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M De Las Heras

Publications and source records attributed to M De Las Heras.

11 recordsLinked to original sources
PubMed2006

In-situ demonstration of mitogen-activated protein kinase Erk 1/2 signalling pathway in contagious respiratory tumours of sheep and goats.

Ovine pulmonary adenocarcinoma (OPA) and enzootic nasal adenocarcinoma (ENA) are two contagious neoplastic diseases of secretory epithelial cells in the respiratory system of sheep and goats. Jaagsiekte sheep retrovirus (JSRV) is the aetiological agent of OPA, and enzootic nasal tumour virus (ENTV) is associated with ENA. The genomes of these retroviruses do not contain known oncogenes but products of the env gene are important in the generation of transforming stimuli. However, the cell signalling pathways activated in vivo are not completely understood. This study was based on the use of activation stage antibodies specifically detecting proteins of the extracellular signal regulated kinase Erk 1/2 cell signalling pathway and transcription factors. Tissue sections were collected from four natural cases of OPA, four experimentally induced OPA tumours, four ENA tumours in sheep, four ENA tumours in goats, two normal sheep lungs and two lungs with chronic inflammation. Routine immunohistochemical procedures with phosphorylation stage-specific antibodies were carried out. Representative proteins of the Erk1/2 pathway (Raf-1, Mek1/2 and p44/42MAPK) were activated in natural cases of OPA and ENA in sheep and goats and also in experimentally induced OPA. Transcription factors 90Rsk and Elk-1 were activated in OPA and ENA tumours. However, c-Myc was activated only in OPA tumours. In contagious respiratory neoplasms of sheep and goats the Erk1/2 pathway appears to be important for the in-vivo generation of the transforming stimuli.

Adenocarcinoma↗
PubMed2005

An influx of macrophages is the predominant local immune response in ovine pulmonary adenocarcinoma.

Infection with a retrovirus, Jaagsiekte sheep retrovirus (JSRV), causes ovine pulmonary adenocarcinoma (OPA). The excess production of surfactant proteins by alveolar tumour cells results in increased production of pulmonary fluid, which is characteristically expelled through the nostrils of affected sheep. The immune response to JSRV and the tumour is poorly understood: no JSRV-specific circulating antibodies or T cells have been detected to date. The aim of the present study was to obtain phenotypic evidence for a local immune response in OPA lungs. Specific-pathogen free lambs were infected intratracheally with JSRV. When clinical signs of OPA were apparent, the lungs were removed at necropsy and immunohistochemistry (IHC) was performed on lung sections using a panel of mouse anti-sheep mAbs. No influx of dendritic cells, B cells, CD4, CD8 or gammadelta T cells was seen in the neoplastic nodules or in their periphery. MHC Class II-positive cells were found intratumourally, peritumourally and in the surrounding alveolar lumina. In the tumours, many of these cells were shown to be fibroblasts and the remainder were likely to be mature macrophages. In the alveolar lumen, the MHC Class II-positive cells were CD14-positive and expressed high levels of IFN-gamma. They appeared to be immature monocytes or macrophages which then differentiated to become CD14-negative as they reached the periphery of the tumours. A high level of MHC Class I expression was detected on a range of cells in the OPA lungs but the tumour nodules themselves contained no MHC Class I-positive cells. On the basis of these findings, it is proposed that the lack of an effective immune response in OPA could result from a mechanism of peripheral tolerance in which the activity of the invading macrophages is suppressed by the local environment, possibly as a consequence of the inhibitory properties of the surfactant proteins.

Animals↗
PubMed2003

Neoadjuvant radiation and chemotherapy in rectal cancer does not increase postoperative complications.

BACKGROUND AND AIMS: Neoadjuvant radiation and chemotherapy in rectal cancer reduces local recurrences and increases the rate of conservative sphincter surgery. However, an increase in postoperative morbidity and mortality has also been observed. This study analyzed the operative difficulty and postoperative complications in patients with this treatment. PATIENTS AND METHODS: Retrospective review of 103 patients with rectal cancer, divided into two groups: group A, 53 patients undergoing preoperative radiotherapy with 45 Gy combined with chemotherapy, and group B, 50 patients with rectal cancer who received surgery after diagnosis. Both groups were homogeneous. The two groups were compared for both technical difficulty, using intraoperative data and rate of complications. RESULTS: There were no statistically significant differences between the two groups with regard to intraoperative or postoperative data. In group A there were 20 complications in 17 patients (32%) and in group B 22 complications in 19 patients (38%). The rates of perineal wound infection were similar. The percentage of anastomotic leaks was higher in group A. A greater number of anterior resections was performed in group A. CONCLUSION: Preoperative radiation and chemotherapy in rectal cancer does not increase postoperative complications and increases the rate of sphincter-preserving surgery.

Adult↗
PubMed2001

[Temporary dependency of steroid-receptor prognostic value in breast cancer].

BACKGROUND: The influence of prognostic factors in breast cancer may change during follow-up. Our aim was therefore to look for time-related changes in hazard ratios for steroid receptor status and the risk of relapse. PATIENTS AND METHOD: We studied 455 patients with operable primary breast cancer during a mean follow-up period of 72 months (range, 42-130 months). Clinical and histological characteristics were assessed and estrogen receptor (ER) and progesterone receptor (PgR) status were determined and compared to disease-free survival (DFS) and overall survival (OS). Analysis of DFS included fitting a multivariate Cox proportional hazards model, testing for non-proportionality, and examining diagnostic plots. RESULTS: A total of 66.8% of the tumors were ER positive and 54.7% PgR positive. Receptor status is highly associated with menopausal status, histological grade, peritumoral lymphatic or blood vessel invasion and mitotic index. No correlation was found between steroid receptor status and tumor size, node status or tumor stage. In univariate analysis, ER/PR vs ER+/PR+ display a hazard ratio of 2.15 (IC del 95%, 1.59-2.99) for DFS (p = 0.001) and 1.95 (IC del 95%, 1.38-2.59) for OS (p = 0.0043). In multivariate analysis, steroid receptor status, node status and mitotic index were independent prognostic factors for DFS and OS. By using Cox regression time-dependent covariates model, we show that the steroid receptor status hazard ratio is 5.6 at diagnosis, decreases after 4 years, and loses its significance after 10 years of follow-up. CONCLUSION: In patients with breast cancer the status steroid receptor have a relatively limited prognostic value and is lost within the first years.

Adult↗
PubMed2001

Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins.

There are some contradicting data about clinical allergic cross-reactivity to cephalosporins among patients who have had a previous allergic reaction to penicillins. The purpose of this study was to assess the safety of administering cephalosporins to penicillin-allergic patients. The diagnosis of penicillin allergy was made by positive skin tests to penicillin reagents and/or provocation tests with the penicillin suspected of causing the allergic reaction. To assess the clinical tolerance to cephalosporins, 41 well-characterized penicillin allergic patients diagnosed by positive skin tests and/or provocation tests were challenged with three cephalosporins that do not share the same side chain to the penicillin that induced the reactions: cephazoline, cefuroxime and ceftriaxone. Skin prick and intradermal tests with all cephalosporins tested were negative. All penicillin-allergic patients tolerated therapeutic doses of the three cephalosporins tested (cephazoline, cefuroxime and ceftriaxone) without any ill effect. These results indicate that the risk of suffering from an allergic reaction on administering cephalosporins to penicillin-allergic patients seems to be very low, provided that cephalosporins with a different side chain to the penicillin responsible for the allergic reaction are used.

Adult↗
PubMed2001

Jaagsiekte sheep retrovirus can be detected in the peripheral blood during the pre-clinical period of sheep pulmonary adenomatosis.

Peripheral blood leukocytes (PBLs) and tissue samples from 36 sheep were examined for jaagsiekte sheep retrovirus (JSRV) by hemi-nested PCR. Animals were classified according to the status of sheep pulmonary adenomatosis (SPA), which was confirmed by pathological examination, as follows: (i) sheep with classical SPA (cSPA, n=10), (ii) sheep with atypical SPA (aSPA, n=6), (iii) non-affected sheep from SPA-affected flocks (in-contact, n=10) and (iv) non-affected sheep from SPA-free flocks (control, n=10). JSRV proviral DNA was detected in the PBLs of 10/10 cSPA, 5/6 aSPA, 4/10 in-contact and 0/10 control sheep. Lung tumours and lymphoid organs were also found to be JSRV-positive. The number of positive PCR results was greater for sheep in the cSPA group than for those in the aSPA and in-contact groups. For the first time, it is concluded that JSRV can be detected in naturally infected sheep before the onset of clinical disease and even before the development of discernible tumours.

Animals↗
PubMedDate not supplied

Association of jaagsiekte sheep retrovirus with pulmonary carcinoma in Sardinian moufflon (Ovis musimon).

Bronchiolo-alveolar carcinoma has been described in man and in several animal species, including cattle, dogs, opossums, goats and sheep. In sheep, a bronchiolo-alveolar carcinoma, known as ovine pulmonary carcinoma (OPC), is caused by jaagsiekte sheep retrovirus (JSRV), an exogenous type D retrovirus. In the mid-1980s, a severe outbreak of a disease resembling OPC was described in captive Sardinian moufflon (Ovis musimon). In the present study, the use of polymerase chain reaction (PCR) amplification of nucleic acids extracted from archival material established that JSRV was associated with OPC in affected moufflon. JSRV was detected in the lungs and mediastinal lymph nodes. Immunohistochemical and in-situ PCR demonstrated that in the lungs, JSRV proviral DNA was localized in transformed and untransformed type II pneumocytes and in the alveolar macrophages. In the mediastinal lymph nodes, JSRV DNA was mainly located in the cortical follicles and paracortex. These data suggest that JSRV is the cause of OPC in Sardinian moufflon, as it is in Sardinian sheep.

Animals↗
PubMedDate not supplied

Preoperative values of CA 15-3 and CEA as prognostic factors in breast cancer: a multivariate analysis.

The role of circulating tumor markers in providing prognostic information has not been widely studied. In the current study, serum levels of the carbohydrate antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) were determined preoperatively in 364 breast cancer patients with no clinical signs of metastasis. The prognostic relevance of these markers for recurrence (175/364) and death of disease (104/175) was determined by Cox multivariate analysis, including the comparison with classical prognostic factors. High levels of both tumor markers were associated with aneuploid tumors with high S-phase fraction and high ornithine decarboxylase activity. CA 15-3 was highly associated with the number of positive lymph nodes and peritumoral lymphatic or blood vessel invasion. No significant associations were found between CEA or CA 15-3 levels and histologic grade, necrosis and steroid receptor status. In univariate analysis, preoperative values, using optimum cutoff values of CA 15-3 (40 U/ml) and CEA (6 ng/ml), were statistically significant for relapse-free survival and overall survival. In multivariate analysis, only node status, DNA ploidy and ornithine decarboxylase activity were independent predictors for relapse-free survival; the estrogen receptor status was a predictor of overall survival. In node-negative patients, ornithine decarboxylase activity was the only factor selected for relapse-free survival. In node-positive patients, the number of lymph nodes and DNA ploidy were the only variables selected for relapse-free survival or overall survival. Estrogen receptor and ornithine decarboxylase activity were excluded for relapse-free survival, but were significant prognostic factors for overall survival.

Adult↗