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Biomedical subjects

M G Alvarez

Publications and source records attributed to M G Alvarez.

17 recordsLinked to original sources
PubMed2003

Increased gap junctional intercellular communication is directly related to the anti-tumor effect of all-trans-retinoic acid plus tamoxifen in a human mammary cancer cell line.

Additive effects against tumor cells might be achieved by combining anti-neoplastic agents directed against one or more altered mechanisms in cancer. We investigated the participation of gap junctional intercellular communication (GJIC), which is commonly dysfunctional in tumor cells as a possible mediating mechanism of the effect of all-trans-retinoic acid (RA) and tamoxifen (Tx) in MCF-7 human breast cancer cell lines. The combination of RA + Tx stimulated GJIC in approximately 53 +/- 3% of MCF-7 cells as early as after 6 h of treatment remaining communicated through 144 h of culture. The GJIC enhancement occurred along with immunolocalization of Cx26 and 43 at the membrane of contacting cells and correlated with higher protein levels. Cx40 immunoreactive plaques were detected at cell-to-cell contacts during 48 h of RA + Tx treatment that did not involve higher protein expression, to the contrary, a downregulation occurred after 72 h of treatment. Cell proliferation inhibition upon RA + Tx exposure was observed with optimal effects at 96-120 h of culture with an accumulation of cells primarily in G2/M and G0/G1 cell cycle boundaries. An enhancement of the pre-existing E-cadherin levels was observed after drug exposure along with a downregulation of Bcl-2 and C-myc protein levels and a reduction of telomerase activity, suggesting partial tumor phenotype reversion. Blockage of the RA + Tx-induced GJIC with 18-beta-glycyrrhetinic acid (beta-Gly) prevented in 34% the inhibition of MCF-7 proliferation and the E-cadherin increment in 30% at 96 h of culture. GJIC blockage did not alter the downregulation of Bcl-2, c-Myc, or telomerase activity induced by RA + Tx. Our results showed the participation of GJIC as a mediator mechanism of the combined action of RA and Tx in MCF-7 cells. The chemopreventive modulation of GJIC might represent an approachable alternative for the improvement of cancer therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Physiological parameters and biodistribution of 5,10,15,20-tetra (4-methoxyphenyl) porphyrin in rats.

Physiological parameters on hepatic and renal functionality and biodistribution, accumulation and elimination, in different organs of the 5,10,15,20-tetra (4-methoxyphenyl) porphyrin (TMP) were determined in Wistar rats. The transport of TMP by low-density (LDL) and high-density lipoproteins (HDL) was also investigated. The photosensitizer is accumulated in the spleen, where its concentration is significantly increased 21 d post-injection; it also accumulates in the liver and in a lower proportion, in the duodenum, and poorly in brain and muscle. The urine and serum biochemical parameters reached normal values both in control and treated groups. The glomerular filtrate rate was not affected by the TMP treatment in any of the studied times. These results would indicate that the sensitizer does not modify the renal glomerular function. TMP is mainly eliminated from the organism via the bile-gut pathway. Considering the total amount of porphyrin bound to both lipoproteins (LDL and HDL) in comparison with the total value of the TMP in serum, it can be inferred that a large amount of the agent is transported by lipoproteins in the plasma. This study proves information about the behavior of TMP in vivo under dark conditions. The results can be used to design photodynamic treatments using this porphyrin model as the sensitizer.

Animals↗
PubMed2001

Photodynamic activity of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin on the Hep-2 human carcinoma cell line: effect of light dose and wavelength range.

The photodynamic activity of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) has been investigated in two systems: reverse micelles of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/water-bearing photooxidizable substrates and on a Hep-2 human carcinoma cell line. The effect of variation in the light dose and wavelength range (360-800, 455-800, and 590-800 nm) was compared in both media. The aerobic singlet oxygen-mediated photooxidation of L-tryptophan (Trp) was used as a model of biological substrate in a micellar system. A considerable increase of the observed rate constants of Trp (k(Trp)(obs)) was noted, increasing the irradiated area of the TMP spectrum. In vitro, the survival curves of Hep-2 cells, treated with TMP, were markedly dependent on the light wavelength ranges used for irradiation. A linear behavior between k(Trp)(obs) and the photoinactivation rate of Hep-2 cells was found, indicating that the singlet oxygen (1O2 ) is the main species responsible for cell inactivation. These results contributed to an understanding of the photodynamic process yielded by this porphyrin in vitro and the sensitivity of Hep-2 cells to photodamage.

Animals↗
PubMed2001

Synthesis and biological evaluation of methoxyphenyl porphyrin derivatives as potential photodynamic agents.

A new meso-2,4,6-trimethoxyphenyl porphyrin covalently linked to a 2',6'-dinitro-4'-trifluoromethylphenyl group by an amine bond 5 and its metal complex with Cd(II) 6 was prepared. The photodynamic activities of 5 and 6 were evaluated in vitro on Hep-2 cells. A considerable increase in the photocytotoxic effect was found for 6, which has higher singlet molecular oxygen, O(2)((1)Delta(g)), production.

Humans↗
PubMed2001

Photodynamic studies of metallo 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin: photochemical characterization and biological consequences in a human carcinoma cell line.

The photodynamic activities of the free-base 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) and their metal complexes with zinc(II) (ZnTMP), copper(II) (CuTMP) and cadmium(II) (CdTMP) have been compared in two systems: reverse micelle of n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate/water bearing photooxidizable substrates and Hep-2 human larynx carcinoma cell line. The quantum yields of singlet molecular oxygen, O2(1 delta g), production (phi delta) of TMP, ZnTMP and CdTMP in tetrahydrofuran, were determined yielding values of 0.65, 0.73 and 0.73, respectively, while O2(1 delta g) formation was not detected for CuTMP. In the reverse micellar system, the amino acid L-tryptophan (Trp) was used as biological substrate to analyze the O2(1 delta g)-mediated photooxidation. The observed rate constants for Trp photooxidation (kobsTrp) were proportional to the sensitizer quantum yield of O2(1 delta g). A value of approximately 2 x 10(7) s-1 M-1 was found for the second-order rate constant of Trp (krTry) in this system. The response of Hep-2 cells to cytotoxicity photoinduced by these agents in a biological medium was studied. The Hep-2 cultures were treated with 1 microM of porphyrin for 24 h at 37 degrees C and the cells exposed to visible light. The cell survival at different light exposure levels was dependent on phi delta. Under these conditions, the cytotoxic effect increases in the order: Cu-TMP << TMP < ZnTMP approximately CdTMP, correlating with the production of O2(1 delta g). A similar behavior was observed in both the chemical and biological media indicating that the O2(1 delta g) mediation appears to be mainly responsible for the cell inactivation.

Cell Survival↗
PubMed2000

Expression of Fas antigen and apoptosis caused by 5,10,15, 20-tetra(4-methoxyphenyl)porphyrin (TMP) on carcinoma cells: implication for photodynamic therapy.

The photodynamic effects of 5,10,15, 20-tetra(4-methoxyphenyl)porphyrin (TMP) on a Hep-2 cell line were investigated. TMP toxicity in the dark and in relation to illumination with visible light was examined. Hep-2 cells were treated with different TMP concentrations (1, 5 and 10 microM). The uptake of TMP by Hep-2 cells increased with TMP concentration and an increase of the initial uptake rate was observed with increasing TMP concentrations. However, after 24 h of incubation, a similar value of intracellular TMP concentration was reached at all three concentrations of TMP added. Cell toxicity induced by TMP was analyzed in the dark at different concentrations of the photosensitizer and at several incubation periods. The cell mortality obtained after exposure of the cell cultures to visible light was exclusively due to the photosensitization effect of TMP produced by light irradiation. Staining with the hematoxylin-eosin method demonstrated that treatment with TMP, followed by exposure to visible light, notably increased the apoptotic figures. Fas antigen was only expressed in these conditions. The results contribute to the understanding of the photodynamic therapy (PDT) mechanism produced by TMP on Hep-2 carcinoma cell line.

Apoptosis↗
PubMed2000

Molecular basis of cancer and clinical applications.

This article attempts to show the vertiginous advances that exist today in the concept of what cancer is. The authors chose some multiple biologic concepts that have enabled the progress in the knowledge of this disease to occur at a speed no one could imagine until recently. Although the areas and biologic problems that remain to be solved are more numerous and complex than they expected, the basic fundamentals already partially understood and the multidisciplinary integration of the various medical specialties with biomolecular research enable physicians to face the next millennium with great optimism about the possibilities of therapeutic success, prevention, and effective early diagnosis.

Apoptosis↗
PubMed2000

Effects of alpha-difluoromethylornithine on the Fas expression and apoptosis in Hep-2 cells.

DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis, and has been shown to induce apoptosis. In this paper, the relation between the effects of DFMO on the polyamine content, apoptotic index and Fas expression in HEP-2 cells was determined. Fas is a type I membrane protein with a molecular mass of 45 kDa, which mediates apoptosis. The results suggest that the treatment with the polyamine inhibitor DFMO induced the expression of the surface antigen Fas, which could be responsible for trigger apoptosis in these cells.

Apoptosis↗
PubMed1998

GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier.

The high metabolic requirements of the mammalian central nervous system require specialized structures for the facilitated transport of nutrients across the blood-brain barrier. Stereospecific high-capacity carriers, including those that recognize glucose, are key components of this barrier, which also protects the brain against noxious substances. Facilitated glucose transport in vertebrates is catalyzed by a family of carriers consisting of at least five functional isoforms with distinct tissue distributions, subcellular localizations and transport kinetics. Several of these transporters are expressed in the mammalian brain. GLUT-1, whose sequence was originally deduced from cDNAs cloned from human hepatoma and rat brain, is present at high levels in primate erythrocytes and brain endothelial cells. GLUT1 has been cloned and positionally mapped to the short arm of chromosome 1 (1p35-p31.3; refs 6-8). Despite substantial metabolic requirements of the central nervous system, no genetic disease caused by dysfunctional blood-brain barrier transport has been identified. Several years ago, we described two patients with infantile seizures, delayed development and acquired microcephaly who have normal circulating blood glucose, low-to-normal cerebrospinal fluid (CSF) lactate, but persistent hypoglycorrachia (low CSF glucose) and diminished transport of hexose into isolated red blood cells (RBC). These symptoms suggested the existence of a defect in glucose transport across the blood brain barrier. We now report two distinct classes of mutations as the molecular basis for the functional defect of glucose transport: hemizygosity of GLUT1 and nonsense mutations resulting in truncation of the GLUT-1 protein.

Animals↗
PubMed1991

Contribution of glutathione and glutathione-dependent enzymes in the reversal of adriamycin resistance in colon carcinoma cell lines.

Four human colon cancer cell lines (SW620, LS 180, DLD-I, and HCT-15) and sub-lines isolated in vitro by selection with Adriamycin were studied for reversal of intrinsic and acquired Adriamycin resistance, using buthionine sulfoximine (BSO) to deplete cellular glutathione alone and in combination with the P-glycoprotein antagonist verapamil. GSH levels varied among the parental cell lines but did not increase with resistance. In the parental SW620, DLD-I and HCT-15 and their drug-resistant derivatives, there was no relation between the effect of the glutathione-depleting agent BSO, the mRNA expression of both selenium-dependent glutathione peroxidase (GPx) and glutathione S-transferase pi (GST pi), bulk glutathione S-transferase (GST) activity, and the degree of resistance. However, in LS 180 and its derivative sub-lines, which do not principally rely on P-glycoprotein (Pgp) for Adriamycin resistance, treatment with BSO demonstrated a relatively diminished GSH depletion and enhanced recovery. In comparison with the other acquired cell lines, BSO specifically reversed acquired resistance in the LS 180 Adriamycin-resistant subline (LS 180 Ad150) after short-term drug exposure. Furthermore, the LS 180 Ad150 cells demonstrated an increase in both GPx and GST pi mRNA expression. These observations suggest that glutathione-mediated detoxification of Adriamycin may play a role in the resistance of this sub-line. Verapamil enhanced Adriamycin cytotoxicity 1.2- to 12-fold in the intrinsically resistant cells and as much as 15-fold in cell lines with acquired resistance. Combination of BSO with verapamil resulted in additive, but not synergistic, reversal of resistance. The results underscore the complex nature of Adriamycin resistance, and suggest a role for drug-resistance-modulating agents in the treatment of colon carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1984

[Gastrointestinal involvement in progressive systemic sclerosis].

25 patients with clinical, radiological and manometrical features of PSS in the gastrointestinal tract were reviewed, looking mainly for the esophageal involvement. All of the data obtained in our serie agreed with those of most of the authors. Outlining: The lack of relationship between the evolution of the skin involvement and GI tract involvement. The high incidence of esophageal involvement, especially functional alterations even in the absence of clinical and/or radiological symptomatology. The usefulness of manometric method in the diagnosis of motor involvement of esophages, especially for the evaluation of lower esophageal esphincter. Although the esophageal and intestinal involvement are more frequent and well known, any area of the GI tract may be damaged during the course of this disease. Since up to now, an ethiological therapy to stop the course of the disease is not known, it's important to search for earlier alterations in order to start with a pathophysiological and symptomatic treatment to avoid complications.

Digestive System↗
PubMed1978

Evaluation of job applicants: the effects of age versus success.

177 participants evaluated female job applicants on the basis of a transcript of a job interview. One-half of the participants were told that the applicant was 63, one-half that the applicant was 24. Success or failure in obtaining the job was also manipulated. In addition, participants' scores on an attitude scale were compared to their assessment of the job applicants. There were no clear differences in evaluation of young and old applicants. Scores on the attitude scale were also unrelated to these evaluations. However, female participants rated the older applicants more positively than did males. In addition, knowledge of the outcome of the interview affected ratings. Regardless of age, people who were hired were rated more positively than those who were not. These results are disucssed in terms of implications for future studies of attitudes toward the elderly.

Adult↗
PubMed1975

Electronic tonometry in the newborn.

Mackay-Marg electronic tonometry was performed without any kind of drugs in 604 eyes of newborn babies (up to 4 days of age). The first 100 cases were eliminated from the sample due to the significantly higher intraocular pressures obtained, attributed to small number of tonometries in each eye. The decision is fully discussed. The remaining cases (504 eyes) gave a mean of 12.41 mm Hg and a standard deviation of 2.58. The most important finding was the extreme and continuous variations found in newborn intraocular pressure; some hypotheses are discussed in this regard. The concept of 'basal intraocular pressure' is introduced to use the lowest intraocular pressure as a more homogenous comparative level than the ones previously used. Standardized anesthetic procedure is recommended for baby tonometry. While the possibilities of the Mackay-Marg electronic tonometer are recognized, the Goldmann tonometer (manual model) is found to be more reliable for clinical decisons in babies.

Adult↗