PubMed Health⌕ Search

Biomedical subjects

Vilma Maldonado

Publications and source records attributed to Vilma Maldonado.

10 recordsLinked to original sources
PubMed2006

High Smac/DIABLO expression is associated with early local recurrence of cervical cancer.

BACKGROUND: In a recent pilot report, we showed that Smac/DIABLO mRNA is expressed de novo in a subset of cervical cancer patients. We have now expanded this study and analyzed Smac/DIABLO expression in the primary lesions in 109 cervical cancer patients. METHODS: We used immunohistochemistry of formalin-fixed, paraffin-embedded tissue sections to analyze Smac/DIABLO expression in the 109 primary lesions. Seventy-eight samples corresponded to epidermoid cervical cancer and 31 to cervical adenocarcinoma. The median follow up was 46.86 months (range 10-186). RESULTS: Smac/DIABLO was expressed in more adenocarcinoma samples than squamous tumours (71% vs 50%; p = 0.037). Among the pathological variables, a positive correlation was found between Smac/DIABLO immunoreactivity and microvascular density, a marker for angiogenesis (p = 0.04). Most importantly, Smac/DIABLO immunoreactivity was associated with a higher rate of local recurrence in squamous cell carcinoma (p = 0.002, log rank test). No association was found between Smac/DIABLO and survival rates. CONCLUSION: Smac/DIABLO expression is a potential marker for local recurrence in cervical squamous cell carcinoma patients.

Adenocarcinoma↗
PubMed2006

NF-kappaB does not influence the induction of apoptosis by Ukrain.

Ukrain is a reaction product of different alkaloids from Chelidonium majus L. (celandine) conjugated with thiophosphoric acid. It has immunoregulatory effects on T lymphocyte subsets and cytotoxic and cytostatic effects on various malignant cells. Although Ukrain has been reported to induce alterations in the cell cycle and tubulin polymerization, the specific cellular target has not been described. Since antineoplasic agents induce NF-kappaB and their effects are regulated by this transcription factor, we investigated its possible participation in the apoptotic effects of Ukrain. Ukrain induced apoptosis in a panel of cancer cell lines by activating the intrinsic cell death pathway, as demonstrated by the cleavage of caspase 9 and the upregulation and cleavage of caspase 3. The effect was reversible, since long exposures (24 hours or more) were needed, as verified by clonogenic assays. Gene reporter assays showed that Ukrain activated NF-kappa B. Nevertheless, this activation was not required for, and did not modulate, the Ukrain effect: neither blockage of activation by a dominant negative version of Ikappa-B alpha or a Bcl-3 siRNA, nor activation of the pathway by overexpression of IKK2, changed the response to the drug. In conclusion, Ukrain induced apoptosis in HeLa cervical cancer cells by activating the intrinsic pathway. In contrast to other antineoplasic drugs, the effects of Ukrain were not regulated by NF-kappa B.

Antineoplastic Agents↗
PubMed2006

Inhibitors of apoptosis proteins in human cervical cancer.

BACKGROUND: It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of c-IAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer. METHODS: We used semiquantitative RT-PCR assays to analyze 41 cancer and 6 normal tissues. The study included 8 stage I cases; 16 stage II; 17 stageIII; and a control group of 6 samples of normal cervical squamous epithelial tissue. RESULTS: c-IAP2 and XIAP mRNA levels were similar among the samples, cervical tumors had lower c-IAP1 mRNA levels. Unexpectedly, a clear positive association was found between low levels of XIAP and disease relapse. A log-rank test showed a significant inverse association (p = 0.02) between XIAP expression and tumor aggressiveness, as indicated by disease relapse rates. There were no statistically significant differences in the presence or expression levels of c-IAP1 and c-IAP2 among any of the clinical variables studied. Survivin and its isoforms were undetectable in normal cervical tissues, in contrast with the clear upregulation observed in cancer samples. We found no association between survivin expression and age, clinical stage, histology or menopausal state. Nevertheless, we found that adenocarcinoma tumors expressed higher levels of survivin 2B and DeltaEx3 (p = 0.001 and p = 0.04 respectively, by Kruskal-Wallis). A multivariate Cox's partial likelihood-based analysis showed that only FIGO stage was an independent predictor of outcome. CONCLUSION: There are no differences in the expression of c-IAP2 and XIAP between normal vs. cancer samples, but XIAP expression correlate in cervical cancer with relapse of this disease in the patients. Otherwise, c-IAP1 was downregulated in the cervical cancer samples. The expression of survivin was upregulated in the patients with cervical cancer. We have found that adenocarcinoma presented higher levels of survivin isoforms 2B and DeltaEx3.

Adenocarcinoma↗
PubMed2006

External membrane vesicles from Helicobacter pylori induce apoptosis in gastric epithelial cells.

The Helicobacter pylori infection of gastric mucosa is one of the most common infectious diseases and is associated with a variety of clinical outcomes, including peptic ulcer disease and gastric cancer. Helicobacter pylori-induced damage to gastric mucosal cells is controlled by bacterial virulence factors, which include VacA and CagA. Outer membrane vesicles are constantly shed by the bacteria and can provide an additional mechanism for pathogenicity by releasing non-secretable factors which can then interact with epithelial cells. The present report shows that external membrane vesicles are able to induce apoptosis not mediated by mitochondrial pathway in gastric (AGS) epithelial cells, as demonstrated by the lack of cytochrome c release with an activation of caspase 8 and 3. Apoptosis induced by these vesicles does not require a classic VacA+ phenotype, as a negative strain with a truncated and therefore non-secretable form of this protein can also induce cell death. These results should be taken into account in future studies of H. pylori pathogenicity in strains apparently VacA-.

Apoptosis↗
PubMed2004

Oxaliplatin activity in head and neck cancer cell lines.

Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O'] platinum; Eloxatin) is a third-generation platinum compound with a 1,2-diaminocyclohexane (DACH) carrier ligand, which has a wide spectrum of anticancer activity in vitro systems and has displayed preclinical and clinical activity in a wide variety of tumors. To investigate its in vitro activity against head and neck cancer, we exposed two head and neck cancer cell lines to the compound, created a variant resistant to cisplatin to study cross-resistance to the compound and analyzed the potential radiosensitizing effect of the drug. We report here that oxaliplatin was cytotoxic at similar doses to cisplatin in these cells. There was no cross-resistance to cisplatin, as demonstrated by different IC50 values in these cell lines and the sensitivity to oxaliplatin of the cisplatin-resistant cell line. There was an effective radiosensitizer effect of the compound in either cell line. Additional in vitro and in vivo experimentation is warranted in order to support the use of oxaliplatin as a radiosensitizer in head and neck cancer patients.

Antineoplastic Agents↗
PubMed2004

Tissue inhibitor of metalloproteinases-2 growth-stimulatory activity is mediated by nuclear factor-kappa B in A549 lung epithelial cells.

Tissue inhibitors of metalloproteinases (TIMPs) are pleiotropic factors that function as key regulators of extracellular matrix remodeling. They exhibit multifunctional roles including cell growth-stimulating activities and protection from apoptosis. In the present study, we showed that human recombinant TIMP-2 (hrTIMP-2) promotes growth of A549 lung cells. This effect was accompanied by increase in nuclear factor-kappa B (NF-kappaB) activity 24h after exposure as determined by electrophoretic mobility shift assay (EMSA) analysis. This effect was correlated with downregulation of IkappaBalpha and beta proteins and later increases in Bcl-3, IkappaB, and cyclin D1 proteins. Blocking induction of NF-kappaB activity using a dominant-negative mutated version of IkappaBalpha abrogated NF-kappaB activation and cell proliferation.

B-Cell Lymphoma 3 Protein↗
PubMed2002

Estrogen receptor expression in giant cell tumors of the bone.

Giant cell tumors (GCTs) of the bone are primary skeletal neoplasms that behave intermediately between a true benign and an overtly malignant neoplasm. For two decades, controversial reports have found estrogen receptor (ER) expression in isolated cells or small numbers of samples from these tumors. In this report, we studied by immunohistochemistry 88 cases of GCTs and found that 51% of the samples expressed ER. Furthermore, we found that a subset of seven samples analyzed for ER expression by western blot was positive. To address whether the ER expressed in these samples could be functional, isolated cells were exposed to beta-estradiol and growth curves were generated. Exposure of cells to beta-estradiol induced a small but significant growth in the cells. These results strongly support that GCTs of the bone express functional ERs.

Blotting, Western↗
PubMedDate not supplied

[Caspases: apoptosis inducing molecules].

Caspases are key proteins for the transduction and ejection of the apoptotic signals induced by several stimuli. These proteins are present within the cell as inactive precursors that need a proteolytic cleavage in order to be active. There are two main caspases group, the initiators and executors. The formers are activated by autoproteolysis when translocated to specific cell compartments or trough the coupling of adapters and or activators. The executors caspases are activated by cleavage of an initiator caspase. These proteases are responsible then for the final cleavage of diverse substrates that mediate the morphologic changes during apoptosis. Among these there are signalization, DNA repairing, structure, transcription proteins, etc. Caspases represent a new paradigm in the signal transduction pathway, and are implicated in a large number of physiologic and pathologic processes. In a near future they could be useful pathologic markers and therapeutic targets.

Animals↗
PubMedDate not supplied

Tissue inhibitor of metalloproteinases-4 is expressed in cervical cancer patients.

BACKGROUND: Tissue Inhibitors of Metalloproteinases (TIMPs) play a critical role in extracellular matrix remodeling, which is involved in tumor growth and metastasis. Elevated TIMP levels are reported in association with cancer progression. In particular, it has been shown that TIMP-1 and -2 levels are increased in cervical cancer patients. We analyzed, for the first time, TIMP-4 expression in cervical tumor samples. MATERIALS AND METHODS: Semiquantitative RT-PCR was performed in 26 tumor and 6 normal cervical samples. RESULTS: The study included 32 samples, 7 IB samples, 9 IIB samples, 10 IIIB samples and a control group (n =6) of normal cervical squamous epithelial tissues. Whereas none of the control samples expressed TIMP-4, 24 (88%) of the 26 cervical cancer samples expressed the inhibitor. Higher TIMP-4 levels were found in advanced stage disease (p=0.016, Chi-square test). CONCLUSION: TIMP-4 is expressed de novo in cervical cancer. Higher inhibitor expression levels were found in stages II and III.

Adult↗