N-methylformamide affects spontaneous metastases of 3LL lines and increases natural killer activity of tumor-bearing mice

Greco, C.; Bufalo, Donatella Del; Giannarelli, Diana; Marangolo, M.; Fuggetta, Maria Pia; Bonmassar, Enzo; Zupi, Gabriella

doi:10.1007/bf00117788

Cited by 7 publications

(7 citation statements)

References 24 publications

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“…The effect of NMF on spontaneous metastases has also been demonstrated previously in different model systems, and several mechanisms have been postulated for the antimetastatic effect of the agent (Iwakawa et al, 1987;Tofilon et al, 1987;Iwakawa et al, 1989;Greco et al, 1990;Iwakawa et al, 1994). It has been hypothesized that NMF may induce tumour cells to form a less aggressive differentiated phenotype, resulting in a decrease in metastatic potential (Spremulli and Dexter, 1984).…”

Section: Effect Of Anti-integrin Antibodies On Cell Adhesionmentioning

confidence: 73%

“…It has been hypothesized that NMF may induce tumour cells to form a less aggressive differentiated phenotype, resulting in a decrease in metastatic potential (Spremulli and Dexter, 1984). In a previous paper we demonstrated that NMF produces a significant increase in splenic NK cell activity in Lewis lung carcinoma-bearing mice and we suggested that NMF could promote differentiation of NK precursor cells in tumour-bearing hosts in which maturation defects had been caused by the neoplastic disease (Greco et al, 1990). Alternatively, NMF could act as an immunomodulating agent whose effect is specifically detectable in immunodepressed hosts (Parhar and Lala, 1985).…”

Section: Effect Of Anti-integrin Antibodies On Cell Adhesionmentioning

confidence: 79%

“…The mice were killed and the lungs were excised and fixed in Bouin's solution and the median number of metastatic nodules counted with the aid of a dissecting microscope. The mice were also examined daily and tumour growth was monitored, as reported previously (Greco et al, 1990).…”

Section: Evaluation Of Metastatic Ability In Athymic Micementioning

confidence: 99%

“…Among these putative candidates, N-methylformamide (NMF) is a differentiating compound that has been shown to affect metastasis in several murine tumour cells, including lung carcinoma (Greco et al, 1990), hepatocarcinoma Iwakawa et al, 1987), neuroblastoma (Iwakawa et al, 1994) and mammary carcinoma (Iwakawa et al, 1987;Iwakawa et al, 1989). Depending on the experimental setting, NMF may exert both enhancing and inhibiting effects on tumour metastases.…”

mentioning

confidence: 99%

“…Depending on the experimental setting, NMF may exert both enhancing and inhibiting effects on tumour metastases. In particular, the enhancement of metastases is observed when murine tumour cells are treated with NMF before intravenous inoculation Takenaga, 1984), whereas there is a reduction when the agent is given after tumour cell inoculation (Iwakawa et al, 1987;Tofilon et al, 1987;Greco et al, 1990;Iwakawa et al, 1994).…”

mentioning

confidence: 99%

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N-methylformamide induces changes on adhesive properties and lung-colonizing potential of M14 melanoma cells

Bufalo¹,

Leonetti²,

Bucci

et al. 1998

Br J Cancer

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Summary We have studied whether N-methylformamide can affect the expression pattern of adhesion molecules and the attachment behaviour of M14 human melanoma cells. The role of N-methylformamide on experimental and spontaneous pulmonary metastases from M14 cells in nude mice was also investigated. We demonstrate that N-methylformamide in vitro pretreatment of M14 cells, although inducing a significant increase in the expression of a2,1l, a611 and avj3 integrin receptors, slightly modifies a5p1 heterodimer and P1 subunit expression. After this modulation, enhancement of cell adhesion to laminin, collagen 1, vitronectin and fibrinogen, which is blocked by specific anti-integrin antibodies, also occurs. No changes in binding to fibronectin are observed. In vitro N-methylformamide pretreatment also results in an increased number of experimental nodules and in a decrease in spontaneous metastases. Moreover, in vivo treatment with Nmethylformamide significantly reduces the number of spontaneous metastases. Collectively, these data show that N-methylformamide modulates the expression of some adhesion receptors, cell adhesion to laminin, collagen 1, vitronectin and fibrinogen as well as the metastatic behaviour of M14 cells. Our data also suggest that the effect of N-methylformamide might be evaluated in combination with antineoplastic agents for the treatment of human melanoma.

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Section: Effect Of Anti-integrin Antibodies On Cell Adhesionmentioning

confidence: 73%

Section: Effect Of Anti-integrin Antibodies On Cell Adhesionmentioning

confidence: 79%

Section: Evaluation Of Metastatic Ability In Athymic Micementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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N-methylformamide induces changes on adhesive properties and lung-colonizing potential of M14 melanoma cells

Bufalo¹,

Leonetti²,

Bucci

et al. 1998

Br J Cancer

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Pre‐Treatment of human osteosarcoma cells with N‐methylformamide enhances P‐glycoprotein expression and resistance to doxorubicin

Scotlandi

Serra

Manara

et al. 1994

Intl Journal of Cancer

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N-methylformamide (NMF), a powerful differentiating agent, has been extensively used in experimental and preclinical cancer chemotherapy studies, alone or in association with conventional anti-cancer drugs. To evaluate the use of this molecule in the treatment of osteosarcoma (OS), we have analyzed the effects of NMF and doxorubicin (DXR) on DXR-sensitive and -resistant human OS cell lines. Our study shows that NMF exerts remarkable effects on cell proliferation and, in Saos-2 and SARG cells, also induces differentiation, as shown by increasing alkaline phosphatase activity. Moreover, NMF increases the cytotoxic activity of DXR when administered after the drug, in both DXR-sensitive and -resistant cells. However, when this agent is given before DXR, it enhances P-glycoprotein expression in U-2 OS cell lines. This over-expression is associated with reduced DXR accumulation within cells and with significant enhancement of resistance to DXR.

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Antitumor and antimetastatic effects of dacarbazine combined with cyclophosphamide and interleukin-2 in Lewis lung carcinoma (3LL)

Tentori

Leonetti²,

Lozupone³

et al. 1995

Cancer Immunol Immunother

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The antitumor and antimetastatic activity of dacarbazine (DTIC) alone or in combination with cyclophosphamide (CY) was tested in C57BL/6 mice bearing Lewis lung carcinoma (3LL). Treatment with both agents significantly reduced tumor growth and the number of metastases. These effects were associated with marked changes of the biochemical and immunological properties of drug-treated 3LL cells, i.e. (a) reduction of alpha 6 integrin expression, (b) increased susceptibility to natural immunity in vivo, as measured in terms of rapid clearance from mouse lungs of prelabeled 3LL cells injected i.v. and (c) increased immunogenicity, as assessed by T-cell-mediated immune responses (i.e. graft rejection by intact syngeneic mice, and frequency of specific CTL precursors recognizing DTIC/CY-treated cancer cells). The immunotherapeutic advantage afforded by increased immunosensitivity and immunogenicity of 3LL cells exposed to DTIC + CY appears to be markedly reduced in vivo by the profound immunodepressive effects of these drugs. Within this context, addition of interleukin-2 was found to increase the antitumor and antimetastatic activity of this chemotherapeutic regimen. The present study shows, for the first time in a solid tumor model, that a biological response modifier increases the antitumor efficacy of drugs that are able to affect the immunological properties of cancer cells.

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N-methylformamide affects spontaneous metastases of 3LL lines and increases natural killer activity of tumor-bearing mice

Cited by 7 publications

References 24 publications

N-methylformamide induces changes on adhesive properties and lung-colonizing potential of M14 melanoma cells

N-methylformamide induces changes on adhesive properties and lung-colonizing potential of M14 melanoma cells

Pre‐Treatment of human osteosarcoma cells with N‐methylformamide enhances P‐glycoprotein expression and resistance to doxorubicin

Antitumor and antimetastatic effects of dacarbazine combined with cyclophosphamide and interleukin-2 in Lewis lung carcinoma (3LL)

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