[Diagnosis of gastrointestinal tract malignancies using positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG)].
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Fluorodeoxyglucose F18↗
Biomedical subjects
Hiroyuki Kuwano
Publications and source records attributed to Hiroyuki Kuwano.
Antitumor effect of a splenic injection of 5-fluorouracil on metastatic liver cancer in mice.
The regional administration of 5-fluorouracil (5-FU) has been the fundamental therapy against liver metastases for the improvement of patient prognosis; however, there have been few reports about the immunological effects of this agent. It is also unknown whether it affects the spleen, one of the major lymphoid organs. The objective of the present study was to determine the immunological effect of an intrasplenic injection of 5-FU against liver metastases. We investigated the effect of an intrasplenic injection of 5-FU on the formation of experimental liver metastasis resulting from an intraportal vein injection of colon 26 carcinoma cells in BALB/c mice and elucidated some of the underlying mechanisms involving the effects of this on cellular immunity. Liver metastases were significantly diminished by the splenic injection of 5-FU, particularly in comparison with the portal injection or systemic administration. This was followed by augmentation of the interleukin-12 (IL-12) level in the spleen and activation of hepatic mononuclear cells. In those cells, NK1.1+ (NKT) cells played a central role against metastases. A splenic injection of 5-FU is more effective on the involution of liver metastases than portal or systemic injection. This effect may be attributed to the augmentation of the IL-12 level in the spleen and of NKT cells in the liver rather than to the original effect of 5-FU, which is the so-called inhibition of DNA synthesis.
Animals↗
Sentinel lymph nodes with technetium-99m colloidal rhenium sulfide in patients with esophageal carcinoma.
BACKGROUND: The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium-99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging. METHODS: The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium-99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium-99m injection. After surgery, the resected lymph nodes were evaluated by CK staining. RESULTS: Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false-negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false-negative (sentinel lymph node-negative and nonsentinel lymph node-positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23). CONCLUSIONS: Lymphatic mapping with technetium-99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node.
Aged↗
RASSF1A gene inactivation in non-small cell lung cancer and its clinical implication.
Methylation-associated inactivation of RASSF1, a putative tumor suppressor identified at 3p21.3, is reported in several cancers. We examined RASSF1 in non-small lung cancer (NSCLC) to search for clinical implications. RT-PCR analysis showed no expression of RASSF1A in 12 of 20 lung cancer cell lines. Loss of expression correlated well with promoter methylation status of these lines. Sequence analysis revealed 2 polymorphisms (codons 21 and 133) in RASSF1A transcripts, but not in RASSF1C transcripts. No somatic mutations were found. Of 7 cell lines with K-ras mutations at codon 12 or 61, 2 lost expression of RASSF1A, whereas in 13 cell lines with wild-type K-ras gene, 10 lost RASSF1A gene expression (p = 0.0521). We investigated methylation status of this putative tumor suppressor gene in 100 primary NSCLCs to determine whether there is a clinical significance. Forty-two of primary NSCLCs demonstrated methylated allele. There is no correlation between promoter methylation of RASSF1A and clinicopathological findings, including histological type or grade, tumor staging, p53 and K-ras mutational status, or patients' survival. In the cases of Stage I and II disease, however, RASSF1A methylation was associated with earlier recurrence (p = 0.0247). Epigenetic silencing of RASSF1A is a frequent event in non-small lung cancer and will provide novel opportunities to develop diagnosis and therapy of NSCLC.
Aged↗
Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function.
SAP-1 is a transmembrane-type protein-tyrosine phosphatase that is expressed in most tissues but whose physiological functions remain unknown. The cytoplasmic region of SAP-1 has now been shown to bind directly the tyrosine kinase Lck. Overexpression of wild-type SAP-1, but not that of a catalytically inactive mutant of SAP-1, inhibited both the basal and the T cell antigen receptor (TCR)-stimulated activity of Lck in human Jurkat T cell lines. Lck served as a direct substrate for dephosphorylation by SAP-1 in vitro. Overexpression of wild-type SAP-1 in Jurkat cells also: (i) inhibited both the activation of mitogen-activated protein kinase and the increase in cell surface expression of CD69 induced by TCR stimulation; (ii) reduced the extent of the TCR-induced increase in the tyrosine phosphorylation of ZAP-70 or that of LAT; (iii) reduced both the basal level of tyrosine phosphorylation of p62dok, as well as the increase in the phosphorylation of this protein induced by CD2 stimulation; and (iv) inhibited cell migration. These results thus suggest that the direct interaction of SAP-1 with Lck results in inhibition of the kinase activity of the latter and a consequent negative regulation of T cell function.
Animals↗
Molecular processes of chromosome 9p21 deletions in human cancers.
Interstitial deletions of the chromosome 9p21 segment encoding the p16/CDKN2A tumor suppressor gene (i.e., 9p21 deletions) are frequently observed in a variety of human cancers. A majority of these deletions in lymphoid leukemia have been indicated to be mediated by illegitimate V(D)J recombination. In the present study, to elucidate the molecular processes of 9p21 deletions in nonlymphocytic malignancies, breakpoints for these deletions were analysed in 21 lung cancer cell lines and 32 nonlymphocytic cancer cell lines of nine other histological types. In all, 32 breakpoints in 21 lung cancer cell lines and 56 breakpoints in 32 nonlung cancer cell lines were mapped in a 450-kb segment encompassing the CDKN2A locus with a 10-kb resolution. The largest number of breakpoints (i.e., seven breakpoints in lung cancer and 12 breakpoints in nonlung cancers) was mapped in a 10-kb region containing the CDKN2A gene. More precise mapping of these seven and 12 breakpoints revealed that none of these breakpoints were located within 50-bp intervals to each other in this 10 kb region. Cloning and sequencing of breakpoints in 18 representative cell lines (six lung and 12 nonlung cancers) further revealed that there were no significant homologies among breakpoints in these 18 cell lines. In 11 (61%) cell lines, 1-5-bp nucleotides were overlapped at breakpoint junctions. These results indicate that DNA double-strand breaks triggering 9p21 deletions do not occur at specific DNA sequences, although they preferentially occur in or near the CDKN2A locus. It was also indicated that two broken DNA ends are rejoined by nonhomologous end-joining repair, preferentially utilizing microhomologies of DNA ends, in the occurrence of 9p21 deletions.
Acid Anhydride Hydrolases↗
Regulation of cell proliferation by autocrine motility factor/phosphoglucose isomerase signaling.
Autocrine motility factor (AMF)/phosphoglucose isomerase (PGI; EC 5.3.1.9) is a housekeeping cytosolic enzyme that plays a key role in both glycolysis and gluconeogenesis pathways. AMF/PGI is also a multifunctional protein that displays cytokine properties, eliciting mitogenic, motogenic, and differentiation activities, and has been implicated in tumor progression and metastasis. Because little is known about AMF/PGI-dependent signaling in general and during tumorigenesis in particular, we sought to study its effect on the cell cycle. To elucidate the functional role of PGI, we stably transfected its cDNA into NIH/3T3 and BALB/c 3T3-A31 fibroblasts. Ectopic overexpression of PGI results in the acquisition of a transformed phenotype associated with an acceleration of G1 to S cell cycle transition. These were manifested by up-regulation of cyclin D1 expression and cyclin-dependent kinase activity and down-regulation of the cyclin-dependent kinase inhibitor p27Kip1. The reduced p27Kip1 protein expression level in PGI-overexpressing cells could be restored to control levels by treatment with proteasome inhibitor. PGI-overexpressing cells also exhibited elevated expression of Skp2 involved in p27Kip1 ubiquitination and elevation in the levels of retinoblastoma protein hyperphosphorylation. Thus, we may conclude that the overexpression of AMF/PGI enhances cell proliferation together with up-regulation of cyclin/cyclin-dependent kinase activities and down-regulation of p27Kip1, whereas the induction of 3T3 fibroblast transformation by PGI is regulated by the retinoblastoma protein pathway.
3T3 Cells↗
The role of P-glycoprotein in intestinal tumorigenesis: disruption of mdr1a suppresses polyp formation in Apc(Min/+) mice.
P-glycoprotein (P-gp) mediates the active transport of various substrates including xenobiotics, and it thus has a protective function in various cell types and tissues/organs including the intestinal epithelium. However, whether or not P-gp plays a positive role in the intestinal tumorigenesis is unclear. We have introduced disrupted alleles of the murine P-gp gene, mdr1a, into Apc(Min/+) mice to evaluate whether P-gp plays any role in intestinal carcinogenesis. Spontaneously occurring DNA damage was significantly increased in both the small and large intestine of mdr1a(-/-), Apc(Min/+) mice compared with mdr1a(+/+), Apc(Min/+) mice. Furthermore, we observed active proliferation and rapid migration/disappearance of enterocytes in the intestine of the compound mice deficient in mdr1a. Finally, we found that the number of polyps and cancers was markedly decreased in mdr1a(-/-), Apc(Min/+) mice (P=0.0016). P-gp thus appears to play a positive role during intestinal tumorigenesis.
ATP Binding Cassette Transporter, Subfamily B↗
High frequency of DAP-kinase gene promoter methylation in colorectal cancer specimens and its identification in serum.
Death-associated protein (DAP)-kinase is frequently inactivated by promoter methylation in human cancers. To understand the involvement of the DAP-kinase gene in colorectal cancer (CRC), we investigated the methylation of the DAP-kinasegene in primary CRC to define the frequency of this epigenetic aberration and the clinicopathological significance. For this reason, methylation-specific polymerase chain reaction (MSP) was used to detect DAP-kinase gene methylation in DNA from 122 cases of CRC and 18 paired serum samples. Methylation of the DAP-kinase gene was found in 67 of 122 (55%) cases of primary CRC. Study of the serum DNA from 14 patients exhibiting methylated DAP-kinase gene revealed aberrant methylation in three patients (21%). False positives were not obtained in any of the patients who did not exhibit methylation. No association was found between the promoter methylation of the DAP-kinase gene in primary CRC and gender, localization, tumor differentiation, invasion depth, regional lymph node involvement, or tumor stage. In conclusion, methylation of the DAP-kinase gene is common in CRC. The detection of the methylation of the DAP-kinase gene has a potential clinical application as a diagnostic tumor marker for CRC.
Apoptosis Regulatory Proteins↗
Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma.
Transforming growth factor-beta (TGF-beta) inhibits epithelial cell proliferation. Inactivation of the TGF-beta signaling pathway is thought to play a role in tumorigenesis. Our purpose was to clarify the correlation between TGF-beta receptors or TGF-beta 1 expression and the clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for TGF-beta type I receptor (TGF-beta R-I), TGF-beta R-II and TGF-beta 1 was performed on surgical specimens obtained from 80 patients with esophageal SCC. Preoperative plasma TGF-beta1 levels were measured and correlated with pathologic features and clinical outcomes. Expression of TGF-beta R-I and TGF-beta R-II was reduced in 43 (53.8%) and 23 (28.8%) specimens, respectively. TGF-beta 1 was overexpressed in 29 (36.3%). Reduced expression of TGF-beta R-I and TGF-beta R-II showed a significant association with depth of invasion (p = 0.0015 and p = 0.0012), lymph node metastasis (p = 0.0309 and p = 0.0059) and pathologic stage (p = 0.0103 and p = 0.0401). Overexpression of TGF-beta 1 had a significant association with depth of invasion only (p = 0.0335). Reduced expression of TGF-beta R-I and TGF-beta R-II was correlated with cancer-specific survival (p = 0.0324 and p = 0.0243). The mean preoperative plasma TGF-beta 1 level was 10.5 +/- 0.8 ng/ml in patients with esophageal carcinoma and was significantly higher compared to healthy controls (p < 0.01). We demonstrate that reduced expression of TGF-beta receptors in esophageal SCC appears to be correlated with depth of invasion, lymph node metastasis, pathologic stage and poor prognosis. TGF-beta receptor expression may play a key role in the progression of this cancer.
Adult↗
EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma.
EphA2 is a member of the Eph family of receptor tyrosine kinases, which interact with cell-bound ligands known as ephrins. EphA2 expression was investigated by immunohistochemistry with an anti-EphA2 monoclonal antibody in 80 patients with esophageal squamous cell carcinoma (ESCC) who had undergone surgery. EphA2 overexpression was positive in 40 of the 80 patients (50%). A significant correlation was observed between EphA2 expression and regional lymph node metastasis (p=0.023), number of lymph node metastases (p=0.011) and poor degree of tumor differentiation (p=0.004). The survival rates of EphA2-positive patients were poorer than those of EphA2-negative patients (p=0.014). The 5-year survival rate of patients without EphA2 overexpression was 68%, whereas that of patients with EphA2 overexpression was 29%. EphA2 expression was also investigated in 7 ESCC cell lines (TE-1, -2, -8, -13, -15, TT and TTn) and 1 immortalized human esophageal keratinocyte cell line (CHEK-1). Western blotting revealed different levels of EphA2 expression in the 8 cell lines. EphA2 was expressed at a high level in the ESCC cell lines compared to CHEK-1. EphA2 phosphorylation was demonstrated in all cell lines. Northern blot analysis showed that EphA2 mRNA expression in TE-1 was greater than that in the other ESCC cell lines. The observation of small gaps on Western blot analysis of the ESCC cell lines suggests that there may be a mechanism for EphA2 regulation at the point of translation. In conclusion, EphA2 overexpression appears to be related to poor degree of tumor differentiation and lymph node metastasis in ESCC. Consequently, patients with EphA2 overexpression have a poorer prognosis than those without. EphA2 is a potential target to prevent ESCC cells spreading into the lymphatic drainage.
Adult↗
A new proliferation marker, minichromosome maintenance protein 2, is associated with tumor aggressiveness in esophageal squamous cell carcinoma.
BACKGROUND: Our aim was to determine whether minichromosome maintenance protein (MCM) 2 expression is useful in predicting tumor proliferation rates and outcome after therapy in patients undergoing surgery for esophageal squamous cell carcinoma (SCC). In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki-67, in esophageal SCC. METHODS: We examined immunohistochemical expression of MCM2 and Ki-67 in surgically resected tissues from 93 patients with esophageal SCC. RESULTS: The mean nuclear labeling index of MCM2 was markedly higher in SCC than in normal epithelia (P < 0.0001). A comparison of MCM2 labeling index and clinicopathological characteristics in 93 patients with esophageal cancer revealed significant associations between MCM2 labeling index and tumor status (P < 0.05), lymph node status (P < 0.01), metastatic status (P < 0.01), pathologic stage (P < 0.01), histologic grade (P < 0.05), and poor prognosis (P < 0.05). A comparison of Ki-67 labeling index and clinicopathological characteristics revealed significant associations between Ki-67 labeling index and lymph node status (P < 0.01), metastatic status (P < 0.05), pathologic stage (P < 0.05), histologic grade (P < 0.05), and poor prognosis (P < 0.05). The relationship between MCM2 and Ki-67 labeling indices in the primary tumor showed a significant correlation (P < 0.05), but the MCM 2 labeling index was considerably higher. CONCLUSIONS: MCM2 may be a more reliable and useful marker than Ki-67 in assessing the growth of normal and tumor cells and in evaluating tumor aggressiveness and prognostic value in patients with esophageal SCC.
Adult↗
Prediction of hematogenous recurrence in patients with esophageal carcinoma.
OBJECTIVES: Despite recent advances in diagnosis and treatment of esophageal carcinoma, the future risk of hematogenous recurrence is still unpredictable. To identify risk factors of hematogenous recurrence in esophageal carcinoma, we used pathological and immunohistochemical analysis to examine relationships among clinical outcomes, clinicopathological features, and E-cadherin expression. METHODS: Subjects were 102 patients with thoracic esophageal cancer who had undergone curative esophagectomy without preoperative treatment. We used univariate and multivariate logistic regression analyses to examine the relationship among clinical outcomes, clinicopathological features, and E-cadherin expression. RESULTS: There was no significant relationship between E-cadherin expression and clinicopathological features at operation. However, the survival rates of patients with E-cadherin-negative tumors were significantly lower than those of patients with E-cadherin-weak and E-cadherin-positive tumors (P < 0.01). Disease recurrence had occurred in 49 (48.0%), with hematogenous recurrence in 29 (28.4%), of the 102 patients at the time of analysis. Metastasis occurred in liver in 14 patients, lung in 13, bone in 6, and brain in 2. Comparisons of hematogenous recurrences and clinicopathological features by multivariate regression analyses revealed significant associations between hematogenous recurrences; particularly in liver and lung metastasis and negative E-cadherin expression. With regard to the associations between the organ with the recurrence and the number of positive nodes; hematogenous recurrence, equal to or higher than lymphatic recurrence, was more likely to have occurred in patients with high numbers of positive nodes. Interestingly, with regard to the sites of positive nodes, liver metastasis was closely correlated with lymph node metastasis in the mid-thoracic as opposed to the abdominal region. Further, lung metastasis was most likely to occur in patients with cervical lymph node metastasis. CONCLUSIONS: Esophageal carcinoma with negative E-cadherin expression tended to be associated with hematogenous recurrence, particularly with liver and lung metastasis. Hematogenous recurrences were significantly associated with high numbers and the site of positive nodes, as well as with lymphatic recurrence.
Adult↗
Tuberculosis of axillary lymph nodes with primary breast cancer.
A rare case of tuberculosis of axillary lymph nodes occurring with primary breast cancer is presented. A 78-year-old woman with no history of pulmonary tuberculosis was admitted to our hospital to undergo examination for a lump in her right breast. The tumor was in the upper outer quadrant of the right breast. On palpation, the tumor was 1.2 cm in diameter and axillary lymph node swelling was noted. Mammography disclosed a spiculated mass and swelling and calcification of the axillary lymph nodes. Sonography showed an irregular hypoechoic mass in the right breast and lymph node swelling in the right axilla, indicating breast cancer with axillary lymph nodes metastases. Chest X-ray showed clustered calcifications in the right axilla and a granular shadow in the right upper lobe. Breast conserving therapy was carried out. Invasive papillotubular carcinoma of the right breast and granulomas with calcification of lymph nodes, compatible with tuberculosis, was diagnosed. Tubercle bacillis were detected by culture of lymph nodes. This case suggests that X-ray is useful for diagnosing lymph node tuberculosis. Lymph node tuberculosis should be suspected when lymph node swelling is noted and X-ray shows clustered calcifications in axillary lymph nodes.
Aged↗
Malignant mixed Mullerian tumor of the ovary growing into an inguinal hernia sac: report of a case.
Malignant tumors presenting as an inguinal hernia are rare. We present the case of a malignant mixed Mullerian tumor (MMMT) of the ovary growing into an inguinal hernia sac. In this case, magnetic resonance imaging was useful in making a diagnosis of an ovarian neoplasm growing into the inguinal canal, and to the best of our knowledge, this is only the tenth case of a malignant ovarian tumor and the first case reported in the English-language literature of MMMT of an ovary which grew into an inguinal hernia sac.
Aged↗
Usefulness of flexible colonoscopic microwave coagulation therapy for a colorectal anastomotic stricture.
PURPOSE: Several methods of treatment for benign anastomotic strictures after anterior resection have been described. We describe a simple, safe, effective, and inexpensive method for treating benign colorectal anastomotic stricture by means of microwave coagulation under flexible colonoscopic visualization. METHODS: Eighteen patients with rectal or rectosigmoidal cancer underwent low anterior resection or anterior resection without colonic pouch and colorectal anastomosis by a double-stapling technique with PCEEA. Two of 18 patients (11.1 percent) developed an anastomotic stenosis. A microwave electrode was passed through the biopsy channel of the flexible colonoscope. Under flexible colonoscopic visualization, microwave irradiation was performed at four points (3, 6, 9, and 12 o'clock) in the stricture site because of granulation scar to obtain an adequately coagulated area. No bougies were performed thereafter. RESULTS: The anastomotic strictures could be dilated adequately, the patients could defecate satisfactorily, and their abdominal distentions and bowel symptoms were resolved. No complications occurred. No occurrence of restricture has been observed. CONCLUSION: Flexible endoscopic, microwave coagulation therapy is a useful, simple, effective, and safe method for the treatment of benign colorectal anastomotic strictures.
Anastomosis, Surgical↗
Effects of OPC-6535 on lipopolysaccharide-induced acute liver injury in the rat: involvement of superoxide and tumor necrosis factor-alpha from hepatic macrophages.
BACKGROUND: The objective of this study was to investigate the effects of OPC-6535 on Propionibacterium acnes-primed and lipopolysaccharide-induced liver injury in the rat. METHODS: P. acnes was administered intravenously to the rat at 16 mg/kg 7 days before the experiments. In liver perfusion experiments, lipopolysaccharide was mixed in perfusion buffer at 2.5 microg/mL. The chemiluminescence method and histochemical reduction of nitro blue tetrazolium were used for detecting superoxide. Release of cytokines into the perfusate was examined. In in vivo experiments, lipopolysaccharide was administered intravenously to the rat at 200 microg/kg. Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were determined in the plasma, and myeloperoxidase activity was measured in the liver tissue. OPC-6535 was given intravenously at 1 mg/kg 30 minutes before lipopolysaccharide challenge, and was then, in perfusion experiments, added to the buffer at 10 micromol/L. RESULTS: In perfusion experiments, P. acnes and lipopolysaccharide caused dramatic production of superoxide, tumor necrosis factor-alpha (TNF-alpha) and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1). Superoxide was mainly from hepatic macrophages. Treatment with OPC-6535 suppressed superoxide and TNF-alpha but did not affect GRO/CINC-1. In in vivo experiments, P. acnes and lipopolysaccharide increased the level of TNF-alpha, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase activity in the liver. OPC-6535 reduced TNF-alpha, AST, and ALT, but did not affect GRO/CINC-1 or myeloperoxidase. CONCLUSION: Attenuation of liver injury by OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF-alpha production by hepatic macrophages in P. acnes- and lipopolysaccharide-treated rats.
Animals↗
Expression of cancer/testis (CT) antigens in lung cancer.
Cancer/testis (CT) antigens are considered promising candidates for vaccine-based immunotherapy. The aim of this study was to investigate which CT antigens should be targeted in immunotherapy of Japanese lung cancer. To determine the expression of 12 CT antigens in Japanese primary lung cancers and cell lines, a reverse-transcription polymerase chain reaction (RT-PCR) analysis was performed. Among 46 primary lung cancers, high expression rates were found for MAGE-3 (41%, 19/46), and SSX-4 (35%, 16/46). A similar pattern of CT antigen expression was observed in 29 lung cancer cell lines. The expression frequency of a certain CT antigen, namely NY-ESO-1, in Japanese cases was drastically different from that in Caucasians. Polyvalent CT antigen vaccine may be effective to increase the number of lung cancer patients eligible for cancer-specific immunotherapy. Vaccination with MAGE-3 and SSX-1 would cover 57% of all patients, with three antigens, MAGE-3, SSX-1, and MAGE-4, would cover 65%, and with four antigens, MAGE-3, SSX-1, MAGE-4 and SSX-4, would cover 70%. Simultaneous expression of two or more CT antigens was observed in 25/46 (54%) primary lung cancers and 18/29 (62%) lung cancer cell lines. Polyvalent CT antigen vaccines may be also effective to reduce a chance of emergence of antigen loss variants, thus preventing tumors from escaping from the immune system. For this purpose, vaccination with combinations of MAGE-3 with MAGE-6, SSX-4, MAGE-1 or BAGE may be effective for a quarter of Japanese lung cancer patients. In addition, in silico surveys of dbEST database were used for identification of new CT antigens. We identified a novel gene, TES101RP, expressed only in some small cell lung cancers (SCLC) and in testis, as confirmed by RT-PCR analysis.
Antigens, Neoplasm↗