Therapeutic effect of interleukin 12 on mouse haemangiosarcomas is not associated with an increased anti-tumour cytotoxic T-lymphocyte activity.

In syngeneic mice, the H5V polyoma middle-T oncogene-transformed endothelioma cell line induces Kaposi's sarcoma-like cavernous haemangiomas that regress transiently, probably because of an anti-tumour immune response, but eventually grow progressively and kill the host. To evaluate the generation of tumour-specific cytotoxic T lymphocytes (CTLs), spleen cells of tumour-bearing mice were restimulated with irradiated H5V cells in mixed leucocyte-tumour cell cultures. Tumour-specific CTLs were demonstrable only when low numbers of H5V stimulator cells were used (<1 H5V cell per 50 splenocytes). We found that H5V cells secrete immunosuppressive mediators because CTL generation was blocked when H5V cells culture supernatants were added to allogeneic mixed leucocyte cultures. As numerous tumour-derived immunosuppressive mediators may interfere with interleukin 12 (IL-12) production, we tested whether IL-12 treatment of the tumour-bearing mice would augment their immune response and thus suppress tumour growth. Indeed, IL-12 inhibited tumour growth and prevented mortality, but did not increase anti-H5V CTL generation either in vitro or in vivo. Moreover, the anti-tumour activity in IL-12-treated mice was abrogated by anti-interferon (IFN)-gamma monoclonal antibody (MAb) co-administration. These results strongly suggest that the anti-tumour effect of IL-12 is principally mediated by IFN-gamma release that in turn blocks H5V cell proliferation and induces the release of factors that suppress angiogenesis

IL-13 inhibits TNF production but potentiates that of IL-6 in vivo and ex vivo in mice

: IL-13 was reported to inhibit the synthesis of various cytokines in vitro, including that of TNF. It has divergent effects on IL-6 production, which is increased in endothelial cells and decreased in monocytes. We studied the effect of IL-13 administration on TNF and IL-6 production in vivo in mice. IL-13 (1 microg/mouse, i.v., 10 min to 6 h before LPS) decreased LPS (100 ng/mouse, i.v.)-induced serum TNF levels by 50%, while it increased the levels of IL-6 by fourfold. IL-13 potentiated IL-1beta (100 ng/mouse, i.v.)-induced serum IL-6 levels as well as IL-1- or LPS-induced serum amyloid A. When blood from IL-13-treated mice was stimulated with LPS in vitro, TNF production was decreased fivefold, and that of IL-6 was slightly decreased. We also cultured in vitro the aorta obtained from IL-13-pretreated mice and found that they produce more IL-6 (up to sevenfold) than aorta from control mice. Little or no TNF could be detected in these samples. Thus, IL-13 in vivo inhibits serum TNF but up-regulates serum IL-6. The differential regulation of IL-6 and TNF together with the results of ex vivo experiments could be explained by hypothesizing that the cellular origins of the two cytokines are different

Centrally mediated inhibition of local inflammation by ciliary neurotrophic factor

: Since ciliary neurotrophic factor (CNTF) inhibits the production of TNF and activates the hypothalamus-pituitary-adrenal axis (HPAA), we investigated whether CNTF can produce antiinflammatory actions and whether it may act through a central mechanism, using the murine air pouch model of inflammation. In this model, inflammation is evaluated by measuring the induction of TNF and IL-6 as well as cell recruitment in the pouch fluid 24 h after carrageenan. Intracerebroventricular injection, but not intravenous or local injection of CNTF markedly inhibited inflammation. This was associated with high serum corticosterone levels, and antiinflammatory action was not observed in adrenalectomized mice, indicating that an intact HPAA is required. A CNTF receptor antagonist increased carrageenan inflammation, suggesting that endogenous CNTF might have a centrally mediated antiinflammatory role

STADIAZIONE PREOPERATORIA DEL CANCRO DELL’ENDOMETRIO: ECOGRAFIA TRANSVAGINALE E RISONANZA MAGNETICA A CONFRONTO

INTRODUZIONE La stadiazione preoperatoria del cancro dell’endometrio, in particolare la definizione dell’infiltrazione miometriale e del canale cervicale risulta cruciale per programmare la strategia chirurgica e in particolare l’esecuzione della linfoadenectomia pelvica e di un’isterectomia radicale. Lo scopo di questo studio è stato quello di confrontare l’accuratezza diagnostica dell’ecografia transvaginale (TVS) e della risonanza magnetica (MRI) nella valutazione preoperatoria dell’invasione miometriale e del canale cervicale del cancro endometriale. METODI 75 pazienti con diagnosi di cancro endometriale sono state reclutate dal 1998 al 2004 presso la Clinica Ginecologica di Bologna e il Policlinico Gemelli di Roma, e sottoposte a stadiazione preoperatoria mediante ecografia transvaginale eseguita da ecografisti “esperti” e risonanza magnetica eseguita da radiologi altrettanto dedicati al settore della oncologia ginecologica. Per entrambe le metodiche sono state valutate la profondità di invasione miometriale della neoplasia (più o meno del 50% dello spessore totale del miometrio) e l’invasione del canale cervicale e confrontate con l’esito istologico finale. Sensibilità, specificità, valore predittivo positivo, negativo ed accuratezza diagnostica sono stati calcolati per le due metodiche a confronto. RISULTATI La sensibilità, specificità, valore predittivo positivo e negativo e l’accuratezza di TVS e MRI nel predire l’infiltrazione miometriale maggiore del 50% sono rispettivamente: 79%, 87%, 84%, 83%, 84% e 77%, 87%, 84%, 81% e 82%. Per quanto riguarda l’invasione del canale cervicale da parte della neoplasia, le percentuali sono rispettivamente: 72%, 98%, 93%, 92% e 92% per la TVS e 58%, 93%, 84%, 87% e 84% per MRI. Alla analisi statistica mediante K di Cohen e confronto delle curve ROC le differenze non sono risultate significative. CONCLUSIONI In mani esperte TVS e MRI hanno una buona accuratezza, che è risultata sovrapponibile, nel predire l’infiltrazione del miometrio e l’estensione al canale cervicale da parte del carcinoma endometriale. Pertanto riteniamo che la TVS in mani di ecografisti “esperti e dedicati” dovrebbe essere considerata il primo esame diagnostico per la stadiazione preoperatoria del cancro dell’endometrio mentre la MRI dovrebbe essere riservata solo nei rari casi di difficile stadiazione ecografica (pazienti obese, utero fibromatoso, presenza di piometra intracavitario ecc.) o nei casi avanzati con sospetta diffusione extrauterina e pelvica della neoplasia

Preoperative local-regional staging of endometrial cancer: transvaginal sonography versus magnetic resonance imaging

Objectives: The aim of this study was to compare the accuracy of transvaginal sonography (TVS) and magnetic resonance imaging (MRI) in the preoperative staging of endometrial carcinoma. Methods: Some 74 consecutive women diagnosed as having endometrial carcinoma were prospectively evaluated at TVS by physicians trained in gynecological sonography and at MRI by radiologists with a special interest in gynecology. All patients underwent surgical/pathological staging after removal of the uterus, adnexa and pelvic lymph nodes. Sensitivity, specificity, positive and negative predictive values were calculated for both imaging modalities as regards neoplastic invasion of the outer half of the myometrium and cervical involvement. Results: TVS and MRI performed equally well in the preoperative staging of endometrial cancer, with no statistical differences. Sensitivity, specificity, positive and negative predictive values and overall diagnostic accuracy for TVS in the evaluation of myometrial infiltration were 79%, 87%, 84%, 83% and 84%. Values for MRI were respectively 77%, 87%, 84%, 81% and 81%. Corresponding features for detection of cervical involvement were 72%, 98%, 93%, 92% and 92% for TVS, and 58%, 94%, 79%, 87% and 85% for MRI. Conclusions: In expert hands, TVS shows a good accuracy in local regional staging of endometrial carcinoma. Owing to its high costs, MRI should be offered only to those cases in which TVS gives images of poor quality