hymecromone and Adenocarcinoma--Clear-Cell

Ovarian clear cell carcinomas often show a spherule-like mucoid stroma. In ascitic fluid, they form spheroids with a hollow acellular space. In spite of the absence of stromal cells, both the mucoid stroma and hollow spheroids contain abundant extracellular matrix, and one of the major components is hyaluronan. It has been suggested that tumor-derived hyaluronan plays a significant role in the formation of these structures. To clarify this, a hyaluronan inhibition assay was performed on HAC-2, a clear cell carcinoma cell line, in vitro. When hyaluronan synthesis was inhibited by 4-methylumbelliferone, HAC-2 failed to show the spherule-like accumulation of hyaluronan or hollow spheroids. Inhibition of hyaluronan synthesis was associated with the reduction of cell growth. Analysis of 28 archival ascites cytology specimens showed that clear cell carcinomas expressed hyaluronan more frequently than serous carcinomas (11 of 14 vs 3 of 14, respectively, P < 0.05). All of these facts indicate that tumor-derived hyaluronan is essential for the formation of the mucoid stroma or hollow spheroids, and that hyaluronan is also involved in the regulation of cell growth in ovarian clear cell carcinomas. The inhibition of hyaluronan synthesis could be a potential adjunctive therapy for refractory clear cell carcinomas outside the ovary.

Topics: Adenocarcinoma, Clear Cell; Adjuvants, Immunologic; Ascites; Cell Line, Tumor; Cystadenocarcinoma, Serous; Extracellular Matrix; Female; Humans; Hyaluronic Acid; Hymecromone; Ovarian Neoplasms

To investigate whether the activity of lysosomal enzymes is increased in the peritoneal fluid of patients with gynecologic cancers compared to activity in the peritoneal fluid from normal subjects and those with pelvic inflammatory disease, and fluid from benign ovarian cysts.. beta-glucuronidase, beta-galactosidase, and alpha-mannosidase activity was measured in the peritoneal fluid from patients with gynecologic cancer, pelvic inflammatory disease, and normal subjects, and fluid from benign ovarian cysts.. The mean+/-SD of beta-glucuronidase, beta-galactosidase, and alpha-mannosidase activity in the gynecologic cancers was 120+/-50 nmol, 203+/-86 nmol, and 240+/-119 nmol 4-methylumbelliferone/ml/h, respectively; in the normal control subjects it was 22+/-9 nmol, 46+/-10 nmol, and 80+/-23 nmol, respectively (P=0.00003, 0.0001, and 0.0001, respectively). The activity was increased even in cases without malignant cells in the peritoneal fluid. In pelvic inflammatory disease it was 148+/-82 nmol, 278+/-112 nmol, and 291+/-140 nmol, respectively. The activity in the fluid of the ovarian cysts was similar to that of the normal peritoneal fluid. There was a significant positive correlation between enzyme activity and stage of cancer, that was stronger for beta-glucuronidase (r=0.889, P=0.003).. The increased lysosomal enzyme activity in gynecologic cancers, without overlapping between patients and normal subjects or benign ovarian cyst fluid, indicates that such measurements might be applied for diagnostic purposes.

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; alpha-Mannosidase; Ascitic Fluid; beta-Galactosidase; Case-Control Studies; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Glucuronidase; Humans; Hymecromone; Lysosomes; Neoplasms; Ovarian Cysts; Ovarian Neoplasms; Pelvic Inflammatory Disease