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Biomedical subjects

G Forni

Publications and source records attributed to G Forni.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Immunotherapy. I: Cytokine gene transfer strategies.

The cytokine approach to gene therapy of cancer stems from early studies of direct, repeated injection of recombinant cytokines at the tumor site, and extension of the bystander effect that enables a few cytokine gene transduced cells in a tumor to bring about its total destruction. This effect can be extended through the immune system, since cytokine-activated regression of a small mass of tumor cells can afford systemic protection. Transduced cells used as a vaccine provide a local concentration of both cytokine and tumor antigens. Cytokines sustain antigen uptake and presentation by increasing the immunogenic potential of the environment through the recruitment of antigen presenting cells and leukocytes, and activation of a cascade of events which amplify and tone up the efficacy of a vaccine. The promises and difficulties of this approach are discussed by considering what is still missing from experimental studies and what can best be done as soon as possible in animals and humans to reach compelling conclusions.

Animals↗
PubMedDate not supplied

Radiofrequency destruction of the tuberoinfundibular region of hypothalamus permanently abrogates NK cell activity in mice.

Natural killer (NK) cells have an important role in non-adaptative resistance to tumours and their metastatic spread in vivo. Maturation of NK cells and the intensity of their activity are affected by many endogenous and external factors, as well as by regulatory cells. The possibility that some effects of the central nervous system on tumour resistance are mediated via NK activity has also been suggested. Destruction of the tuberoinfundibular region of the hypothalamus in rodents led to a significant increase in tumour growth. We show here that destruction of its ventromedial, dorsomedial and arcuate nuclei persistently abrogates NK activity in mice. By contrast, cortical lesion and operative stress depress it partially, and for a brief period only. Abrogation is the result of a block of NK lineage maturation, causing a severe decrease in the number of large granular lymphocytes (LGL), a lymphocyte population associated with NK activity. Macrophage, B- and T- lymphocyte functions, however, are not significantly affected. Agents inducing NK-cell maturation or activation such as polyinosinic-polycytidylic acid (poly(I:C], interferon (IFN) and interleukin-2 (IL-2) restore NK activity, and normalize the number of LGL.

Animals↗
PubMedDate not supplied

Genotypic, phenotypic and biological characterization of a novel human lung adenocarcinoma cell line (LC 89)

A cell line termed LC 89 was established from a peritracheal lymph node metastasis removed from a 54-year-old patient who underwent surgery for pulmonary adenocarcinoma. Chromosomal analyses demonstrated structural and numerical aberrations, with a mode of 54 chromosomes per cell and several nonrandom abnormalities. The localization of intermediate filament antigens, low-molecular-weight (LMW) cytokeratins and vimentin, demonstrated a switch from LMW cytokeratins, predominantly expressed in primary tumor cells, to vimentin detected in LC 89 cells that were grown in vitro or transplanted into nude mice. In view of the phenotypic and chromosomal features, LC 89 should provide a useful addition to the cell lines currently available for in vitro and in vivo studies of lung cancer.

Adenocarcinoma↗
PubMedDate not supplied

A limited autoimmunity to p185neu elicited by DNA and allogeneic cell vaccine hampers the progression of preneoplastic lesions in HER-2/NEU transgenic mice.

Prevention of the progression of precancerous lesions by vaccines is virtually uncharted territory. Their potential, however, is being assessed in transgenic mice which develop autochthonous tumors with defined stages of progression. In this paper we show that the DNA micro-array technology significantly helps assessment of the preventive efficacy of a combined DNA and cell vaccine. All female rat Her-2/neu transgenic BALB/c (BALB-neuT) mice develop an invasive carcinoma in each of their mammary glands within 25 weeks of age. This is elicited by the activated transforming rat Her-2/neu oncogene embedded in their genome. We have previously shown that vaccination of mice bearing multiple in situ carcinomas with DNA plasmids which code for the extracellular and transmembrane domain of rat p185neu, the product of the rat Her-2/neu oncogene, followed by a boost with rat p185neu+ allogeneic cells engineered to secrete interferon-gamma, keeps 48% of mice tumor free until week 32. We have now extended our follow-up until mice reach one year of age and show that protection vanishes as time progresses. This observation suggests that the accuracy of the results studying immunotherapy against life-threatening tumors is a function of the length of the follow-up. The application of microarrays, and the concordance of morphologic and gene expression data led us to identify antibody as the main mechanism induced by vaccination. Protection is associated with a break of tolerance and a limited autoimmunity against the endogenous mouse p185neu.

Animals↗
PubMedDate not supplied

Prevention by delay: nonspecific immunity elicited by IL-12 hinders Her-2/neu mammary carcinogenesis in transgenic mice.

As a natural consequence of the expression of the activated transforming rat Her-2/neu oncogene all mammary glands of female transgenic BALB/c (BALB-neuT) mice develop atypical epithelial hyperplasia which progresses to invasive carcinoma. A lobular carcinoma is palpable in all mammary glands of 33-week-old BALB-neuT mice. This progression is markedly delayed by systemic administration of IL-12. In a series of studies the best administration schedule, the lowest dose and the most effective administration time have been defined. The cellular and molecular mechanisms resulting in the delay of carcinogenesis have been established. By means of a series of downstream mediators IL-12 inhibits the angiogenic burst that goes along with the passage from preneoplastic to neoplastic and invasive lesions; it also recruits lymphoid cells in the mammary pad and activates their cytotoxicity towards neoplastic cells and newly formed vessels; and furthermore, it induces lymphoid cells to trigger antiangiogenic activities in neoplastic epithelial cells. Effective, low-dose and non-toxic IL-12 treatments may thus be envisaged as a possible option in the management of preneoplastic mammary lesions and in mammary cancer prevention.

Animals↗
PubMedDate not supplied

[Perilymphatic injection of interleukin-2 (IL-2) in recurrent squamous cell carcinoma of the head and neck].

Twenty patients with recurrent squamous cell carcinoma of the head and neck received daily injections of interleukin-2 (IL-2) from the Jurkat T-cell line, purified by high pressure liquid chromatography for 10 days. Two hundred (ten patients), one thousand (five patients) and five thousand (five patients) units of IL-2 in 0.5 ml were injected 1.5 cm from the point where the sternocleidomastoid muscle inserts itself on the mastoid. Whenever possible, the treatment cycles were repeated at 45 day intervals. In 13 patients with contralateral or bilateral cervical lymph nodes, complete or partial disappearance of the tumor was observed. There were non systemic disturbances after injection and only moderate local swelling and pain.

Adult↗
PubMedDate not supplied

Ability of interleukin-4 to elicit an immunoreaction against a murine tumor.

A T cell-derived lymphokine, IL-4, has been shown to have activating and growth promoting properties on macrophages, T cells and B cells. IL-4 could thus be used to augment immunoreactivity in the treatment of tumors. To evaluate its ability to promote an immune reaction capable of hampering tumor growth, we injected mice with small amounts of recombinant IL-4 perilymphatically daily for ten days near the challenge site of a poorly immunogenic syngenic fibrosarcoma (CE-2). These low doses activated such a strong immune reaction that incipient syngenic tumors were rejected. Our results suggest that the host immune system plays a fundamental role in this IL-4 dependent lymphokine-activated tumor inhibition (LATI).

Animals↗