Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epipodophyllotoxin derivatives, etoposide (VP-16) and teniposide (VM-26), are highly lipophilic anticancer drugs supplied with novel commercial solvent systems. A BALB/c mouse skin toxicity model was used to evaluate the ulcerative potential of intradermal (ID) VP-16 and its lipophilic solvent system along with the main ingredient of the VM-26 solvent, polyethoxylated castor oil (PECO). ID VP-16 caused dose-dependent ulceration following 0.17 mg, 0.33 mg (50 mg/M2) or 1.0 mg (150 mg/M2). Both normal saline (0.05 ml ID) and hyaluronidase (7.5 u ID) were effective as local VP-16 antidotes, presumably by diluting out the extravasated drug. The VP-16 solvent alone was as toxic as the 1.0 mg (undiluted) ID VP-16 injection. ID PECO was mildly ulcerative in mouse skin. When given to P-388 lymphocytic leukemia-bearing mice, both VP-16 (24 mg/kg IP for 3 doses) and VM-26 (8 mg/kg IP for 2 doses) were active, producing increased life spans (ILS) of 160% and 90%, respectively. The solvents, given IP at the same schedule, did not increase or decrease the life span of tumor-bearing mice, but did increase morbidity. In an in vitro human tumor clonogenic assay (WiDr colon carcinoma and HEC-1A endometrial carcinoma in soft agar), both VP-16 and VM-26 showed moderate to complete inhibition of tumor colony forming units (TCFUs) by continuous exposure. 1-h drug exposures were marginally active at reducing TCFUs. None of the epipodophyllotoxin diluents at clinical concentrations reduced TCFUs. At very high concentrations, both epipodophyllotoxins were cytotoxic. They were more effective at reducing TCFUs when plated as a continuous exposure rather than a 1-h exposure.
 ...
PMID:Skin ulceration potential without therapeutic anticancer activity for epipodophyllotoxin commercial diluents. 667 64

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.
 ...
PMID:Hyaluronidase activity in gynaecological cancer tissues with different metastatic forms. 919 86