Gefitinib-induced autologous antitumor immunity

Aim:   We previously reported that thromboxane (TX) B2, p-selectin, and the cytokine that is regulated on activation, normal T expressed and secreted (RANTES) were elevated in patients with non-small cell lung cancer (NSCLC) treated with gefitinib. It is reported that macrophages are activated by platelets. We hypothesized that macrophages were activated in patients medicated with gefitinib, and we measured their plasma macrophage inflammatory protein (MIP)-1 beta.
Methods:   Patients with NSCLC not curable by surgery were entered in the study and received gefitinib at a dose of 250 mg/day over a period of two weeks. Blood samples were drawn before and after administration and MIP-1 beta was measured by enzyme-linked immunosorbent assay.
Results:   A total of 28 patients, 42–82-years of age (median, 67); 16 men and 12 women, were the subjects of the study: 21 had adenocarcinomas and seven squamous cancers. Partial response to gefitinib occurred in 11 patients, 12 had stable disease and five had progressive disease. The mean serum level of MIP-1 beta in the 28 evaluable patients increased significantly after gefitinib medication for 1 and 2 weeks from a baseline of 101 ± 19 pg/mL to 139 ± 25 pg/mL at one week ( P  < 0.05) and 131 ± 29 pg/mL at 2 weeks ( P  < 0.05).
Conclusion:   Immunological markers related to activated platelets including MIP-1 beta as well as thromboxane A2 p-selectin and RANTES, are elevated in patients undergoing therapy with gefitinib. We speculate that gefitinib has a potential autologous immunological anti-tumor activity.     

Electrophysiological Demonstration of Anterograde Concealed Conduction in Accessory Atrioventricular Pathways Capable Only of Retrograde Conduction

Anterograde concealed conduction into the concealed accessory atrioventricular (AV) pathway has been postulated to be one of the factors preventing the reciprocating process via the accessory pathway in patients with the concealed Wolff-Parkinson-White(WPW) syndrome but its presence has not been documented. To demonstrate the occurrence of anterograde concealment, 12 patients with the concealed WPW syndrome were selected for study. A pacing protocol was designed in which the retrograde conduction of the ventricular extrastimulus over the accessory pathway was assessed during ventricular pacing aione (conventional method) and during the AV simultaneous pacing (simultaneous method); the results were then compared. When the high right atrium was simultaneously paced, the effective refractory period of the concealed accessory pathway shortened as compared with the conventional method in five of 12 patients (from 341.7 ± 110.8 to 312.5 ± 108.2 msec, n = 12), whereas, it decreased in all patients studied when the coronary sinus near the accessory pathway was simultaneously paced (from 375.7 ± 135.0 to 287. ± 116.1 msec, n = 7). These results demonstrate that the AV simultaneous pacing frequently shortens the refractoriness of the concealed accessory AV pathway and such facilitation seems to he well explained by the probable anterograde concealment in it and peeling back of the refractory barrier.     

Production of Blocking Antibodies by Vaccination With Husband's Lymphocytes in Unexplained Recurrent Aborters: The Role in Successful Pregnancy

ABSTRACT: To elucidate an immunological mechanism in terms of the effectiveness of vaccination of the unexplained habitual aborters with their husband's lymphocytes, 20 patients were selected as the experimental group, and 10 fertile couples were selected as the control group. Subjects were studied by mixed lymphocyte reaction-blocking assay so as to determine whether they had blocking antibodies (BAbs) in their sera. In the experimental group, BAb levels were found to be significantly lower as compared to the ten control multiparous wives; 17 cases (85%) of them were proved not to have sufficient BAbs. Significant sharing of HLA-D/DR antigens was observed in experimental couples. Then, 10 out of 17 patients with evidence of no produced BAbs were vaccinated with their husband's lymphocytes, and all of them were observed to produce BAbs within three vaccinations. After vaccination, seven out of ten patients have so far become pregnant, five of these pregnancies have been successful, with evidence of continuing production of BAbs. In conclusion, vaccination of the patients with husband's lymphocytes was found to stimulate a production of BAbs, and it was thus strongly suggested that this may lead to their production in a subsequent pregnancy, which would allow its success.     

Arginine-dependent generation of reactive nitrogen intermediates is instrumental in the in vitro killing of protoscoleces of Echinococcus multilocularis by activated macrophages

The interaction between protoscoleces of Echinococcus multilocularis and activated murine macrophages was examined in this study. Marked protoscolicidal activity was displayed by peritoneal macrophages (PM) activated with interferon-γ (IFN-γ), or IFN-y plus lipopolysaccharide. Pretreatment of the parasites with heat-inactivated specific murine infection serum, but not with normal serum rendered them more susceptible to PM killing. N^G-monomethyl-Larginine, a competitive inhibitor of L-arginine completely inhibited the killing activity of activated PM. while reconstitution of arginine-free medium with L-arginine restored the killing properties of the activated PM. The results show that activated PM have the ability to kill E. multilocularis protoscoleces in vitro and suggest that reactive nitrogen intermediates (RNl) play an important role in the mechanism. An oxygen-mediated mechanism did not appear to play a role because scavengers of reactive oxygen species did not reduce the killing activity. The arginine-dependent killing mechanism was enhanced by superoxide dismutase (SOD), probably because SOD might prolong the effect of nitric oxide. Secretion of RNI by activated macrophages may be capable of a significant role in preventing of the dissemination of E. multilocularis infection in vivo.     

Laparoscopy Assisted Colectomy with Extracorporeal Anastomosis

Abstract: Laparoscopy assisted colectomy with extracorporeal anastomosis was carried out in five patients. In three patients, the lesions were carcinoma with submucosal invasion and the histological results of the polypectomy specimen indicated the necessity of the subsequent colectomy. In the other two patients the lesions were either adenoma or carcinoma in adenoma. Under pneumoperitoneum, mobilization of the colon was performed using the laparoscopic technique. In three patients the mesenteric vessels of a segment of the colon were ligated and divided extracorporeally. In two patients the mesenteric vessels were clipped and divided intracorporeally. In all cases, extracorporeal resection of the colon and hand suture anastomosis were performed. Surgery time ranged from 3 hours and 20 minutes to 4 hours and 50 minutes. No postoperative complications were experinced. Four patients began to walk on the first postoperative day. Postoperative administration of analgesics was needed in four patients for two days or less after the operation. In all but one case, bowel sounds were audible from the first post-operative day onwards. In only one patient was the postoperative recovery delayed. Although sufficient future studies should be accumulated to confirm the advantages of this procedure, we can expect that laparoscopy assisted colectomy will become a useful procedure for benign and early malignant lesions in which colonoscopic removal was not possible or was suspected to be insufficient. (Dig Endosc 1944; 6 : 52–58)