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Biomedical subjects

M Sacchi

Publications and source records attributed to M Sacchi.

At least 37 records · Page 2Linked to original sources
PubMed1991

Induction of tumor regression in experimental model of human head and neck cancer by human A-LAK cells and IL-2.

In a nude mouse model of human squamous-cell carcinoma of the head and neck (SCCHN), locoregional therapy with interleukin 2 and human lymphokine-activated killer (LAK) cells resulted in a significant inhibition of growth of 3-day established tumors. The same model was used for therapy of 7-day established tumors with highly enriched populations of human adherent (A)-LAK (CD3- CD56+) cells and IL-2. Peritumoral transfer of 10 x 10(6) A-LAK cells, whose in vitro cytotoxicity against a SCCHN cell line (PCI-I) was not significantly different from that of LAK cells, resulted in complete regression of all 3-day or 7-day human SCCHN in nude mice. An initial inflammatory-type reaction, which appeared within hours of the first peritumoral cell transfer, was accompanied by infiltration initially by granulocytes and plasma cells, and later by mononuclear cells into the tumor stroma. A-LAK cells labelled with a fluorescent dye prior to injection appeared in the tumor stroma within 24 hr and were localized around or in the basal epithelial tumor layer by 48 hr. Histologic sections revealed an increasing epithelial disorganization and progressively decreasing basal epithelial layer, which were proportional to the increasing number of A-LAK cells transferred. Within 4 weeks, the tumors were reduced to amorphous keratinic remnants surrounded by the connective tissue containing abundant mononuclear cells. Local administration of human A-LAK cells and IL-2 to SCCHN tumors growing in nude mice led to accelerated tumor differentiation, keratinization and regression.

Animals↗
PubMed1991

Antiproliferative effects of cytokines on squamous cell carcinoma.

A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly.

Carcinoma, Squamous Cell↗
PubMed1990

The absence of lymphoid suppressor cells in tumor-involved lymph nodes of patients with head and neck cancer.

Patients with head and neck cancer often have decreased local or regional immunocompetence. Lymphocytes obtained from tumor-involved or -uninvolved lymph nodes (LNL) of these patients showed low or undetectable levels of antitumor cytotoxicity and low proliferative responses in vitro to interleukin 2 (IL2) or mitogens in comparison to peripheral blood lymphocytes (PBL). Lymphokine-activated killer (LAK) cell activity of LNL was lower (P less than 0.05) than that of autologous PBL. Fresh LNL were neither enriched in cells with the CD8+ CD11b+ "suppressor" phenotype nor did they suppress proliferative or cytotoxic responses of autologous PBL in mixing experiments. LNL did not inhibit LAK cell generation from autologous PBL in the presence of IL2. Also, no evidence for the inhibition of autotumor-restricted responses by IL2-activated LNL was obtained. Spontaneous or in vitro-induced production of IL1 beta. TNF alpha, and IFN-tau was low or undetectable in LNL from tumor-involved and -uninvolved lymph nodes in comparison to that in normal or autologous PBL. Mitogen-induced IL2 production was normal in LNL. The depressed ability to produce certain cytokines may be in part responsible for a state of unresponsiveness present in lymph nodes obtained from patients with head and neck cancer. No evidence for the presence of lymphoid suppressor cell in LNL of these patients was obtained.

Aged↗
PubMed1990

Local adoptive immunotherapy of human head and neck cancer xenografts in nude mice with lymphokine-activated killer cells and interleukin 2.

The efficacy of local adoptive immunotherapy with human lymphokine-activated killer cells and recombinant interleukin 2 (rIL-2) in growth inhibition of established squamous cell carcinoma of the head and neck (SCCHN) was evaluated in a nude mouse model. The model of xenografted SCCHN was established by s.c. injections of in vitro maintained tumor cells (2-10 x 10(6) cells/mouse) into the flank of splenectomized animals pretreated with cyclophosphamide (200 mg/kg). The SCCHN line used was tumorigenic in 95% of the appropriately conditioned nude mice. Inhibition of tumor growth by locally administered effector cells was the end point of the study, since the tumors did not metastasize within 6 weeks of tumor challenge. Either i.p. or local administration of rIL-2 alone (1000 units/day) to the tumor site daily for 2 weeks resulted in a significant inhibition of tumor growth. In the absence of detectable natural killer activity in these mice, a modest dose of rIL-2 had a direct antitumor effect on SCCHN cells in vivo. In addition, complete inhibition of tumor growth was achieved with 3 times weekly injections of 5-10 x 10(6) lymphokine-activated killer cells delivered to the tumor site and 1000 units of rIL-2 administered locally every day for 2 weeks. Our data indicate that local or systemic immunotherapy with rIL-2 alone or local adoptive immunotherapy with an adequate dose of lymphokine-activated killer cells plus rIL-2 may be effective in preventing the growth of established SCCHN tumors in vivo.

Animals↗
PubMed1988

[Computerized tomographic evaluation of latero-cervical lymphatic metastasis of carcinoma of the larynx. Personal experience in 170 cases].

CT can be considered the most reliable technique in detecting nodal metastases of the cervical district. The Authors have studied 170 patients with laryngeal cancer (104 N0, 21 N1, 21 N2 and 24 N3 clinically) with CT of the cervical region during infusion of contrast material. All patients underwent radical neck dissection with pathological examination of the nodes. CT diagnosis and pathological findings were correlated. Our findings show that CT has an overall accuracy of 91.8% (100% in groups N2 and N3) and fed false positives and false negatives.

Adult↗
PubMed1988

[X-ray computed tomography in latero-cervical lymph nodes, clinically undetectable, in preoperative staging of malignant neoplasms of the larynx].

Postoperative CT of the latero-cervical lymph nodes was carried out in 25 patients suffering from laryngeal cancer. The surgically removed lymph nodes themselves were measured and examined histologically. 529/621 removed lymph nodes (about 85%) were recognisable with CT. The metastasized lymph nodes were clearly identified because of the presence of hypodense, poorly vascularised central foci. Some lymph nodes with a diameter of more than 15 mm on CT investigation proved free from metastatic lesions. This criterion should therefore be considered inadequate for diagnostic purposes. The CT cannot be held to be sufficiently precise to avoid conservative functional latero-cervical emptying as it is probably not able to recognise metastases without capsular rupture, not present in this series.

Adult↗
PubMed1987

Specific lymphokine responses in cervical nodes of patients with laryngeal cancer.

The role of lymphokines in modulating the immune response in patients suffering from neoplastic disease is still controversial. Recent studies indicate that in patients with head and neck cancer, a decrease in LIF (leukocyte migration inhibiting factor) production is usually present in advanced disease. In this study, the authors investigate: the LIF production in lymphocytes derived from the peripheral blood and cervical nodes of patients with laryngeal carcinoma by using an autologous pattern (i.e., for each patient, the specific LIF production was challenged by means of an autologous cell extract derived from his own tumor); the influence of histologically confirmed cervical node metastases on LIF production. Our results indicate that: There is a significant decrease in LIF production in patients with histologically proven cervical node metastases as compared to patients with no metastatic foci. The decrease of LIF production is related to the presence of mononuclear adherent cells. When the latter are removed, there is a significant reversal of specific LIF suppression. The possible meaning of the data is discussed.

Cell Adhesion↗
PubMed1985

Treatment of bleeding esophageal varices by portoazygos disconnection and esophageal transection with the button of Boerema and EEA stapler: ten years' experience.

We present 64 patients with bleeding esophageal varices who have been treated with portoazygos disconnection, devascularization of the esophagogastric junction, and esophageal transection with the button of Boerema (32 patients) and EEA stapler (32 patients). The patients were treated between 1973 and 1983. Their ages ranged from 50 to 70 years. Based on Child's classification, 26 (37.5%) of the patients fell into class A, 35 (54.6%) in class B, and five (7.8%) in class C. These patients were also divided into three subgroups: group I--21 patients (32.8%) underwent emergency operations; group II--40 patients (62.5%) underwent semiemergency operations; and group III--three patients (4.7%) underwent elective operations. The perioperative mortality rate was 10.8%. With the Fischer exact test, we found the combined death rate of Child's classes A and B to be significantly lower than that for class C patients. The duration of follow-up ranged from 6 months to 9 years (average 32.9 months) in the 80% of the patients that we were able to follow. There was a 6.5% incidence of recurrent gastrointestinal bleeding and a 28% incidence of late encephalopathy. The incidence of transitory dysphagia was 40% when the button of Boerema was used as compared with 9% when the EEA stapler was used. The surgical approach presented herein is an attractive alternative to portosystemic decompression for patients in whom hepatic dysfunction is complicated by uncontrolled variceal hemorrhage.

Aged↗
PubMed1978

[An atypical case of subacute sclerosing panencephalitis (SSPE), (with special reference to psychiatric and psychological evaluations)].

An atypical case of subacute sclerosing panencephalitis is described, with particular reference to its psychiatric and psychological aspects in the light of the neurological and laboratory data: slow-gamma electrophoresis of the spinal fluid, periodic delta signs in the EEG over about 6 yr, 1/160 blood titre of anti-measles virus antibodies. The history displayed an ingravescent dementia course and the patient's continuing survival for more than 11 yr makes the case the longest recorded in the literature. Both the psychiatric-psychological and neurological symptoms had occurred in distinct stages. It is suggested that neurological recrudescence was responsible for the pattern of symptomatological stabilisation followed by sudden relapses. The symptoms regarded as characteristic of the terminal stage have not yet appeared, especially on the neurological side.

Adult↗