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Biomedical subjects

D Santoli

Publications and source records attributed to D Santoli.

100 records · Page 6Linked to original sources
PubMed1973

Nonproductive infection of guinea pig cells with human cytomegalovirus.

Human cytomegalovirus was capable of adsorbing to and penetrating guinea pig cells, but was unable to replicate new virus. Cultures infected with virus inoculum of high titer showed a cytopathic effect (CPE) characterized by cell rounding. This CPE depended upon the presence of infectious virus, and its extent was directly related to the multiplicity of infection. Staining by indirect immunofluorescence by using human convalescent sera was positive as early as 4 h postinfection. Maximal fluorescence was observed 24 h postinfection when 50% of the cells contained fluorescent antigens both in nuclei and cytoplasm. No evidence for viral replication was found, and no defective particles were detected by electron microscopy. Treatment with actinomycin D or with cycloheximide strongly inhibited both the fluorescent antigens and the CPE, whereas 5-fluorodeoxyuridine and bromodeoxyuridine were ineffective.

Animals↗
PubMedDate not supplied

Two unique human leukemic T-cell lines endowed with a stable cytotoxic function and a different spectrum of target reactivity analysis and modulation of their lytic mechanisms.

We have reported the establishment of two interleukin (IL)-2-dependent human leukemic cell lines (TALL-103/2 [CD3+TCR gamma delta +] and TALL-104 [CD3+ TCR alpha beta +]) which display major histocompatibility complex nonrestricted tumoricidal activity. Whereas TALL-103/2 cells lyse only natural killer cell-susceptible targets, TALL-104 cells display a broad range of tumor target reactivity. In reverse antibody-dependent cell-mediated cytotoxicity (ADCC), lysis by both cell lines is triggered by monoclonal antibodies (mAb) recognizing CD3 and, to a lesser extent, CD2, but not CD8 or CD56 antigens. In conventional cytotoxic assays, the lytic activity of both cell lines is strictly Ca(2+)-dependent. In reverse ADCC, lysis by TALL-103/2 cells is highly dependent on the presence of Ca2+, whereas TALL-104 cells seem to only partially require extracellular Ca2+. The cytoplasm of both cell lines contains azurophilic granules typical of cytotoxic cells. Northern blot analysis demonstrates mRNA expression of pore-forming protein (PFP; perforin) and serine esterases (SE). The magnitude of expression of these transcripts and of lytic activity depends on the doses of IL-2. Upon deprivation of IL-2, TALL-103/2 cells completely lose cytotoxic granules and function within 16 h, whereas TALL-104 cells progressively lose expression of PFP and SE mRNA, as well as killer activity, within 4 wk. Both anti-CD3 mAb and lysable target cells induce efficient BLT-esterase secretion from TALL-103/2 and TALL-104 cells analogous to findings with conventional cytotoxic T lymphocytes. The stable expression of tumoricidal activity over 2 yr in culture renders these cell lines unique and very useful for studies on the regulation of cell-mediated lysis in vitro and in animal models.

Antibody-Dependent Cell Cytotoxicity↗
PubMedDate not supplied

Inducible expression of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interferon-gamma in two human cytotoxic leukemic T-cell lines.

We investigated the ability of the TALL-103/2 and TALL-104 leukemic cell lines to produce lymphokines in response to activation signals, such as tumor cells and anti-CD3 (OKT3) or -CD2 (B67.1) monoclonal antibodies (mAb) or both. Both cell lines were found to produce high levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The latter lymphokine is induced by lysable tumor cells and by immobilized OKT3 and B67.1 mAb only in the presence of interleukin (IL-2). IFN-gamma and TNF-alpha are induced upon CD3 but not CD2 stimulation, both in the presence and absence of IL-2. Interestingly, the B67.1 mAb amplifies the OKT3-induced responses by 2- to 10-fold, bringing the IFN-gamma and TNF-alpha levels of production up to 200 U/ml. Thus, simultaneous triggering of the CD2 and CD3 signaling pathways results in a very efficient lymphokine release. Of all the tumor cell lines tested as inducers, only K562 cells are able to stimulate the production of IFN-gamma and TNF-alpha in TALL-103/2 and TALL-104 cells, especially upon culture in IL-2. Lymphokine mRNA expression after stimulation with mAb or K562 cells peaks at 2 h in both cell lines. No messages are detectable in TALL-103/2 cells at 8 h, whereas in TALL-104 cells, IFN-gamma and GM-CSF transcripts are still present at 8 and 20 h, respectively. The inducible and highly regulatable expression of lymphokine release by these cell lines provides a unique model for studying mechanisms of lymphokine induction by different biological agents.

Culture Media↗
PubMedDate not supplied

New insights on disintegrin-receptor interactions: eristostatin and melanoma cells.

Viper venom disintegrins have been used frequently to study the cellular receptors which characterize various types of cells, including platelets, endothelial cells and cancer cells. While the majority of such analyses have pointed to involvement of integrin receptors alphavbeta3, alpha5beta1 or alphaIIbbeta3, this may not always be so. Eristostatin, from Eristocophis macmahoni, is a potent inhibitor of ADP-induced platelet aggregation as well as of human and murine melanoma metastases in mouse model systems. This disintegrin requires an RGDW motif, as well as an intact C-terminus, in order to interact with both platelets and four different types of melanoma cells. Eristostatin causes nonmetastatic SBc12 melanoma cells to show higher susceptibility to specific killing by NK-like TALL-104 cells. While it is known that eristostatin binds to alphaIIbbeta3 on platelets, the receptor with which eristostatin binds to the melanoma cells has not yet been identified.

Binding Sites↗
PubMedDate not supplied

Adoptive therapy of canine metastatic mammary carcinoma with the human MHC non-restricted cytotoxic T-cell line TALL-104.

Adoptive transfer of human TALL-104 killer cells into a dog with metastatic mammary adenocarcinoma resulted in 50% reduction of the largest lung metastasis and stabilization of the other lesions for 10 weeks, accompanied by the development of tumor-specific immune responses. Upon halting cell therapy, the dog developed new lung lesions within 10 weeks and died of slowly progressive disease. TALL-104 cell therapy of mice bearing the dog's tumor xenograft induced 65% reduction of local tumor growth and regression of lung metastases in 100% of the animals. The overall findings indicate the therapeutic potential of TALL-104 cells for canine mammary tumors.

Animals↗
PubMedDate not supplied

Conjugated linoleic acid suppresses the growth of human breast adenocarcinoma cells in SCID mice.

Conjugated linoleic acid (CLA), which is mainly derived from dairy products, has been shown both in vitro and in animal models to have strong anti-tumor activity. Particular effects were observed on the growth and metastatic spread of transplantable mammary tumors. In this study, we examined the effect of dietary CLA on the growth of human breast adenocarcinoma cells in severe combined immunodeficient (SCID) mice. Mice were fed 1% CLA for two weeks prior to subcutaneous inoculation of 10(7) MDA-MB468 cells and throughout the study. Dietary CLA inhibited local tumor growth by 73% and 30% at 9 and 14 weeks post-inoculation, respectively. Moreover, CLA completely abrogated the spread of breast cancer cells to lungs, peripheral blood, and bone marrow. These results indicate the ability of dietary CLA to block both the local growth and systemic spread of human breast cancer via mechanisms independent of the host immune system.

Adenocarcinoma↗
PubMedDate not supplied

Synergistic effects of adriamycin and TALL-104 cell therapy against a human gastric carcinoma in vivo.

The single and combined antitumor effects of adriamycin and a major histocompatibility complex non-restricted human cytotoxic T cell line (TALL-104) were evaluated in severe combined immunodeficient (SCID) mice engrafted subcutaneously with a biopsy sample from a patient with a highly metastatic gastric carcinoma. Chemotherapy was initiated 3 weeks after tumor implantation, when local growth was advanced, and consisted of 2 weekly injections of adriamycin. gamma-irradiated (40 Gy) TALL-104 cells were administered daily for 2 weeks, starting 1 day after the end of chemotherapy. While TALL-104 cells or adriamycin alone did not inhibit tumor growth, synergistic antitumor effects were seen with the two treatments combined. These findings suggest that chemotherapy in conjunction with cell therapy are effective in overcoming tumor resistance to single therapeutic agents through mechanisms independent from the host immune system.

Animals↗
PubMedDate not supplied

Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice.

The relationship between dietary fat intake (level and type) and cancer development is a matter of concern in Western society. The purpose of this study was to determine the effect of three different diets on the local growth and metastatic properties of DU-145 human prostatic carcinoma cells in severe combined immunodeficient (SCID) mice. Animals were fed a standard diet or diets supplemented with 1% LA or 1% CLA for 2 weeks prior to subcutaneous (s.c.) inoculation of DU-145 cells and throughout the study (total of 14 weeks). Mice receiving LA-supplemented diet displayed significantly higher body weight, lower food intake and increased local tumor load as compared to the other two groups of mice. Mice fed the CLA-supplemented diet displayed not only smaller local tumors than the regular diet-fed group, but also a drastic reduction in lung metastases. These results support the view that dietary polyunsaturated fatty acids may influence the prognosis of prostatic cancer patients, thus opening the possibility of new therapeutic options.

Animals↗
PubMedDate not supplied

TALL-104 cell therapy of human solid tumors implanted in immunodeficient (SCID) mice.

We have developed a novel approach to adoptive therapy of cancer based on the use of a human T cell line (TALL-104) which is endowed with major histocompatibility complex non-restricted cytotoxic activity against a broad range of tumors and across several species, while sparing cells from normal tissues. The present study investigates the efficacy of TALL-104 cell therapy in severe combined immunodeficient (SCID) mice implanted with human solid tumors. The human cell lines DU-145 (prostate cancer), A549 (lung carcinoma) and WM451 (melanoma) were implanted subcutaneously (s.c.) in the flank region of the mice. Multiple intraperitoneal (i.p.) transfers of lethally irradiated TALL-104 cells into animals bearing small tumor masses (150 mg) resulted in 50-75% reduction of local tumor growth and complete prevention of pulmonary metastasis. In mice implanted s.c. with A549 cells, dramatic antitumor effects against both local and metastatic disease were observed when cell therapy was initiated after surgical excision of the primary tumor mass. In another set of experiments, the DU-145 and WM451 cells were injected intravenously (i.v.); cells disseminated aggressively in various organs and all animals died within 6-10 weeks from engraftment. However, experimental mice that received TALL-104 cell therapy i.p. daily, starting 1 week after tumor inoculation, showed longer survival and a slower tumor growth (as measured monthly by plasmatic levels of the sICAM-1 tumor marker). At necropsy 1/6 of these animals were disease free. Taken together, these data indicate the effectiveness of this novel antitumor agent in prolonging disease-free survival and controlling tumor growth and invasion.

Adoptive Transfer↗