Bone regeneration in critical-sized mandibular symphysis defects using bioceramics with or without bone marrow mesenchymal stem cells in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats.

OBJECTIVES: To compare new bone formation in mandibular critical-sized bone defects (CSBDs) in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats filled with bioceramics (BCs) with or without bone marrow mesenchymal stem cells (BMSCs). METHODS: A total of 64 adult female Sprague-Dawley rats were randomized into four groups (n = 16 per group): Group 1 healthy, Group 2 diabetic, Group 3 osteoporotic, and Group 4 diabetic-osteoporotic rats. Streptozotocin was used to induce type 1 diabetes in Group 2 and 4, while bilateral ovariectomy was used to induce osteoporosis in Group 3 and 4. The central portion of the rat mandibular symphysis was used as a physiological CSBD. In each group, eight defects were filled with BC (hydroxypatatite 60% and ß-tricalcium phosphate 40%) alone and eight with BMSCs cultured on BC. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS: In all groups (healthy, diabetics, osteoporotics, and diabetics-osteoporotics), the CSBDs filled with BC + BMSCs showed greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with CSBDs treated with BC alone (at 4 and 8 weeks). CONCLUSIONS: Application of BMSCs cultured on BCs improves bone regeneration in CSBDs compared with application of BCs alone in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats.

Use of buccal fat pad-derived stem cells cultured on bioceramics for repair of critical-sized mandibular defects in healthy and osteoporotic rats.

OBJECTIVE: To compare new bone formation in mandibular symphysis critical-sized bone defects (CSBDs) in healthy and osteoporotic rats filled with bioceramics (BCs) with or without buccal fat pad mesenchymal stem cells (BFPSCs). MATERIALS AND METHODS: Thirty-two adult female Sprague-Dawley rats were randomized to two groups (n = 16 per group): group 1 healthy and group 2 osteoporotic (with bilateral ovariectomy). The central portion of the rat mandibular symphysis was used as a physiological CSBD. In each group, eight defects were filled with BC (hydroxyapatite 60% and ß-tricalcium phosphate 40%) alone and eight with BFPSCs cultured on BC. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS: In both groups, CSBDs filled with BC + BFPSCs showed greater radiological bone union, BMD and histological bone union, and more VEGF and BMP-2 positivity, compared with CSBDs treated with BC alone at 4 and 8 weeks. CONCLUSIONS: The application of BFPSCs cultured on BCs improves bone regeneration in CSBDs compared with BCs alone in healthy and osteoporotic rats. CLINICAL RELEVANCE: Our results may aid bone regeneration of maxillofacial CSBDs of both healthy and osteoporotic patients, but further studies are necessary.

In Vitro Study of Synergic Effect of Cisplatin and Low Molecular Weight Heparin on Oral Squamous Cell Carcinoma.

OBJECTIVES: To evaluate the possible synergic effect of cisplatin and low molecular weight heparin (LMWH) on oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Cisplatin and enoxaparin sodium, alone or in combination, were administered at doses of 1, 2, 4, 8 and 10 µM and 0.1, 0.5, 1, 5, 10, 50, and 100 µg/ml, respectively, to the H357 human OSCC line. The effects on cell viability and apoptosis were evaluated after 24, 48, and 72 h and on cell migration after 18 and 24 h. RESULTS: 10 µM concentration of cisplatin produced the greatest decrease in cell viability, with significant differences at 24 (p=0.009), 48 (p=0.001) and 72 h (p = 0.003); the 100 µg/ml dose of enoxaparin produced the greatest decrease in cell viability but without significant differences (p>0.05). When different concentrations of cisplatin and enoxaparin were combined, it was found that 100 µg/ml enoxaparin sodium produced the greatest synergic effect on cell viability reduction. In analyses of apoptosis and cell migration, it was found that the combination of cisplatin at 8 or 10 µM and 100 µg/ml enoxaparin produced a higher rate of apoptosis at 24, 48, and 72 h and a greater reduction in cell migration at 18 and 24 h. CONCLUSIONS: A combination of cisplatin and enoxaparin sodium shows a synergic effect that reduces cell viability and cell migration capacity and increases the apoptosis of human OSCC cells. CLINICAL RELEVANCE: Enoxaparin may be beneficial in chemotherapy for patients with OSCC; this finding requires further clinical and laboratory investigation.

Salivary myeloperoxidase and malondialdehyde are increased in patients exhibiting an asymptomatic mandibular impacted third molar.

BACKGROUND: To determine whether saliva is a good means of evaluating concentrations of oxidative stress biomarkers, analyzing the correlation between concentrations in saliva and in follicular tissue, and to compare biomarker concentrations in patients with one asymptomatic mandibular impacted third molar (MITM) (before extraction) with a healthy control, and to determine how biomarkers are modified by extraction. MATERIAL AND METHODS: 80 patients with one asymptomatic MITM and 80 healthy controls were included. Saliva samples were collected from all subjects (before extraction in the study group) to evaluate Myeloperoxidase (MPO) and Malondialdehyde (MDA) concentrations. Follicular tissues were obtained during surgery to measure biomarkers. One month after extraction, saliva samples were collected to assess changes of oxidative stress. RESULTS: Salivary MPO and MDA showed positive correlation with concentrations in follicular tissue (MPO: correlation coefficient=0.72, p=0.025; MDA: =0.92, p=0.001). Patients with asymptomatic MITMs showed higher salivary concentrations of oxidative stress biomarkers than healthy control subjects, with statistical significance for both MPO (p<0.001) and MDA (p<0.001). One month after extraction, salivary biomarkers decreased significantly in the study group (p<0.001). CONCLUSIONS: Salivary MPO and MDA are higher among patients with one asymptomatic MITM, but these levels decrease significantly one month after surgical extraction. The large decrease in oxidative stress biomarkers could justify third molar extraction despite the absence of symptoms.

Synergistic effect of photodynamic therapy and alendronate on alveolar bone loss in rats with ligature-induced periodontitis.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) and antiresorptive drugs, such as alendronate (ALN), have been shown to reduce alveolar bone loss. The aim of this study was to evaluate the possible synergic effects of combining PDT and ALN on bone loss in periodontitis in rats. MATERIAL AND METHODS: Periodontitis was induced by ligature in 60 Wistar rats randomized into the following groups: control (Group 1); PDT (Group 2); ALN 0.01 mg/kg (Group 3); ALN 0.25 mg/kg (Group 4); PDT + ALN 0.01 mg/kg (Group 5); and PDT + ALN 0.25 mg/kg (Group 6). The rats were killed on day 12 and the mandibles were processed for macroscopic morphometric analysis, micro-computed tomography to analyze bone mineral density (BMD) and histological analysis. Gingival samples were collected to evaluate myeloperoxidase (MPO) and malonaldehyde (MDA) levels. RESULTS: Bone loss and inflammatory activity in histological studies, from the greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg, while the order from least to greatest BMD was: control < ALN 0.01 mg/kg < PDT < ALN 0.25 mg/kg < PDT + ALN 0.01 mg/kg < PDT + ALN 0.25 mg/kg. The order of MPO and MDA activity from greatest to least was: control > ALN 0.01 mg/kg > PDT > ALN 0.25 mg/kg > PDT + ALN 0.01 mg/kg > PDT + ALN 0.25 mg/kg. The positive results obtained in the group treated with PDT + ALN 0.25 mg/kg showed statistically significant differences (P ≤ .05) compared with the other 5 groups for BMD, MPO and MDA. CONCLUSION: Combined approach therapy of PDT + ALN 0.25 mg/kg demonstrated a protective effect on alveolar bone loss.

Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization.

A limited repertoire of PPP family of serine/threonine phosphatases with a highly conserved catalytic domain acts on thousands of protein targets to orchestrate myriad central biological roles. A major structural reorganization of human calcineurin, a ubiquitous Ser/Thr PPP regulated by calcium and calmodulin and targeted by immunosuppressant drugs cyclosporin A and FK506, is unveiled here. The new conformation involves trans- to cis-isomerization of proline in the SAPNY sequence, highly conserved across PPPs, and remodels the main regulatory site where NFATc transcription factors bind. Transitions between cis- and trans-conformations may involve peptidyl prolyl isomerases such as cyclophilin A and FKBP12, which are known to physically interact with and modulate calcineurin even in the absence of immunosuppressant drugs. Alternative conformations in PPPs provide a new perspective on interactions with substrates and other protein partners and may foster development of more specific inhibitors as drug candidates.

Novel functions of chromatin-bound IκBα in oncogenic transformation.

The nuclear factor-κB (NF-κB) signalling pathway participates in a multitude of biological processes, which imply the requirement of a complex and precise regulation. IκB (for Inhibitor of kappaB) proteins, which bind and retain NF-κB dimers in the cytoplasm, are the main contributors to negative regulation of NF-κB under non-stimulation conditions. Nevertheless, increasing evidences indicate that IκB proteins exert specific nuclear roles that directly contribute to the control of gene transcription. In particular, hypophosphorylated IκBß can bind the promoter region of TNFα leading to persistent gene transcription in macrophages and contributing to the regulation of the inflammatory response. Recently, we demonstrated that phosphorylated and SUMOylated IκBα reside in the nucleus of the cells where it binds to chromatin leading to specific transcriptional repression. Mechanistically, IκBα associates and regulates Polycomb Repressor Complex activity, a function that is evolutionary conserved from flies to mammals, as indicate the homeotic phenotype of Drosophila mutants. Here we discuss the implications of chromatin-bound IκBα function in the context of tumorigenesis.

Synergic effect of curcumin or lycopene with irradiation upon oral squamous cell carcinoma cells.

OBJECTIVE: An in vitro study was carried out to evaluate the effect of curcumin, lycopene, and irradiation upon oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Curcumin and lycopene were administrated at doses of 3, 4.25, 5.50, and 6.75 µM in PE/CA-PJ15 OSCC cultures irradiated with different doses (1, 2.5, and 5 Gy), followed by evaluation of the effects upon cell viability, apoptosis, and migration after 24, 48, and 72 h of incubation. RESULTS: The application of curcumin or lycopene to the tumor cells during 24, 48, and 72 h without irradiation exerted an inhibitor effect upon cell viability and increased cell apoptosis. The maximum reduction in cell viability and the peak apoptotic effect was recorded with the 5.50 and 6.75 µM doses, for both curcumin and lycopene. Likewise, curcumin and lycopene exerted a synergic effect upon both variables on applying irradiation. Lastly, the 5.50 and 6.75 µM drug doses, together with 5 Gy of irradiation, yielded the greatest decrease in cell migration capacity with both curcumin and lycopene. CONCLUSIONS: Curcumin and lycopene increase cytotoxic activity in the PE/CA-PJ15 cell line and reduce cell migration capacity, while the combination of curcumin or lycopene with irradiation exerts a synergic effect.

Acute administration of grape seed proanthocyanidin extract modulates energetic metabolism in skeletal muscle and BAT mitochondria.

Proanthocyanidin consumption might reduce the risk of developing several pathologies, such as inflammation, oxidative stress and cardiovascular diseases. The beneficial effects of proanthocyanidins are attributed to their antioxidant properties, although they also can modulate gene expression at the transcriptional level. Little is known about the effect of proanthocyanidins on mitochondrial function and energy metabolism. In this context, the objective of this study was to determine the effect of an acute administration of grape seed proanthocyanidin extract (GSPE) on mitochondrial function and energy metabolism. To examine this effect, male Wistar rats fasted for fourteen hours, and then they were orally administered lard oil containing GSPE or were administered lard oil only. Liver, muscle and brown adipose tissue (BAT) were used to study enzymatic activity and gene expression of proteins related to energetic metabolism. Moreover, the gastrocnemius muscle and BAT mitochondria were used to perform high-resolution respirometry. The results showed that, after 5 h, the GSPE administration significantly lowers plasma triglycerides, free fatty acids, glycerol and urea concentrations. In skeletal muscle, GSPE lowers FATP1 mRNA levels and increases mitochondrial oxygen consumption, using pyruvate as the substrate, suggesting a promotion of glycosidic metabolism. Furthermore, GSPE increased the genetic expression of key genes in energy metabolism such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α), and modulated the enzyme activity of proteins, which are involved in the citric acid cycle and electron transport chain (ETC) in BAT. In conclusion, GSPE affects mainly the skeletal muscle and BAT mitochondria, increasing their oxidative capacity rapidly after acute supplementation.

A fluorescent polarization-based assay for the identification of disruptors of the RCAN1-calcineurin A protein complex.

Calcineurin is a Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase involved in many biological processes and developmental programs, including immune response. One of the most studied substrates of calcineurin is the transcription factor NFAT (nuclear factor of activated T cells) responsible for T-cell activation. Different anticalcineurin drugs, such as cyclosporine A and FK506, are the most commonly used immunosuppressants in transplantation therapies. Unfortunately, their mechanism of action, completely blocking the calcineurin phosphatase activity while also requiring continuous administration, bears severe side effects. During recent years, the family of regulators of calcineurin (RCAN) has been described and studied extensively as modulators of calcineurin signaling pathways. The RCAN1 region, spanning amino acids 198 to 218 and responsible for inhibiting the calcineurin-NFAT signaling pathway in vivo, has been identified. An RCAN1-derived peptide spanning this sequence interferes with the calcineurin-NFAT interaction without affecting the general calcineurin phosphatase activity. Here we report the development of an optimized in vitro high-throughput fluorescence polarization assay based on the disruption of the RCAN1(198-218)-CnA interaction for identifying molecules with immunosuppressant potential. This approach led us to identify dipyridamole as a disruptor of such interaction. Moreover, three small molecules with a potential immunosuppressive effect were also identified.

RCAN3, a novel calcineurin inhibitor that down-regulates NFAT-dependent cytokine gene expression.

The regulators of calcineurin (RCAN) proteins, previously known as calcipressins, have been considered to be a well conserved family from yeast to human based on the conservation of their FLISPP motif. Here, after performing a RCAN comparative genomic analysis we propose the existence of a novel functionally closely related RCAN subfamily restricted to vertebrates, the other RCAN proteins being considered only as distantly related members of the family. In addition, while three paralogous RCAN genes are found in vertebrates, there is only one in the other members of Eukarya. Moreover, besides the FLISPP motif, these paralogous genes have two others conserved motifs, the Cn-inhibitor RCAN (CIC) and the PxIxxT, which are restricted to vertebrates. In humans, RCAN1 and RCAN2 bind and inhibit Cn through their C-terminal region. Given the high amino acid identity in this region among human RCANs, authors in the field have hypothesized a role for RCAN3 in inhibiting Cn activity. Here, we demonstrate for the first time that human RCAN3, encoded by the RCAN3 (also known as DSCR1L2) gene, interacts physically and functionally with Cn. This interaction takes place only through the RCAN3 CIC motif. Overexpression of this sequence inhibits Cn activity towards the nuclear factor of activated T cells (NFAT) transcription factors and down-regulates NFAT-dependent cytokine gene expression in activated human Jurkat T cells.

Functional characterization of the calcipressin 1 motif that suppresses calcineurin-mediated NFAT-dependent cytokine gene expression in human T cells.

Inhibition of the calcineurin-NFAT signalling pathway is one of the main challenges for immunosuppression therapy to avoid the severe side effects of the current anticalcineurinic drugs, cyclosporin A and FK506. The members of the calcipressin family are endogenous inhibitors of calcineurin. We describe for the first time that two independent motifs within human calcipressin 1, the ELHA and the PxIxxT motifs, interact with calcineurin in an independent functional manner. However, the main finding here is that the ELHA-containing calcineurin-inhibitor CALP1 (CIC) motif is the responsible for the in vivo inhibition of calcineurin-mediated NFAT-dependent cytokine gene expression in human T cells. We believe that the identification of the CIC motif could be used as a starting point for the development of new immunosuppressive drugs for use in transplantation and autoimmune diseases.

[Clinical significance of tumor content of epidermal growth factor receptor in breast cancer]. / Significación clínica del contenido tumoral del receptor del factor de crecimiento epidérmico en el cáncer de mama.

OBJECTIVE: To determine the content of epidermal growth factor receptor (EGFR) using a radioligand method in breast cancer and to analyze the relationship between the EGFR levels and the characteristics of patients and tumors. Prognostic significance was also analyzed. MATERIAL AND METHODS: EGFR was measured by a single point radioligand assay in 265 invasive breast carcinomas tissues. In addition, estrogen and progesterone receptors (ER and PR) were measured by enzymatic immunoassays. We analyze the relationship of EGFR levels with the different clinico-pathologic parameters. RESULTS: EGFR levels in breast carcinomas varied widely (0.1 to 403) with a median at 4 fmol/mg prot. The significantly higher concentrations of EGFR were detected in patients under 60 years old (p = 0.042), undifferentiated tumors (p = 0.04), and carcinomas with negative ER and PR (p < 0.019 y p < 0018, respectively). In addition, there was a negative correlation between EGFR and the ER and PR levels (p < 0.05). EGFR levels did not show any relationship with the patient's prognosis. CONCLUSIONS: In addition, intratumoral levels of EGFR in breast carcinomas vary widely and the highest concentrations are associated with the most aggresive characteristics of the tumor.

Significación clínica del contenido tumoral del receptor del factor de crecimiento epidérmico en el cáncer de mama / Clinical significance of tumor content of epidermal growth factor receptor in breast cancer

Objetivo: Cuantificar el contenido del receptor del factor de crecimiento epidérmico (EGFR) mediante técnica de radioligando en el cáncer de mama, y analizar su relación con las características de las pacientes y de sus tumores así como su significado pronóstico. Material y método: Se cuantificó la concentración de EGFR mediante técnica de radioligando de un sólo punto en 265 carcinomas invasivos de mama. Igualmente se determinaron los receptores de estrógenos (RE) y progesterona (RP) mediante inmunoensayo enzimático. Analizamos el contenido de EGFR y su relación con los diferentes parámetros clínico-patológicos. Resultados: Los niveles de EGFR en carcinomas de mama oscilaron ampliamente (de 0,1 a 403) con una mediana de 4 fmol/mg prot. Los niveles significativamente más altos de EGFR se detectaron en las pacientes menores de 60 años (p < 0,042), en los tumores indiferenciados (p < 0,004) y en los que eran negativos para RE y RP (p < 0,019 y p < 0,018, respectivamente). Además, hubo correlación negativa entre los niveles de EGFR y los de RE y RP (p < 0,05). No observamos relación entre los niveles de EGFR y el pronóstico de las pacientes. Conclusión: Los niveles intratumorales de EGFR en los carcinomas mamarios presentan una amplia variabilidad, y las concentraciones más elevadas se relacionan con las características más agresivas del tumor (AU)

Aluminum-induced pro-oxidant effects in rats: protective role of exogenous melatonin.

In recent years, it has been suggested that oxidative stress is a feature of Alzheimer's disease in which aluminum (Al) could exacerbate oxidative events. The goal of the present study was to assess in rats the pro-oxidant effects induced by Al exposure, as well as the protective role of exogenous melatonin. Two groups of male rats were intraperitoneally injected with Al only or melatonin only, at doses of 5 and 10 mg/kg/day, respectively for 8 wk. During this period, a third group of animals received Al (5 mg/kg/day) and melatonin (10 mg/kg/day). At the end of the treatment period, rats were anesthesized and arterial blood was obtained. Thereafter, animals were killed and liver and brain (cortex, hippocampus and cerebellum) were removed. These tissues were processed to examine oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Samples of these tissues were also used to determine Al, Fe, Mn, Cu and Zn concentrations. The results show that Al exposure promotes oxidative stress in different neural areas, including those in which Al concentrations were not significantly increased. The biochemical changes observed in neural tissues show that Al acts as pro-oxidant, while melatonin exerts an antioxidant action in Al-treated animals. The protective effects of melatonin against cellular damage caused by Al-induced oxidative stress, together with its low toxicity, make melatonin worthy of investigation as a potential supplement to be included in the treatment of neurological disorders in which the oxidative effects must be minimized.

Parameters related to oxygen free radicals in erythrocytes, plasma and epidermis of the hairless rat.

The following parameters related to oxygen free radicals (OFR) were determined in erythrocytes and the epidermis of hairless rats: catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced (GSH) and oxidized (GSSG) glutathione, glutathione S-transferase (GST), superoxide dismutase (SOD) and thiobarbituric acid reactive substances (TBARS). GSH, GSSG and TBARS were also analyzed in plasma. In erythrocytes, the Pearson correlation coefficients (r) were significant (p < 0.001) between glutathione and other parameters as follows: GSH correlated negatively with GSSG (r = -0.665) and TBARS (r = -0.669); GSSG correlated positively with SOD (r = 0.709) and TBARS (r = 0.752). Plasma GSSG correlated negatively with erythrocytic thermostable GST activity (r = -0.608; p=0.001) and with erythrocytic total GST activity (r = -0.677; p < 0.001). In epidermis (p < 0.001 in all cases), GSH content correlated with GSSG (r = 0.682) and with GPx (r = 0.663); GSSG correlated with GPx (r = 0.731) and with GR (r = 0.794). By multiple linear regression analysis some predictor variables (R(2)) were found: in erythrocytes, thermostable GST was predicted by total GST activity and GSSG, GSSG content was predicted by GSH and by the GSH/GSSG ratio and GPx activity was predicted by GST, CAT and SOD activities; in epidermis, GSSG was predicted by GR and SOD activities and GR was predicted by GSSG, TBARS and GPx. It is concluded that the hairless rat is a good model for studying OFR-related parameters simultaneously in blood and skin, and that it may provide valuable information about other animals under oxidative stress.

Expresión y significación clínica del pepsinógeno c y la colagenasa-3 en el carcinoma de endometrio / Expression and clinical significance of pepsinogen C and collagenase-3 in endometrial carcinoma

Objetivo: Analizar la expresión tumoral del pepsinógeno C y de la colagenasa-3 en el adenocarcinoma de endometrio y la relación con las características de las pacientes y de sus tumores.Sujetos y métodos: Analizamos retrospectivamente mediante análisis inmunohistoquímico, utilizando anticuerpos monoclonales, 58 pacientes diagnosticadas y tratadas de adenocarcinoma de endometrio.Resultados: Se detectó pepsinógeno C en 21 tumores (36 por ciento) y colagenasa-3 en 30 (51 por ciento). La expresión de estas proteínas se asoció significativamente con la profundidad de la invasión miometrial, de forma que a mayor invasión del miometrio, menor expresión de pepsinógeno C y mayor de colagenasa-3 (p < 0,005 y p < 0,02, respectivamente). El análisis combinado de ambas enzimas proteolíticas predijo significativamente el grado de invasión miometrial (p < 0,001).Conclusión: Un porcentaje significativo de adenocarcinomas de endometrio expresan pepsinógeno C y colagenasa-3, lo cual refleja un comportamiento biológico diferente, y pueden ser útiles en la predicción preoperatoria de la invasión miometrial en el cáncer de endometrio (AU)

[Analysis of the cytosolic content of the pS2 protein in breast cancer]. / Análisis del contenido citosólico de la proteína pS2 en el cáncer de mama.

OBJECTIVE: To analyze pS2 cytosolic levels in breast carcinomas and their correlation with different clinical characteristics of the patients and their tumours. MATERIAL AND METHODS: Cytosolic pS2 levels were measured by radioimmunometric assay in tumours from 168 breast cancer patients. RESULTS: The pS2 values ranged from 0 to 251 ng/mg protein (mean SD: 21.8 38.1; median: 7.9 ng/mg protein). These protein levels were significantly (p < 0.05) higher in premenopausal patients (27.6 45.2) than in postmenopausal patients (19.5 33.8). Intratumour pS2 levels were also significantly (p < 0.05) correlated with histologic grade of the tumours, and were higher in well diferentiated tumours (grade I: 28.8 42.8) than in moderately differentiated tumours (grade II: 19.7 35.6) and than in poorly differentiated tumours (grade III: 18.9 37.3). Similarly, significant differences in pS2 content were found between positive estrogen receptor (ER) tumours and ER-negative tumours (29.1 46.5 vs 11.3 15.9, respectively; p<0.0001), as well as between positive progesterone receptor (PR) tumours and PR-negative tumours (29.1 49.8 vs 15.3 21.5, respectively; p < 0.05). CONCLUSIONS: The results suggest that pS2 may be a useful prognostic marker in breast cancer, and may also be useful to identify patients who are likely to benefit from hormone therapy.

Análisis del contenido citosólico de la proteína ps2 en el cáncer de mama / Analysis of the cytosolic content of the ps2 protein in breast cancer

Objetivo: Analizar los niveles citosólicos de pS2 en carcinomas de mama y su correlación con las diferentes características clínicas de las pacientes y de sus tumores.Material y métodos: Se determinaron por método inmunorradiométrico los niveles citosólicos de pS2 en 168 tumores de pacientes con cáncer de mama. Resultados: Los valores de pS2 variaron de 0 a 251 ng/mg proteína (media ñ DE: 21,8 ñ 38,1; mediana: 7,9 ng/mg proteína). Esos niveles de la proteína fueron significativamente (p < 0,05) más elevados en las pacientes premenopáusicas (27,6 ñ 45,2) que en las pacientes postmenopáusicas (19,5 ñ 33,8). Los niveles intratumorales de pS2 también estuvieron significativamente (p < 0,05) correlacionados con el grado histológico de los tumores, siendo más elevados en los tumores bien diferenciados (grado I: 28,8 ñ 42,8) que en los tumores moderadamente diferenciados (grado II: 19,7 ñ 35,6) y que en los tumores pobremente diferenciados (grado III: 18,9 ñ 937,3). Similarmente, se encontraron diferencias significativas en el contenido de pS2 entre los tumores receptor de estrógeno (RE)-positivos y los tumores RE-negativos (29,1 ñ 46,5 vs 11,3 ñ 15,9, respectivamente; p < 0,0001), así como también entre los tumores receptor de progesterona (RP)-positivos y los tumores RP-negativos (29,1 ñ 49,8 vs 15,3 ñ 21,5, respectivamente; p < 0,05). Conclusión: Estos resultados sugieren que la pS2 puede ser un útil marcador pronóstico en el cáncer de mama, así como también para identificar pacientes que pueden beneficiarse de terapia hormonal (AU)