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A Villanueva

Publications and source records attributed to A Villanueva.

At least 19 recordsLinked to original sources
PubMed2006

Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer.

Nuclear functions for IkappaB kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm. In these tumors, IKKalpha associates to the chromatin of specific Notch targets, leading to the release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing dominant negative IKKalpha restores the association of SMRT with Notch target genes, resulting in specific gene repression. Finally, BAY11-7082 significantly reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude mice.

Animals↗
PubMed2006

Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo.

Ceramidases (CDases) play a key role in cancer therapy through enhanced conversion of ceramide into sphingosine 1-phosphate (S1P), but their involvement in hepatocarcinogenesis is unknown. Here, we report that daunorubicin (DNR) activated acid CDase post-transcriptionally in established human (HepG2 cells) or mouse (Hepa1c1c7) hepatoma cell lines as well as in primary cells from murine liver tumors, but not in cultured mouse hepatocytes. Acid CDase silencing by small interfering RNA (siRNA) or pharmacological inhibition with N-oleoylethanolamine (NOE) enhanced the ceramide to S1P balance compared to DNR alone, sensitizing hepatoma cells (HepG2, Hep-3B, SK-Hep and Hepa1c1c7) to DNR-induced cell death. DNR plus NOE or acid CDase siRNA-induced cell death was preceded by ultrastructural changes in mitochondria, stimulation of reactive oxygen species generation, release of Smac/DIABLO and cytochrome c and caspase-3 activation. In addition, in vivo siRNA treatment targeting acid CDase reduced tumor growth in liver tumor xenografts of HepG2 cells and enhanced DNR therapy. Thus, acid CDase promotes hepatocarcinogenesis and its antagonism may be a promising strategy in the treatment of liver cancer.

Animals↗
PubMed2006

Systematic review: evidence-based management of hepatocellular carcinoma--an updated analysis of randomized controlled trials.

The treatment strategy of hepatocellular carcinoma applied following scientific guidelines is only supported by 77 randomized controlled trials published so far, a figure that clearly pinpoints hepatocellular carcinoma as an 'orphan' cancer in terms of clinical research when compared with other high-prevalent cancers worldwide. A systematic review analysing 61 randomized controlled trials (1978-2002) showed a modest survival benefit from chemoembolization in patients with intermediate tumours, and the lack of an effective first-line treatment option for patients with advanced disease. These conclusions have been endorsed by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. The present updated evidence-based approach includes 16 randomized controlled trials published from 2002 to 2005 assessing percutaneous ablation (seven), other loco-regional therapies (three) and systemic therapies (six). Eight showed high-quality methodological profiles. Four randomized controlled trials demonstrated a better local hepatocellular carcinoma control in tumours larger than 2 cm treated by radiofrequency ablation compared with ethanol injection. No survival advantages were obtained from systemic treatments in patients with advanced hepatocellular carcinoma, an area that is an unmet need. Therefore, there is an urgent request to conduct well-designed phase III investigations in hepatocellular carcinoma patients.

Carcinoma, Hepatocellular↗
PubMed2005

Morphological criteria to distinguish cell death induced by apoptotic and necrotic treatments.

We present a comparative study of apoptotic and necrotic morphology (light and scanning electron microscopy), induced by well known experimental conditions (photodynamic treatments, etoposide, hydrogen peroxide, freezing-thawing and serum deprivation) on cell cultures. Our results indicate that morphological criteria (apoptotic cell rounding and shrinkage, and appearance of membrane bubbles in early necrosis) allow to distinguish these cell death mechanisms, and also show that, independently of the damaging agents, the necrotic process occurs in a characteristic sequence (coalescence of membrane bubbles in a single big one that detaches from cells remaining on the substrate).

Apoptosis↗
PubMed2005

Safety of percutaneous ethanol injection as neoadjuvant therapy for hepatocellular carcinoma in waiting list liver transplant candidates.

UNLABELLED: Orthotopic liver transplantation (OLT) as therapy of hepatocellular carcinoma (HCC) improves the survival of a selected group of patients. Unfortunately, the progressive increase in waiting time for OLT may allow tumor progression. Percutaneous ethanol injection (PEI) has been proposed as neoadjuvant therapy for HCC in patients awaiting OLT, but its safety has not been defined. PATIENTS AND METHODS: During a 60-month period, 34 patients (27 men, overall mean age of 58.5 years, range 41-67) with HCC, were listed for OLT. Ultrasonography-guided PEI was delivered into 39 nodules at 117 sessions on an inpatient basis. Written informed consent was obtained from all patients before PEI. Doppler-ultrasonography was done before PEI, immediately after, and 4 weeks later. Noninvasive monitoring of arterial pressure, cardiac rate, and temperature was performed during the procedure and during a 24-hour period after each session. Pain was considered significant if analgesia was required or discontinuation of PEI necessary. Fever was defined as a temperature > or =37.5 degrees C after PEI. RESULTS: Minor complications included pain in 45 sessions (38.5%), fever in 17 (14.5%), arterial hypertension in 14 (12%), hypotension in 7 (7%), and vomiting in 2 (1.7%). The major complications were segmental liver infarction (n = 3), portal branch venous thrombosis (n = 2), ascites (n = 2), and one case each of subcapsular hematoma, duodenal ulcer, pneumonia, hepatic encephalopathy, and hepatic artery thrombosis. In all cases, clinical outcomes were favorable with conservative treatment. No evidence of tumor seeding in the needle track was reported and no PEI-related mortality observed. CONCLUSIONS: PEI is a safe neoadjuvant therapy for HCC on waiting list liver transplant candidates. In our series, pain and self-limited fever were the most frequent complications. Clinically significant severe complications were uncommon, and nonconservative treatments were not required.

Administration, Cutaneous↗
PubMed2005

[Sentinel node in tumours of the lip and the oral cavity].

OBJECTIVES: This study shows the results obtained by the application of the sentinel node (SN) in oral and lip cancer and performs a lymphatic map of these tumours. PATIENTS AND METHOD: We prospectively studied 14 patients with lip and oral tumours, all of them N0. We injected colloidal particles of serum albumin labeled with Tc-99 peritumoraly and we located the SN intraoperatively. The SN was then sent for anatomopathological study. RESULTS: Sentinel node was identified in all of the patients. In 11 of them the sentinel node was negative for metastases and correctly predicted the status of the neck. In 3 patients the sentinel node was the only node that contained metastases. There were no false negatives. The sensibility of the technique was 100%. CONCLUSIONS: The results showed that this technique is a feasible method for tumours in these locations and can avoid neck dissections in N0 patients.

Adult↗
PubMed2004

[Phimosis].

Explore the source record for details and available documents.

Circumcision, Male↗
PubMed2004

Congenital self-healing reticulohistiocytosis: report of a case and review of the literature.

UNLABELLED: Congenital self-healing reticulohistiocytosis (CSHRH), a rare disorder initially seen at birth or in the newborn period, is characterized by spontaneously involuting skin lesions. We present the case of a 12-d-old female who was born with many red-brownish nodules scattered over her entire body, and which regressed spontaneously. CONCLUSION: Although there are no clues to differentiate CSHRH from Letterer-Siwe disease, some signs and symptoms might enable us to reach an accurate diagnosis. A long-term follow-up to detect evidence of relapse or progression of the disease would be well advised.

Female↗
PubMed2004

Necrotic cell death induced by photodynamic treatment of human lung adenocarcinoma A-549 cells with palladium(II)-tetraphenylporphycene.

In this study we describe photodamaging and photokilling effects of palladium(II)-tetraphenylporphycene (PdTPPo) (previously incorporated into dipalmitoylphosphatidylcholine liposomes) on the human lung adenocarcinoma A-549 cell line. No dark cytotoxicity was found when the drug was applied at 10(-6) M or 5 x 10(-7) M for 1 or 18 h, respectively. After 1-h treatment with 10(-7) M or 5 x 10(-7) M PdTPPo followed by red light irradiation for variable times, dose-dependent lethal effects were observed in A-549 cells. Apoptosis was not found after the above photodynamic treatments or under even milder sublethal conditions. In contrast to HeLa cells subjected to PdTPPo photosensitization where either apoptosis or necrosis were induced, morphological analysis and electrophoretical DNA pattern of A-549 cells always revealed a clearly necrotic death mechanism. However, A-549 cells died by apoptosis after serum and L-glutamine deprivation, indicating that only the photodynamically induced apoptosis was inhibited. Immunofluorescent labeling revealed that microtubules and actin microfilaments were immediately and strongly damaged by photodynamic treatments with PdTPPo. No metaphase arrest and/or mitotic alterations were observed after phototreatments. Present results show that the cell type plays a fundamental role in relation to the apoptotic or necrotic response to photosensitization, and that cytoskeletal components are important targets implicated in cell death processes.

Actin Cytoskeleton↗
PubMed2003

Papillary squamous cell carcinoma of the oropharynx.

A case of papillary squamous cell carcinoma of the oropharynx is reported. The lesion was located in the base of the tongue and grossly presented a characteristic finger-like pattern of growth. The clinicopathological profile of the neoplasm is presented and the differential diagnosis with other exophytic squamous cell carcinomas is discussed.

Adult↗
PubMed2003

[Preliminary results of the relevance the sentinel node in head and neck tumors].

OBJECTIVES: The objective of this study is to assess the value of the sentinel node (SN) in head and neck tumours and to create a lymphatic mapping of these tumors. PATIENTS AND METHODS: We prospectively studied 13 patients with head and neck tumours N0. We divided these patients in two groups depending on the location of the primary tumour. We injected colloidal particles of serum albumin labeled with Tc-99 peritumoraly and we located the SN intraoperatively. The SN was then sent for anatomopathological study. RESULTS: In the oropharynx and oral cavity group, with 5 patients, the SN correctly predicted the pathological status of the neck in all of them. In the group of larynx and hypopharynx, with 8 patients, in 6, the SN correctly predicted the pathological status of the neck. In 2 patients, the SN was negative for metastases but there were metastases in the neck dissection. CONCLUSIONS: This technique represents an advance over selective dissection as an accurate method of neck staging, but its value in this field remains unclear.

Aged↗
PubMed2003

The pesticide malathion induces alterations in actin cytoskeleton and in cell adhesion of cultured breast carcinoma cells.

We have studied the effects of the organophosphorous pesticide malathion on cell viability, actin cytoskeleton, cell adhesion complex E-cadherin/beta-catenin, and Rho and Rac1 GTPases from the human mammary carcinoma cell line MCF-7. Malathion induced cell lethality, determined by the MTT assay, depending on the treatment conditions. Cells incubated with low concentrations of malathion, 16-32 microg/ml, showed high survival rates (>95%) at any evaluated time (1-5 days), whereas complete cell lethality was found using 512 microg/ml and 5 days of treatment. Deep morphological changes were induced with high doses of 64 and 128 microg/ml, and long incubation time (5 days); cells showed perinuclear vacuoles, rounding, shrinkage, and a gradual loss of adhesion. These changes were related to a decrease in the expression of the adhesion molecules, E-cadherin and beta-catenin, and to the distribution and reactivity of actin microfilaments to TRITC-phalloidin. Disruption of microfilaments, accompanied by the collapse of actin to perinuclear region, were characteristic of cells with loss of adhesion. At lower concentrations, some cells presented deformations on the plasma membrane as lamellipodia-like structures, which were particularly evident from 32 to 128 microg/ml. Conversely, we observed an increase in the expression of Rho and Rac1 GTPases, modulators of actin cytoskeleton and cell adhesion.

Actins↗
PubMed2003

[Surgical treatment of nystagmus with horizontal torticollis].

PURPOSE: To study the effect of modified Anderson's procedure in nystagmus surgery with pure horizontal torticollis. METHOD: Retrospective study of 8 patients with nystagmus and pure horizontal torticollis that were surgically treated in our hospital in a 4 years period. Mean age of the sample was 9 years, SD 8.6 (range 4-30). Large bilateral recessions were made in the yoke rectus muscles that are responsible for the versions to obtain the null position. The amount of surgery was variable according to the torticollis intensity and the association of strabismus. Follow-up length ranged from 15 to 45 months (average 31.14, SD 11.55). RESULTS: Torticollis improved in all patients at the end of the study. A good result was achieved in 62.5% of the cases, with a residual torticollis inferior to 10 degrees. In two cases, severe torticollis improved to a moderate one (10-20 degrees ). Torticollis reversal occurred in one patient, who needed a second operation. Neither clinically significant ductions limitations, nor secondary strabismus were found. CONCLUSIONS: The modified Anderson's procedure was effective for treating moderate horizontal torticollis with nystagmus. Severe torticollis were not totally corrected. Large muscle recessions were not associated with clinically significant ductions limitations. There was not secondary strabismus (Arch Soc Esp Oftalmol 2003; 78: 481-486).

Adult↗
PubMed2002

Improving extracellular production of food-use enzymes from Aspergillus nidulans.

Filamentous fungi, and particularly those of the genus Aspergillus, are major producers of enzymatic activities that have important applications in the food and beverage industries. Prior to the availability of transformation systems improvement of industrial production strains was largely restricted to the strategy of mutagenesis, screening and selection. Aspergillus nidulans is a genetically amenable filamentous fungus the ease of handling and analysis of which has led to its use as a model system for the investigation of eukaryotic gene regulation. Although not used industrially it is able to produce a wide variety of extracellular enzymatic activities. As a consequence of half a century of study a considerable resource of characterised mutants has been generated in conjunction with extensive genetic and molecular information on various gene regulatory systems in this micro-organism. Investigation of xylanase gene regulation in A. nidulans as a model for the production of food-use extracellular enzymes suggests strategies by which production of these enzymes in industrially useful species may be improved.

Aspergillus nidulans↗
PubMed2002

Skeletal efficacy with parathyroid hormone in rats was not entirely beneficial with long-term treatment.

We report the consequences of prolonged treatment with recombinant human parathyroid hormone (1-34) (PTH) in male and ovariectomized female rats with mature skeletons. Intact male and osteopenic, ovariectomized, female F-344 rats were evaluated after 1 year of treatment with 0, 8, or 40 microg/kg/day s.c. PTH. Males and females were about 6 months of age at study initiation; females were ovariectomized (Ovx) for 5 weeks before initiation of PTH treatment. PTH did not affect the survival of either intact males or ovariectomized females. Qualitative histopathology showed expected changes associated with aging in kidneys and proximal tibiae, with no treatment-related anomalies after 1 year of PTH administration. PTH slightly increased the femoral length of ovariectomized females but not that of males. No significant differences in femoral length were observed between sham and Ovx controls. Proximal femora of the males and ovariectomized females given the high dose of 40 microg/kg showed 211 and 186% greater trabecular bone area, 118 and 94% greater cortical thickness, 170 and 189% greater trabecular number, and 321 and 404% greater connectivity (node-to-node struts) compared with respective vehicle controls. Increased trabecular and endocortical surface apposition coincided with a 78 and 70% loss of marrow space for males and females treated with PTH, respectively. Biomechanical strength (ultimate load) of the femoral neck increased by 73 and 76%, respectively, in males and ovariectomized females. Cortical bone analyses of the femoral midshaft showed 105 and 72% increases in bone mineral content, 67 and 55% increases in bone mineral density, and 22 and 10% increases in cross-sectional area for males and ovariectomized females, respectively, with altered shape of femora. Biomechanical analyses of the midshaft showed substantial increases in strength and stiffness but a reduction in ultimate strain, which was likely due to the altered geometry of the midshaft for PTH groups. Aging effects on strength of vertebra and femoral midshaft were reversed by PTH treatment. In summary, the 1-year treatment duration, which represents about 50% of lifetime, did not affect survival and was not associated with any treatment-related anomalies in the kidney or skeleton. PTH reversed the aging process in bones but not kidneys and substantially increased bone mass and strength to well beyond normally attained levels. However, compared with short-term studies reported previously, there seemed to be no advantages to extending PTH treatment to 12 months in rat bones.

Absorptiometry, Photon↗
PubMed2001

A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis.

Caspofungin is a new broad-spectrum antifungal drug. A multicenter, double-blind, randomized trial was conducted to assess the efficacy, safety, and tolerability of caspofungin relative to amphotericin B in adults with endoscopically documented symptomatic Candida esophagitis. By use of a modified intent-to-treat analysis, endoscopically verified clinical success was achieved in 74% (95% confidence interval [CI], 59%-86%) and 89% (95% CI, 72%-98%) of patients receiving caspofungin at 50 and 70 mg/day, respectively, and in 63% (95% CI, 49%-76%) of patients given amphotericin B at 0.5 mg/kg/day. Therapy was stopped because of drug-related adverse events in 24% of patients in the amphotericin B group and 4% and 7%, respectively, for the caspofungin groups. This report provides the first demonstration of clinical utility for an echinocandin compound. Caspofungin appeared in this study to be as effective as and better tolerated than amphotericin B for the treatment of esophageal candidiasis.

Adult↗
PubMed2001

jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans.

Although in vitro evidence suggests two c-Jun N-terminal kinase (JNK) kinases, MKK4 and MKK7, transactivate JNK, in vivo confirmation is incomplete. In fact, JNK deficiency may differ from the composite deficiency of MKK4 and MKK7 in Drosophila and mice. Recently, the Caenorhabditis elegans homolog of human JNK, jnk-1, and two MKK-7s, mek-1 and jkk-1, were cloned. Here we characterize jnk-1, which encodes two isoforms JNK-1 alpha and JNK-1 beta. A null allele, jnk-1(gk7), yielded worms with defective body movement coordination and modest mechanosensory deficits. Similarly to jkk-1 mutants, elimination of GABAergic signals suppressed the jnk-1(gk7) locomotion defect. Like mek-1 nulls, jnk-1(gk7) showed copper and cadmium hypersensitivity. Conditional expression of JNK-1 isoforms rescued these defects, suggesting that they are not due to developmental errors. While jkk-1 or mek-1 inactivation mimicked jnk-1(gk7) locomotion and heavy metal stress defects, respectively, mkk-4 inactivation did not, but rather yielded defective egg laying. Our results delineate at least two different JNK pathways through jkk-1 and mek-1 in C.elegans, and define interaction between MKK7, but not MKK4, and JNK.

Alternative Splicing↗