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Biomedical subjects

R Giavazzi

Publications and source records attributed to R Giavazzi.

At least 109 records · Page 6Linked to original sources
PubMed1983

Mononuclear phagocyte adherence in the presence of laminin. A possible marker of cellular differentiation.

The effect of laminin on the vitro adhesive behavior of mononuclear phagocytes was investigated. Laminin significantly inhibited the adhesion of guinea pig, mouse, and rat alveolar or peritoneal macrophages and of human peripheral blood monocytes. Adhesion of these cells was unaffected by similar concentrations of fibronectin. Experiments performed with monocytes maintained in culture showed that the degree of laminin-mediated inhibition of adherence was dependent on the state of differentiation of the cells: the less mature the monocytes, the greater the degree of inhibition. Laminin also reduced the attachment capacity of polymorphonuclear leukocytes isolated from human peripheral blood. These results suggest a possible role for laminin in the regulation of the passage of cells across the basement membrane during inflammation.

Animals↗
PubMed1983

Metastatic behavior of an adriamycin-resistant murine tumor.

The metastatic behavior of a murine fibrosarcoma (UV-2237M-ADMR) resistant to Adriamycin (ADM) (doxorubicin) was investigated. Subclones isolated from the UV-2237M-ADMR line, which originated from a single colony, generally displayed a similar degree of resistance to ADM (eight out of nine clones did not differ from this UV-2237M-ADMR line). In contrast, they differed significantly in their capacity to form lung colonies after i.v. injection (six of nine clones differed significantly from the UV-2237M-ADMR line, p less than or equal to 0.005, Mann-Whitney U test). The UV-2237M-ADMR cell line maintained resistance to ADM even after 17 weeks of growth in syngeneic mice, although a gradual decrease in resistance was observed over this time. Spontaneous metastases from the UV-2237M-ADMR tumor commonly retained resistance to ADM. Of 18 cell lines, each established from an individual lung nodule, 16 showed plating efficiencies in the presence of ADM comparable to that of the primary UV-2237M-ADMR tumor. The remaining two lines had partially reverted to the sensitive state. The i.v. administration of ADM significantly reduced the lung tumor burden of mice with ADM-sensitive UV-2237M tumors but failed to affect the lung tumor burden of mice with UV-2237M-ADMR tumors. The UV-2237M-ADMR tumor line, exhibiting as it does both drug-resistant and metastatic behavior, provides a useful model system with which to investigate the metastatic process and the development of drug resistance.

Animals↗
PubMed1983

Isolation and preliminary characterization of an Adriamycin-resistant murine fibrosarcoma cell line.

A variant cell line (UV-2237-ADMR) resistant to the anthracycline antibiotic Adriamycin (Doxorubicin) was selected in vitro from the murine UV-2237 fibrosarcoma tumor cell line. Resistance to Adriamycin proved to be a stable characteristic of the UV-2237-ADMR line, whether the line was grown in vivo or in vitro. The UV-2237-ADMR line also exhibited increased resistance to N-trifluoroacetyladriamycin-24-valerate, daunorubicin, actinomycin D, amsacrine, mitomycin C, vinblastine, and vincristine but not to bleomycin. Cell-cell hybridization studies showed that the Adriamycin resistance is an incompletely dominant trait. Uptake and efflux studies with [14C]Adriamycin indicated that the resistance exhibited by the UV-2237-ADMR line was due to both reduced uptake of the drug and an increased active efflux.

Animals↗
PubMed1982

Metastatic potential of metastases, tumor cell heterogeneity, and therapeutic implications.

The metastasizing capacity of spontaneous metastases of several murine tumors of different histology, origin, and disseminative pattern was investigated to test the hypothesis that metastases originate from various subpopulations within the primary tumor. Overall, tumor cells from individual metastases did not show greater metastasizing capacity than the cells of the original tumor, although a degree of heterogeneity was seen. Differences in the immunologic profile among metastases of the same tumor were also observed. The possible therapeutic implications of these findings are discussed.

Animals↗
PubMed1982

Natural cytotoxic activity in human lungs.

Disease-free surgical lung specimens from 13 patients with neoplastic or infectious diseases and from three subjects with non-neoplastic, non-infectious pathology were mechanically disaggregated. Natural cytotoxicity was tested against 51Cr-labelled K562 target cells. Unseparated lung cells had little cytotoxicity against K562 cells. Removal of plastic and nylon-wool-adherent cells resulted in cell preparations (morphologically 80% lymphoid) with increased cytolytic activity against K562 but cytotoxicity levels were considerably lower than those of blood lymphocytes tested in parallel. Similar results were obtained when phagocytic adherent cells were removed with carbonyl iron. The NK-resistant murine TU5 and human Raji lines were not affected by lung effector cells. In vitro exposure to partially purified fibroblast interferon enhanced the cytotoxicity of unseparated or non-adherent lung cells. Thus, unlike in mouse pulmonary tissue, low levels of natural cytotoxic activity are associated with the humans lung.

Cell Survival↗
PubMed1981

Tumour sublines with different metastatic capacity induce similar blood coagulation changes in the host.

This paper is aimed at investigating how metastatic tumour growth influenced the haemostatic system of the host. Blood platelet count, blood fibrinogen level, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) were determined at various intervals during growth and metastasis of a murine fibrosarcoma (mFS6) or one of its sublines with different metastatic capacity. Progressive thrombocytopenia and increase in fibrinogen level were observed during development of the tumour in all the animal groups studied, irrespective of the metastatic potential of the various sublines. No significant changes were observed in the PT or APTT values. These data support the concept that primary rather than metastatic growth influences the haemostatic system of tumour-bearing animals.

Animals↗
PubMed1981

Procoagulant activity of sarcoma sublines with different metastatic potential.

It has been suggested that cancer cell procoagulant activity influences metastasis formation by promoting fibrin deposition around tumors. We have investigated the procoagulant activity of various tumor cell sublines with different metastatic capacity derived from metastatic nodules of a murine fibrosarcoma. All the cells tested possessed a marked thromboplastin-like activity; they were, however, heterogeneous as regards the degree of procoagulant activity; the two cell lines with virtually no metastatic capacity showed 6--8 times higher procoagulant activity than the cells from the parent line; in contrast, the procoagulant activity of the two sublines with higher metastatic capacity did not differ significantly from that of the parent line. These findings support the hypothesis that fibrin is part of a defence reaction against cancer cell invasiveness.

Animals↗
PubMed1980

Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice.

The effects of silica and carrageenan on primary tumor growth and metastases were evaluated in c57bl/6 and BALB/c mice transplanted with the poorly immunogenic Lewis lung (3ll) carcinoma, mFS6 sarcoma and Madison 109 carcinoma spontaneously metastasizing to the lungs. Silica and carrageenan significantly enhanced lung metastases and decreased primary tumor weight in all three experimental models. A similar augmentation of lung secondaries was found after i.v. inoculation of 3LL tumor cells. The effects of carrageenan on primary 3LL tumor growth and metastases were observed also in thymus-deprived animals. The effect of macrophage toxins was studied also in C57BL/6 mice transplanted with the M5076/73A ovarian carcinoma. This tumor spontaneously metastasizes to various abdominal organs, but not to the lung. After treatment with carrageenan, lung metastases were observed, but no effect on secondaries at other anatomical sites or on the primary tumor was detectable. It is suggested that host defense mechanisms impaired by silica and carrageenan may have divergent effects in the regulation of growth of some primary tumors and spontaneous lung metastases.

Animals↗
PubMed1980

Metastasizing capacity of tumour cells from spontaneous metastases of transplanted murine tumours.

We investigated the metastasizing capacity of spontaneous lung metastases from the MN/MCA1 and mFS6 sarcoma, the B16 melanoma and colon 26 carcinoma. Spontaneous metastases at other visceral organs (liver, spleen, kidney, ovary, uterus) from the M5076/73A (M5) ovarian carcinoma and colon 26 carcinoma were also studied. Tumour cells from individual spontaneous metastases were used immediately after isolation from the normal parenchyma (mFS6, M5 and colon 26) and/or after 1 s.c. passage in syngeneic mice (MN/MCA1, mFS6, B16 and M5). Spontaneous metastases were examined for all tumours and their secondaries after i.m. or s.c. inoculation of tumour cells; artificial lung colonies were measured after i.v. injection only of cells from the primary mFS6 and MN/MCA1 and B16 or their spontaneous metastases. Individual spontaneous metastases were to some extent heterogeneous in their metastatic potential, a minority of the secondaries having greater or lesser metastatic capacity than the appropriate primary. Overall, tumour cells from spontaneous metastases did not show greater metastasizing capacity than primary neoplasms, nor was there evidence that metastases from specific organs (e.g. spleen and kidney) tended to home to the specific anatomical sites from which they were originally isolated. These observations in a series of murine tumours of different histology, transplantation history and pattern of metastasis, do not support the hypothesis that metastases are the ultimate expression of strong selection of variant cells with greater intrinsic metastatic potential, pre-existing within the primary tumour.

Animals↗
PubMedDate not supplied

Growth and metastatic behavior of human tumor cells implanted into nude and beige nude mice.

The growth and metastatic behavior of several human tumor lines grown in adult nude mice, nude mice pretreated with antiserum against asialo GM1 glycoprotein, and beige nude mice were studied. The cell lines were all injected s.c. and i.v. A human colon carcinoma line was also injected into the spleen, and two human renal carcinoma lines were injected into renal subcapsule. All the tumor lines grew as fast or faster in adult nude mice compared with beige nude mice. There were no discernible differences in the production of experimental lung metastasis among the three groups of mice, but human colorectal carcinoma cells and human renal carcinoma cells produced more metastases in nude mice than in beige nude mice after intrasplenic or renal subcapsule injection, respectively. In vitro cytotoxicity assays confirmed that adult nude mice had high levels of natural killer (NK) cell activity whereas nude mice pretreated with anti-asialo GM1 serum and beige nude mice did not. The in vitro NK cell activity of nude mice was demonstrable against mouse lymphoma cells but not against human leukemia cells which were sensitive to lysis by human NK cells. These results suggest that the implantation of human tumor cells into beige nude mice, which are deficient in NK cell activity does not provide an advantageous model for the study of growth and metastasis of human neoplasms.

Animals↗
PubMedDate not supplied

Organ-specific growth of a murine lymphoma of spontaneous origin in nude mice.

The MOC-25 tumour arose spontaneously in a female nude mouse and was established as a continuous line intraperitoneally in nude mice, where it reproduces the topological features of its origin, growing preferentially in the uterus, ovaries and liver. Karyotype analysis showed that MOC-25 cells are hyperdiploid. Tumorigenicity and malignant behaviour were studied by transplanting tumour cells into different sites in nude mice. The comparison of tumour take after i.p. and s.c. injections of scaled concentrations of MOC-25 cell suspension showed preferential growth in the peritoneum. Regardless of the route of implantation (s.c., i.v., i.p.), this tumour rapidly and preferentially disseminated to the liver, uterus, ovaries, spleen and bone marrow. No significant differences in tumour growth and metastatic behaviour were observed when MOC-25 was injected in ovariectomized nude mice or in male nude mice. Morphology studies using light and electron microscopy, immunophenotyping and molecular analysis indicated a B-lymphoid origin of the MOC-25 tumour.

Animals↗
PubMedDate not supplied

Organ distribution of experimental metastases of a human colorectal carcinoma injected in nude mice.

The metastatic behavior of the HT-29 human colorectal carcinoma cell line was studied following injection into nude mice by different routes. After intrasplenic injection, experimental metastases formed in the livers of most mice. Variant lines were established in culture from the liver lesions and from tumors growing at the site of injection, the spleen. Cells of the HT-29 LMM line exhibited slightly enhanced ability to form liver metastases compared with cells of the non-selected parent line. When injected i.v., the HT-29 cells produced only a few small experimental metastases in the lungs, but in most of the mice macroscopic tumors were found in various lymph nodes and the interscapular fat. Analyses of the distribution of IdUrd-labeled cells did not reveal a preferential localization of the HT-29 cells in sites where metastases subsequently formed. This suggested that the growth of the human colon carcinoma cells in those sites might be the result of a stimulatory interaction between the tumor and host cells as opposed to growth in sites such as the lungs, where numerous cells arrested after i.v. injection but only a few, small metastases were seen 60 days later.

Animals↗
PubMedDate not supplied

A human acute lymphoblastic leukemia line with the T(4;11) translocation as a model of minimal residual disease in SCID mice.

This study describes a new human acute lymphoblastic leukemia (ALL) cell line (ALL-PO) with the t(4;11) translocation established in SCID mice. The ALL-PO line can be maintained by serial transplant in SCID mice with stable immunophenotypic, molecular and karyotypic features. After intravenous (i.v.) injection ALL-PO spread systemically involving the hematopoietic organs and the central nervous system (CNS) of all mice. The homing and the progression of the disease are evaluated by histological analysis and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the t(4;11) translocation in the bone marrow, spleen and CNS of SCID mice at different times after engraftment. Occult leukemia was detectable by PCR in the bone marrow of SCID mice as early as three days after the i.v. injection of leukemic cells whereas the first signs of involvement of the spleen and CNS appeared after 14 days; after 24 days all the mice were euthanized because they were moribund and the bone marrow, spleen and CNS showed ample infiltration by leukemic cells. The sensitivity to conventional chemotherapy was tested in this model. ALL-PO in SCID mice did not respond to treatment with vincristine or idarubicin but cyclophosphamide (150 mg kg(-1) i.v., single injection) significantly increased the survival of the mice. The efficacy of such a treatment was more evident when cyclophosphamide was given in the early stages of the disease (detectable only by molecular analysis) but much less effective when the drug was administered when the disease could be detected by conventional histological analysis. The biological behavior and molecular characteristics of ALL-PO make it a good model for studying novel therapeutic strategies for a better control of minimal residual disease.

Animals↗
PubMedDate not supplied

Driving p53 response to Bax activation greatly enhances sensitivity to taxol by inducing massive apoptosis.

The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt) p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold) to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3) were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment) by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

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