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At least 649 records · Page 36Linked to original sources
PubMed2003

Effects of 17beta-estradiol and tamoxifen on the selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA expression in male reproductive organs of rats.

The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) is highly expressed in testes under gonadotropin control. The expression patterns of PHGPx mRNA by 17beta-estradiol (E2) as an estrogen and tamoxifen (Tam) as an estrogen antagonist were investigated in the reproductive organs of male rats. Twelve-week-old male Sprague-Dawley rats were subcutaneously injected with E2 (7.5 microg/kg/day) or Tam (5 mg/kg/day) for 1 week. The E2 treatment significantly increased the levels of PHGPx mRNA in both testes and prostates, whereas the Tam treatment significantly decreased the levels of PHGPx mRNA, compared to the vehicle control (p<0.01). The treatment with E2 or Tam slightly decreased the levels of PHGPx mRNA in epididymides. In histopathological examination, severe vacuolization and depletion of germ cells in the seminiferous tubules, cell debris in the tubular lumen, and mild proliferative changes in interstitial tissues were observed in the testes of Tam-treated rats, whereas only mild spermatogonial proliferation was observed in the seminiferous tubules of E2-treated rats. There were no typical histopathological changes in the epididymides of any of the laboratory rats but mild epithelial proliferation in the prostates of E2- and Tam-treated rats. These results suggest that PHGPx mRNA expression may be influenced by estrogen in the male reproductive organs.

Animals↗
PubMed2000

Toxicity assessment of tamoxifen by means of a bacterial model.

A strain of Bacillus stearothermophilus was used as a model to study physical perturbations induced in the membrane by the cytostatic tamoxifen (TAM). This study was carried out using two lines of criteria: (1) bacterial growth, and temperature growth range, with determination of growth parameters as a function of TAM concentration; and (2) biophysical studies by differential scanning calorimetry (DSC) and by means of two fluorescent probes to evaluate perturbations promoted by the drug on the structural order of bacterial lipid membranes. The inhibition of growth induced by TAM, the structural bilayer disordering, and the shift in the phase transition temperature to a lower range were also determined in the presence of Ca2+, i.e., a natural membrane stabilizer, to elucidate further perturbing effects of TAM on membranes with putative implications in cell toxicity. Growth inhibition promoted by TAM is potentiated by an increase in growth temperature above the optimal range, but attenuated or relieved by the addition of 2.5 mM Ca2+ to the culture medium. Consistently, fluorescence polarization and DSC studies showed that Ca2+ ions (2.5 mM) effectively compensated for the destabilizing effects promoted by TAM in bacterial lipid membranes.

Antineoplastic Agents, Hormonal↗
PubMed1988

Adjuvant treatment of postmenopausal patients with high risk primary breast cancer. Results from the Danish adjuvant trials DBCG 77 C and DBCG 82 C.

The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients (tumor greater than 5 cm, positive axillary nodes, or invasion to skin/fascia) were randomized after total mastectomy and axillary sampling to postoperative radiotherapy (control) or to radiotherapy plus treatment with tamoxifen (TAM), 30 mg daily for 1 year. A total of 1,716 patients entered the study. At 8 years of follow-up, (7 years median time of observation), we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality, which is significant for patients less than 70 years of age. Retrospectively, an increased recurrence-free survival in TAM treated patients was significant in the following subgroups: tumor less than 5 cm, positive lymph nodes, anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein. In the subsequent trial (DBCG 82 C), 1,347 postmenopausal patients less than 70 years were randomized to one of the following 3 regimens: radiotherapy + tamoxifen, 30 mg daily for 1 year (TAM), TAM alone, or TAM + CMF (CMF i.v. day 1 every 4 weeks x 9). The survival is similar in the 3 groups at 4 years (2 years median time of observation).

Aged↗
PubMed1993

Differential sensitivity of rat uterine growth and epithelium hypertrophy to estrogens and antiestrogens.

Triphenylethylene antiestrogens are considered weak estrogen agonists based on their limited ability to induce estrogen responses, in particular uterine growth. We compared the uterotrophic activity of naturally occurring and synthetic estrogens with that of antiestrogens by quantitating uterine wet weight and hypertrophy in the uterine luminal and glandular epithelium. Immature rats received five daily injections of either an estrogen (17 beta-estradiol [E2], diethylstilbestrol [DES], or ethynyl estradiol [EE]) or an antiestrogen (tamoxifen [TAM], monohydroxytamoxifen [OH-TAM], or clomiphene citrate [CC]) (0.001-100 micrograms/rat/day) subcutaneously in sesame oil and were sacrificed approximately 2 hr after the last injection. Both DES and EE increased uterine weight at doses between 0.01-100 micrograms/rat/day; E2 was about 10-fold less potent. The antiestrogens increased uterine weight only slightly. DES, EE, and the three antiestrogens each increased luminal epithelium hypertrophy to over 3-fold above that in controls. While the potencies of these synthetic compounds differed (DES = EE > OH-TAM > TAM = CC), each hypertrophic response occurred over two log doses, and the response curves displayed identical slopes. E2, however, required a range of four log doses to achieve the same degree of luminal epithelium hypertrophy. The three antiestrogens elicited glandular epithelium hypertrophy up to 2-fold above controls at the same doses that induced luminal epithelium hypertrophy; the order of potency was OH-TAM > TAM = CC. However, the three estrogens increased glandular epithelium hypertrophy only marginally. Thus, under dosing conditions commonly used to assess uterotrophic activity, these "antiestrogens" are complete, albeit less potent, estrogen agonists in the luminal epithelium and, unlike estrogens, induce hypertrophy in the glandular epithelium.

Animals↗
PubMed2007

Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group.

BACKGROUND AND OBJECTIVES: There are no widely accepted criteria for the definition of hematopoietic stem cell transplant -associated microangiopathy (TAM). An International Working Group was formed to develop a consensus formulation of criteria for diagnosing clinically significant TAM. DESIGN AND METHODS: The participants proposed a list of candidate criteria, selected those considered necessary, and ranked those considered optional to identify a core set of criteria. Three obligatory criteria and four optional criteria that ranked highest formed a core set. In an appropriateness panel process, the participants scored the diagnosis of 16 patient profiles as appropriate or not appropriate for TAM. Using the experts' ratings on the patient profiles as a gold standard, the sensitivity and specificity of 24 candidate definitions of the disorder developed from the core set of criteria were evaluated. A nominal group technique was used to facilitate consensus formation. The definition of TAM with the highest score formed the final PROPOSAL RESULTS: The Working Group proposes that the diagnosis of TAM requires fulfilment of all of the following criteria: (i) >4% schistocytes in blood; (ii) de novo, prolonged or progressive thrombocytopenia (platelet count <50 x 109/L or 50% or greater reduction from previous counts); (iii) sudden and persistent increase in lactate dehydrogenase concentration; (iv) decrease in hemoglobin concentration or increased transfusion requirement; and (v) decrease in serum haptoglobin. The sensitivity and specificity of this definition exceed 80%. INTERPRETATION AND CONCLUSIONS: The Working Group recommends that the presented criteria of TAM be adopted in clinical use, especially in scientific trials.

Bone Marrow Transplantation↗
PubMed2002

Factors influencing the distribution of Myxobolus cerebralis, the causative agent of whirling disease, in the Cache la Poudre River, Colorado.

Oligochaetes, triactinomyxons (TAMs), and age-0 trout were sampled in the upper Cache la Poudre River, Colorado, to determine the distribution of Myxobolus cerebralis during 1997 and 1998. Densities of the intermediate host, the oligochaete Tubifex tubifex, were 3.5 orders of magnitude higher in the M. cerebralis-infected Poudre Rearing Unit (PRU) trout rearing ponds than at any of the river sampling reaches. Oligochaetes, including T. tubifex, were rare in the river (1 oligochaete m(-2)), except in a few stream side alcoves and eddies (50 oligochaete m(-2)). Species composition of oligochaetes in the river reaches was more diverse than in the PRU. Tubifex tubifex constituted 50% or less of the oligochaete community in the river and 98% in the PRU. Infection rates of T tubifex were 1% in the area above the PRU, 2% in the PRU, and 6% below the PRU. An increased M. cerebralis intensity of infection in age-0 trout below the PRU could not be attributed entirely to the high numbers of TAMs in its effluent (3.7 TAMs l(-1)). Low densities of TAMs ranging from 0 to 0.2 TAMs l(-1) were found in the river reaches, yet nearly all of the age-0 trout were infected soon after emergence. This suggests that very few TAMs, as measured by filtration, need be present in the water column to bring about infection in the majority of trout present. This also indicates that the parasite can persist and potentially cause reduced juvenile trout recruitment in cold, oligotrophic, sediment poor, high-gradient streams.

Age Factors↗
PubMed1997

Efficacy of Post-operative Adjuvant Therapy for Stage IIIa Berast Cancer: Futraful vs Futraful+Tamoxifen for ER-positive Patients and Futraful vs Futraful+Adriamycin for ER-negative Breast Cancer.

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located thruoughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage III a breast cancer. Patients with estrogen receptor-positive [ ER(+)] breast cancer were treated with two types of regimens, ie, cyclophosphamide+adriamycin+fluorouracil (CAF; 2 cycles) +Futraful(FT) or CAF (2 cycles+FT+tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER(+) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation.The 5-year survival rate was 77.2% for the CAF+FT group and 74.6% for the CAF+FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF+FT+TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF+FT+TAM group was significantly higher than that for the corresponding patients in the CAF+FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF+FT+TAM group than in the CAF+FT group). Patients with estrogen receptor-negative [ ER(-)]breast cancer were treated with two types of regimens, ie, CAF+FT or CAF+FT+adriamycin(ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478(93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF+FT group and 63.0% for the CAF+FT+ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF+FT and CAF+FT+ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF+FT+ADR group than in the CAF+FT group.

Journal Article↗
PubMed2001

Carboxymethyl benzylamide dextran and tamoxifen combination inhibits tumor growth and angiogenesis.

We showed previously that a carboxymethyl dextran benzylamide (CMDB7) blocks angiogenesis of MDA-MB-435 carcinoma and its lung metastases in nude mice. In this study, we examined the combination effects of CMDB7 and tamoxifen (TAM) on cell proliferation, tumor growth, and angiogenesis on the MCF-7RAS cells. We showed that CMDB7 and TAM acted in a synergistic manner to inhibit the growth of MCF-7RAS cells, blocking them in G(0)/G(1) phase of the cell cycle. For 7 weeks, the CMDB7- (300 mg/kg/week) and TAM- (20 mg/kg/week) treated groups showed tumor growth inhibition of about 66% and 76%, respectively. Combined treatments with CMDB7 and TAM block the tumor development by 94% and induce a complete regression of 4 of 8 mice. Histological analysis showed markedly less neovascularization (88%) in the tumors treated with a combination of CMDB7 and TAM. This antiangiogenic activity was further demonstrated by direct inhibition of endothelial cell proliferation. Overall, this study points to the potential use of a combination of CMDB7 and TAM to inhibit tumor angiogenesis that can prevent tumor progression.

Animals↗
PubMed2001

Novel antitumor effect of estradiol in athymic mice injected with a T47D breast cancer cell line overexpressing protein kinase Calpha.

PURPOSE: Resistance to tamoxifen (TAM) represents a significant challenge to the management of breast cancer. We previously reported that the estrogen receptor (ER)-negative hormone-independent T47D:C42 cell line has both elevated protein kinase Calpha (PKCalpha) protein expression and basal activator protein-1 activity compared with the parental ER+ (hormone-dependent) T47D:A18 cell line. Stable transfection of PKCalpha to the T47D:A18 breast cancer cell line results in increased basal activator protein-1 activity, reduced ER function, increased proliferation rate, and hormone-independent growth (Tonetti et al., Br. J. Cancer, 83: 782-791, 2000). In this report, we further characterize the role of PKCalpha overexpression in vivo to elucidate a possible molecular mechanism of tamoxifen resistance. EXPERIMENTAL DESIGN: To determine whether the T47D:A18/PKCalpha cell line would produce hormone-independent tumors in athymic mice, we injected T47D:A18, T47D:A18/neo, or the T47D:A18/PKCalpha20 cell clones bilaterally into the mammary fat pads of athymic mice. Tumor growth was evaluated following treatment with estradiol (E2), TAM, and the pure antiestrogen, ICI 182,780. RESULTS: Mice receiving either T47D:A18 or T47D:A18/neo cells produced tumors that grew in response to E2 treatment, whereas the untreated control and TAM-treated groups showed no tumor growth. Interestingly, mice receiving the T47D:A18/PKCalpha20 clone produced tumors in both the control and TAM groups, whereas tumor growth was inhibited in mice treated with E2. PKCalpha was also overexpressed in an MCF-7 tumor model that also exhibited TAM-stimulated and E2-induced regression. CONCLUSIONS: These results suggest that overexpression of PKCalpha in breast tumors results in hormone-independent tumor growth that cannot be inhibited by TAM treatment. Furthermore, the finding that E2 has an antitumor effect on breast tumors overexpressing PKCalpha is a novel observation that may have important therapeutic implications.

Animals↗
PubMed2001

The Arabidopsis gene tardy asynchronous meiosis is required for the normal pace and synchrony of cell division during male meiosis.

Male meiosis in higher organisms features synchronous cell divisions in a large number of cells. It is not clear how this synchrony is achieved, nor is it known whether the synchrony is linked to the regulation of cell cycle progression. Here, we describe an Arabidopsis mutant, named tardy asynchronous meiosis (tam), that exhibits a phenotype of delayed and asynchronous cell divisions during male meiosis. In Arabidopsis, two nuclear divisions occur before simultaneous cytokinesis yields a tetrad of haploid cells. In tam, cell divisions are delayed, resulting in the formation of abnormal intermediates, most frequently dyad meiotic products, or in rare cases, dyad pollen (two gametophytes within one exine wall). Temperature-shift experiments showed that the percentage of the abnormal intermediates increased at 27 degrees C. Analysis of tam and the tam/quartet1 double mutant showed that most of these abnormal intermediates could continue through the normal rounds of cell divisions and form functional pollen, though at a slower than normal pace. The asynchrony of cell division started at the G2/M transition, with cells entering metaphase at different time points, during both meiosis I and II. In addition, chromosome condensation defects and mis-segregation were sometimes observed in tam. These observations suggest that the TAM protein positively regulates cell cycle progression, perhaps by promoting the G2/M transition. We speculate that there is a signal, perhaps TAM, that couples the normal pace of cell cycle progression with the synchrony of cell division during male meiosis.

Arabidopsis↗
PubMed2000

[Effect of tamoxifen on apoptosis and drug resistance of breast cancer cells in vitro].

OBJECTIVE: To study the effect of estradiol (E2) and tamoxifen (TAM) on the apoptosis regulatory genes (bax, bcl-2) and mdr-1 in MCF-7 cells. METHODS: Immunohistochemistry, in situ hybridization were used to observe the changes in bax, bcl-2 and mdr-1 genes after treatment with E2 and TAM. RESULTS: E2 had ability to increase the expression of bcl-2 and mdr-1 but TAM decrease the expression of both. Synthetic bax oligodeoxynucleotide (ODN) was used as probe to perform in situ hybridization. It was shown that bax mRNA in MCF-7 cells was down-regulated by E2 and up-regulated by TAM. Significant correlation between bcl-2 and mdr-1 was observed after TAM treatment of MCF-7 cells (P < 0.05). CONCLUSION: TAM regulates cell apoptosis and inhibits development of drug-resistance of MCF-7 breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2002

Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer.

Tumor-associated macrophages (TAMs) produce angiogenic factors and in breast cancer are associated with high vascular grade and poor survival. TAMs preferentially migrate to hypoxic areas within tumors and strongly express hypoxia-inducible factor (HIF)-2 alpha. This study examined whether HIF-2 alpha was involved in TAM angiogenic activation by correlating its expression with tumor microvessel density as a marker of angiogenesis, and other tumor variables, in a series of human primary invasive breast carcinomas. A correlation was found between high TAM HIF-2 alpha and high tumor vascularity (P < 0.0001), as well as high tumor grade (P = 0.007). The relation of HIF-2 alpha expression to a recently described oxygen-dependent pathway of angiogenesis was also studied, and an inverse relationship was found between TAM HIF-2 alpha and tumor thymidine phosphorylase expression (P = 0.02). These results suggest that TAM HIF-2 signaling may be a useful target for future antiangiogenic strategies but show that tumors use both oxygen-dependent and oxygen deficiency-regulated pathways for angiogenesis. Thus, combined blockade of pathways and careful assessment of these pathways in trials are necessary.

Adult↗
PubMed2002

[Tamsulosin with or without Serenoa repens in benign prostatic hyperplasia: the OCOS trial].

OBJECTIVE: In the treatment of the symptoms of benign prostatic hyperplasia (BPH), a French guideline opposes the use of drugs in conjunction, in the absence of proven utility. The OCOS trial therefore compared one of the possible drug combinations (tamsulosin and Serenoa repens) with tamsulosin alone, to see if there was any difference in effectiveness and to evaluate the clinical tolerance of each in patients with symptoms of BPH. MATERIAL AND METHODS: In this double-blind, randomised trial, patients had to have an IPSS (International Prostate Symptom Score) > or = 13 and a Qmax between 7 and 15 mL/s. Tamsulosin (0.4 mg) was to be administered once a day for 52 weeks, with, twice daily, a placebo (TAM) or Serenoa repens 160 mg (TAM + SR). RESULTS: 352 patients were recruited by 47 centres; 329 (average age 65) were randomised: 161 into the TAM group and 168 into the TAM + SR group. No statistically significant difference was found between the two groups, neither for the major end-point [change in total IPSS between the baseline value and the final evaluation (TAM: -5.2; TAM + SR: -6.0; p = 0.286)], nor for the secondary end-points [changes in the voiding scores (p = 0.239) and in filling scores (p = 0.475) of the IPSS, Qmax (p = 0.564), percentage of respondents according to the IPSS (p = 0.361), improvement in quality of life (IPSS-QoL: p = 0.091; UROLIFE BPH QoL: p = 0.442), safety]. CONCLUSION: The addition of Serenoa repens to tamsulosin did not provide any significant benefit to the patients: the OCOS trial does not cast doubt on the guideline applicable to the treatment of BPH.

Adrenergic alpha-Antagonists↗
PubMed2003

Effect of thymosin-alpha1 on the production of nitric oxide by tumor-associated macrophages.

The present investigation was conducted to study the effect of thymic peptide: thymosinalpha1 (thyalpha1) on the activation of tumor associated mphi (TAM) obtained from mice bearing a transplantable T cell lymphoma of spontaneous origin designated as Dalton's lymphoma, to produce nitric oxide (NO). It was found that in vivo administration of aqueous thymic extract obtained from thymus of normal mice or thyalpha1 could activate the TAM to produce enhanced amount of NO which was further augmented on in vivo treatment of these TAM by LPS. These observations suggest that thyalpha1 could prime TAM for activation by second signal of LPS. The study also presents evidence that tumor cell elaborate factors that enhance the effect of thyalpha1 on TAM for production of NO. This is the first study to show that thyalpha1 can activate TAM directly even in the absence of LPS, and may, therefore, have clinical significance.

Animals↗
PubMedDate not supplied

Tamoxifen enhances apoptotic effect of cisplatin on primary endometrial cell cultures.

BACKGROUND: Cisplatin (CDDP) dose-limited by its side-effects is, in some instances, synergistically amplified when combined with tamoxifen (TAM). TAM has been shown to modulate apoptotic pathways of normal endometrial cells, whereas CDDP induces apoptosis in malignant endometrial cells. Their combined effect on normal or malignant endometrium is as yet unknown. This study aimed to evaluate the combined CDDP and TAM's apoptotic effect on normal endometrial tissue in the context of hormonal milieu. MATERIALS AND METHODS: Primary endometrial cell cultures were established and maintained both in the presence and absence of steroidal hormones. The cultures were treated for 24 hours with 20 microM TAM and 50 microM CDDP as single drugs and in combination. Apoptosis was determined by evaluation of pre G1 cell populations in the cell cycle analysis with flow cytometer. RESULTS AND CONCLUSION: CDDP induced apoptosis in all cultures regardless of hormonal environment, while TAM significantly enhanced CDDP-induced apoptosis in steroidal deficient media in an additive manner. These are novel findings depicting CDDP's effect on normal endometrium, singularly and combined with TAM.

Antineoplastic Agents↗
PubMed1992

[Immunohistochemical in situ demonstration of cytokines in Hodgkin and non-Hodgkin lymphoma].

Primary biopsies from 149 patients with malignant lymphomas were examined by histological and immunohistochemical techniques. Twenty eight cases were classified as Hodgkin's disease and 121 as non-Hodgkin's lymphomas. The immunohistochemical distribution of cytokine expression (Il-1 alpha, Il-1 beta, Il-6 and TNF-alpha) was demonstrated in neoplastic cells and in tumor-associated macrophages (TAM). Neoplastic cells showed mostly weak positivity for TNF-alpha in 40% of Hodgkin's disease and in 20% of T cell lymphoma cases. Two groups of malignant lymphomas were established which differed in the numbers of cytokine expressing TAM. The first group consisted of malignant lymphomas which contained large quantities of cytokine-possessing TAM. In the second group significantly lower frequencies of cytokine expressing TAM were found. In both groups high and low grade malignant lymphomas were encountered. There was a significantly positive correlation between the number of Il-6 possessing TAM and the proliferation of lymphoma cells in only the non-Hodgkin's lymphomas. Our results suggest a paracrine tumor growth stimulating mechanism which is created by a self perpetuating cytokine production loop. A supposed cytokine produced by neoplastic cells dependent from their proliferative activity may induce Il-6 secretion by TAM. Il-6 in turn may stimulate the proliferation of the lymphoma cells without maturation thus leading to a self-sustaining growth.

Antibodies↗
PubMed1992

Influence of T-actemodulin on herpes simplex virus infection.

The aim of the investigation was to study the direct influence of T-actemodulin (TAM) on the Herpes Simplex Virus (HSV) infection in vitro and in vivo. HSV-1 (strain Vic) and HSV-2 (strain Nissa) were used in the experiments in vitro. The experiments were performed using multicycle and singlecycle growth tests. Seventy-five patients suffering from HSV infections (labialis and genitalis) were locally treated by 0.04% TAM-containing hydrophilic gel or water-washable cream (applied every 3 h). The results showed that TAM: decreased the infectious virus titre; reduced the infectious virus yield at the end of the single cycle of the virus replication; prolonged the latent period; and exerted an irreversible inhibitory effect on the infectious virus titre when applied at immediate early intervals after the infection. No relapses were observed in 84% of the patients treated with TAM. Eight percent of the patients were with only reduced relapses and in 8% of the patients TAM had a mild effect. TAM exerted a preventive effect against the disease when the treatment was initiated in the period of paresthesia.

Administration, Topical↗
PubMed1992

Different patterns of macrophage infiltration into allogeneic-murine and xenogeneic-human neoplasms growing in nude mice.

This study determined the distribution pattern of tumor-associated macrophages (TAM) in murine and human neoplasms growing subcutaneously in nude mice. Seven different human neoplasms (cancers of the breast, kidney, colon, prostate, lung, and skin, and a melanoma) and five different murine neoplasms (carcinomas of the lung, colon, and kidney, melanoma, and fibrosarcoma) were injected into nude mice. The murine tumors also were injected into syngeneic mice. Tumor-associated macrophages in small and large tumors were studied immunohistochemically by the use of several antibodies, including the macrophage-specific F4/80. The pattern of TAM distribution differed between mouse and human tumors. Regardless of histologic classification, TAM were uniformly distributed throughout all the murine neoplasms growing in syngeneic or nude mice. In the human neoplasms, TAM were found on the periphery of the lesions and in association with fibrous septae. The distribution of TAM in murine and human tumors was associated with a pattern of vascularization as determined by antibodies to basement membrane collagen type IV. Because the pattern of TAM distribution in neoplasms influences their antitumor activity, the data question the validity of the nude mouse model for the study of macrophage infiltration into human neoplasms.

Animals↗