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Koshi Mimori, Microsatellite instability-high CRC acquires frequent sub-clonal immune escape mechanisms by Darwinian evolution., 第40回国際がんシンポジウム, 2022.06. |
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Koshi Mimori, A Basic Traits of ctDNA To Be Applied for the Early Diagnosis of Recurrence in CRC cases, 12th Int’l Symposium on Minimal Residual Cancer, 2020.10. |
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三森功士, An overview of liquid biopsy and basic traits of ctDNA & Opinions: Liquid biopsy in the future, 第79回日本癌学会学術総会 The 79th Annual Meeting of the Japanese Cancer Association, 2020.10. |
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三森 功士, 高橋佑典, 内龍太郎, 新井田厚司, 宮野悟, 森正樹, Proposal of new tactics to overcome resistance to molecular target therapy provoked heterogenetiy., 第71回日本消化器外科学会, 2016.07. |
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三森 功士, PLS3 Expression in Circulating Blood Is a Good Marker for Colon Cancer Recurrence., Ninth AACR-JCA Joint Conference, 2013.02. |
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三森 功士, Clinical Significance of mir-144-ZFX Axis in Isolated Tumor Cells in Bone Marrow in Gastric Cancer Cases., 65th Annual Cancer Synposium, SSO, 2012.03. |
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Identification of non coding RNA as carcinogenic or recurrence/metastatic markers by Next Generation Sequencer, and the magnitude for surgeons.. |
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Introduction To predict the cancer recurrence, the evaluation of isolated tumor cells (ITC) in the peripheral blood (PB) or bone marrow (BM) by using epithelial cell markers such as CEA or cytokeratins (CK) would be useful. On the other hand, the significance of the expression of cancer related genes such as urokinase type plasminogen activator receptor (u-PAR) in PB or BM has not been clarified.
Patients and Methods 1) We examined ITC in PB and BM from 744 cases of breast cancer (and 29 non-malignant patients as a negative control) by the quantitative real-time RT-PCR with CEA, CK-19, and CK-7. The ITC positive was determined when each one of the three genes was expressed. 2) The expressions of u-PAR in PB and BM were examined by real time RT-PCR. 3) We combined data of u-PAR and CK in comparison with each gene. 4) Serum CEA and CA15-3 levels in 298 of 744 cases were measured to compare with the u-PAR or CK status.
Results 1) The positive result was recognized in 262 (35.4%) cases in PB, and these showed poorer disease free survival than 482 negative cases (pu-PAR (+) BM showed significantly poorer disease free survival and overall survival than 575 cases of u-PAR (-) BM (pu-PAR (+) and 435 cases of u-PAR (-) (pu-PAR and CK in BM, u-PAR (+)/CK(+) showed the highest recurrence rate, however, u-PAR status alone was adequate to predict recurrence in comparison with the combined data. 4) The hazard ratio for prediction of recurrence are significantly higher in u-PAR (pConclusion We found that the significance of u-PAR was much greater than the ITC alone. This means that the tumor-host reactions (one of those parameters may be the u-PAR) would be very important to predict the cancer recurrence rather than the existence of cancer cells in the circulating system, and would be much more reliable than the established serum tumor markers preoperatively.. |
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Introduction: This report examines the clinical outcomes of cancer patients after 12 post-operative years to determine the prognostic value of CEA mRNA in peripheral blood (PB) (Mori M., JCO 1997). In addition, a novel ITC marker, identified by microarray analysis, was validated with 959 cases of gastric cancer (GC) by Taqman RT-PCR.
Patients and methods: 1) The clinical outcomes of 102 cases were reinvestigated and compared to evaluate CEA expression in PB. 2) Metastatic-related genes present in bone marrow (BM) were identified by cDNA microarray analysis of total RNA from the whole blood of four metastatic and four non-metastatic cases. Among the up-regulated genes in the metastatic cases, MT1MMP was chosen for further analysis. 3) MT1MMP expression was validated by Taqman RT-PCR using the PB and BM from 959 cases of GC.
Results: 1) Among 102 cases, 12 that were CEA (-) showed novel distant metastasis; however, the incidence of CEA in PB was not associated with OS and DFS. 2) Expression levels of MT1MMP were up-regulated in metastases. MT1MMP1 localizes to the cell surface to regulate tumor invasion, and is expressed from cancer cells and/or interstitial cells via cell-cell interactions. 3) The positive rate of GC cases with MT1MMP expression in PB was larger in 13 (72%) cases with distant metastasis than in 296 (31%) cases without distant metastasis (p=0.0002). Five (27.8%) cases with distant metastasis showed a higher incidence of MT1MMP (+) in BM compared with 71 (7.3%) cases without distant metastasis. Furthermore, 3 (25%) cases with recurrence were MT1MMP (+) in BM, while 73 (7.5%) cases without recurrence were MT1MMP (-) in BM, a significant association (p=0.020).
Conclusion: Based on the long follow-up period, we conclude that presence of the epithelial marker CEA in PB cannot be used as a prognostic or recurrent marker for GC. This large-scale study revealed that MT1MMP expression could be an effective predictor of clinical outcome in GC cases. In GC, metastasis from primary cancer tissues may require cancer cells with high metastatic potential and/or circumstances, such as MT1MMP expression in PB or BM. . |
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MAL expression is diminished in esophageal cancer cases and cell lines.
MAL expression in tumor cells exerts an anti-tumorigenic effect by Fas and/or by keratins of esophageal epithelium.
MAL expression is diminished in pre-cancerous lesions in a rat carcinogenic model, as well as in dysplastic lesions of esophageal cancer. . |
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INTRODUCTION The fragile histidine triad (FHIT) functions as a tumor suppressor and clinical benefits of adenoviral-FHIT (Ad-FHIT) may be expected. However, the pathways through which FHIT induces apoptosis and inhibits cancer cell growth are not known. To determine appropriate targets for Ad-FHIT mediated therapy, we performed microarray analysis between Ad-FHIT transfected cells and control cells using 3 kinds of squamous cancer cell lines. For this purpose, 1) we identified clusters of more repressed genes in Ad-FHIT cells compared to control cells, and 2) we compared clustered genes in apoptosis induced cells H1299 and TE4 by Ad-FHIT infection with genes in non apoptotic non-induced cell line, TE2.
METHOD Three cell lines, H1299, TE4 and TE2 were transfected individually with full length FHIT and lacZ cDNA as a control. Total RNAs extracted from Ad-FHIT or AdlacZ infected samples were labeled with Cy3-dCTP or Cy5-dCTP and hybridized with a chip printed with 19,200 oligos. 1) The Ad-FHIT/Ad-control expression ratio was derived by using a random permutation test with high reproducibility from 7 repetitive
Experiments, and 4 spots per gene on a chip. 2) The expression ratio of TE4/TE2 for eachgene was calculated to determine what genes are dominant in Ad-FHIT induced apoptotic cells.
RESULTS 1) We identified clusters of genes reduced in Ad-FHIT, such as arachidonicacid metabolism (Table 1A) and matrix metalloprotease (MMP) related genes (Table 1B). We confirmed a reduction of PGE2 synthesis to 0.75 times control cells (range 0.35 to 0.98) by ELISA assays after exposure to LPS, IL-1 beta, or PMA stimulation in FHIT expressing cells. 2) The expression ratio of TE4 (apoptosis induced) /TE2 (non-apoptosis induced), disclosed that c-Src tyrosine kinase, tyrosine-protein kinase JAK-1 and EST (#Hs.268892) were associated with apoptosis, with ratios of 2.1, 2.4 and 6.6, respectively(Table 2).
CONCLUSION 1) We anticipate that Ad-FHIT may be effective in certain pre-malignant cases involving inflammatory carcinogens, such as COX-2 which leads to the inhibition of apoptosis; invasion, cell proliferation, angiogenesis mediated by the PGE2 receptor Ep4; IL-1 beta which stimulates the release of prostaglandin; and ERG-1 which is a transcription factor for mPGES. Moreover, the MMP family could be a target of the Ad-FHIT gene. 2) Therefore we predict the induction of apoptosis by Ad-FHIT on far advanced esophageal cancer cases with activation of those signal pathways.. |
