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Biomedical subjects

J A Lucci

Publications and source records attributed to J A Lucci.

10 recordsLinked to original sources
PubMed1992

Trafficking of syngeneic murine lymphokine activated killer T cells following intraperitoneal administration in normal and tumor bearing mice.

Nongenetically restricted T cells may be important host effector cells in women with ovarian cancer receiving intraperitoneal (ip) IL-2 therapy. We developed an in vitro technique to produce murine lymphokine-activated killer T cells. Murine splenocytes were cultured in the presence of 1000 U/ml IL-2 for 10 to 15 days. Phenotypical analysis showed 95% of total cells to express the pan T phenotype Thy 1.2 and no NK cell phenotypes by Day 7 in culture. These cells were labeled with 51Cr and their trafficking pattern after ip administration into normal and M5067 tumor bearing mice was examined. Various organs and tissues were collected at different timepoints and monitored for radioactivity. Within 4 hr., about 60% of the counts were associated with the bowel, peritoneum, and omentum of both normal and tumor bearing mice. About 15% of counts were associated with the blood, lung, kidney, spleen, and liver of both normal and tumor bearing mice.

Animals↗
PubMed1992

Immunotherapy of ovarian cancer. II. In vitro generation and characterization of lymphokine-activated killer T cells from the peripheral blood of recurrent ovarian cancer patients.

We examined the in vitro sensitivity of continuous ovarian cancer cells to lymphokine-activated killer T cells (T-LAK) alone or in combination with cytokines. Lymphocyte viability in T-LAK cultures generated from normal donors and ovarian cancer patients declined in the first 2 to 4 days; however, the remaining cells in these cultures maintained a constant rate of proliferation for long periods in vitro. These cells became 90-95% CD3+ TCR+ -alpha/beta T-cells after 7-10 days in culture. The T-LAK cells from normal donors and cancer patients expressed an equal ability to induce lysis of a panel of human target cells (NK-sensitive K562, NK-insensitive RAJI, and two human ovarian tumor lines, SKOV-3 and OVCAR-3), demonstrating that they are nongenetically restricted killers. Preincubation of either the effector or target cells with tumor necrosis factor or interferon-gamma or addition of these cytokines directly to cytolytic assays did not alter the degree of cell lysis in vitro. This is a method for generating large numbers of autologous, cytolytically active T-LAK cells from the blood of ovarian cancer patients that could be employed in adoptive intraperitoneal immunotherapy.

Cell Division↗
PubMed1991

Identification of tumor necrosis factor and lymphotoxin blocking factor(s) in the ascites of patients with advanced and recurrent ovarian cancer.

Ascites obtained from human ovarian cancer patients contains material(s) that inhibit the cytolytic activity of tumor necrosis factor (TNF) and lymphotoxin (LT) in vitro. These inhibitor(s) are found in ascites from ovarian cancer patients and are detected in very low amounts in the ascites from patients with nonmalignant hepatic disease. These ascites TNF/LT blocking factors are heat sensitive and heterogeneous with respect to molecular weight. Kinetic studies indicate these factors inhibited cytolysis at the stage of TNF/LT interaction with membrane receptors on L929 cells. Because TNF and LT are key cytokines in host cell-mediated antitumor mechanisms, factor(s) that inhibit these cytokines could have a profound effect on the tumor host interaction and their presence in the ascitic fluid, should be considered before designing clinical trials that employ intraperitoneal administration of TNF or LT for immunotherapy of ovarian cancer.

Animals↗
PubMed1991

Rat mitogen-stimulated lymphokine-activated T killer cells: production and effects on C6 glioma cells in vitro and in vivo in the brain of Wistar rats.

An in vitro technique was developed to generate activated rat T cells, with antitumor activity. Splenic mononuclear cells (SMC) from outbred Wistar and inbred Wistar-Munich rats were stimulated with Concanavalin A and recombinant human interleukin-2 (rIL-2) in vitro for 48 h. After 2 days, the nonadherent cells began proliferating and were maintained in rIL-2 for up to 18 days in vitro. FACScan analysis revealed that SMC was a mixture of cell types; however, CD5+ T cells rapidly increased and became the predominant cell type after 5 days in culture. SMC induced cytolysis of YAC-1, but not C6 glioma cells in 4 h 51Cr release assays. In contrast, 5- and 9-day T cells lysed C6 glioma and YAC-1 cells. The C6 cells were admixed with cultured effector cells at various effector-to-target (E:T) ratios and were injected into the right cerebral hemisphere of Wistar and Wistar-Munich rats for a Winn assay. Histopathologic evaluations revealed that a) SMC had no effect; b) 2- and 5-day T cells, injected at E:T ratios greater than 5:1, caused significant reduction in tumor size; and c) 2- or 5-day T cells, at a 40:1 E:T ratio, resulted in little or no histologic evidence of tumor. Eighty-three percent of animals receiving C6 and 5-day mitogen-stimulated lymphokine activated killer cells at an E:T ratio of 40:1 were alive 120 days postinjection (p less than 0.05).

Animals↗
PubMed1990

Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients.

Serum ultrafiltrates (SUF) from human patients with different types of cancer contain a blocking factor (BF) that inhibits the cytolytic activity of human tumor necrosis factor alpha (TNF-alpha) in vitro. BF is a protein with a molecular mass of 28 kDa on reducing sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE). The active material was purified to homogeneity by a combination of affinity chromatography, PAGE, and high-pressure liquid chromatography. Amino acid sequence analysis revealed that BF is derived from the membrane TNF receptor. Purified BF blocks the lytic activity of recombinant human and mouse TNF-alpha and recombinant human lymphotoxin on murine L929 cells in vitro. However, BF inhibits the lytic activity of TNF-alpha more effectively than it does that of lymphotoxin. The BF also inhibits the necrotizing activity of recombinant human TNF-alpha when coinjected into established cutaneous Meth A tumors in BALB/c mice. The BF may have an important role in (i) the regulation and control of TNF-alpha and lymphotoxin activity in cancer patients, (ii) interaction between the tumor and the host antitumor mechanisms, and (iii) use of systemically administered TNF-alpha in clinical trials with human cancer patients.

Amino Acid Sequence↗
PubMed1977

Prenatal diagnosis of recurrence of Saldino-Noonan dwarfism.

The occurrence in a family of three spontaneous abortions and two siblings with Saldino-Noonan dwarfism supports an autosomal recessive etiology and raises the possibility of lethality early in utero. No long bones were visualized in radiographs at 19 weeks' gestation in the second affected pregnancy. highlighting the difficulties of distinguishing technical limitations from fetal anatomic abnormalities. Ultrasound studies demonstrated oligohydramnios. Radiologic prenatal diagnosis can rule out this condition prior to 20 to 24 weeks' gestation and affected fetuses can be suspected if not proved by radiographs and ultrasound examination.

Amniotic Fluid↗