The cytological screening turned out effective also for adenocarcinoma: a population-based case-control study in Trento, Italy.

To evaluate the effectiveness of a cytological screening to prevent invasive cervical cancer in the province of Trento, a northern Italian area where a population-based cancer registry is active. The history of Pap test was evaluated through a case-control study in 61 population-based invasive cervical cancer patients, incident during 1995-2000, and in 244 age-matched (between 25 and 75 years old) controls. Women who had at least one Pap test had a reduced risk of invasive carcinoma of 80% (odds ratio=0.20; 95% confidence intervals 0.10-0.40). The protection of a previous Pap test for both squamous cell carcinoma (odds ratio=0.23; 95% confidence intervals 0.09-0.58) and adenocarcinoma (odds ratio=0.24; 95% confidence intervals 0.07-0.78) was similar. The overall protective effect of the Pap test was not seen among younger women (<40 years). The protective effect of the Pap test seems to be stronger for shorter intervals. Our study confirms that Pap-test screening, particularly in middle-aged and older women, is an effective public health intervention with encouraging results also for the prevention of cervical adenocarcinoma.     

The LFA-1/ICAM cell adhesion pathway is involved in tumor-cell lysis mediated by bispecific monoclonal-antibody-targeted T lymphocytes

We investigated the role of the LFA-1 /ICAM, VLA-4/VCAM-1 and CD2/LFA-3 adhesion pathways in the cytolysis of tumor cells mediated by an anti-EGF-R/anti-CD3 bispecific monoclonal antibody (biMAb). The biMAb induced efficient lysis of EGF-R+ tumor cells (A431, HT-29, IGROV-1 and MDA-MB468) by cytotoxic T lymphocytes (CTL) cultured in IL-2. Protreatment of effector cells by anti-LFA-1α (CDI 1a) and anti-LFA-1 β (CD 18) MAbs significantly inhibited cytolysis of all types of EGF-R+ tumor cells, while anti-CD2 and anti-VLA-4 MAbs were virtually ineffective. We investigated the expression of adhesion-molecule counter-receptors on tumor target cells by indirect immunofluorescence. HT-29, A431 and MDA-MB 468 tumor cells expressed an ICAM-1+2^?3^?VCAM-1^?LFA-3⁺ phenotype, while IGROV-1 was ICAM-1^?2⁺3^?VCAM-1 ^?LFA-3+. Pre-treatment of A431, HT-29 and MDA-MB468 with anti-ICAM-1 MAb inhibited cytolysis, further supporting the functional involvement of the LFA-1 /ICAM adhesion pathway in biMAb-targeted tumor-cell lysis. In addition, treatment of target cells with TNFα or IFN-γ for 24 hr increased the expression of ICAM-1 in HT-29, A431 and MDA-MB468 (ICAM-2 was induced on IGROV-1) and also enhanced the sensitivity of these target cells to biMAb-targeted cytotoxicity. These data suggest that up-regulation of ICAM-molecule expression by inflammatory cytokines may increase susceptibility of tumor cells to biMAb-targeted lysis. Anti-LFA-1 MAbs did not significantly inhibit the formation of conjugates between biMAb-coated T lymphocytes and tumor cells. Co-aggregation of LFA-1 molecules with biMAb-bound CD3 molecules resulted in a more sustained and prolonged increase in the intracellular concentration of. free Ca⁺⁺ in CD8⁺ cultured CTL lines. These findings indicate that in T cells targeted by anti-CD3/anti-TAA biMAb LFA-1 may act as a co-receptor molecule which enhances signal transduction through the CD3/TCR complex.     

Lactate dehydrogenase and its isoenzymes in respiratory diseases in children]

Total Lactate Dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were quantified in 161 children (51 with pneumonia at the time of diagnosis, 60 hospitalized for asthma in acute period and 50 healthy subjects) to ascertain the relationship of these markers with injury of lung tissue. No statistical variations, between different groups in total activity, were found. Significantly decreased proportions of LD1 (p less than 0.000001) and of LD2 (p less than 0.000001) with simultaneous increase of LD4 (p less than 0.000001) and LD5 (p less than 0.000001) resulted in children with pneumonia, as to asthmatic or healthy subjects. Investigators conclude that LD should be determined in every patient with pneumonia because of the presence of a specific LD isoenzyme pattern.     

Chronic granulomatous disease and McLeod phenotype. Description of a case

Chronic granulomatous disease (CGD) is a genetic syndrome, mostly inherited as an X-linked recessive trait, characterized by severe and recurrent infections due to defective neutrophil leukocytes and monocytes respiratory burst and microbicidal activity. Consequently, the affected patients are prone to infections by catalase-positive bacteria and fungi. The Authors describe a case of X-linked CGD with red cells of the rare McLeod phenotype. These red cells show acanthocytosis and are not reacting with anti-Kx antibody. Moreover, the Authors discussed the diagnosis and chemotherapy of CGD in addition to biochemical and clinical characterization of McLeod phenotype.     

The 5-HT 1A receptor antagonist WAY 100635 improves rats performance in different models of amnesia evaluated by the object recognition task

The effects of the 5-HT(1A) receptor antagonist WAY 100635 on recognition memory were investigated in two different amnestic models in the rat by using the object recognition task. WAY 100635 at 1 mg/kg, but not at 0.3 mg/kg, counteracted scopolamine-induced performance deficits in the acquisition version of this behavioral paradigm. At the same dose, WAY 100635 antagonized extinction of recognition memory in the normal rat, suggesting that it affected acquisition, storage and retrieval of information. These results support and extend prior findings that interactions between the serotonergic and cholinergic systems are relevant to cognition and indicate that WAY 100635 modulates different aspects of recognition memory.     

Post-menopausal hormonal therapy and gallbladder cancer risk

The relation between post-menopausal hormone replacement therapy (HRT) and gallbladder cancer was analyzed in women above age 45 years, using data of a case-control study conducted in Italy between 1985 and 1997, on 31 incident, histologically confirmed cases and 3,702 controls in hospital for acute, non-neoplastic conditions. The multivariate odds ratio (OR) was 3.2 (95% confidence interval: 1.1-9.3) for those who had ever used HRT and the OR tended to rise with longer duration. Although based on small numbers, due to the rarity of the disease, these findings provide the first direct epidemiological evidence of an association between HRT and gallbladder cancer.     

Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice

We have previously shown that the growth of human tumor xenografts in immunodeficient mice can be efficiently suppressed upon infection with the autonomous parvovirus H-1 or with cytokine-transducing derivatives thereof. To further evaluate the benefits of implementing parvoviruses in cancer gene therapy, we have created a new recombinant vector, MVMp/IP-10, transducing the immunoactive, antiangiogenic chemokine IP-10, and used this virus to treat syngeneic tumors grown in immunocompetent mice. Intratumoral/intraperitoneal administration of only 3 x 10(7) replication units of MVMp/IP-10 per animal strongly inhibited the progression of established H5V cell-induced vascular tumors, a highly malignant mouse model for human cavernous hemangioma and Kaposi's sarcoma. Retardation of recurrent tumor growth and suppression of life-threatening metastatic dissemination to internal organs were accompanied by a striking delay in hemangioma-associated mortality. Parental MVMp did not have a significant effect under these conditions up to the dose of 10(10) infectious units/animal, but had strong antihemangiosarcoma activity when used to infect H5V cells ex vivo prior to implantation. In all cases, virus therapy was very well tolerated. Virus-induced suppression of hemangiosarcoma was dependent on host T cells and associated with intratumoral persistence of IFN gamma-expressing cytotoxic lymphocytes, and led to the reduced expression of hepatic plasminogen activator inhibitor-1 (PAI-1), a metastasis-linked marker. This proof of principle study demonstrates that MVMp/IP-10 can aid the treatment of vascular tumors and that autonomous parvovirus-based vectors can be considered potent tools for cancer gene therapy purposes.     

Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.