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Biomedical subjects

J Blanco

Publications and source records attributed to J Blanco.

At least 73 records · Page 4Linked to original sources
PubMed2001

The effect of mussel size, temperature, seston volume, food quality and volume-specific toxin concentration on the uptake rate of PSP toxins by mussels (Mytilus galloprovincialis Lmk).

The accumulation of paralytic shellfish poisoning (PSP) toxins by bivalves is a serious threat to public health all over the world. However, very little is known about the uptake kinetics of these toxins and the environmental factors that may modify this process. We have studied the effect of mussel size, temperature, seston volume, food quality, and volume-specific toxin concentration (VOSTOC), on the uptake rate of paralytic shellfish poisoning (PSP) toxins by mussels (Mytilus galloprovincialis), by means of a second order factorial experiment. Over a 3-day period, the mussels were fed artificial diets containing Alexandrium minutum AL1V (a PSP toxin producer), Tetraselmis suecica, Ensiculifera sp1 and silt, to the levels required by each treatment. Mussel size, seston volume and VOSTOC were found to be statistically significant when the total toxin accumulated per weight of wet tissue was considered. Mussel size affected the uptake negatively and latter two positively. The interactions, mussel size-VOSTOC and mussel size-food quality were also significant. The response was not linear as shown by the significance of the quadratic term of mussel size. Notwithstanding, when the PSP toxins accumulation per mussel was analysed, only one factor, the VOSTOC and the interactions, food quality-mussel size and food quality-seston volume, were found to be significant. VOSTOC was the most important factor in the accumulation of toxins, in our opinion, probably due to toxin assimilation being mainly regulated by the probability of contact between the toxins and the cellular walls of the digestive system. The size of the bivalve is also especially important because toxin concentration is usually calculated per weight of bivalve tissue and because the weight-specific ingestion increases with mussel size. The food quality, which was directly related to the assimilation of organic matter, had an inverse effect on toxin assimilation. In our opinion, this is probably due to the effect of inorganic particles in enhancing the disruption of Alexandrium cells. Temperature had no effect on the uptake rate except for the accumulation of the gonyautoxin GTX1.

Journal Article↗
PubMed2001

Does renal mass exert an independent effect on the determinants of antigen-dependent injury?

The aim of this retrospective study was to determine whether nephron mass may exert a direct, independent effect on immunological tolerance. To this end, data corresponding to patients transplanted with en block pediatric kidneys (EBPK) (n=48) were compared with those of renal transplants with a low risk of hyperfiltration (LRH) comprised of recipients of a kidney from young donors (age 5-40 years) (n=173), and transplants with a high risk of hyperfiltration (HRH) comprised of patients who had received a graft from an elderly donor (older than 55 years) (n=91). All the patients had been subjected to the same immunosuppressive treatment. The median follow-up period was 54 months (6-127 months). The EBPK group showed lowest serum creatinine and highest creatinine clearance levels at each follow-up time. The rate of proteinuria >500 mg/day was 5.7% in EBPK, 7.4% in LRH, and 27.3% in HRH (P=0.000). The incidence of acute corticoresistant rejection was minor in EBPK (7.0% in EBPK, 21.3% in LRH, and 23.3% in HRH; P=0.04). Logistic regression analysis showed that the type of transplant was predictive of acute corticoresistant rejection [RR 5.33 (95% confidence interval (CI) 1.15-24.62) for HRH and RR 4.75 (95%CI 1.06-21.27) for LRH, P=0.03]. Multivariate analyses for graft failure due to chronic rejection and for graft failure due to acute rejection according to Cox's regression analysis demonstrated that HRH transplant was a significant predictive variable of both types of failure [4.08 (95%CI 1.27-13.04) for graft loss due to chronic rejection and 8.69 (95%CI 1.69-44.67) for graft loss due to acute rejection]. The present stratification of data according to nephronal mass would appear to indicate that the greater the mass, the lower the incidence of both acute and chronic rejection. This finding lends support to the hypothesis that a large mass of transplanted tissue relative to recipient mass may dampen the immune response.

Adult↗
PubMed2001

Comodulation of CXCR4 and CD26 in human lymphocytes.

We provide convergent and multiple evidence for a CD26/CXCR4 interaction. Thus, CD26 codistributes with CXCR4, and both coimmunoprecipitate from membranes of T (CD4(+)) and B (CD4(-)) cell lines. Upon induction with stromal cell-derived factor 1alpha (SDF-1alpha), CD26 is cointernalized with CXCR4. CXCR4-mediated down-regulation of CD26 is not induced by antagonists or human immunodeficiency virus (HIV)-1 gp120. SDF-1alpha-mediated down-regulation of CD26 is not blocked by pertussis toxin but does not occur in cells expressing mutant CXCR4 receptors unable to internalize. Codistribution and cointernalization also occurs in peripheral blood lymphocytes. Since CD26 is a cell surface endopeptidase that has the capacity to cleave SDF-1alpha, the CXCR4.CD26 complex is likely a functional unit in which CD26 may directly modulate SDF-1alpha-induced chemotaxis and antiviral capacity. CD26 anchors adenosine deaminase (ADA) to the lymphocyte cell surface, and this interaction is blocked by HIV-1 gp120. Here we demonstrate that gp120 interacts with CD26 and that gp120-mediated disruption of ADA/CD26 interaction is a consequence of a first interaction of gp120 with a domain different from the ADA binding site. SDF-1alpha and gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize and in which ADA is not present. The physical association of CXCR4 and CD26, direct or part of a supramolecular structure, suggests a role on the function of the immune system and the pathophysiology of HIV infection.

Adenosine Deaminase↗
PubMed2001

Numerical chromosome abnormalities in the spermatozoa of the fathers of children with trisomy 21 of paternal origin: generalised tendency to meiotic non-disjunction.

The purpose of this study was the evaluation of aneuploidy frequencies in the spermatozoa of two fathers (DP-4 and DP-5) who had children with Down syndrome (DS) of paternal origin and in whom a previous sperm analysis by fluoresence in situ hybridisation (FISH) had suggested a generalised tendency to meiotic non-disjunction. Sperm samples were simultaneously hybridised with FISH probes for chromosomes 4, 13 and 22. Disomy frequencies for each of the chromosomes and diploidy frequencies were compared with data obtained from nine control donors. Both DS fathers had a statistically significant increase in the frequency of disomy for chromosomes 13 and 22. DP-5 also had an increased frequency of diploid spermatozoa. Our data suggest that the two DS fathers have a generalised susceptibility to meiotic non-disjunction and that acrocentric chromosomes seem to be more sensitive to such disturbance in the meiotic process.

Child↗
PubMed2001

Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: role of endothelin-1.

Using angiotensin II (AngII) type 1A receptor-deficient mice [AT1(-/-)], in which we induced protein overload nephropathy, we explored the potential implication of AngII and endothelin-1 (ET-1) in the tubulointerstitial damage because of persistent proteinuria. At day 7, AT1(-/-) showed marked proteinuria to a similar extent to that of wild-type mice (WT). However, at day14, AT1(-/-) had significantly less proteinuria, renal damage, transforming growth factor-beta, and matrix mRNA expression and mortality. AT1(-/-) also showed a significant diminution in the activation of the transcriptional factors nuclear factor-kappaB and AP-1. Unexpectedly, AT1(-/-) had a higher interstitial infiltration than WT. The administration of the angiotensin-converting enzyme inhibitor quinapril to WT caused a marked improvement in proteinuria and renal lesions, resembling that seen in untreated AT1(-/-). However, the interstitial infiltration persisted in AT1(-/-) when treated with quinapril. Because ET-1 may participate in the recruitment of mononuclear cells, we also studied the implication of this peptide. AT1(-/-) had a significantly higher ET-1 expression in tubular epithelial cells than WT. The administration of the dual ETA/ETB antagonist bosentan to AT1(-/-) considerably reduced the interstitial infiltrates. Bosentan also exerted a beneficial effect on proteinuria, renal lesions, and mortality in WT. These data show that in overload nephropathy, proteinuria and renal lesions are, to a large extent, AngII-dependent. The up-regulation of ET-1 in tubular epithelial cells in AT1(-/-), associated with interstitial infiltrates, suggests that the combination of drugs interfering with both vasopeptides may be of therapeutic interest in renal diseases with severe proteinuria and tubulointerstitial damage.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Systemic infusion of angiotensin II into normal rats activates nuclear factor-kappaB and AP-1 in the kidney: role of AT(1) and AT(2) receptors.

Recent studies have pointed out the implication of angiotensin II (Ang II) in various pathological settings. However, the molecular mechanisms and the AngII receptor (AT) subtypes involved are not fully identified. We investigated whether AngII elicited the in vivo activation of nuclear transcription factors that play important roles in the pathogenesis of renal and vascular injury. Systemic infusion of Ang II into normal rats increased renal nuclear factor (NF)-kappaB and AP-1 binding activity that was associated with inflammatory cell infiltration and tubular damage. Interestingly, infiltrating cells presented activated NF-kappaB complexes, suggesting the involvement of AngII in inflammatory cell activation. When rats were treated with AT(1) or AT(2) receptor antagonists different responses were observed. The AT(1) antagonist diminished NF-kappaB activity in glomerular and tubular cells and abolished AP-1 in renal cells, improved tubular damage and normalized the arterial blood pressure. The AT(2) antagonist diminished mononuclear cell infiltration and NF-kappaB activity in glomerular and inflammatory cells, without any effect on AP-1 and blood pressure. These data suggest that AT(1) mainly mediates tubular injury via AP-1/NF-kappaB, whereas AT(2) receptor participates in the inflammatory cell infiltration in the kidney by NF-kappaB. Our results provide novel information on AngII receptor signaling and support the recent view of Ang II as a proinflammatory modulator.

Angiotensin II↗
PubMed2001

Metastatic behavior of human breast carcinomas overexpressing the Bcl-x(L) gene: a role in dormancy and organospecificity.

The ability of metastatic cells to survive antiapoptotic signals may contribute to the organospecific-spread patterns of clinical metastasis and dormancy. MDA-MB-435 breast cancer cells (435/Bcl-x(L)), which overexpress the Bcl-x(L) gene, were labeled with the luciferase gene and injected orthotopically into homozygous athymic Balb/c (nude) mice to study the metastatic behavior of the breast cancer cells. The overexpression of Bcl-x(L) in tumors increased the overall metastatic burden in mice (bones, liver, kidneys, brain, lungs, and lymph nodes) in comparison with control tumors (435/NEO:luc) during the same time interval (ANOVA, p = 0.005). The principal differences after 110 days were found in bones, which had 1.5 x 10(5) +/- 1.2 x 10(5) tumor cell equivalents (p = 0.03), and lymph nodes, which had 7.0 x 10(6) +/- 6.0 x 10(6) tumor cell equivalents (p = 0.08). The analyses of light production by tissues at different times showed that cells from 435/NEO:luc and 435/Bcl-x(L).luc tumors were detectable in several organs by the second day after intramammary fat pad implantation. Although initially arriving at the target organs in similar numbers, 435/Bcl-x(L) cells developed more metastases than 435/Neo cells, indicating that the Bcl-x(L) gene might have a role in breast cancer dormancy, promoting survival of cells in metastatic foci. Thus, we suggest that overexpression of Bcl-x(L) could counteract the proapoptotic signals in the microenvironment and favor the successful development of metastasis in specific organs.

Analysis of Variance↗
PubMed2001

Hydrogen peroxide mediates vascular cell adhesion molecule-1 expression from interleukin-18-activated hepatic sinusoidal endothelium: implications for circulating cancer cell arrest in the murine liver.

The mechanism of intrasinusoidal arrest of circulating cancer cells, which is a critical step in liver metastasis, appears to be facilitated by tumor-derived proinflammatory factors that increase sinusoidal cell adhesion receptors for cancer cells. However, how this prometastatic microenvironment is up-regulated remains unknown. Using intrasplenically injected B16 melanoma (B16M) cells, we show that the expression of vascular cell adhesion molecule-1 (VCAM-1) significantly increased in hepatic sinusoidal endothelium (HSE) cells over physiologic baseline within the first 24 hours of metastatic cancer cell infiltration in the liver. This correlated with increased in vitro adhesion of B16M cells to HSE cells isolated from B16M cell-injected mice. In vivo VCAM-1 blockade with specific antibodies before B16M cell injection decreased sinusoidal retention of luciferase-transfected B16M cells by 85%, and metastasis development by 75%, indicating that VCAM-1 expression on tumor-activated HSE cells had a prometastatic contribution. Because VCAM-1 expression is oxidative stress-inducible, recombinant catalase was in vivo administered, resulting in a complete abrogation of both VCAM-1 expression and B16M cell adhesion increases in HSE cells isolated from B16M cell-injected mice. Catalase also abrogated the proadhesive response of HSE cells to B16M-conditioned medium (B16M-CM) in vitro, although this did not affect the concomitant release of major proinflammatory cytokines by HSE cells. HSE cells treated with B16M-CM released interleukin (IL)-18 via tumor necrosis factor-alpha (TNF-alpha)-dependent IL-1beta in vitro. In turn, H(2)O(2) production from B16M-CM-treated HSE cells was regulated by IL-18. Thus, liver-infiltrating B16M cells activated their adhesion to HSE through a sequential process involving TNF-alpha-dependent IL-1beta, which induced IL-18 to up-regulate VCAM-1 via H(2)O(2). The pivotal position of H(2)O(2) was further supported by the fact that incubation of HSE cells with nontoxic concentrations of H(2)O(2) directly enhanced VCAM-1-dependent B16M cell adhesion in vitro without proinflammatory cytokine mediation, which emphasizes the key role of oxidative stress in the pathogenesis of liver inflammation and metastasis.

Animals↗
PubMed2001

Meiotic behaviour of the sex chromosomes in three patients with sex chromosome anomalies (47,XXY, mosaic 46,XY/47,XXY and 47,XYY) assessed by fluorescence in-situ hybridization.

Meiotic studies using multicolour fluorescent in-situ hybridization (FISH) and chromosome painting were carried out in three patients with sex chromosome anomalies (47,XXY; 46,XY/47,XXY and 47,XYY). In the two patients with Klinefelter syndrome, although variable percentages of XXY cells (88.5 and 28.3%) could be found in the pre-meiotic stages, none of the abnormal cells entered meiosis, and all pachytenes were XY. However, the abnormal testicular environment of these patients probably resulted in meiotic I non-disjunction, and a certain proportion of post-reductional cells were XY (18.3 and 1.7%). The fact that none of the spermatozoa were XY also suggests the existence of an arrest at the secondary spermatocyte or the spermatid level. In the XYY patient, most (95.9%) premeiotic cells were XYY. The percentage of XYY pachytenes was 57.9%. The sex chromosomes were either in close proximity (XYY) or the X chromosome was separated from the two Ys (X + YY). A high proportion (42.1%) of post-reductional germ cells were XY. However, only 0.11% of spermatozoa were disomic for the sex chromosomes. In this case, the data suggest the existence of an arrest of the abnormal cells at the primary and the secondary spermatocyte or the spermatid level, giving rise to the continuous elimination of abnormal cells in the germ-cell line along spermatogenesis. The fact that the proportion of diploid spermatozoa was only increased in one of the three cases (XXY) is also suggestive of an arrest of the abnormal cell lines in these patients. The two apparently non-mosaic patients were, in fact, germ-cell mosaics. This suggests that the cytogenetic criteria used to define non-mosaic patients may be inadequate; thus, the risk of intracytoplasmic sperm injection in apparently non-mosaics may be lower than expected.

Adult↗
PubMed2001

Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be associated with emergence of syncytium-inducing variants in human immunodeficiency virus type 1-positive individuals.

Human immunodeficiency virus type 1 (HIV-1) primary infection is characterized by the use of CCR5 as a coreceptor for viral entry, which is associated with the non-syncytium-inducing (NSI) phenotype in lymphoid cells. Syncytium-inducing (SI) variants of HIV-1 appear in advanced stages of HIV-1 infection and are characterized by the use of CXCR4 as a coreceptor. The emergence of SI variants is accompanied by a rapid decrease in the number of T cells. However, it is unclear why SI variants emerge and what factors trigger the evolution of HIV from R5 to X4 variants. Interleukin-7 (IL-7), a cytokine produced by stromal cells of the thymus and bone marrow and by keratin, is known to play a key role in T-cell development. We evaluated IL-7 levels in plasma of healthy donors and HIV-positive patients and found significantly higher levels in HIV-positive patients. There was a negative correlation between circulating IL-7 levels and CD4(+) T-cell count in HIV-positive patients (r = -0.621; P < 0.001), suggesting that IL-7 may be involved in HIV-induced T-cell depletion and disease progression. IL-7 levels were higher in individuals who harbored SI variants and who had progressed to having CD4 cell counts of lower than 200 cells/microl than in individuals with NSI variants at a similar stage of disease. IL-7 induced T-cell proliferation and up-regulated CXCR4 expression in peripheral blood mononuclear cells in vitro. Taken together, our results suggest a role for IL-7 in the maintenance of T-cell regeneration and depletion by HIV in infected individuals and a possible relationship between IL-7 levels and the emergence of SI variants.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Concentrating versus non-concentrating reactors for solar photocatalytic degradation of p-nitrotoluene-o-sulfonic acid.

The photocatalytic oxidation of the non-biodegradable p-nitrotoluene-o-sulfonic acid (p-NTS) in homogeneous (photo-Fenton reactions) and heterogeneous (with TiO2) solutions has been studied at a pilot-scale under solar irradiation at the Plataforma Solar de Almeria (PSA). In this study two different reactors were tested: a medium concentrating radiation system (Heliomans, HM) and a non-concentrating radiation system (CPC). Their advantages and disadvantages for p-NTS degradation have been compared and discussed. The degradation rates obtained in the CPC collector are around three times more efficient than in the HM collectors. However, in both systems, 100% of the initial concentration of p-NTS was removed. Kinetic experiments were performed in both systems using TiO2 suspensions. During the photodegradation, the disappearance of p-NTS was followed by HPLC, the mineralization of the solution by the TOC technique, the evolution of NO3-, NO2-, and SO4(2-) concentration by ionic chromatography, the toxicity by the standard Microtox test, and the biodegradability by BOD5 and COD measurements. The obtained results demonstrated the utility of the heterogeneous catalysis (using TiO2 as catalyst) as a pretreatment method that can be followed by a biological process.

Benzenesulfonates↗
PubMed2001

A comparison of prototype compound parabolic collector-reactors (CPC) on the road to SOLARDETOX technology.

Solar photocatalytic detoxification of non-biodegradable chlorinated hydrocarbon solvents (NBCS) is carried out in different concentrating and non concentrating devices using TiO2 as a photocatalyst fixed on the inner surface of the reaction tubes or as a slurry catalyst which has to be removed from the treated water. The reaction is most effective using 200 mg/l of TiO2 as a slurry in a non concentrating CPC reactor. The concentrating parabolic trough reactor has a poor activity because of its minor irradiated reactor surface. Catalyst coated glass tubes are less efficient then the used slurry catalyst. Their advantage is that no catalyst has not to be removed from the treated water and there is no loss of activity during treatment. Yet their physical stability is not sufficient to be competitive to the slurry catalyst. Nevertheless the degradation results are very promising and will possibly lead to commercial applications of this technology.

Catalysis↗
PubMed2001

Giant cell arteritis and renal amyloidosis: report of a case.

Polymyalgia rheumatica and giant cell arteritis are rarely associated with renal diseases such as amyloidosis. Here is a case of a 72-year-old man, who developed some renal failure and a nephrotic syndrome while presenting clinical symptoms of giant cell arteritis. Percutaneous renal biopsy showed secondary amyloidosis, and temporal artery biopsy revealed some lesions which suggested temporal arteritis. In spite of aggressive steroid treatment, chlorambucil, and colchicine, the patient's renal function continued to deteriorate and the patient is now being given hemodyalisis.

Aged↗
PubMed2000

Apoptosis control in syncytia induced by the HIV type 1-envelope glycoprotein complex: role of mitochondria and caspases.

Syncytia arising from the fusion of cells expressing a lymphotropic HIV type 1-encoded envelope glycoprotein complex (Env) with cells expressing the CD4/CXC chemokine receptor 4 complex spontaneously undergo cell death. Here we show that this process is accompanied by caspase activation and signs of mitochondrial membrane permeabilization (MMP), including the release of intermembrane proteins such as cytochrome c (Cyt-c) and apoptosis-inducing factor (AIF) from mitochondria. In Env-induced syncytia, caspase inhibition did not suppress AIF- and Cyt-c translocation, yet it prevented all signs of nuclear apoptosis. Translocation of Bax to mitochondria led to MMP, which was inhibited by microinjected Bcl-2 protein or bcl-2 transfection. Bcl-2 also prevented the subsequent nuclear chromatin condensation and DNA fragmentation. The release of AIF occurred before that of Cyt-c and before caspase activation. Microinjection of AIF into syncytia sufficed to trigger rapid, caspase-independent Cyt-c release. Neutralization of endogenous AIF by injection of an antibody prevented all signs of spontaneous apoptosis occurring in syncytia, including the Cyt-c release and nuclear apoptosis. In contrast, Cyt-c neutralization only prevented nuclear apoptosis, and did not affect AIF release. Our results establish that the following molecular sequence governs apoptosis of Env-induced syncytia: Bax-mediated/Bcl-2-inhibited MMP --> AIF release --> Cyt-c release --> caspase activation --> nuclear apoptosis.

Apoptosis↗
PubMed2000

[Mediterranean diet improves low density lipoprotein susceptibility to oxidative modifications].

UNLABELLED: Most experts, specially from Anglo-Saxon countries, recommend a low fat diet in order to prevent cardiovascular diseases. However, mortality rate by ischemic cardiopathy is low in Mediterranean countries, probably because of the consumption of a Mediterranean diet, with a high level of monounsaturated fats provided by the olive oil. We have conducted this study in order to investigate the possible influence of this kind of diet on the oxidation of LDL in vitro, the key element for the development of atherosclerosis. PATIENTS AND METHODS: 41 healthy male subjects were submitted to three consecutive 4-week diets. The first was a saturated fat-rich diet (SAT diet, 38% fat, 20% saturated). This was followed by a low fat diet (NCEP-I, 28% fat, 10% saturated) and after that a Mediterranean diet (38% fat, 22% monounsaturated fat). Plasma levels of total cholesterol, LDL-c, HDL-c, triglycerides, apolipoproteins A-I and B, -tocopherol, and the in vitro susceptibility to oxidation of LDL particles. Both hypolipidemic diets produced a significant decrease in total cholesterol, LDL-c, and apo-B plasma levels. However, it was only the NCEP-I diet that revealed a decrease in the HDL-c. The shift from a saturated fat-rich diet, or a diet rich in carbohydrates, to a Mediterranean diet increased the resistance of LDL particles to oxidation increasing the lag time period (p < 0.038), and decreasing (p < 0.001) the progression rate of the curve of oxidation of LDL. Our results point out two positive consequences of the consumption of a Mediterranean diet by healthy young males, compared with the low fat diet recommended by most Anglo-Saxon experts. On the one hand, the Mediterranean diet increases HDL-c plasma levels, and on the other hand, it decreases the susceptibility of LDL to oxidation. This is why the Mediterranean diet must be recommended in order to prevent cardiovascular diseases.

Adult↗
PubMed2000

The HIV-1 gp120 inhibits the binding of adenosine deaminase to CD26 by a mechanism modulated by CD4 and CXCR4 expression.

HIV-1 external envelope glycoprotein gp120 inhibits adenosine deaminase (ADA) binding to its cell surface receptor in lymphocytes, CD26, by a mechanism that does not require the gp120-CD4 interaction. To further characterize this mechanism, we studied ADA binding to murine clones stably expressing human CD26 and/or human CD4, and transiently expressing human CXCR4. In this heterologous model, we show that both recombinant gp120 and viral particles from the X4 HIV-1 isolate IIIB inhibited the binding of ADA to wild-type or catalytically inactive forms of CD26. In cells lacking human CXCR4 expression, this gp120-mediated inhibition of ADA binding to human CD26 was completely dependent on the expression of human CD4. In contrast, when cells were transfected with human CXCR4 the inhibitory effect of gp120 was significantly enhanced and was not blocked by anti-CD4 antibodies. These data suggest that the interaction of gp120 with CD4 or CXCR4 is required for efficient inhibition of ADA binding to CD26, although in the presence of CXCR4 the interaction of gp120 with CD4 may be dispensable.

Adenosine Deaminase↗
PubMed2000

Metastatic burden in nude mice organs measured using prostate tumor PC-3 cells expressing the luciferase gene as a quantifiable tumor cell marker.

BACKGROUND: Sensitive procedures for quantitative measurement of tumor cell spread as a function of time and primary tumor size are necessary to generate models of metastasis and formulate therapies. METHODS: Prostate carcinoma cells PC-3.luc expressing the luciferase gene were intramuscularly inoculated in nude mice to generate experimental tumors. Metastatic cells in target organs were easily counted by their capacity to produce light. RESULTS: Tumor cells were very mobile and migrated to all the target organs examined: lymph nodes, brain, bone, lungs, liver, kidney, spleen, testicles, prostate, seminal vesicle, and scrotum. Organ colonization started very early, 14 days after inoculation, when primary tumors were very small and produced an amount of light equivalent to that generated by 2 x 10(4) tumor cells in vitro (tumor cell equivalents, TCEs). Tumor cell burden could be quantitatively described by power functions of time or primary tumor light-producing capacity. The ratio of metastatic TCEs to primary tumor TCEs clustered around organ characteristic values: 10(-3) for femur and lumbar lymph nodes, 10(-6) for the spleen, and 10(-3) for the added set of organs. CONCLUSIONS: Dispersal of PC-3 tumor cells from IM experimental tumors started early before the third week postinoculation and when primary tumors had 2 x 10(4) TCEs. Tumor cells were found widely spread in all the organs tested. The possibility of easily quantifying tumor cell burden should make this approach useful for the study of metastasis and the development of antimetastatic therapies.

Adenocarcinoma↗