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PubMed1993

Induction of tamoxifen-dependent rat mammary tumors.

We have observed previously that animals given tamoxifen (TAM) and the carcinogen dimethylbenzanthracene develop exclusively hormone-independent tumors. Since our data implied that the TAM-associated tumors were different from control tumors, we undertook studies to examine the role of TAM in the induction and growth of these tumors. Following cessation of TAM administration, almost one-third [29.0 +/- 1.7% (SEM)] of the tumors regressed and more tumors appeared. Resumption of TAM administration resulted in regrowth of some tumors and regression of the new tumors. These studies demonstrate that some of the TAM-associated tumors are actually dependent upon TAM for growth, while the appearance of new tumors suggests that TAM does not totally prevent tumor formation but may only delay it.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Pathological effects of dietary zearalenone and/or tamoxifen on female mink reproductive organs.

The efficacy of dietary tamoxifen (TAM) to alleviate the hyperestrogenic effects of the mycotoxin zearalenone (ZEN) was assessed by pathologic examination of the reproductive organs of female mink (Mustela vison). Mink were fed 20 mg/kg ZEN, 10 mg/kg TAM, or 20 mg/kg ZEN + 10 mg/kg TAM from about 2 mo prior to breeding until the kits reached 3 w of age. All female mink fed ZEN mated, but only 25% whelped. No mink fed TAM or TAM + ZEN mated. Postmortem examination revealed moderate to severely distended uteri filled with caseated necrotic substances in the TAM, ZEN and ZEN + TAM fed mink. Histologic examination revealed mild to severe endometrial hyperplasia to uterine atrophy, endometritis, metritis and pyometra. Ovarian follicles were atrophied and degenerated. TAM was not effective in alleviating the hyperestrogenic effects of ZEN but was a potent estrogen agonist in mink.

Animals↗
PubMed1998

[Late phase II study of TAT-59 (miproxifene phospate) in advanced or recurrent breast cancer patients (a double-blind comparative study with tamoxifen citrate)].

The efficacy and safety of TAT-59 (miproxifene phospate) were compared with tamoxifen citrate (TAM) in ER-positive or ER-unknown patients with advanced or recurrent breast cancer, using the double-blind method. TAT-59 and TAM were both given 20 mg/body orally for over 12 weeks in daily doses. Eligible cases were 93 in the TAT-59 group and 102 patients in the TAM group. The response rate was shown to be 30.1% (28/93) in the TAT-59 group and 26.5% (27/102) in the TAM group. Statistical equivalence between both treatments was proven at 90% confidence interval (-8.5% < or =, < or = 12.8%). Adverse reactions observed in the patients receiving TAT-59 were hot flush, nausea and vomiting, sweating, anorexia, abnormal values in liver function tests, and anemia, showing no differences from the TAM group. Leukopenia (4.9%) and thrombopenia (2.9%) reactions were found only in the TAM group. Two patients in the TAT-59 group and three in the TAM group discontinued treatment due to adverse reactions. However, these adverse reactions were reversible in both groups. In conclusion, TAT-59 was showed comparable efficacy and safety with TAM in ER-positive or ER-unknown patients with advanced or recurrent breast cancer.

Administration, Oral↗
PubMed1996

Modulatory effect of tamoxifen and ICI 182,780 on adriamycin resistance in MCF-7 human breast-cancer cells.

In this study the ability of the new pure anti-estrogen ICI 182,780 to modulate the cytotoxic action of adriamycin (ADR) on parental and ADR-resistant MCF-7 (MCF-7 ADRr) human breast-cancer cells was investigated and compared with that of tamoxifen (TAM). TAM enhanced ADR cytotoxicity in MCF-7 ADRr cells in a dose-related manner, but this effect was slight or absent in MCF-7 WT. In contrast, ICI 182,780 was able to enhance ADR toxicity both in MCF-7 ADRr and in the parental cell line. ICI 182,780 was up to 2.5-fold more effective than TAM in reducing the IC50 of ADR in MCF-7 ADRr cells. Analysis of the data by the isobole method showed that the combination ADR/TAM and ADR/ICI 182,780 produced synergistic anti-proliferative activity in MCF-7 ADRr cells. Because ADR resistance in these cells is associated with the expression of high levels of P-glycoprotein (Pgp), we evaluated the effect of anti-estrogens on Pgp expression and activity. Both ICI 182,780 and TAM failed to modulate Pgp expression as assessed by flow cytometry and Western-blot analysis, performed using the monoclonal antibodies MM4.17 and C 219, which are specific for an external or an internal determinant respectively. Pgp activity was investigated by flow cytometry measuring the extrusion of ADR and the cationic dye Rhodamine 123 (Rh 123). ICI 182,780, but not TAM, reduced the activity of Pgp in MCF-7 ADRr cells. Flow cytometry was also used to investigate cell-cycle modifications induced by ADR in MCF-7 ADRr cells, both in the presence and in the absence of anti-estrogens. After 72 hr, higher doses induced an arrest of cells at the G2/M phase. The same effect was visible when lower doses of ADR were combined with ICI 182,780 or TAM. In terms of cell-cycle-blocking activity ICI 182,780 was largely more effective than TAM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Comparative study on the induction of cytostasis and apoptosis by ICI 182,780 and tamoxifen in an estrogen receptor-negative ovarian cancer cell line.

We have compared the effects of a broad range of clinically relevant concentrations (0.1 to 10 microM) of the steroidal pure anti-estrogen ICI 182,780 and the non-steroidal partial anti-estrogen tamoxifen (TAM) on cell proliferation and induction of apoptosis in the estrogen receptor (ER)-negative ovarian carcinoma cell line A2780. Cell proliferation was assessed by evaluating the number of viable cells, changes in cell-cycle distribution and cell replication rate; while apoptosis induction was assessed by examining nuclear morphological changes associated with apoptotic death and DNA cleavage into 300 and 50 kbp units (large DNA fragmentation) and into 180 bp units (internucleosomal DNA fragmentation). We provide evidence that 0.1 to 10 microM ICI 182,780 and TAM significantly inhibit the growth of A2780 cells in a dose-dependent fashion. Cytokinetic analysis revealed that only 10 microM TAM caused a significant blockade in G1 and a diminished replication rate. Conversely, we show that 0.1 to 10 microM ICI 182,780 and TAM induce apoptosis in a dose-dependent fashion. The earliest recognizable apoptotic change induced by treating the cells with these 2 drugs was DNA cleavage into 300 and 50 kbp units. This started to be visible in adherent cells, implying that apoptosis induction by ICI 182,780 and TAM was not determined by the loss of cell-substrate interaction. A further degradation of 300 and 50 kbp DNA fragments occurred in cells that had lost their adhesion to the culture plate. We observed the ladder pattern typical of internucleosomal DNA cleavage by treating A2780 cells with the highest dose (10 microM) of ICI 182,780 and TAM. Lower concentrations of these 2 drugs (0.1 to 1 microM) did not produce such a pattern of DNA fragmentation. Typical features of apoptotic nuclei were detectable after both drug treatments. However, cells undergoing apoptosis induced by ICI 182,780 showed hyper-aggregation of chromatin, whereas TAM-treated cells preferentially exhibited chromatin clumping.

Antineoplastic Agents↗
PubMed2005

Modulation of tamoxifen sensitivity by antisense Bcl-2 and trastuzumab in breast carcinoma cells.

BACKGROUND: Because the overexpression of HER-2 and Bcl-2 is associated with resistance to tamoxifen (TAM), the authors examined the effect of antisense (AS) Bcl-2 on sensitivity to TAM compared with the effect of trastuzumab on sensitivity to TAM in breast carcinoma cell lines. METHODS: Drug sensitivity was assessed in vitro using a [3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay with the breast carcinoma cell lines ZR-75-1, MDA-MB-453, and BT-474. AS Bcl-2 18-mer phosphorothioate oligonucleotide was applied. Apoptotic cell death was assessed with the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling method, and gene expression was evaluated with Western blot analysis. RESULTS: The expression of Bcl-2 was identified in ZR-75-1 and BT-474 cells and, to a lesser extent, in MDA-MB-453 cells. Overexpression of HER-2 was identified in BT-474 cells, and moderate expression was identified in MDA-MB-453 and ZR-75-1 cells. Combination treatment with trastuzumab or AS Bcl-2 enhanced TAM sensitivity in ZR-75-1 cells, which showed 50% inhibitory concentration (IC50) values of 0.9 microM (7.2-fold increase) and 0.5 microM (13.0-fold), respectively. Combination treatment with trastuzumab or AS Bcl-2 slightly enhanced TAM sensitivity of BT-474 cells, with IC50 values of 3.0 microM (1.3-fold) and 1.5 microM (2.6-fold), respectively. The sensitivity of MDA-MB-453 cells to TAM was not enhanced by combination with trastuzumab or AS Bcl-2. Modulation of TAM sensitivity by AS Bcl-2 was superior to modulation by trastuzumab in HER-2-expressing and Bcl-2-expressing breast carcinoma cells. Enhanced sensitivity in combination with AS Bcl-2 was associated with down-regulation of Bcl-2 and pAkt, which was correlated with the induction of Bax and caspase-3, leading to apoptosis. CONCLUSIONS: AS Bcl-2 appeared to be superior to trastuzumab with respect to regulating the signal-transduction pathways involved in breast carcinoma cells.

Antibodies, Monoclonal↗
PubMed2004

Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis.

In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1-2 days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17beta-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class II(+) inflammatory cells and low expression of TNF-alpha, IL-1beta, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-gamma production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis.

Animals↗
PubMed1996

Changes in rat liver gene expression induced by thioacetamide: protective role of S-adenosyl-L-methionine by a glutathione-dependent mechanism.

Chronic liver damage induced by thioacetamide (TAM) was accompanied by changes in the expression of genes related to growth (beta-actin) and function (albumin and haptoglobin) of the liver. Their messenger RNA (mRNA) levels increased during the first days after TAM administration, but 4 to 7 days after prolonged treatment with this drug, liver gene expression was considerable decreased. TAM-induced changes in albumin and beta-actin mRNA levels were prevented by cotreatment with S-adenosyl-L-methionine (SAM). We have investigated the possible involvement of glutathione in the protective mechanism of SAM. Firstly, we found that TAM treatment in the rat induced changes in liver glutathione disulfide (GSSG) levels, with a concomitant increase in the glutathione reductase enzymatic activity, these changes being abolished when animals were cotreated with TAM and SAM. Secondly, when rats were pretreated with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, before thioacetamide administration, the beneficial effect of SAM on liver gene expression was completely abolished. These results were confirmed by assaying the alanine transaminase serum activity, a parameter of liver injury. TAM-treated animals had increases in this serum enzyme, this effect being partially blocked by SAM. However, in BSO-pretreated rats, the protective effect of SAM was impaired. Taking together all these results, we propose a glutathione-dependent mechanism in the SAM protection against TAM hepatotoxicity in the rat.

Actins↗
PubMed2002

Resistance to tamoxifen-induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer.

Overexpression of Her2/neu is implicated in the development of resistance to the antiestrogen tamoxifen (TAM) that exerts its inhibitory effect through interaction with estrogen receptor (ER). Whereas Her2/neu and ER are believed to be important cell survival/death factors in human breast cancer cells, if and how they interact to confer resistance to hormone therapy is not known. This prompted us to investigate whether modulation of the effect of TAM occurs via the Her2/neu pathway and whether targeting the interaction between the Her2/neu pathway and the ER pathway is beneficial. There are 2 forms of ER that are localized to the cell membrane and to the nucleus. For the first time, we found that Her2/neu directly interacts with ER at the cell membrane. We then investigated the role of Her2/neu overexpression in the regulation of the cell membrane ER pathway in TAM-resistant breast cancer cells and the nature of this interaction in apoptotic signaling. Relief of TAM resistance was associated with Her2/neu downregulation and ER upregulation. TAM-induced apoptosis occurred immediately after dissociation of Her2/neu from cell membrane ER. These results demonstrate a novel mechanism by which Her2/neu regulates the cell membrane ER-coupled apoptosis and the possible involvement of the Her2/neu in TAM resistance of breast cancer cells. Moreover, the antiproliferative activity of TAM should rely on the integration between the signal transduction from the cell membrane ER and the gene regulation by the nuclear ER. Coordinated modulation on the cell membrane ER/Her2/neu pathway and the nuclear ER/RAR pathway may provide a new approach for treatment of ER-positive, Her2/neu overexpressing breast cancer.

Antineoplastic Agents↗
PubMed1993

Tamoxifen modulation of cisplatin cytotoxicity in human malignancies.

Recent clinical trials have indicated that addition of tamoxifen (TAM) to a combination of cisplatin (DDP), carmustine and dacarbazine markedly increases the overall objective response rate of patients with metastatic malignant melanoma. Previous studies have determined that there is remarkable synergy between TAM and DDP in a human melanoma cell line T-289. Using the technique of median effect analysis, in clonogenic assay, we observed a highly synergistic interaction between TAM and DDP. To determine whether or not this synergistic interaction was unique to human melanomas, or is generally observed in other types of malignancy, we examined the nature of this interaction using a human ovarian carcinoma and small cell lung cancer cell line. Synergy was observed in both cell lines. In the case of all 3 types of malignancy, synergy was observed at concentrations of both TAM and DDP that can be achieved in patients. Our results demonstrate that cytotoxic synergy between the DDP and TAM is observed in cell lines established from multiple types of human malignancies. It is important to note that the synergy between TAM and DDP is not dependent on the presence of estrogen or progesterone receptors. Since TAM is well tolerated by patients, it is particularly attractive as a potential agent with which to sensitize human tumors to DDP.

Carcinoma, Small Cell↗
PubMed1984

In situ proliferation of intratumor macrophages.

This investigation was carried out to assess whether the progressive increase in the number of macrophages associated with growing tumors was the result of an influx of monocytes from the circulation as well as proliferation of macrophages in situ. Tumor-associated macrophages (TAM) were identified in cell suspensions prepared from three C57BL/6J (B6), methylcholanthrene-induced sarcomas, designated MCA/76-9, 76-64, and 77-23, growing in normal or irradiated mice. When the sarcomas were implanted in B6 mice exposed to a sublethal dose (800 R) of whole body irradiation ( WBI ), tumors grew very slowly compared with control tumors. The TAM numbers were small and the percentages of macrophages were very low. The levels of TAM corresponded with the low number of circulating blood monocytes. However, compared with the number of TAM in the initial inoculum of tumor cells injected into the WBI or control mice, the TAM numbers over a period of 14 days increased several fold in WBI mice. That this increase was initially due to infiltration from the circulation was shown by injecting macrophage-free, cultured tumor cells into WBI or control mice. Proliferation in situ was demonstrated by autoradiography experiments. When 3H-thymidine was injected 1 hr before excision of MCA/76-9 tumors, labeled cells were seen in histological sections and in cell suspensions. The labeling indices for TAM from tumors growing in WBI or normal mice were not significantly different from tumor cell labeling indices. The overall data indicated that the progressive increase in TAM in these sarcomas was the combined result of monocyte infiltration and proliferation of macrophages in situ.

Animals↗
PubMed1987

FACS analysis of tumor-associated macrophage replication: differences between metastatic and nonmetastatic murine mammary tumors.

The proliferation activity of adherent, tumor-associated macrophages (TAM) from three related murine mammary carcinoma lines was measured by fluorescence-activated cell sorter (FACS) analysis of the incorporation of 5'-Bromo-2'deoxyuridine (BrdU) in vivo during a 1 hr period prior to tumor removal. The tumor lines examined were line 67 which is nonmetastatic following either subcutaneous (SC) or intravenous (IV) injection, line 168 which colonizes the lung after IV injection but not SC, and line 66 which can colonize the lung from either site. The percentage of total cells identified morphologically as macrophages were similar for tumors from lines 66 and 67 (41% and 38%, respectively), as compared to line 168 tumors, in which, after digestion, 27% of cells were identified as macrophages (P less than or equal to 0.05). Adherent TAM from line 66 tumors had the greatest percentage of BrdU incorporating cells, with an average of 22%. This was statistically significant (P less than or equal to 0.01) from TAM from tumors of line 67, which were 13% positive. The percentage of adherent TAM from line 168 tumors (18% positive) was also significantly different from 67 TAM (P less than or equal to 0.01). These results demonstrate a possible correlation between the percentage of TAM undergoing replication and the ability of the host tumor to colonize the lung. There is no apparent relationship between the percentage of TAM in replication and the number of macrophages associated with a tumor.

Animals↗
PubMed2004

Thymidine analogue reverse transcriptase inhibitors resistance mutations profiles and association to other nucleoside reverse transcriptase inhibitors resistance mutations observed in the context of virological failure.

During ZDV or d4T exposure, mutations at codons 41, 67, 70, 210, 215, and 219 can be selected and were named thymidine analogue mutations (TAMs). Some previous results suggested that different TAMs patterns could exist and that the kind of TAMs pattern could influence the virological response to some nucleoside reverse transcriptase inhibitors (NRTIs). In order to get more data about the relative prevalence of these patterns, their associations with other NRTI resistance mutations and the identification of the different stages observed during the acquisition of TAMs under treatment by NRTIs, we collected 1,098 RT sequences harbouring at least one TAM from patients failing to antiretroviral regimen. Sequences were stored in a database designed specifically to allow the retrieval of sequences that met specific criteria such as the occurrence and frequency of a particular mutation, the nature and frequency of the amino acid substitution at a given codon, and/or the rate of association between resistance mutations. Two pathways of TAMs can be identified: profile #1 (T215Y mutation linked) and profile # 2 (T215F mutation linked). The frequency of selection of profile # 1 is two times higher than profile # 2. The E44D/A + V118I complex, 69 insertions, and L74V mutation are associated to profile #1, whereas the Q151M complex and M184V mutation are associated to both profiles. As some NRTI resistance mutations were associated preferentially with profile #1, further studies are needed to explore if, the weaker efficacy observed on viruses harbouring this profile using some NRTIs, could be explained by the TAMs profile itself or the other associated NRTI resistance mutations.

Anti-HIV Agents↗
PubMed1994

Influence of joint injury on motor and functional recovery of finger replantation.

A series of 82 consecutive cases were studied concentrating on the influence of joint injury on the final motor and functional recovery of the successfully replanted or revascularized finger. In this series a 32.0% (41/128) incidence of joint injury was found. When the proximal interphalangeal (PIP) joint was injured and preservation was not possible, arthrodesis was done. This would cause a significantly lower Tamai's score (70.9), total active range of motion (TAM; 99.4 degrees) and TAM-minus the metacarpophalangeal joint TAM-MP; (15.6 degrees). The influence of arthrodesis on the distal interphalangeal (DIP) joint was relatively minor. When preservation of the joint was possible, the PIP arthroplasty group had a significantly higher Tamai's score (83.7, P < 0.01), TAM (157.9 degrees, P < 0.05), and TAM-MP (70.0 degrees, P < 0.001). Preservation of the DIP joint also significantly increased the TAM and TAM-MP degrees, yet with no significant improvement in Tamai's score. Our study proves what most hand surgeons would expect, in that sacrifices of the PIP and MP joint would cause a significantly detrimental effect on the functional recovery of a finger. We also recommend joint preservation during replantation surgery whenever possible, especially for the PIP and MP joints, in order to achieve better functional recovery of the finger.

Adolescent↗
PubMed2002

Proton electron double resonance imaging of the in vivo distribution and clearance of a triaryl methyl radical in mice.

Proton electron double resonance imaging (PEDRI) measures the spatial distribution of paramagnetic species in biological samples using the Overhauser effect. Triaryl methyl (TAM) free radicals have been developed as a spin probe for PEDRI since they have very long T(1e). Therefore, low RF power levels are sufficient to saturate the electron spin system with resultant high NMR enhancement facilitating application of PEDRI in living animals. In this report, PEDRI studies were performed at 0.02 T. The power-dependent image enhancement was studied using phantoms of TAM in saline, then the distribution and pharmacokinetics of TAM in living mice were measured. Following intravenous administration of 0.7 mmol/kg of TAM, enhancements of up to -34 were observed enabling visualization of its distribution within the body. Maximum uptake of TAM in the vascular compartment was seen 1 min postadministration with half-clearance within 5 min. Maximum uptake in the kidneys occurred at 10 min with half-clearance at 26 min and maximum accumulation in the bladder after 50 min. Thus, TAM is initially compartmentalized in the vasculature and this is followed by rapid uptake and excretion by the kidneys. PEDRI enabled rapid imaging of the distribution and clearance of this paramagnetic probe and this information should facilitate the use of TAM as a label for oximetry and other applications. Magn Reson Med 48:530-534, 2002.

Animals↗
PubMed1991

Effect of nasal CPAP on thoracoabdominal motion in neonates with respiratory insufficiency.

Thoracoabdominal motion (TAM) profiles were determined in ten infants requiring nasal continuous positive airway pressure (CPAP) and supplemental oxygen, in order to assess the influence of CPAP on chest wall function in infants with respiratory insufficiency. (TAM) was quantitated by respiratory inductive plethysmography, measuring relative motion of the rib cage and abdomen. Baseline pulmonary function (without CPAP support) was assessed from simultaneous measurements of transpulmonary pressure, air flow, and tidal volume. Measurements of (TAM) were acquired at baseline and at nasal CPAP levels of 0, 3, 5, and 8 cm H2O, in randomized order. Without CPAP, relative paradoxical motion occurred, i.e., the rib cage collapsed inward instead of expanding outward early in inspiration. With CPAP, TAM resembled the pattern in preterm infants, without lung disease. We found that nasal CPAP lowers the phase angle in infants with respiratory insufficiency (P less than 0.003), indicating improved synchrony of TAM. In addition, the improvement with nasal CPAP was related to the severity of pulmonary compromise at baseline. We speculate that changes in TAM associated with nasal CPAP arise from an interaction between pulmonary mechanics and an enhanced stability of the chest wall. In this context, the greater synchrony of TAM is suggestive of an improved breathing strategy. This may be a noninvasively obtainable marker of an effective nasal CPAP level in infants with altered pulmonary and chest wall mechanics.

Humans↗
PubMed1998

Rapid fragmentation of vimentin in human skin fibroblasts exposed to tamoxifen: a possible involvement of caspase-3.

Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemotherapy of breast cancer, although the molecular mechanisms underlying TAM cytotoxicity are obscure. Here, we show that TAM dramatically caused degradation of vimentin (VIM) in human skin fibroblasts, in a time and dose dependent manner. Addition of caspase-3 inhibitor, Z-DEVD-FMK, inhibited formation of some fragments of VIM, and caspase-3 was proteolytically activated by TAM treatment. Expression of functional estrogen receptors were negative in these cells, and neither transcription nor protein synthesis was required for TAM-induced degradation of VIM. Moreover, quinestrol, an ethinyl estradiol derivative, weakly degraded VIM, whereas neither estradiols nor estriol had any effects. Taken together, TAM may induce fragmentation of VIM associated with an activation of caspase-3, which may be attributed to non-genomic actions of TAM.

Antineoplastic Agents, Hormonal↗
PubMed2002

Tumor-associated macrophages as a source of functional dendritic cells in ovarian cancer patients.

We have generated dendritic cells (DCs) from tumor-associated macrophages (TAMs) obtained from ascites fluid or tumor specimens of ovarian cancer patients, and compared them phenotypically and functionally to DCs derived from the patients' peripheral blood mononuclear cells (PBMCs). Both immature and mature DCs could be generated from TAMs. However, TAM-derived DCs underwent maturation to a lesser degree than PBMC-derived DCs, as measured by DC receptor surface expression. Nonetheless, in allogeneic mixed lymphocyte reactions, TAM-derived DCs stimulated T cell proliferation as efficiently as PBMC-derived DCs. In addition, TAM-derived DCs presenting tumor Ags were capable of stimulating IFN-gamma secretion by tumor-specific T cell lines. Thus, TAMs isolated from ovarian cancer patients can be used to generate significant numbers of DCs. Therefore, TAMs have potential use for either ex vivo or in vivo DC-based immunotherapy, particularly in individuals in which more conventional sources of DCs have been depleted.

Adenocarcinoma↗