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Biomedical subjects

A Albini

Publications and source records attributed to A Albini.

At least 73 records · Page 4Linked to original sources
PubMed1999

Potentiation of the malignant phenotype of the undifferentiated ARO thyroid cell line by insertion of the bcl-2 gene.

We have reported that bcl-2 is expressed in normal human thyroid epithelium and that its expression is down-regulated in undifferentiated thyroid tumors. Production of IL-6 was concomitantly down-regulated in these forms. Based on these observations, we analyzed whether insertion of bcl-2 would reverse the highly malignant phenotype of a thyroid cell line (ARO) derived from an undifferentiated carcinoma. This cell line fails to produce Bcl-2 and IL-6. By infection with a bcl-2 retroviral vector, ARO cells expressing bcl-2 (ARObcl-2) were obtained. Compared with parental cells, expression of bcl-2 was associated with enhancement of growth potential (DNA synthesis, in vitro proliferation rate, anchorage-independent growth in semi-solid media). Chemotaxis and invasive potential in Boyden chambers were also increased. bcl-2-expressing cells showed a reduced response to apoptotic stimuli (low-serum conditions or anti-neoplastic drugs). Large branched colonies were formed in Matrigel from ARObcl-2 cells but not from parental cells. Finally, ARObcl-2 cells showed a decreased latency of tumor appearance when injected into immunodeficient mice. Potentiation of the malignant phenotype of ARO cells by bcl-2 was not ascribed to altered expression of (i) cytokine/growth factors (IL-4, IL-6, IL-8, IL-10, IL-12, TGF-alpha, TGF-beta), (ii) thyroid-specific transcripts (TG, TPO, TSH-R, PIGF, PAX-8) or (iii) genes influencing tumor aggressiveness [VEGF, HMGI (Y), HMGI-C]. Our data indicate that bcl-2 potentiates the malignant phenotype of ARO cells not only by limiting the response to apoptotic stimuli but also by enhancing proliferation and tumor aggressiveness.

Animals↗
PubMed1999

Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma.

To assess whether the progression of plasma cell tumors is accompanied by angiogenesis and secretion of matrix-degrading enzymes, bone marrow biopsy specimens from 20 patients with monoclonal gammopathy of undetermined significance (MGUS), 18 patients with nonactive multiple myeloma (MM), and 26 patients with active MM were evaluated for their angiogenic potential and matrix-metalloproteinase (MMP) production. A fivefold increase of the factor VIII+ microvessel area was measured by a planimetric method of point counting in the bone marrow of patients with active MM as compared with nonactive MM and MGUS patients (P <.01). When serum-free conditioned media (CM) of plasma cells isolated from the bone marrow of each patient were tested in vivo for their angiogenic activity in the chick embryo chorioallantoic membrane (CAM) assay, the incidence of angiogenic samples was significantly higher (P <. 01) in the active MM group (76%) compared with nonactive MM (33%) and MGUS (20%) groups. Moreover, a linear correlation (P <.01) was found between the extent of vascularization of the bone marrow of a given patient and the angiogenic activity exerted in the CAM assay by the plasma cells isolated from the same bone marrow. In vitro, a significantly higher fraction of the plasma cell CM samples from the active MM group stimulated human umbilical vein endothelial cell (HUVEC) proliferation (53%, P <.01), migration (42%, P <.05), and/or monocyte chemotaxis (38%, P <.05) when compared with nonactive MM and MGUS groups (ranging between 5% and 15% of the samples). Also, immunoassay of plasma cell extracts showed significantly higher (P <. 01) levels of the angiogenic basic fibroblast growth factor (FGF)-2 in the active MM patients than in nonactive MM and MGUS patients (153 +/- 59, 23 +/- 17, and 31 +/- 18 pg FGF-2/100 micrograms of protein, respectively). Accordingly, neutralizing anti-FGF-2 antibody caused a significant inhibition (ranging from 54% to 68%) of the biological activity exerted on cultured endothelial cells and in the CAM assay by plasma cell CM samples from active MM patients. Finally, in situ hybridization of bone marrow plasma cells and gelatin-zymography of their CM showed that active MM patients express significantly higher (P <.01) levels of MMP-2 mRNA and protein when compared with nonactive MM and MGUS patients, whereas MMP-9 expression was similar in all groups. Taken together, these findings indicate that the progression of plasma cell tumors is accompanied by an increase of bone marrow neovascularization. This is paralleled by an increased angiogenic and invasive potential of bone marrow plasma cells, which is dependent, at least in part, by FGF-2 and MMP-2 production. Induction of angiogenesis and secretion of MMPs by plasma cells in active disease may play a role in their medullary and extramedullary dissemination, raising the hypothesis that angiostatic/anti-MMP agents may be used for therapy of MM.

Adult↗
PubMed1999

Thrombospondin-1 inhibits Kaposi's sarcoma (KS) cell and HIV-1 Tat-induced angiogenesis and is poorly expressed in KS lesions.

Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released by both KS and host cells, as well as HHV-8 and HIV viral products, have been implicated in the pathogenesis of this lesion. Angiogenesis is the result of imbalance among angiogenesis promoters and inhibitors, which disrupts homeostasis. The aim of this study was to investigate the expression and mechanism of KS control of thrombospondin-1 (TSP), a physiological inhibitor of angiogenesis. Immunohistochemical analysis of four KS lesions showed only spotty reactivity for TSP in the stroma and in less than 10 per cent of lesional blood vessels. In addition, the typical KS spindle cells were not stained. In agreement with these findings, decreased levels of TSP were measured with an ELISA assay in the supernatants of cultured KS cells, compared with endothelial cells. In vitro, TSP inhibited the endothelial cell proliferation and motility induced by KS cell supernatants. TSP also prevented endothelial cell motility induced by Tat, a product of HIV-1 endowed with angiogenic potential and implicated in the pathogenesis of AIDS-KS. In vivo, TSP inhibited the angiogenic activity exerted by Tat in the Matrigel sponge model. These results suggest that TSP down-regulation might be permissive for the development of KS-associated angiogenesis.

Animals↗
PubMed1999

Motility induced by human immunodeficiency virus-1 Tat on Kaposi's sarcoma cells requires platelet-activating factor synthesis.

In the present study, we evaluated whether motility of Kaposi's sarcoma (KS) spindle cells induced by HIV-1 Tat protein is dependent on the synthesis of platelet-activating factor (PAF). The results obtained indicate that Tat induced a dose-dependent synthesis of PAF from KS cells at a concentration as low as 0.1 ng/ml. PAF production started rapidly after Tat stimulation, peaking at 30 minutes and declining thereafter. Tat-induced cell migration was also a rapid event starting at 30 minutes. The motility was abrogated by addition of a panel of chemically unrelated PAF receptor antagonists (WEB 2170, CV 3988, CV 6209, and BN 52021), suggesting that the synthesized PAF mediates the motogenic effect of Tat. This effect was also present on cells plated on a type-I collagen-, fibronectin-, or basement membrane extract-coated surface. Expression of PAF receptor-specific mRNA was detected in KS cells. In addition, examination of the cytoskeletal organization showed that Tat-mediated KS cell redistribution of actin filaments and shape change was also inhibited by a PAF receptor antagonist. Moreover, PAF receptor blockade prevented the up-regulation of beta1 integrin and the down-regulation of alphavbeta3 observed after stimulation of KS cells with Tat. In conclusion, the results of the present study indicate that Tat-induced PAF synthesis plays a critical role in triggering the events involved in motility of KS cells.

Azepines↗
PubMed1999

Somatostatin controls Kaposi's sarcoma tumor growth through inhibition of angiogenesis.

Somatostatin and its analogs are active in the inhibition of SST receptor-positive endocrine neoplasms, but their activity and mechanism in nonendocrine tumors is not clear. Somatostatin potently inhibited growth of a Kaposi's sarcoma xenograft in nude mice, yet in vitro the tumor cells did not express any known somatostatin receptors and were not growth inhibited by somatostatin. Histological examination revealed limited vascularization in the somatostatin-treated tumors as compared with the controls. Somatostatin was a potent inhibitor of angiogenesis in an in vivo assay. In vitro, somatostatin inhibited endothelial cell growth and invasion. Migration of monocytes, important mediators of the angiogenic cascade, was also inhibited by somatostatin. Both cells types expressed somatostatin receptor mRNAs. These data demonstrate that somatostatin is a potent antitumor angiogenesis compound directly affecting both endothelial and monocytic cells. The debated function of somatostatin in tumor treatment and the design of therapeutic protocols should be reexamined considering these data.

Animals↗
PubMed1999

Osteoblasts modulate secretion of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in human prostate cancer cells promoting migration and matrigel invasion.

Prostate carcinoma (PRCA) cells metastasize to the skeleton with high frequency. Bone stores growth regulatory factors, which are released in active form during bone remodeling. We propose that bone cell-derived growth factors may induce the development of PRCA bone metastasis by recruiting tumor cells and increasing their proliferation in the bone microenvironment. Serum-free conditioned medium harvested from osteoblast cultures (OB CM) stimulated the in vitro chemotaxis of PRCA cells and invasion of a reconstituted basement membrane (Matrigel), suggesting enhanced invasive activity. Preosteoblastic cell CMs were less effective than CMs obtained from mature OB. CMs harvested from differentiated osteoblast cultures capable of matrix mineralization were more active compared to CMs from proliferating osteoblasts. OB CMs stimulated secretion of urokinase (uPA) and matrix metalloproteinase-9 (MMP-9). Inhibition of these matrix-degrading proteases by neutralizing antibodies and/or by inhibitors of their catalytic activity reduced Matrigel invasion. Secretion of uPA and activation of MMP-9 were most prominent by differentiated OB CMs with respect to poorly differentiated cells in vitro. These results are in agreement with several in vivo studies and indicate that factors produced during osteogenesis by bone cells stimulate PRCA cell chemotaxis and matrix proteases expression, thus representing potential targets for alternative therapies deterring the progression of PRCA metastasis to bone.

Cell Movement↗
PubMed1999

N-acetylcysteine inhibits endothelial cell invasion and angiogenesis.

The thiol N-acetylcysteine (NAC) is a chemopreventive agent that acts through a variety of mechanisms and can prevent in vivo carcinogenesis. We have previously shown that NAC inhibits invasion and metastasis of malignant cells as well as tumor take. Neovascularization is critical for tumor mass expansion and metastasis formation. We investigated whether a target of the anti-cancer activity of NAC could be the inhibition of the tumor angiogenesis-associated phenotype in vitro and in vivo using the potent angiogenic mixture of Kaposi's sarcoma cell products as a stimulus. Two endothelial (EAhy926 and human umbilical vein endothelial [HUVE]) cell lines were utilized in a panel of assays to test NAC ability in inhibiting chemotaxis, invasion, and gelatinolytic activity in vitro. NAC treatment of EAhy926 and HUVE cells in vitro dose-dependently reduced their ability to invade a reconstituted basement membrane, an indicator of endothelial cell activation. Invasion of HUVE cells was inhibited with an ID50 of 0.24 mM NAC, whereas inhibition of chemotaxis required a 10 fold higher doses, indicating that invasion is a preferential target. NAC inhibited the enzymatic activity and conversion to active forms of the gelatinase produced by endothelial cells. The matrigel in vivo assay was used for the evaluation of angiogenesis; NAC strongly inhibited neovascularization of the matrigel sponges in response to Kaposi's sarcoma cell products. NAC prevented angiogenesis while preserving endothelial cells, implying that it could be safely used as an anti-angiogenic treatment.

Acetylcysteine↗
PubMed1998

HIV-1 Tat protein mimicry of chemokines.

The HIV-1 Tat protein is a potent chemoattractant for monocytes. We observed that Tat shows conserved amino acids corresponding to critical sequences of the chemokines, a family of molecules known for their potent ability to attract monocytes. Synthetic Tat and a peptide (CysL24-51) encompassing the "chemokine-like" region of Tat induced a rapid and transient Ca2+ influx in monocytes and macrophages, analogous to beta-chemokines. Both monocyte migration and Ca2+ mobilization were pertussis toxin sensitive and cholera toxin insensitive. Cross-desensitization studies indicated that Tat shares receptors with MCP-1, MCP-3, and eotaxin. Tat was able to displace binding of beta-chemokines from the beta-chemokine receptors CCR2 and CCR3, but not CCR1, CCR4, and CCR5. Direct receptor binding experiments with the CysL24-51 peptide confirmed binding to cells transfected with CCR2 and CCR3. HIV-1 Tat appears to mimic beta-chemokine features, which may serve to locally recruit chemokine receptor-expressing monocytes/macrophages toward HIV producing cells and facilitate activation and infection.

Amino Acid Sequence↗
PubMed1998

Identification of a novel domain of HIV tat involved in monocyte chemotaxis.

Human immunodeficiency virus (HIV) Tat is chemotactic for monocytes and dendritic cells, an activity that could play a key role in the expansion of HIV infection of accessory cells. To date, domains of Tat previously found to interact with cell surface molecules have shown only partial chemotactic activity toward monocytes. Using overlapping Tat peptides, we identify a novel region of Tat with a potent chemotactic activity for monocytes, reaching levels equal to Tat itself. This peptide also provokes monocyte polarization similar to Tat and is able to compete with Tat for induction of monocyte migration. Specific high affinity (kd = 3 x 10(-9) M) cell surface binding sites on monocyte cell surfaces for this region of Tat are demonstrated. These data indicate that the majority of Tat effects on monocytes are mediated by a novel region in the cysteine-rich and core domains. These domains are highly conserved among different HIV isolates, suggesting an important role in the establishment of HIV infection.

Cell Polarity↗
PubMed1998

Monocyte-derived dendritic cells and monocytes migrate to HIV-Tat RGD and basic peptides.

OBJECTIVE AND DESIGN: Extracellular Tat released from HIV-1-infected cells is a mitogenic and motogenic factor for endothelial and Kaposi's sarcoma (KS)-derived cells and is angiogenic in vivo. Here we show for the first time that Tat induces migration of human dendritic cells in a concentration-dependent manner and that the Arg-Gly-Asp (RGD) and basic Tat peptides contribute to dendritic and monocyte cell migration. In vivo, Tat stimulates invasion of macrophages into a matrigel sponge. METHODS: Monocyte and dendritic cell chemotaxis was assessed using the Boyden chamber assay. RESULTS: Tat induced migration of monocyte-derived dendritic cells at the same levels as the N-formyl-Met-Leu-Phe peptide, and of monocytes at levels comparable to RANTES. Peptide mapping of the chemotactic activity of Tat showed that the RGD domain, which has been shown to support integrin-mediated cell migration, and the basic domain which binds and activates the tyrosine kinase receptor KDR on endothelial cells, both had activity. Antibody-blocking experiments indicate that responses to the RGD domain was inhibited by beta1 and alpha vbeta3 integrin blocking antibodies. Combination of the Tat RGD and basic peptides did not show additive effects; however, Tat co-operated with macrophage-chemotactic protein or RANTES in inducing monocyte migration. CONCLUSIONS: Our results show that Tat can act as a chemoattractant for dendritic cells, and that both the RGD and basic domains are involved in this response. These same domains attract monocytes. The alpha vbeta3 and beta1 integrins are equally involved in Tat-induced monocyte migration, while the alpha vbeta3 integrin largely mediates the dendritic cell response to Tat.

Cells, Cultured↗
PubMed1998

In vitro regulation of pericellular proteolysis in prostatic tumor cells treated with bombesin.

Bombesin is a potent inducer of signal trasduction pathways involved in the proliferation and invasion of androgen-insensitive prostatic tumor cells. This study examines the bombesin-mediated modulation of pericellular proteolysis, monitoring cell capability to migrate and invade basement membranes, using a chemo-invasion assay and analyzing protease production. The results suggest that bombesin could modulate the invasive potential of prostatic cell lines regulating secretion and cell-surface uptake of uPA and MMP-9 activation. In fact, in PC3 and DU145 cells but not in LNCaP cells, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) are induced by bombesin treatment. Bombesin also stimulates cell proliferation and this effect can be inhibited blocking uPA by antibodies and/or uPA inhibitor p-aminobenzamidine. Moreover, HMW-uPA induces cell proliferation in LNCaP cells, which do not produce uPA in the basal conditions, while PC3 and DU145 cell growth is supported by autocrine production of uPA. The increment of uPA activity on the external plasma membrane causes an increased pericellular plasmin activation. This effect is inhibited by antibodies against uPA and by p-aminobenzamidine. Similarly to EGF, bombesin stimulates secretion and activation of MMP-9 and TIMP-1 production. MMP-9 activation can be also obtained by HMW-uPA treatment, suggesting that plasma-membrane-bound uPA can start a proteolytic cascade involving MMP-9. Therefore, in in vitro assays, bombesin is able to modulate pericellular proteolysis and cell proliferation, differently distributing and activating proteolytic activities. This effect can be related to the "non-random" degradation of the extracellular matrix in which membrane uPA-uPAreceptor complexes could start bombesin-induced directional protein degradation during metastatic spread.

Antibodies↗
PubMed1998

TIMP-2 over-expression reduces invasion and angiogenesis and protects B16F10 melanoma cells from apoptosis.

The matrix metalloproteinase (MMP) inhibitor TIMP-2 has a high specificity for gelatinase A/MMP-2. An imbalance between gelatinase A and TIMP-2 in favor of enzymatic activity is linked to the degradation of the extracellular matrix (ECM) associated with several physiologic and pathologic events, including angiogenesis, invasion and metastasis. Since TIMPs are secreted molecules, they have the potential to be used for gene therapy of certain tumors. We transfected B16F10 murine melanoma cells, a highly invasive and metastatic cell line, with an expression vector harboring a cDNA encoding for human TIMP-2. The clones obtained were isolated and examined for TIMP-2 over-expression and changes in tumor cell phenotype. The amount of recombinant TIMP-2 produced correlated with a reduction in invasion. In an in vivo angiogenesis assay, TIMP-2-transfected clones showed reduced levels of blood vessel formation, and in vitro conditioned media from TIMP-2 transfectants showed diminished induction of endothelial cell migration and invasion. TIMP-2 over-expression limited tumor growth in vivo and neoangiogenesis when cells were injected subcutaneously in mice in the presence of Matrigel. However, TIMP-2 overexpressing clones were found to be more resistant to apoptosis than parental and control melanoma cells, while necrosis was increased. Our data confirm the role of TIMP-2 in the down-regulation of metastasis and angiogenesis but indicate a possible involvement in tumor cell survival.

Animals↗
PubMed1998

Tumor and endothelial cell invasion of basement membranes. The matrigel chemoinvasion assay as a tool for dissecting molecular mechanisms.

The spread of cancer cells from a primary tumor to distant organs is the major cause of death of cancer patients. Metastatic lesions are often resistent to cancer therapy because of the progressive phenotypic changes that they have undergone. Several genetic and epigenetic factors, both in the cell and in the host, contribute to the development of tumor progression towards metastases. In this review we will analyze the steps involved in tumor metastases, which can be potential targets for anti-metastatic therapy. One of the most critical events in cancer metastasis is the invasion of basement membranes. An assay which we developed over ten years ago, the matrigel "chemoinvasion" assay, has been a useful tool for studying the mechanisms involved in tumor and endothelial cell invasion of basement membranes and for the screening of anti-invasive agents. Here we will describe the assay and review some of the major results obtained with it.

Animals↗
PubMed1998

Human lymphoblastoid cells produce extracellular matrix-degrading enzymes and induce endothelial cell proliferation, migration, morphogenesis, and angiogenesis.

Human lymphoproliferative diseases can be hypothesized to invade locally and to metastatize via mechanisms similar to those developed by a variety of solid tumors, i.e., the secretion of extracellular matrix-degrading enzymes and stimulation of angiogenesis. To assess this hypothesis, Namalwa, Raji, and Daudi cell lines (Burkitt's lymphoma), LIK and SB cell lines (B-cell lymphoblastic leukemia), CEM and Jurkat cell lines (T-cell lymphoblastic leukemia), and U266 cell line (multiple myeloma) were evaluated for their capacity to produce matrix metalloproteinase-2 and -9, and urokinase-type plasminogen activator. These cell lines were also assessed for their ability: (1) to produce the angiogenic basic fibroblast growth factor and vascular endothelial growth factor; (2) to induce an angiogenic phenotype in cultured endothelial cells, represented by cell proliferation, chemotaxis, and morphogenesis; (3) to stimulate angiogenesis in different in vivo experimental models. All cell lines expressed the mRNA for one or both metalloproteinases. Namalwa, Raji, LIK, SB, and U266 cells secreted the active form of both metalloproteinases, while Daudi, CEM, and Jurkat cells produced metalloproteinase-2 but not-9. In contrast, urokinase-type plasminogen activator was secreted only by SB cells. While Raji, LIK, SB, CEM, and Jurkat cells secreted both basic fibroblast growth factor and vascular endothelial growth factor, Daudi and U266 cells produced only the former, and Namalwa cells only the latter. Accordingly, the conditioned medium of all cell lines stimulated cell proliferation and/or chemotaxis in cultured endothelial cells, with the exception of that of Namalwa cells which was ineffective. The conditioned medium of CEM and Jurkat cells induced morphogenesis in cultured endothelial cells grown on a reconstituted basement membrane (Matrigel). Lastly, Namalwa, Raji, LIK, SB, U266, CEM, and Jurkat cells induced angiogenesis and mononuclear cell recruitment in the murine Matrigel sponge model and in a chick embryo chorioallantoic membrane assay. The extent of angiogenesis in both models was strictly correlated with the density of the mononuclear cell infiltrate. The results indicate that human lymphoproliferative disease cells possess both local and remote invasive ability via the secretion of matrix-degrading enzymes and the induction of angiogenesis which is fostered by host inflammatory cells and by an intervening ensemble of angiogenic factors.

Animals↗
PubMed1998

beta Interferon inhibits HIV-1 Tat-induced angiogenesis: synergism with 13-cis retinoic acid.

Kaposi's sarcoma (KS) is a highly angiogenic lesion which frequently presents as an aggressive form in HIV-infected male patients. We have previously shown that the HIV-1 Tat protein induces endothelial cell migration and invasion in vitro and a rapid angiogenic response in vivo, suggesting that it acts as a cofactor in epidemic KS. In this study we tested beta interferon (IFN beta) and retinoic acid (RA) for the inhibition of Tat-induced angiogenesis using in vivo and in vitro models. IFN beta, at a concentration above 2500 U/ml, was an effective inhibitor of Tat-stimulated growth, migration and morphogenesis of an endothelial cell line in vitro and of angiogenesis in vivo. A strong reduction of properties associated with neovascularisation was induced by 10,000 U/ml. In vivo, RA alone was on ineffective inhibitor of angiogenesis, and in vitro gave only a limited inhibition of endothelial cell growth. However, 13-cis RA used in combination with IFN beta impressively potentiated its effects. A combination of lower doses of IFN beta (2500 U/ml) and 13-cis RA induced a virtually complete inhibition of the Tat-related angiogenic phenotype both in vivo and in vitro. The potentiation of the anti-angiogenic activity of IFN beta by 13-cis RA suggests that this combination could be a useful approach for the therapy of epidemic KS.

Antineoplastic Agents↗
PubMed1998

Inhibition by oral N-acetylcysteine of doxorubicin-induced clastogenicity and alopecia, and prevention of primary tumors and lung micrometastases in mice.

The thiol N-acetylcysteine (NAC), an analog and precursor of glutathione, displays cancer preventive properties not only in early stages of the carcinogenesis process but also in its advanced stages. NAC inhibited type-IV collagenase activity as well as invasion, tumor take, and metastasis of malignant cells in murine models. Previously, we provided evidence for synergistic effects of oral NAC with intravenously injected doxorubicin (DOX). In the present study B16-BL6 melanoma cells were injected s.c. into the footpad of C57BL/6 mice. The animals were divided into 5 groups: i) untreated mice; ii) mice receiving daily NAC with drinking water (12.25 mmol/kg body weight) starting 16 h after injection of cancer cells; iii) mice receiving a single i.v. injection of DOX (2 micromol/kg body weight) 24 h after injection of cancer cells; iv) mice receiving a combination of NAC and DOX, with NAC treatment starting 72 h before injection of cancer cells; and v) mice treated as in iv) but with NAC treatment starting 16 h after injection of cancer cells. Both NAC and DOX, either individually or in combination, significantly enhanced the survival time as compared to controls. The weight of local primary tumors was significantly decreased by either drug, and was further decreased to a significant extent, compared to the individual treatments, in the two groups of mice receiving combinations of NAC and DOX. No lung micrometastases, evaluated by immunohistochemistry as S-100-positive foci of melanocytic cells, were detectable in the two groups of mice receiving the combined treatments. NAC significantly, attenuated the time-related increase of micronucleated polychromatic erythrocytes in the peripheral blood of DOX-treated mice. All mice individually treated with DOX developed a partial but well evident alopecia, diffusely affecting their back hair, which was totally prevented by NAC, irrespective of the combination schedule. Thus, besides preventing DOX cardiotoxicity, as extensively documented in the literature, oral NAC protects mice from DOX-induced myelogenotoxicity and alopecia, and at the same time interacts with this cytotoxic agent in inhibiting cancer cell invasion and metastasis.

Acetylcysteine↗