a fusion of the amino-terminus of EWS with the DNA-binding domain of an ETS transcription factor. Although previous reports suggested that these chimeric proteins would act as aberrant transcription factors, their downstream targets have not been fully elucidated. To identify downstream targets of these EWS-ETS fusion proteins, we introduced EWS-ETS fusion constructs into a human fibrosarcoma cell line, HT-1080, by retroviral transduction. Here we report that the LAMB3 gene encoding the beta3 chain of basement membrane protein laminin-5 is induced to a significantly higher level in cells expressing EWS-ETSs than in cells expressing normal ETSs. Additionally through use of an antisense oligonucleotide for EWS-ERG in the W-ES EFT cell line, laminin beta3 protein was reduced coordinately with EWS-ERG fusion protein expression. Furthermore, we found small mRNAs were preferentially transcribed from the LAMB3 gene in EFT cell lines. Molecular cloning of the entire coding region shows that the alternative transcripts from different promoter(s) located within the intron 14, which encode small proteins, likely are major products of the LAMB3 gene in EFT cells. We show that the small isoforms conferred increased anchorage-independent proliferation to NIH3T3 cells. Together with previous studies showing that laminin-5 is involved in the invasive and malignant phenotype of several tumor types, our data suggest that the oncogenic effect of EWS-ETS may be mediated in part by upregulation of LAMB3 expression.

Animals↗

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

Adjacent segment stenosis after lumbar fusion requiring second operation.

BACKGROUND: Whereas degeneration of the segment adjacent to lumbar fusion has been often seen on radiographs, a small number of patients with such degenerative changes undergo reoperation. Most follow-up studies have focused on adjacent segment disease based on analysis of radiographs. The present study was conducted to understand the pathology of reoperation cases of adjacent segment disease and factors associated with this condition. Operative indication was consistently restricted to patients with neurological involvement. METHODS: The subjects were 117 patients who had undergone posterior lumbar fusion and were followed for a minimum of 2 years (mean 7 years). Among them, nine patients (7.7%) required a second operation owing to symptomatic adjacent segment disease (stenosis). The reoperation rate was assessed in relation to sex, age, initial pathologic condition, and initial spinal fusion and decompression methods. Data were analyzed in a 2 x 2 cross contingency table using Fisher's exact probability test. A probability of <0.05 was defined as statistically significant. RESULTS: Of the variables examined, only multilevel fusion was associated with a high rate of reoperation with statistical significance (P < 0.04). Two patients (100%) suffering from loss of coronal balance (degenerative scoliosis) also required a second operation. CONCLUSIONS: The reoperation rate of 7.7% for adjacent segment disease in this study was consistent with the prevalence of adjacent segment stenosis in the literature. Given the risk of later occurrence of adjacent segment stenosis following multisegment posterolateral fusion, correction of coronal and sagittal balance, preventive decompression of the adjacent segment, or selective decompression without fusion may have to be considered as an additional or alternative procedure.

Adult↗

PubMed2005

Value of pharmacologic stress myocardial perfusion imaging for preoperative risk stratification for aortic surgery.

BACKGROUND: Aortic surgery is an invasive, high-risk noncardiac procedure and the patients who require it have a high prevalence of coronary artery disease. Therefore, preoperative risk stratification for this subset is essential. METHODS AND RESULTS: To assess the perioperative risk for aortic surgery, pharmacologic stress single-photon emission computed tomography (SPECT) was performed in 302 patients: aortic dissection in 56, thoracic aortic aneurysm in 124, and abdominal aortic aneurysm in 122. Not only was the presence or absence of perfusion defects analyzed, but also the 20-segment model. Pharmacologic thallium SPECT revealed negative findings in 210 patients and positives in 92. Perioperative cardiac events occurred in 9 patients: 7 occurred in patients with positive SPECT, and in only 2 of those with negative SPECT (2/210 vs 7/92; p<0.05). Multivariate analysis using logistic regression model revealed that a summed stress score>or=14 was the most important factor to identify patients who subsequently had perioperative cardiac events. CONCLUSIONS: Pharmacologic stress SPECT has significant value in the risk stratification of patients before aortic surgery. In patients with positive SPECT, an aggressive approach to reduce the preoperative risk is necessary, whereas aortic surgery can be performed safely in patients with negative SPECT.

Aged↗

PubMed2004

Preoperative risk stratification for endovascular surgery using pharmacologic stress myocardial imaging.

To stratify perioperative cardiac risk for endovascular surgery, pharmacologic stress single-photon emission computed tomography (SPECT) was performed in 206 patients. Of 8 patients who had cardiac events, 7 occurred in 67 patients with positive SPECT results, whereas only 1 occurred in 139 patients with negative SPECT results (7 of 67 vs 1 of 139, p <0.002). Furthermore, a scintigraphic marker of a summed stress score >/=14 was the most important factor identifying patients who subsequently had cardiac events by multivariate analysis.

Aged↗

PubMed2004

Identification of human autologous cytotoxic T-lymphocyte-defined osteosarcoma gene that encodes a transcriptional regulator, papillomavirus binding factor.

The prognosis for patients with osteosarcoma who do not respond to current chemotherapy protocols still remains poor. Toward the goal of establishing efficacious peptide-based immunotherapy for those patients, we previously developed an autologous pair of CTLs and an osteosarcoma cell line. In the current study, we screened the cDNA library of this osteosarcoma cell line using an autologous CTL clone and identified cDNA encoding an antigen. The isolated cDNA was identical to papillomavirus binding factor (PBF), which was recently reported as a DNA binding transcription factor cooperating with RUNX1. Reverse transcription-PCR analysis revealed that PBF was expressed in 16 of 19 cases of bone and soft-tissue sarcoma cell lines (5 of 6 of osteosarcoma lines) and 57 of 76 sarcoma tissue samples (11 of 14 of osteosarcoma tissues). Also, PBF was expressed in 10 of 13 epithelial cancer cell lines and 20 of 34 of cancer tissues. In contrast, PBF was detected in some normal organs including ovary, pancreas, spleen, and liver by reverse transcription-PCR but was restricted in the cytoplasm by immunostaining and undetectable by Western blotting. Furthermore, a 12-mer peptide, CTACRWKKACQR, located at the COOH terminus of PBF, was found to be a minimum requirement for recognition by the CTL clone in the context of the HLA-B*5502 molecule. These findings suggest that PBF is a shared tumor-associated antigen, which may serve as a source of peptides applicable to peptide-based immunotherapy for osteosarcoma and other malignant tumors.

Antigens, Neoplasm↗

PubMed2004

Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute.

To investigate the effects of anchor substitutions in SYT-SSX junction peptide, an HLA-A24 anchor residue (position 9) of the SYT-SSX B peptide (GYDQIMPKK) was substituted to more favorable residues according to the HLA-A24-binding motif. Among four substitutes constructed, a substitute with isoleucine (termed K9I peptide) most apparently enhanced the affinity for HLA-A24 molecule. Subsequent in vitro CTL induction analysis using PBMCs of 15 HLA-A24(+) synovial sarcoma patients revealed that the original B peptide allowed to induce synovial sarcoma-specific CTLs from 7 patients (47%), whereas such CTLs were inducible from 12 patients (80%) with K9I peptide. Moreover, the extent of cytotoxicity against HLA-A24(+) synovial sarcoma cell lines was higher in K9I peptide-induced CTLs than B peptide-induced CTLs. Influence of anchor substitution on peptide/TCR interaction was evaluated by cytotoxicity assays against autologous cells and tetramer analysis. CTLs induced from a synovial sarcoma patient using K9I peptide did not lyse autologous PHA blasts or EBV-infected B cells. In vitro stimulations of PBMCs from 5 HLA-A24(+) synovial sarcoma patients with K9I peptide increased the frequency of T cells reacting with both HLA-A24/K9I peptide tetramer and HLA-A24/B peptide tetramer. In contrast, the frequency of T cells reacting with HLA/HIV-derived peptide tetramer remained low. These findings support the validity in design of anchor residue substitution in SYT-SSX fusion gene-derived peptide, and provide a potential clue to the current stagnation in vaccination trials of fusion gene-derived natural junction peptides.

Amino Acid Substitution↗

PubMed2004

Abdominal small round cell tumor with osteoid and EWS/FLI1.

In this report, we described a case of multiple intraperitoneal tumors. Histologically, the tumors were composed of small round cells with malignant phenotype, necrotic areas, and islands of osteoid matrix in the stroma. In immunohistochemical and molecular analyses, the tumors expressed CD99 and EWS-Fli1 fusion gene. Production of osteoid by small round tumor cells was consistent with the histologic criteria of small-cell osteosarcoma, whereas expression of EWS-Fli1 was a characteristic genetic feature of Ewing's sarcoma family of tumor. Such tumors have been limited to a case in which histologically proven small-cell osteosarcoma of the scapula showed a chromosomal translocation, t(11;22)(q24;q12).

12E7 Antigen↗

PubMed2004

One-bone forearm reconstruction using vascularized fibular graft for massive forearm soft-tissue and bone defect: case report.

The authors report a case of recurrent malignant fibrous histiocytoma with extensive bone- and soft-tissue involvement, successfully treated with one-bone forearm reconstruction using a vascularized fibular graft and multiple tendon transfer. Twenty-four months after surgery, elbow and hand functions were maintained, and the patient had no disturbance of hand function in daily activity, although rotation of the forearm was sacrificed. No local recurrence or metastasis was noted. The procedure is a useful reconstructive option for complex tissue defects following wide excision of sarcoma of the forearm.

Bone Transplantation↗

PubMed2003

Vertebral body ischemia in the posterior spinal artery syndrome: case report and review of the literature.

STUDY DESIGN: A case of posterior spinal cord syndrome in which magnetic resonance images showed predominant T2 hyperintense signal in the adjacent vertebral body is reported. OBJECTIVES: To present the case for abnormal bone marrow magnetic resonance signal in the radiologic diagnosis of posterior spinal cord syndrome and to review its significance. SUMMARY OF BACKGROUND DATA: Infarction in the region of posterior spinal arteries has been rarely described. This is attributable not only to the infrequent occurrence of infarction of posterior spinal arteries, but also to a lack of well-established diagnostic procedures. It is of clinical value to define diagnostic images of posterior spinal cord syndrome, especially early in the course of the disease. METHODS: The subject was a 52-year-old man who was presented with acute nontraumatic myelopathy. Magnetic resonance imaging, performed serially after onset of the disorder from 5 hours to 11 months, was evaluated in comparison with neurologic findings. The literature was reviewed to discuss the magnetic resonance images of spinal cord infarction. RESULTS: The neurologic findings were consistent with posterior spinal cord syndrome. A magnetic resonance image taken at 5 hours after onset of the syndrome showed T2 hyperintense signal in the T12 vertebral body. At 3 days after onset, T2 hyperintense signal became obvious in the posterior portion of the spinal cord at T9-T12 vertebral levels. Follow-up magnetic resonance imaging at 41 days, 8 months, and 11 months showed a decrease in the size and intensity of the T2 signal change in the spinal cord and T12 vertebral body. In the literature, T2 hyperintense bone marrow signal was defined in one case of posterior spinal cord syndrome and seven cases of anterior spinal cord syndrome. CONCLUSIONS: Associated bone marrow abnormalities likely reflect the underlying pathology of the blood supply to the vertebral body, and may be an additional key sign for radiologic diagnosis of posterior spinal cord syndrome.

Acute Disease↗

PubMed2003

Extraskeletal myxoid chondrosarcoma: a Multi-Institutional Study of 42 Cases in Japan.

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm. Despite a consensus for the distinct clinicopathologic entity of EMC, its clinical features remain controversial. In addition, most studies have contained a small number of patients who underwent definitive surgical treatment. METHODS: Forty-two cases of EMC, which had been identified from files of eight affiliated hospitals and confirmed for histologic diagnosis at the Pathology Center, were analyzed for histologic grade, demographics, treatments, outcomes, and prognostic factors. The average follow-up period was 7.4 years. RESULTS: Included in the study were 20 men and 22 women with a mean age at diagnosis of 52.1 years. The tumors were located mainly in the lower extremities (69%). Thirty-three tumors (79%) were classified as Grade 1 and nine as Grade 2 according to the modified French System. Overall survival was 100% at 5 years and 88% at 10 years. Disease-free survival was 45% at 5 years and 36% at 10 years. Inadequate initial surgery was defined as a significant risk factor for local recurrence by univariate analysis of all 42 patients but not by the analysis of those 30 patients who had undergone wide tumor excision or amputation. Wide excision led to the recurrence rate of 14%. CONCLUSIONS: These findings supported the role of wide excision in the local control of EMC, irrespective of the previous excision procedure or recurrence. The protracted clinical course of the tumors and the presence of patients who had distant metastasis develop after definitive surgery of the primary tumor represented EMC as intermediate malignancy.

Adult↗

PubMed2003

Combined gene therapy with adenovirus vectors containing CTLA4Ig and CD40Ig prolongs survival of composite tissue allografts in rat model.

BACKGROUND: The blockade of costimulatory signal pathway by anti-CD40 ligand antibody or cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4Ig) prolongs allograft survival in various vascularized organ transplantations. Because of the short half life of these agents, repeated administration of proteins is required to achieve significant graft survival. Furthermore, there is limited information regarding the effect of cosimulatory blockade on the survival of composite tissue allografts. Therefore, we examined the effect of adenovirus-mediated gene transfer of CTLA4Ig or CD40Ig gene or both in composite tissue allotransplantation. METHODS: The hind limbs removed from male ACI rats (RT1 ) were transplanted into female Lewis rats (RT1 ) heterotopically. The recombinant adenovirus carrying CTLA4Ig (AxCTLA4Ig) or CD40Ig (AxCD40Ig) was intravenously administered after limb transplantation. RESULTS: Limb allograft survival was significantly prolonged by either AxCTLA4Ig or AxCD40Ig treatment at 1 x 10 plaque forming unit (mean survival time [MST] of 39.4+/-6.0 and 13.0+/-2.9, respectively) compared with the adenovirus vector containing beta-galactosidase-treated group (MST of 4.8+/-0.8). Combination of AxCTLA4Ig and AxCD40Ig led to significant prolongation of graft survival (MST of 49.2+/-6.6). Serum levels of CD40Ig were higher in rats treated with combination therapy than those treated with AxCD40Ig alone, whereas the serum levels of CTLA4Ig in rats treated with AxCTLA4Ig alone and AxCTLA4Ig and AxCD40Ig combined were very similar. CONCLUSION: This study indicates that an adenovirus-mediated gene therapy of CTLA4Ig or CD40Ig has a therapeutic potential for preventing rejection in composite tissue transplantation. Furthermore, a combination therapy of AxCTLA4Ig and AxCD40Ig was even more effective in preventing acute rejection and prolonging the survival of allografted limbs without apparent complication.

Abatacept↗

PubMed2003

Induction of tenascin-C by tumor-specific EWS-ETS fusion genes.

Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumors (PNETs) are associated with a chromosomal translocation resulting in a fusion of the amino-terminus of EWS with the DNA-binding domain of an ETS transcription factor (most commonly FLI1 or ERG). Although previous reports suggested that these chimera proteins would act as aberrant transcription factors, their downstream targets have not been fully elucidated. To identify downstream targets of these EWS-ETS fusion proteins, we introduced EWS-ETS fusion constructs into a human fibrosarcoma cell line, HT-1080, by retroviral transduction. Here we report that Tenascin-C (TNC) is induced to a significantly higher level in cells expressing EWS-ETSs than in cells expressing normal ETSs. Furthermore, through use of an antisense cDNA expression vector we show that expression of endogenous TNC mRNA and protein were reduced coordinately with attenuation of EWS-FLI1 fusion protein expression. A chromatin immunoprecipitation assay showed direct interaction between the TNC promoter and the EWS-FLI1 fusion protein in vivo. In addition, a luciferase reporter assay revealed that EWS-ETSs upregulated the TNC gene through four ETS binding sites in the TNC promoter. High levels of TNC expression were observed in a subset of ES cell lines (3 of 6) and primary tumors (4 of 6). Together with previous studies showing that TNC expression is involved in the invasive and malignant phenotype of several tumor types, our data suggest that the oncogenic effect of EWS-ETS may be mediated in part by upregulating of TNC expression.

DNA, Antisense↗