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At least 757 records · Page 42Linked to original sources
PubMed2004

Comparison between angiographic right coronary artery motion and echocardiographic tricuspid annulus motion.

OBJECTIVE: To compare echocardiographic M-mode measurements of tricuspid annulus motion (TAM) with angiographic M-mode measurements of right coronary artery motion (RAM). DESIGN: Twenty-four patients were included and examined by echocardiography before the angiographic examination. The amplitudes and the velocities of TAM and the atrial contribution to the total amplitude of TAM were measured. The obtained values were compared with angiographic M-mode measurements of RAM at a proximal and a distal site of the second segment of the right coronary artery. RESULTS: There was no significant difference between several of the echocardiographic M-mode measurements of TAM and the angiographic M-mode measurements of RAM. However, the agreement was rather poor for some variables. CONCLUSION: Different parameters obtained from echocardiographic TAM are not interchangeable with values from angiographic RAM. If measurements of RAM are to be used in the assessment of right ventricular (RV) function further studies are needed to examine the correlation and agreement between RAM and different methods of measuring RV function, i.e. radionuclide angiography or magnetic resonance imaging.

Adult↗
PubMed2004

Phthalates inhibit tamoxifen-induced apoptosis in MCF-7 human breast cancer cells.

Environmental estrogens represent a class of compounds that can mimic the function or activity of the endogenous estrogen 17 -estradiol (E2). Phthalates including butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP) are used as plasticizers, and also widely used in food wraps and cosmetic formulations. Phthalates have been shown to mimic estrogen and are capable of binding to the estrogen receptor (ER). It has been demonstrated that estrogen promotes drug resistance to tamoxifen (TAM) in breast cancer. In order to further evaluate the potential role of the phthalates as environmental estrogens, the effect of phthalates was investigated on TAM-induced apoptosis in MCF-7 human breast cancer cells. Our results show that phthalates, BBP (100 M), DBP (10 M), and DEHP (10 M), significantly increased cell proliferation in MCF-7, but not in MDA-MB-231 cells. In addition, BBP, DBP, and DEHP mimicked estrogen in the inhibition of TAM-induced apoptosis in MCF-7 cells. Our data suggest that the inhibitory effect of phthalates on TAM-induced apoptosis involves an increase in intracellular Bcl-2 to Bax ratio. Given that the phthalates are widely used in cosmetics mainly for women, our findings that revealed the promoting effect of BBP, DBP, and DEHP on chemotherapeutic drug resistance to TAM in breast cancer may be of biological relevance.

Antineoplastic Agents, Hormonal↗
PubMed2005

Effect of Tinospora cordifolia on the antitumor activity of tumor-associated macrophages-derived dendritic cells.

We and others previously have reported that extract prepared from medicinal plant Tinospora cordifolia shows a wide spectrum of immunoaugmentary effects. Tinospora cordifolia was shown to upregulate antitumor activity of tumor-associated macrophages (TAM). In this article we present evidence to show that an alcoholic extract of Tinospora cordifolia (ALTC) enhances the differentiation of TAM to dendritic cells (DC) in response to granulocyte/macrophage-colony-stimulating factor, interleukin-4, and tumor necrosis factor. DC differentiated in vitro from TAM that were harvested from tumor-bearing mice after i.p. administration of ALTC (200 mg/kg body weight) 2 days posttumor transplantation shows an enhanced tumor cytotoxicity and production of tumoricidal soluble molecules like TNF, IL-1, and NO. Adoptive transfer of these TAM-derived DC to Dalton's lymphoma-bearing mice resulted in prolongation of survival of tumor-bearing mice. This is the first report regarding the differentiation and antitumor functions of TAM-derived DC obtained from tumor-bearing host administered with ALTC. The possible mechanisms involved also are discussed.

Animals↗
PubMed1994

Differential effects of zeta and eta transgenes on early alpha/beta T cell development.

The zeta-family dimers (zeta, eta, and gamma) are a group of structurally and functionally related proteins that are expressed in developing thymocytes and function as signal transducing subunits of the T cell antigen receptor (TCR) and certain Ig Fc receptors. Zeta, eta, and gamma each contain one or more copies of a conserved tyrosine-based activation motif (TAM) that is known to be required for signal transduction. To examine the developmental importance of multiple or individual TAM elements we generated transgenic mice that express: (a) full-length (FL) zeta-chain (3 TAMs); (b) eta-chain, a naturally occurring variant of zeta that is derived from alternative splicing (2 TAMs); or (c) truncated zeta-chain (CT108; 1 TAM), under the control of the human CD2 promoter and regulatory elements. Unexpectedly, we found that overexpression of the FL zeta chain caused premature termination of RAG-1 and RAG-2 expression, prevented productive rearrangement of the TCR-alpha and TCR-beta genes and blocked entry of thymocytes into the CD4/CD8 developmental pathway. In contrast, we found that overexpression of eta or CT108 had no effect on normal thymocyte maturation. These results suggest that an early signaling pathway exists in precursor TCR- thymocytes that can regulate RAG-1 and RAG-2 expression and is differentially responsive to individual members of the zeta-family dimers.

Animals↗
PubMed2004

Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an acquired thrombophilic state?

BACKGROUND: Current understanding of hemostatic systems enables us to better explore the enigmatic pathobiology of tamoxifen (TAM)-induced thrombotic diathesis. We have therefore aimed to assess the hemostatic changes in breast cancer patients receiving TAM on an adjuvant basis. PATIENTS AND METHODS: The study population consisted of 43 female patients with hormone receptor-positive breast cancer who received TAM 20 mg/day as part of their adjuvant treatment. Mean age was 52+/-12 years (range 25-74). Twenty-one patients (49%) were premenopausal. Plasma samples were collected prior to and following 6 months of TAM therapy and were assayed for total tissue factor pathway inhibitor (TFPI), free TFPI, lipid-bound TFPI, thrombomodulin, D dimer, activated protein C resistance (APC res), factors VIIa, II, V, VII and X, and global fibrinolytic capacity (GFC). RESULTS: Median total TFPI decreased significantly from 48.5 ng/ml to 36.2 ng/ml (P=0.001), free TFPI from 10 to 7.6 ng/ml (P=0.001) and lipid-bound TFPI from 39.1 to 28.7 ng/ml (P=0.001). There were significant decreases in the levels of factor II (P=0.03), factor V (P=0.001), factor VII (P=0.06), thrombomodulin (P=0.01) and D dimer (P=0.001). However, APC res times were significantly prolonged (P=0.04). The remaining parameters that we have studied were not significantly affected. CONCLUSION: Our findings suggest that TAM tends to activate the coagulation pathway by counteracting major molecules involved in coagulation inhibition, namely TFPI and TM. As reflected by unchanged GFC, the drug appears to impair the expected compensatory activation of the fibrinolytic system, which removes fibrin polymers resulting from coagulation activation.

Activated Protein C Resistance↗
PubMed1997

Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen.

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.

Animals↗
PubMed1998

Suppression of arachidonic acid cascade-mediated apoptosis in aflatoxin B1-induced rat hepatoma cells by glucocorticoids.

It has been shown that hypophysectomy protects aflatoxin B1 (AFB1) hepatocarcinogenesis and the prevention of apoptosis is a critical process for tumorigenesis. In this paper, we analyzed the cell death of AFB1-induced rat hepatoma Kagura-2 (K2) cells elicited by an estrogen antagonist, tamoxifen (TAM), and transforming growth factor-beta1 (TGF-beta1) to elucidate the function of endocrine factors in AFB1 hepatocarcinogenesis. TAM and TGF-beta1 induced a typical apoptosis in K2 cells. The apoptotic cell death was efficiently suppressed by glucocorticoids (GCs), but not by other steroid compounds including 17beta-estradiol (E2). Cyclo-oxygenase (COX) inhibitors such as aspirin (ASP) and indomethacin (IND) also inhibited the apoptosis, while inhibitory effects of general lipoxygenase (LOX) inhibitors such as nordihydroguaiaretic acid (NDGA) and 5,8,11-eicosatrienoic acid (ETI) were not observed. TAM and TGF-beta1 enhanced the release of [3H]arachidonic acid (AA) from pre-labeled K2 cells, which was inhibited by dexamethasone (DEX). Furthermore, cytosolic phospholipase A2 (cPLA2) activity in K2 cells treated with TAM for 2 h was higher than that in the control. Prostaglandin J2 (PGJ2) and delta12-PGJ2, AA metabolites formed in the COX pathway, induced K2 cell death. These results suggest that AA metabolites are involved in apoptotic K2 cell death elicited by TAM and TGF-beta1, and GCs could act as a tumor promoter in AFB1 hepatocarcinogenesis through the prevention of apoptosis induced by AA metabolites formed in vivo.

Aflatoxin B1↗
PubMed2000

Genetic analysis of transcription-associated mutation in Saccharomyces cerevisiae.

High levels of transcription are associated with elevated mutation rates in yeast, a phenomenon referred to as transcription-associated mutation (TAM). The transcription-associated increase in mutation rates was previously shown to be partially dependent on the Rev3p translesion bypass pathway, thus implicating DNA damage in TAM. In this study, we use reversion of a pGAL-driven lys2DeltaBgl allele to further examine the genetic requirements of TAM. We find that TAM is increased by disruption of the nucleotide excision repair or recombination pathways. In contrast, elimination of base excision repair components has only modest effects on TAM. In addition to the genetic studies, the lys2DeltaBgl reversion spectra of repair-proficient low and high transcription strains were obtained. In the low transcription spectrum, most of the frameshift events correspond to deletions of AT base pairs whereas in the high transcription strain, deletions of GC base pairs predominate. These results are discussed in terms of transcription and its role in DNA damage and repair.

DNA Primers↗
PubMed1995

A phase II study of tamoxifen combined with cisplatin-interleukin 2 and alpha-interferon in metastatic melanoma.

Tamoxifen (TAM) has been reported to enhance cisplatin (CDDP) cytotoxicity in experimental and clinical melanoma studies. Based on our previous experience with sequential cisplatin-interleukin-2 (IL2)-interferon (IFN), we performed a phase II study of TAM combined with our original CDDP-IL2-IFN regimen in 22 pretreated metastatic melanoma patients. With a 41% response rate (95% CI, 21-61) we confirmed the interesting antitumor activity of CDDP-IL2-IFN combination; however, TAM enhanced neither the response rate nor the duration of response, but appeared to induce significantly more myelotoxicity, as compared to our previous results with CDDP-IL2-IFN alone. Whereas mechanisms by which TAM may modulate CDDP cytotoxicity in melanoma tumors remain unknown, the exact place of TAM, if any, and its safety in chemotherapeutic or chemoimmunotherapeutic combinations require further investigations.

Adult↗
PubMed2000

Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion.

Inhibitors of cell-swelling-activated anion channels, including the antiestrogenic compound tamoxifen (TAM), have been shown to attenuate the increase in excitatory amino acids (EAA) during ischemia. Since TAM enters the CNS we tested whether it provides protection from damage due to reversible middle cerebral artery occlusion (rMCAo) in rats. TAM (5 mg/kg, i.v.) infused 25 min before ischemia, potently reduced the total volume of the infarct from 328 +/- 34 mm3 to 41 +/- 21 mm3, a reduction of 87%, as measured by TTC staining. It was equally effective when infused starting at 1 h after reperfusion, i.e. 3 h after initiation of rMCAo. Protection of neurons was also found histologically. TAM had no effect on CBF as measured by hydrogen clearance. This appears to be the first report of a marked neuroprotective effect of TAM. Further studies are needed to determine whether its effects are due to inhibition of EAA release and/or other potential neuroprotective sites of action.

Animals↗
PubMed2002

Strain differences in tamoxifen sensitivity of Sprague-Dawley and Fischer 344 rats.

Why some women are at increased risk for the development of endometrial carcinoma while taking the antiestrogen tamoxifen (Tam) for breast cancer treatment or prevention is unknown. Various strains of rodents display differences in sensitivity to compounds with estrogenic activity, but whether differences in Tam sensitivity exist in rodent strains has not been investigated. In the present study, we investigated whether rat strain differences in reproductive tract sensitivity to Tam and estrogen exist between Fischer 344 (F344) and Sprague Dawley (SD) rats. Immature (21-23 day; 6/group), ovariectomized F344 and SD rats were treated with vehicle (control), 17beta-estradiol (E2) [1 x 10 (-6) to 1.0 micro g/kg body weight (BW)] or 4-OH tamoxifen (4-OHT) (1 x 10 (-4) to 10 mg/kg BW) for 2 days and then sacrificed on day 3. Reproductive tracts were collected, weighed, and examined for changes in histomorphology and expression of ER and nuclear receptor co-regulators (SRC1, p300, CARM1, GRIP1, SPA, REA and Uba3). Treatment with E (1 x 10(-5) micro g/kg BW) increased ( <0.05) uterine epithelial cell height in F344 but not SD rats, demonstrating increased sensitivity of the F344 strain to E. Conversely, treatment with 1 x 10(-3) mg/kg BW 4-OHT increased ( <0.05) uterine weight and epithelial cell height in SD but not F344 rats, demonstrating that the SD strain is more sensitive to the antiestrogen. Northern and Western blot and immunohistochemical analysis revealed that ER expression levels in the SD and F344 uterus were not different. Expression of receptor co-regulators was higher in the uterus compared to the vagina regardless of strain and higher CARM1 expression was seen in SD uterus compared to F344 rats. Understanding differences in Tam sensitivity may help us to better understand why some women develop endometrial cancer while taking Tam and be beneficial in treatment decisions for breast cancer patients.

Animals↗
PubMed1998

Effects of oncostatin M and tamoxifen on human melanoma cells.

New agents are required in the treatment of malignant melanoma, to be used alone or in combination with established therapies. Oncostatin M (OSM), a member of the gp130 family of cytokines, has previously been shown to inhibit the growth of melanoma cell lines. Tamoxifen (TAM) is widely used in the treatment of melanoma, typically in combination with chemo- and/or immunotherapy. A component of the antitumour activity of TAM is via modulation of transforming growth factor-beta (TGF beta) which has previously been shown to be synergistic with OSM in vitro. To further investigate the clinical potential of OSM, alone and in combination with TAM, set concentrations of each were added to nine fresh and two well-established melanoma cell lines. The proliferation of seven of the 11 cell lines was inhibited by OSM, while two were unresponsive at the dose range tested. Of particular interest was the finding that the growth of two of the cell lines was significantly stimulated at low doses of OSM. The combination of OSM with TAM produced widely divergent results, most frequently resembling the effects of OSM alone. No synergism between the two was evident in any of the cell lines tested. Our results indicate that a combination of OSM and TAM in clinical trials needs further evaluation before it can be recommended. Furthermore, while OSM alone may be useful in the treatment of melanoma, this may be complicated by the possibility of stimulating tumour growth in some instances.

Antineoplastic Agents↗
PubMed1998

Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma.

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.

Adolescent↗
PubMed2005

Tumour-associated macrophage infiltration, neovascularization and aggressiveness in malignant melanoma: role of monocyte chemotactic protein-1 and vascular endothelial growth factor-A.

The objective of this study was to evaluate the role of tumour-associated macrophages (TAMs) in malignant melanoma progression, invasion and angiogenesis. We examined the levels of macrophage infiltration and monocyte chemotactic protein-1 (MCP-1), neovascularization and vascular endothelial growth factor-A (VEGF-A) in different Clark's level melanomas with varying thicknesses and metastases. The level of TAM density was significantly higher in thick (>0.75 mm) than thin ( 0.75 mm) than thin (<or=0.75 mm) melanomas and negatively correlated with melanoma aggressiveness and invasion. We did not observe any significant difference in the levels of neovascularization between thin and thick melanomas, and no correlation with VEGF-A expression, TAM density or melanoma aggressiveness and invasion. Interestingly, levels of VEGF-A were significantly higher in metastatic melanoma than in thick melanoma. In addition, we observed lower levels of MCP-1 messenger RNA (mRNA) expression in more aggressive melanomas and in cell lines with higher metastatic potential. In summary, our data suggest a distinct pattern of TAM infiltration, MCP-1 expression, neovascularization and VEGF-A expression during human melanoma progression, and a complex interaction between TAMs and melanoma cells in the regulation of melanoma progression, angiogenesis and metastasis.

Cell Line, Tumor↗
PubMed2005

Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitors in patients with renal cell carcinoma: correlation with tumor associated macrophage and prognosis.

PURPOSE: Urokinase-type plasminogen activator (uPA) has an important role in tumor progression through the degradation of extracellular matrix. In addition, uPA receptor (uPAR) and plasminogen activator inhibitors (PAIs), composed of PAI-1 and 2, are also known to affect such activities. Tumor associated macrophage (TAM) is an important regulator of tumor progression that is associated with the uPA system in various cancers. However, to our knowledge the clinical significance of PAI-2 and the relationship between the uPA system and TAM in human renal cell carcinoma (RCC) tissues have not been investigated. We investigated and clarified these issues. MATERIALS AND METHODS: The subjects of the current study were 106 consecutive surgically resected specimens from patients with RCC. The expression of uPA, uPAR, PAI-1 and PAI-2 was determined by immunohistochemistry. We also examined the relationships among these molecules, survival and TAM. RESULTS: The mean immunoreactive scores (range 0 to 6) of uPA, uPAR, PAI-1 and PAI-2 were 3.09, 2.22, 1.99 and 0.56, respectively. These scores correlated with the grade and presence of metastasis. The expression of uPA, uPAR and PAI-1 but not PAI-2 correlated negatively with cause specific survival. Of uPA family members multivariate analysis showed that PAI-1 independently influenced cause specific survival. TAM counts correlated with PAI-1 only (p <0.001). CONCLUSIONS: Our results suggest that PAI-1 is an important regulator of tumor progression and survival, and PAI-1 may modulate them via TAM. On the other hand, PAI-2 has a minimum role in survival. Our results may help discussions of treatment strategy in patients with RCC.

Aged↗
PubMed1992

Recombinant human interferon-alpha 2a increases hormone receptor level of a human breast carcinoma xenograft in nude mice and enhances the anti-proliferative activity of tamoxifen.

The effect of recombinant human interferon-alpha 2a (rhIFN-alpha 2a) on the hormone receptor level and antitumor activity of tamoxifen (TAM) was investigated in nude mice using ZR-75-1, an estrogen receptor (ER)-positive, and progesterone receptor (PgR)-negative human breast carcinoma xenograft. ER levels (maximum binding sites) of tumors treated with rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day for 1 or 3 wk were not significantly different from the control, whereas those with rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day for 1 or 3 wk were higher than the control (3.9- to 4.4-fold) with a significant difference at P < 0.01. The increase of ER by rhIFN-alpha 2a was investigated using a sucrose density gradient method. The peak was only seen at 8S in both rhIFN-alpha 2a-treated tumor and control ER, and the sedimentation patterns were almost the same, suggesting that both ERs were essentially equivalent. On the other hand, PgR of all the treated groups could be detected, while that of the control group was undetectable. The antitumor effect of the combination treatment of rhIFN-alpha 2a and TAM was compared with those of single treatments. While rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day and TAM did not show a combination effect, rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day and TAM showed a synergistic combination effect, and ER was decreased to the threshold of detection by the combination treatment. These findings indicated that a low dose of rhIFN-alpha 2a increased the ER levels of ER-positive human breast cancer in vivo as well as in vitro and enhanced the anti-proliferative effect of TAM, and the newly synthesized ER was essentially the same as the original ER.

Animals↗
PubMed1985

The influence of oestrogens on the sensitivity of PRL, TSH and LH to the inhibitory actions of dopamine in hyperprolactinaemic patients.

The effects of oestrogen priming on the response of serum PRL, LH and TSH to dopamine (DA) infusion have been studied in hyperprolactinaemia. Seven hyperprolactinaemic females (aged 22-57 years; basal PRL 911-5130 mU/l, normal less than 420 mU/l), had submaximal DA infusions (0.06 micrograms/kg/min) over 3 h. The DA was repeated at the same dose after pretreatment with ethinyl oestradiol (E2) 100 micrograms daily by mouth for 3 d, and after a further 2 week interval, following pretreatment with tamoxifen (TAM) 20 mg twice a day by mouth for 3 d. Ethinyl oestradiol pretreatment stimulated a rise in basal PRL levels in all subjects (mean +/- SE, mU/l; 2903 +/- 761 vs 2293 +/- 684, P less than 0.05) while TAM produced a higher but more variable increase in basal PRL levels (mean +/- SE, mU/l; 3402 +/- 757, P = n.s.). The individual increments in basal PRL levels after both E2 and TAM pretreatment showed a significant positive correlation with the greater decrement in PRL levels during E2 and TAM primed DA infusions (E2, r = 0.93, P less than 0.01, TAM, r = 0.83, P less than 0.05). E2 pretreatment produced a rise in basal LH levels in 5/7 patients, and there was a significant positive correlation between the rise in basal LH levels after E2 and the decremental change in LH levels in E2 primed DA infusions (r = 0.94, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Tumour-associated macrophages and melanoma tumourigenesis: integrating the complexity.

When the body discovers a tumour cell (foreign antigen), several kinds of mechanisms and cells operate in what is called an immune response. The latter has evolved into two mechanisms: non-specific immunity and specific immunity, which are closely linked to and influence each other. The former represents the first line of defence against neoplastic cells. The adaptive (specific) immunity is orchestrated by antigen-specific T and B lymphocytes. The effector cells of innate immunity include granulocytes, macrophages and natural killer cells. Among these cells, macrophages represent the most important part of innate immunity against tumours. Tumour-associated macrophages (TAMs) are important antigen-presenting cells and as such an understanding of their interactions with tumour cells gives insights into novel therapeutic strategies. In tumours, the effect of TAMs is the outcome of their two concomitantly competing interactions: tumour growth reduction and tumour growth promotion. The macrophage (TAMs) content of melanoma ranges from 0 to 30% and their density increases with increasing tumour thickness. The melanoma cells and TAMs seem to interact with each other through the release of soluble factors that either prevent or enhance tumour growth. For instance, syngeneic macrophages from tumour-bearing mice can inhibit melanoma growth in the nude mice more than the control macrophages. Alternatively, metastatic B16 melanoma cells can produce some macrophage cytotoxic substances that help tumour cells not only escape the host immunosurveillance system but also prevent distant metastasis. Together, these observations suggest opposing effects for these soluble factors in melanoma. To date, little is available in the literature about the interactions between TAMs and melanoma cells. This viewpoint not only tries to examine these interactions but also provides relevant speculations.

Animals↗