Wound seeding associated with endometrial cancer.

We report a patient with well-differentiated adenocarcinoma of the endometrium who developed a recurrence in the anterior abdominal wall probably secondary to wound seeding at the time of her original surgery. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy. She then received 15 mCi of 32P for positive peritoneal washings. She was free of disease until 2 years later when a large lower incision mass developed. She had no evidence for intra-abdominal disease and a radical resection with a myocutaneous flap was undertaken. Radical resection for isolated metastases may be of benefit for patients with endometrial cancer. Patients with positive cytology should be observed closely for incisional recurrence.

Effect of tumor necrosis factor on the human fibrinolytic system.

We report the effects on the fibrinolytic system of intravenous (IV) recombinant tumor necrosis factor-alpha (rTNF-alpha) infusions in patients with advanced cancers. During a phase I clinical trial of rTNF-alpha, the plasma fibrinolytic system was closely monitored, measuring tissue-type plasminogen activator (tPA) antigen, plasminogen activator (PA) inhibitor activity, and plasma fibrinolytic activity. Thirteen patients with refractory malignancies received 40, 80, or 160 micrograms/m2 rTNF-alpha as 2-hour IV infusions. After a 1-week rest, the same dose was repeated daily for 5 days every 3 weeks for a maximum of four courses. The serum rTNF-alpha levels peaked at the completion of the IV infusion and rapidly declined thereafter, becoming unmeasurable within 1 hour in all patients. rTNF-alpha infusion markedly alters the plasma fibrinolytic system. During the 2-hour infusion, significant increases in the tPA antigen and plasma fibrinolytic activity were seen. After the infusion, PA inhibitor activity increased, neutralizing the plasma fibrinolytic activity. The increase in PA inhibitor activity was maximal 6 hours after the onset of the rTNF-alpha infusion. Fibrinolytic properties returned to pretreatment values within 24 hours. Daily rTNF-alpha infusions caused changes in plasma tPA antigen and PA inhibitor similar to those of single infusions. We conclude from these observations that the administration of rTNF-alpha in vivo to cancer patients causes profound alterations of endothelial cell-derived components of the fibrinolytic system.

Inhibition of the activation of Hageman factor (factor XII) by complement subcomponent C1q.

Hageman factor (HF, Factor XII) is activated by glass, collagen, and ellagic acid, and initiates blood coagulation via the intrinsic pathway. C1q inhibits collagen-induced platelet aggregation and adherence of platelets to glass, effects attributable to the collagen-like region of C1q. We examined the actions of C1q on HF activation. Incubation of C1q with HF before addition of HF-deficient plasma extended the activated partial thromboplastin time. Similarly, when glass tubes were coated with C1q before testing, the partial thromboplastin time of normal plasma was increased. C1q reduced the activation of HF by ellagic acid, as measured by the release of p-nitroaniline from the synthetic substrate H-D-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide dihydrochloride, an effect inhibited by monoclonal anti-human C1q murine IgG and by digestion of C1q by collagenase. Thus, C1q inhibits activation of HF in vitro in clot-promoting and amidolytic assays and suggests a regulatory mechanism for the inhibition of coagulation.

Immunochemical comparison of mutant glucocorticoid receptors and wild type receptor fragments produced by neutrophil elastase and chymotrypsin.

We characterized the glucocorticoid receptor fragments produced by neutrophil elastase and compared these receptor fragments to nuclear transfer increased (nti) mutant receptors. Neutrophil elastase and chymotrypsin digested [3H]dexamethasone 21-mesylate labeled receptors at different sites to produce 52 kDa and 42 kDa fragments respectively. Both the 52 kDa elastolytic receptor fragments and 42 kDa chymotryptic receptor fragments bound to DNA-cellulose and were immunoadsorbed by anti-glucocorticoid receptor monoclonal antibodies (BUGR2). More extensive digestion of labeled receptors by neutrophil elastase produced 29 kDa receptor fragments that did not bind to DNA-cellulose and did not react with BUGR2 antibodies. The size of nti mutant receptors from S49 mouse lymphoma cell variants is intermediate between that of the 52 kDa elastolytic receptor fragments and 42 kDa chymotryptic receptor fragments. The nti receptors bound to DNA-cellulose with the same affinity as the 52 kDa elastolytic receptor fragments. However, the nti receptors were not immunoadsorbed by BUGR2 antibodies and did not react with these antibodies on Western blot analysis of denatured cellular proteins. The results indicate that 52 kDa elastolytic receptor fragments, 42 kDa chymotryptic receptor fragments and nti mutant receptors correspond to the same region of the receptor molecule. The failure of nti receptors to react with BUGR2 antibodies suggests that the nti receptors may have an altered sequence compared to the corresponding region of normal receptors.