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Biomedical subjects

Jorge Meléndez-Zajgla

Publications and source records attributed to Jorge Meléndez-Zajgla.

5 recordsLinked to original sources

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↗

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↗

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↗

[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↗