Papers - TAMAKOSHI, Koji

Hyaluronidase activity in gynaecological cancer tissues with different metastatic forms. Reviewed

Tamakoshi K, Kikkawa F, Maeda O, Suganuma N, Yamagata S, Yamagata T, Tomoda Y.

Br J Cancer.   Vol. 75 ( 12 ) page： 1807-1811   1997

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We investigated hyaluronidase activity in gynaecological normal and malignant tissues. Hyaluronidase activity in culture medium of tissue specimens was detected by hyaluronic acid zymography and quantified by densitometry. Hyaluronidase activity was shown as one dominant band (molecular weight 65 kDa) at pH 3.5. Hyaluronidase activity was significantly higher in normal ovary (P < 0.05) and normal endometrium (P< 0.05) than in normal cervix. One dominant 65-kDa hyaluronidase was expressed in 100% (14 out of 14) of ovarian cancer tissues and in 91% (10 out of 11) of endometrial cancer tissues. However, hyaluronidase activity was not observed in cervical cancer tissues. Hyaluronidase activity was significantly higher in ovarian (P < 0.001) and endometrial (P < 0.01) cancer tissues than in cervical cancer tissue and was significantly higher in ovarian cancer tissue than in endometrial cancer tissue (P < 0.05). These facts suggest that the cancer cells make use of the original characteristic of the organ to invade and metastasize. Moreover, these results reflect the difference in metastatic forms and are suggestive of a strong relationship between hyaluronidase activity and invasion and metastasis of ovarian and endometrial cancers compared with cervical cancer.

Clinical value of CA125, CA19-9, CEA, CA72-4, and TPA in borderline ovarian tumor. Reviewed

Tamakoshi K, Kikkawa F, Shibata K, Tomoda K, Obata NH, Wakahara F, Tokuhashi Y, Ishikawa H, Kawai M, Tomoda Y.

Gynecol Oncol.   Vol. 62 ( 1 ) page： 67-72   1996.7

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Five tumor markers were analyzed clinically in 101 patients with borderline ovarian tumors who were treated by the Tokai Ovarian Tumor Study Group, an association comprising Nagoya University and its affiliated hospital, between January 1986 and December 1994. The positive rate of CA125 was 68.2% in serous tumor and 51.9% in mucinous tumor. The positive rate of CA19-9 was 51.5% in serous tumor and 44.7% in mucinous tumor. The positive rates and mean serum levels of CA125 in serous and mucinous tumor by stage had rising tendencies with an increase in each stage. The mean serum levels of CA19-9 in serous and mucinous tumor by stage had rising tendencies with an increase in each stage. CA125 and CA19-9 were useful for screening of borderline ovarian tumors. The positive rates of CEA and TPA in mucinous tumor were 32.5 and 27.3%, respectively, although none of the patients with serous tumor were positive in CEA and TPA. The positive rates and mean serum levels of CEA in mucinous tumor by stage had rising tendencies with an increase in each stage. The positive rate of CA72-4 was significantly lower than that of CA125 (P < 0.05).

Characterization of extracellular matrix-degrading proteinase and its inhibitor in gynecologic cancer tissues with clinically different metastatic form. Reviewed

Tamakoshi K, Kikkawa F, Nawa A, Ishikawa H, Mizuno K, Tamakoshi A, Yamagata S, Suganuma N, Tomoda Y.

Cancer.   Vol. 76 ( 12 ) page： 2565-2571   1995.12

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BACKGROUND. The authors conducted a comparison study of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) activities in clinically different metastatic types of ovarian cancer, cervical cancer, and endometrial cancer tissues. METHODS. Gelatinase activity in culture medium obtained from each cancer tissue was detected by zymography and was quantitated by densitometer. Tissue inhibitor of metalloproteinase-1 activity was measured in culture medium by the human TIMP-1 enzyme immunoassay kit. RESULTS. Six dominant gelatinases were detected in ovarian, cervical, and endometrial cancers: 200-kDa; 130-kDa; 92-kDa (MMP-9); 83-kDa, which is an active form of 92-kDa gelatinase; 72-kDa (MMP-2); and 66-kDa gelatinase, which is an active form of 72-kDa gelatinase. The 92-kDa and 72-kDa gelatinolytic bands were present in all samples. The expression rates of 200-, 130-, and 83-kDa gelatinase in endometrial cancer and cervical cancer tissues were higher than that observed in ovarian cancer tissue. Densitometric analysis showed that the 92-kDa/72-kDa ratio was significantly higher in cervical cancer tissue than in ovarian and endometrial cancer tissues (P < 0.05), and the 66-kDa/72-kDa ratio was significantly higher in endometrial cancer tissue than in ovarian cancer tissue (P < 0.01). Tissue inhibitor of metalloproteinase-1 activity was significantly lower in cervical cancer tissue than in ovarian and endometrial cancer tissues (P < 0.01). CONCLUSIONS. These results reflect the difference of metastatic forms and are indicative of the possibility of the strong relationship to MMP activity in the invasion and metastasis of cervical cancer and endometrial cancer, compared with those of ovarian cancer.

Clinical value of a new serum tumor marker, CA125II, in gynecologic disease: comparison with CA125. Reviewed

Tamakoshi K, Kikkawa F, Hasegawa N, Ishikawa H, Mizuno K, Kawai M, Tomoda Y.

Gynecol Obstet Invest.   Vol. 39 ( 2 ) page： 125-129   1995

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CA125 II, an improved version of the conventional CA125 was compared with CA125 as to which was more useful in gynecologic disease. In the diagnosis of tumors around the adnexal field (primary epithelial ovarian cancer, metastatic ovarian cancer, benign ovarian tumor and endometrial cyst), CA125 II showed the same sensitivity and specificity as CA125. CA125 II also has high simultaneous reproducibility in the low concentration area. The examination by the receiver operating characteristic curve revealed that CA125 II has higher precision than that of CA125 when it is used for the screening test. In conclusion, CA125 II is a better tumor marker than conventional CA125.

Different pattern of zymography between human gynecologic normal and malignant tissues. Reviewed

Tamakoshi K, Kikkawa F, Nawa A, Maeda O, Kawai M, Sugamuma N, Yamagata S, Tomoda Y.

Am J Obstet Gynecol.   Vol. 171 ( 2 ) page： 478-484   1994.8

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OBJECTIVE: Our purpose was to evaluate type IV collagenase in ovarian and endometrial cancer tissues. STUDY DESIGN: Tissue specimens were obtained from patients with ovarian and endometrial cancer and uterine myoma. Gelatinase activity was detected by zymography and quantitated by densitometer. RESULTS: Four dominant gelatinases were detected in ovarian and endometrial cancer tissues: 200, 130, 92, and 72 kd gelatinase. Other forms observed were 83 kd gelatinase, which is an active form of 92 kd gelatinase, and 66 kd gelatinase, which is an active form of 72 kd gelatinase. Densitometric analysis showed that the 92 kd/72 kd ratio in ovarian cancer tissues was significantly higher than in normal ovarian tissues (p < 0.05) and that the 66 kd/72 kd ratio was higher in ovarian cancer tissues (p = 0.07). Both ratios in endometrial cancer tissues were significantly higher than in normal endometrial tissues (p < 0.05). CONCLUSION: Gelatinase activity was remarkably higher in ovarian and endometrial cancer tissues. Especially, 92, 83, and 66 kd gelatinases were clearly detected in cancer tissues, suggesting that these gelatinases were related to the malignant phenotype, because degradation of the components of the basement membrane such as type IV collagen is necessary for cancer cells to metastasize.