thromboxane-b2 and Neoplasms

Platelet function in 12 cancer patients was studied sequentially over 97 hr of interleukin-6 (IL-6) daily bolus or continuous infusion (C.I.) therapy. During this period, enhanced ex vivo agonist-induced platelet maximum aggregation (MA) was paralleled by an increase in plasma levels of TXB2 and PF4 as measured by RIA and ELISA, respectively. Platelet-rich plasma (PRP) specimens from bolus IL-6-treated patients demonstrated an increased incorporation of actin-binding protein and myosin in the cytoskeletal core (triton insoluble residue) as shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in comparison to control specimens. Similarly, the integrin glycoprotein IIIa (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. A significant decrease in hypotonic shock response (HSR) was observed over 87 hr of treatment in IL-6 C.I. patients, whereas in IL-6 bolus patients, a significant increase in HSR occurred immediately after the bolus, which was followed by a significant decrease in HSR after 23 hr. These results suggest that IL-6 alters platelet function in vivo.

Topics: Adenosine Diphosphate; Antineoplastic Agents; Arachidonic Acid; Blood Platelets; Enzyme-Linked Immunosorbent Assay; Epinephrine; Humans; In Vitro Techniques; Infusions, Intravenous; Injections, Intravenous; Interleukin-6; Kinetics; Neoplasms; Platelet Aggregation; Platelet Count; Platelet Factor 4; Radioimmunoassay; Thromboxane B2

Thromboxane A2 (TxA2) is implicated in the pathogenesis of various forms of drug-induced renal damage. Based on previous functional studies, we postulated that cis-dichlorodiammineplatinum (cisplatin) induces intrarenal TxA2 synthesis. To test this hypothesis, we measured urinary excretion of thromboxane B2 (TxB2), the stable inactive metabolite of TxA2, during and after cisplatin administration.. The study included 16 patients with malignant disease who were scheduled to receive cisplatin (100 mg/m2) and 11 healthy subjects who received the same amount of fluid loading and the same concomitant medication as the patients but no cisplatin. Total urine output was collected in seven intervals from 24 hours before until 72 hours after the start of prehydration. Urinary immunoreactive TxB2 was measured.. There was a marked increase (4.5 +/- 1.6-fold; mean +/- SEM) in urinary TxB2 excretion in patients during and immediately after cisplatin infusion. This increase was significant compared with baseline and the control group.. High-dose cisplatin causes an acute increase in urinary excretion of TxB2. This likely represents enhanced intrarenal synthesis of TxA2, in response to an acute damaging effect of cisplatin on the kidneys. These findings warrant further studies to evaluate the renoprotective effect of anti-TxA2 intervention in patients receiving high-dose cisplatin.

Topics: Acetylglucosaminidase; Adult; Aged; Antineoplastic Agents; Cisplatin; Female; Humans; Infusions, Intravenous; Kidney; Male; Middle Aged; Neoplasms; Thromboxane B2

We have evaluated in a homologous system the mechanisms of platelet activation by cells isolated from fresh human tumor tissues and the role of thromboxane B2 (TxB2) generation in this process. Thirty-eight of the 46 tumor tissues considered showed a high platelet-aggregating activity, with no particular distribution in any specific tumor type. Apyrase caused a nonsignificant reduction in the aggregation response, hirudin did not change it, while iodoacetic acid or p-hydroxymercuriphenylsulfonate, specific cysteine proteinase inhibitors, significantly reduced the platelet-aggregating capacity of these tumor cells. In 9 colon carcinomas and in 8 breast carcinomas the levels of TxB2 produced by platelets after addition of tumor cells were measured: tumor cell-induced platelet aggregation was accompanied by a significant production of the metabolite; indobufen, a cyclooxygenase inhibitor, significantly reduced aggregation and particularly TxB2 production, while the drug had no effect on both parameters if preincubated with tumor cells only. These data suggest that cells isolated from different human tumor tissues activate platelets through the activity of tumor-associated cysteine proteinase(s); platelet aggregation by tumor cells is largely dependent on arachidonic acid metabolism in platelets, while such metabolism in tumor cells does not play a significant role.

Topics: Adult; Apyrase; Blood Platelets; Dose-Response Relationship, Drug; Hirudins; Humans; Iodoacetates; Iodoacetic Acid; Isoindoles; Neoplasms; Phenylbutyrates; Phenylmercury Compounds; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Radioimmunoassay; Thromboxane B2

A single injection of a streptococcal preparation, OK-432, with fresh frozen plasma (FFP) (or fresh human serum) into the peritoneal or pleural cavity for the treatment of malignant ascites or pleurisy resulted in a complete reduction of ascitic fluid or pleural effusion in 5 out of 11 patients. FFP was used a further source of complement for the effective accumulation of antitumor polymorphonuclear leukocytes (PMNs) by complement-derived chemotactic factors in the cavity. C5a increased in the fluids 3-9 h after the injection and preceded a massive increase in PMNs. C1 inhibitor (C1INH) and C3b inactivator (C3bINA) decreased in several cases 6 h after the treatment. Chemotactic arachidonic acid metabolites, thromboxane B2(TXB2) as a characteristics of TXA2, and leukotriene B4(LTB4) also increased at the same time even in cases where C5a changed only minimally, and may play a role in accumulating antitumor PMNs in the cavity.

Topics: Adult; Aged; Aged, 80 and over; Ascites; Biological Products; Complement Activation; Complement C5; Complement C5a; Female; Freezing; Humans; Immunization, Passive; Leukotriene B4; Male; Middle Aged; Neoplasms; Neutrophils; Picibanil; Pleurisy; Thromboxane B2

Plasma thromboxane B2 (TxB2) level were measured in patients with various disease, and its changes were investigated in patients who underwent various operations. The following results were obtained. Plasma TxB2 values in patients with TAO, heart disease, and malignant disease were significantly elevated compared with healthy control. Plasma TxB2 values during operation and immediate period after operation were significantly elevated compared with preoperative values. Plasma TxB2 level was markedly elevated in bypass operation when synthetic prosthesis were used. In patients with malignant disease, plasma TxB2 values significantly decreased after removal of tumor compared with preoperative values. In cardiopulmonary bypass, TxB2 level were markedly elevated ten minutes after beginning, and then decreased gradually until the end of cardiopulmonary bypass. The factors which are considered to be related to elevation of plasma TxB2 level during the operation and the postoperative period are as follows: a) surgical intervention, b) anesthesia, c) thromboembolic complication, d) grafting of synthetic prosthesis. e) valve replacement and f) cardiopulmonary bypass. The positive correlation between beta-TG and TxB2 level was found. TxB2 measurement is complex and too expensive, while measurement of beta-TG is very easy and cheap. Because of their good correlation, beta-TG is used as substitute for TxB2 in daily practice.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Vessel Prosthesis; Cardiopulmonary Bypass; Female; Heart Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Monitoring, Physiologic; Neoplasms; Surgical Procedures, Operative; Thromboxane B2