Adolescents' trajectory through peer loss after a road traffic accident.

This mixed method study investigated the short- and long-term effects of peer loss on eight adolescents after a fatal school bus accident. Phenomenological analysis of their retrospective narratives revealed three patterns (living in despair, collecting my pieces, remembering, and moving on). Quantitative findings indicate progressive decrease in post-traumatic stress symptoms severity across time; increase in positive changes in perceptions of self, others, and life between 18 and 34 months; and stable continuing bond with the deceased peers.

Greek teachers' knowledge about attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a neurobiological disorder, which affects about 5.2% of school-aged children worldwide. Children with ADHD present teachers with a special challenge, since they interfere with teaching process and do not respond to typical classroom management techniques. In order to meet this challenge teachers must have accurate, up-to-date, information about the disorder so that they can respond to the needs of the student with ADHD. Studies that have examined teachers' beliefs and knowledge relating to ADHD highlighted the need for providing training to increase Greek teachers' knowledge and understanding of the disorder. Thus, the aims of the present study were: (a) to develop and evaluate brief ADHD training seminar for teachers; and (b) to investigate whether the training format (half-day versus two-day seminar) would have a differential effect on teachers' knowledge about ADHD. A total of 143 teachers formed the two sample groups; Group 1 (n=68) attended a half-day training (5 hours), and Group 2 (n=75) a two-day training (18 hours). Seminar topics included: (a) gaining basic knowledge about the symptoms, causes and natural history of ADHD, (b) understanding the key underlying cognitive deficits of the disorder and their impact on learning and behavior, (c) implementation of specific learning strategies for children with ADHD, (d) benefits and limitations of existing treatment approaches including the pharmacological treatment, and (e) available instruments for teachers that could inform their decision to refer the student to CAMHS for an assessment. A self-report ADHD Knowledge Questionnaire (ADHD-KQ), which covers four domains (clinical presentation, causes, cognitive deficits, interventions) was developed for the purpose of the present study, and was administered pre- and post-seminar. Teachers were generally knowledgeable about clinical presentation of ADHD, with more than 80% of the sample responding correctly to items pertaining to core symptoms. The internal consistency of the total ADHD-KQ scale measured by Cronbach's alpha coefficient was found to be good (0.89). The alpha coefficients for the sub-scales were acceptable (0.70 for the Symptoms/Diagnosis sub-scale, 0.73 for the Cognitive Deficits sub-scale, and 0.75 for the Intervention sub-scale), except for the Causes sub-scale, which was poor (0.59). In addition, each of the sub-scales showed a significant correlation with the total scales score (range r=0.66 to r=0.79), and there also was significant correlation between the four sub-scales (range r=0.39 to r=0.45). As expected, gaps in knowledge were identified, particularly in the area of causes, pharmacological treatment and cognitive deficits associated with ADHD. The results, using paired samples t tests, showed a highly significant increase in ADHD-KQ total and all sub-scale scores in both groups (p<0.001), indicating an overall improved knowledge about ADHD irrespective of the training format, i.e. half-day versus two-day training seminar. One-way MANOVA revealed significant difference between the two training seminars in mean pre-post difference sub-scale scores considered simultaneously. Subsequent univariate tests of between-subjects effects revealed that the group (training format) had a statistically significant effect on ADHD knowledge of symptoms sub-scale only [F(1,141)=10.46, p<0.01], with those who participated in the two-day training seminar having significantly higher mean pre-post difference scores as compared to teachers who attended the half-day training seminar (p<0.01). The present findings merit replication and, if confirmed in larger samples, have important implications for undergraduate curriculum development and training of practicing teachers, so that to overcome specific knowledge gaps and misconceptions with regards to ADHD. Future study should incorporate the use of classroom interventions and teaching strategies for students with ADHD, before and after brief training seminar, for a more thorough evaluation of its effectiveness.

High Farnesoid X Receptor (FXR) expression is a strong and independent prognosticator in invasive breast carcinoma.

Farnesoid X Receptor (FXR), a nuclear receptor superfamily member, is related with bile acids, glucose and lipids metabolism and recently with cancer. In the present study the clinical significance of FXR expression in invasive breast carcinoma was evaluated. FXR protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissues obtained from 115 breast cancer patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. FXR positivity was noted in 91 (79.1%) and high FXR expression in 51 (44.3%) out of 115 invasive breast carcinoma cases. High FXR expression was significantly associated with smaller tumor size (p=0.0318) and increased tumor cells' proliferative rate (p=0.0375). Invasive breast carcinoma patients presenting high FXR expression showed significantly longer overall and disease-free survival times compared to those with low FXR expression (log-rank test, p=0.0052 and p=0.0058). In multivariate analysis, FXR expression was identified as independent prognostic factor of overall and disease-free patients' survival (Cox-regression analysis, p=0.0023 and p=0.0049, respectively). The present data support evidence that FXR may be implicated at the earlier stage of breast malignant disease progression, being a strong and independent prognosticator of favorable overall and disease-free survival in invasive breast carcinoma.

Comparison of inflammatory responses and muscle damage indices following a soccer, basketball, volleyball and handball game at an elite competitive level.

Inflammatory responses and muscle damage indices were compared between four popular team sports at an elite level. Seventy two male elite players of four team sports: soccer (n = 18), basketball (n = 18), volleyball (n = 18) and handball (n = 18), completed an official match, while 18 non-athletes served as controls. Blood samples were drawn before, immediately after and 13 and 37 h post-match. Soccer produced the greatest increase in inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), which were increased by 3-4 fold immediately after the game, as well as in C-reactive protein, which was increased by threefold in the next morning after the match. Metabolic stress (urea, ammonia and cortisol) and muscle damage indices (creatine kinase and lactate dehydrogenase) were also higher after soccer, with creatine kinase responses being almost 2-3 times higher than the other sports. Volleyball showed the smallest increase in inflammation and muscle damage markers compared with the other three sports.

Y-box-binding protein 1 (YB1) in breast carcinomas: relation to aggressive tumor phenotype and identification of patients at high risk for relapse.

AIMS: To investigate the expression pattern of Y-box-binding protein 1 (YB1) in breast carcinomas, its clinicopathological and prognostic value, and its association with the breast cancer stem cell phenotype [CD44(+)/CD24(-/low)]. METHODS AND RESULTS: Immunohistochemistry was performed on 225 paraffin embedded specimens of invasive breast carcinomas to detect the expression of the proteins YB1, ER, PR, HER2, p53, Ki67, bcl-2, CD44 and CD24. YB1 protein was detected in the nuclei, the cytoplasm and the stroma of the tumor cells. Cytoplasmic YB1 was detected more often in carcinomas of ductal type (p = 0.002), of higher nuclear grade (p < 0.001), with lack of ER expression (p = 0.002), positive expression of p53 and Ki67 (p = 0.002 and p = 022, respectively), and with present CD44(+)/CD24(-/low) breast cancer stem cells (p = 0.001), while its association with bcl-2 was found to be inverse (p = 0.042). Nuclear YB1 was found to exert unfavorable impact on the disease-free survival of the unselected patients (p = 0.05) and the patients having been subjected to adjuvant chemotherapy and radiotherapy (p = 0.036 and p = 0.05, respectively). CONCLUSIONS: Cytoplasmic YB1 is associated with an aggressive and "stem cell-like" tumor phenotype, while nuclear localization discriminates patients at high risk for recurrence, especially those who are subjected to chemo- and radiotherapy.

[Neurobiological inscriptions of psychological trauma during early childhood].

Neurodevelopment is a highly complex process, influenced by a wide range of interacting genetic and environmental factors. Recent developments in fetal, neonatal and infant behavioural genetics and brain imaging methods have allowed for more detailed investigation of the effects of early adverse environment on the developing brain. This review aims to provide background for neurobiological understanding of how the prolonged exposure to stress or trauma during early childhood affects subsequent cognitive, emotional and social development. Initially, a brief overview of brain development is provided - focusing, in particular, on the limbic system structures, which are closely linked to emotional experiences and reactions, learning and memory. Emphasis is placed on the concept of neural plasticity, which is the biological base of memory and learning - the two most important mechanisms through which the environment affects the behavior. Moreover, the concept of sensitive periods, that is to say periods of "vulnerability" or "opportunity" during which particular experiences affect brain growth, functional organization and maturation, is discussed. Brief overview of the neuroendocrine stress response system and the long-term effects of prolonged exposure to stress hormones on early brain development clarify further why children are more vulnerable than adults to the effects of stress. The section dealing with the memory, which is closely linked to the limbic system, attempts to discuss how early exposure to chronic stress or psychological trauma, through neurobiological effects and the process of learning, can lead to dysfunctional behaviors, which in its extreme form can be mental disorders. The two types of memory are discussed: (a) the implicit (nondeclarative), which develops during the prelingual stage of child's development and refers to unconscious memories of previous experiences, and (b) the explicit (declarative) memory, which is closely linked to language development and refers to memories that can be consciously recalled. Given that prenatal or postnatal early experiences can alter the course of brain development, the exposure to maltreatment, whether it takes the form of physical, sexual or emotional abuse, or the kind of extreme neglect and deprivation during the early years of life, is related to alterations in brain structure and function, which in turn contributes to development of chronic post-traumatic disorder (PTSD), anxiety, mood and attachment disorders, memory and learning problems, and other psychopathological conditions. Finally, it is pointed out that a comprehensive and detailed diagnostic assessment of young children who are referred to the child and adolescent mental health services because of presenting with behavioural and emotional disturbances should be an established good clinical practice, given that a wrong diagnosis may have further deleterious effects on the child's psychosocial development. The need for neuropsychological assessment of children who have been exposed to early trauma or stress is thought to have important implications for the recognition and the neurobiological understanding of early trauma, which in turn allows for the development and implementation of appropriate interventions.

Podocyte main slit diaphragm proteins, nephrin and podocin, are affected at early stages of lupus nephritis and correlate with disease histology.

Renal podocytes and their slit diaphragms ensure the integrity of the renal basement membrane that forms the barrier to urinary protein loss. A putative disruption of the slit diaphragm and its main protein components, nephrin and podocin, may be implicated in the pathogenesis of lupus nephritis (LN). We studied the glomerular protein expression of nephrin and podocin in NZB/W LN mice by Western blot and immunofluorescence; mRNA levels were measured by real-time PCR. Human kidney biopsies of class II (n = 5), IV (n = 4), V (n = 7) LN were evaluated for nephrin expression by immunohistochemistry. Glomerular protein expression of nephrin and podocin were significantly reduced in NZB/W LN, starting from the earlier stages (mild mesangial LN) and becoming pronounced at advanced histological forms (focal and diffuse proliferative LN). Nephrin and podocin mRNA levels were substantially decreased in diffuse proliferative disease. Decreased expression of both proteins correlated with electron microscopy findings of distorted slit diaphragms. In patients with LN, nephrin was decreased particularly in diffuse proliferative LN. The main slit diaphragm proteins, nephrin and podocin, are affected from the earlier stages of LN and their expression correlates with disease histology. Our findings suggest a novel role of podocytes and their structures in immune-mediated nephritis.

Peroxisome proliferator-activated receptor gamma expression in urothelial carcinomas of the bladder: association with differentiation, proliferation and clinical outcome.

AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic significance of PPARgamma expression in human urothelial bladder cancer (BUC). METHODS: Immunohistochemistry was applied in 117 paraffin-embedded specimens of human BUC to detect the proteins PPARgamma and Ki67. The image analysis method was used for the evaluation of the immunohistochemical staining. RESULTS: PPARgamma protein was localized in the nuclei of the malignant cells. Its expression was inversely associated with the stage of BUCs (p<0.001), tumor grade (p=0.007) and the expression of the proliferation marker Ki67 (p=0.015) while it was found to exert a favorable effect on patients' overall survival (p=0.001). CONCLUSION: The findings of the present study suggest that in BUC, PPARgamma expression can identify patients with a better prognosis who suffer from more differentiated, non-invasive tumors, of a low proliferative potential.

Prognostic value of microsatellite instability determined by immunohistochemical staining of hMSH2 and hMSH6 in urothelial carcinoma of the bladder.

Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130 specimens from urothelial carcinoma (UC) of the bladder to detect expression of MMR gene products hMSH2 and hMSH6, and to investigate its clinicopathological and prognostic value. hMSH2 and hMSH6 protein expression was exclusively detected in the nuclei of malignant cells. Of the 112 cases evaluable for hMSH2, 29 (25.9%) were negative and of the 130 UCs evaluable for hMSH6, 64 (49.2%) were negative, and were thus considered to depict MSI. Nuclear hMSH2 values were statistically lower in non-invasive UCs (Ta-T1) (p=0.013) and in carcinomas with decreased p53 staining (p=0.04). Lower hMSH6 values were more often met in well-differentiated tumors (p<0.0001) and in tumors with low expression of p53 (p=0.016), topoIIalpha and caspase 3 (p=0.017 and p=0.018, respectively). Both hMSH2- and hMSH6-negative immunoreactions were found to have a favorable impact on overall patient survival (p=0.041 and p=0.034, respectively), this finding being further verified in the multivariate analysis of hMSH2 (p=0.026). This is the first study to show that lack (and not reduction designated according to various cut-off points) of hMSH2 and hMSH6 correlated with non-invasive tumors of lower grade and is of favorable prognostic significance in patients suffering from bladder carcinoma.

Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation with proliferation and VEGF-C and -D proteins expression.

INTRODUCTION: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. METHODS: Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. RESULTS: Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008 respectively), while LV major axis, minor axis and the perimeter inversely correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively) and topoisomerase IIalpha (p=0.015, p=0.024 and p=0.045 respectively). The same LV parameters were found to positively correlate with cancerous VEGF-C (p<0.0001, p=0.092 and p=0.012 respectively) and VEGF-D in the stromal fibroblasts surrounding neoplastic cells (p=0.011, p=0.041 and p=0.026 respectively). High BVD exerted an unfavorable impact on both disease-free (p=0.021) and overall survival (p=0.031) of the patients. High LVD correlated with poor disease-free and overall survival only in the subgroup of patients with ER-negative tumors (p=0.056 and p=0.0312 respectively). CONCLUSION: These findings, for the first time, correlate lymphatic size with tumors of limited proliferative potential and higher nuclear differentiation. Moreover, they suggest that VEGF-C and -D expression influence lymphatic size rather than being involved in the increase of lymphatic vessel number.

The prognostic value of the topographic distribution of uPAR expression in invasive breast carcinomas.

uPA system plays an important role in cancer invasion and metastasis. The binding of uPA to its receptor, uPAR, is necessary for the activation of uPA system. We studied by immunohistochemistry the distribution pattern of uPAR on 173 paraffin-embedded samples of invasive breast carcinomas in relation to clinicopathologic data and patients' survival. uPAR was detected in both the malignant and stromal cells in the 68.8 and 74.6% of the cases, respectively. uPAR of cancerous cells was more often observed in lobular carcinomas (P=0.012). Stromal expression of uPAR was inversely associated with ER of the tumor (P=0.044) and was found to be an independent prognosticator of patients' shortened relapse-free survival (P=0.018). These results suggest that stromal uPAR influences more directly tumor behaviour, being related to an aggressive tumor phenotype and patients' poor relapse-free survival.

Regional differences in abdominal fat loss.

OBJECTIVE: This study determined if the magnetic resonance imaging (MRI) protocol used alters the estimation of change in abdominal fat with weight loss in obese type 2 diabetic women. This study also examined if there is a uniform fat loss across the abdomen. METHODS AND PROCEDURES: Thirty-three obese postmenopausal women with type 2 diabetes (age 50-70 years, body mass index>30 kg/m(2)) had a total abdominal MRI scan pre- and post weight loss intervention. Three different MRI analysis protocols were used and compared: a single slice at L(2)-L(3) vs five slices (centered at L(4)-L(5)) vs all abdominal slices. In addition, the total abdominal scan was divided into four regions (four slices each) with region 3 (critical region) including the traditionally studied L(2)-L(3), and regions 1 and 2 superior and region 4 inferior to critical region 3. Analysis of variance (ANOVA) with repeated measures was used to compare the influence of weight loss on abdominal fat measured both regionally and using the varying number of MR slices. RESULTS: At baseline, the ratio of visceral adipose tissue:subcutaneous adipose tissue (VAT:SAT) was significantly lower using the single-slice method compared to five slices and the total abdomen (P<0.01). Using the single-slice method, a lower %VAT was found than with the other methods (P<0.01). In regions 1, 2, 3, and 4, the absolute change in total fat was 122+/-50, 182+/-48, 182+/-55, and 155+/-40 cm(3), respectively. The regional difference in abdominal fat patterning revealed that the critical region (region 3) had a smaller VAT:SAT ratio than regions 1 and 2 (P<0.05), and the ratio at region 4 was smaller than region 3 (P<0.05). Weight loss resulted in a decrease in the VAT:SAT ratio (P<0.05) for regions 3 and 4 but not for regions 1 and 2. CONCLUSIONS: The number of MR slices analyzed yields differential result in relative VAT distribution. Regional differences in abdominal fat loss occur with a greater relative VAT loss in the critical region, thus if only the critical region is analyzed the overall VAT loss induced by weight loss intervention may be overestimated.

Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma.

AIMS: Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma. MATERIAL AND METHODS: Immunohistochemistry was performed in paraffin-embedded tissue specimens from 177 invasive breast carcinomas to detect the proteins VEGF-C, VEGF-D, VEGFR-3, p53, Ki67, c-erbB-2, topoII alpha and ER/PR. The results were statistically processed. RESULTS: VEGF-C, VEGF-D and VEGFR-3 were found to be predominantly expressed in the cytoplasm of the malignant cells. VEGF-C occasionally showed a submembranous intensification. VEGF-D and VEGFR-3 were also immunodetected in the nuclei of the malignant cells. Nuclear VEGF-D was positively correlated to p53, Ki67 and topoII alpha proteins' expression (p=0.003, p=0.009 and p=0.017 respectively) and nuclear VEGFR-3 to topoII alpha (p=0.034). Cytoplasmic expression of VEGF-C and its submembranous intensification were found to be independent indicators of patients' overall and disease-free survival, respectively (p=0.003 and p=0.044 respectively). The group with high expression of both cytoplasmic VEGF-C and stromal VEGFR-3 showed poor overall survival (p=0.024) and the group with both submembranous VEGF-C and stromal VEGFR-3 immunostaining showed poor both disease-free and overall survival (p=0.012 and p=0.038 respectively). CONCLUSION: VEGF-D and VEGFR-3 seem to exert proliferative activity in invasive breast carcinomas. VEGF-C was found to be an independent indicator of patient's poor prognosis and the simultaneous expression of tumor VEGF-C and stromal VEGFR-3 yielded additional prognostic information.

An immunohistochemical evaluation of phosphorylated Akt at threonine 308 [pAkt(Thr308)] in invasive breast cancer.

BACKGROUND: Akt is a serine/threonine kinase which is fully activated when phosphorylated (pAkt). The aim of this study was to investigate the expression pattern of phosphorylated Akt at Threonine 308 [pAkt(Thr308)] in association with clinicopathological parameters and various biological markers. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 152 invasive breast carcinomas to detect the expression of the proteins pAkt(Thr308), estrogen (ER) and progesterone (PR) receptors, p53, Ki-67 and c-erbB-2. RESULTS: pAkt(Thr308) protein was immunodetected in the cytoplasm and the nuclei of the malignant cells. pAkt was found to be positively associated with the lobular histological type, while it was found to exert no impact on patients' survival. pAkt(Thr308) immunopositivity was inversely related to Ki-67 and p53 (p=0.013 and p=0.020, respectively), while being positively associated with cerbB2 expression (p=0.005). CONCLUSION: This is the first study to show a frequent detection of pAkt(Thr308) in lobular breast carcinomas and an association of its expression with indices of proliferation (c-erbB2, Ki-67) and apoptosis (p53).

Study of phospho-beta-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome.

Beta-catenin has a crucial role in cell-cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated beta-catenin, as well as its relation to the tumors' phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the detection of phospho-beta-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho-beta-catenin index was determined by image analysis. Phospho-beta-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-beta-catenin was statistically higher in carcinomas of smaller tumor size (P = 0.030), lower stage (P = 0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P = 0.052 and P = 0.037, respectively). Nuclear phospho-beta-catenin showed a parallel correlation with ER and ERbeta (P = 0.022 and P = 0.043, respectively), bcl-2 (P = 0.042), uPAR in cancer cells (P = 0.041) and TIMP-1, although the correlation was borderline (P = 0.066). Cytoplasmic phospho-beta-catenin was found to be independently correlated with prolonged disease-free and overall survival (P = 0.046 and P = 0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P = 0.046). In conclusion, phospho-beta-catenin may have a different involvement in invasive breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive tumor phenotype, negatively affecting patients' overall survival, whereas cytoplasmic localization is associated with a favorable tumor phenotype and a longer disease-free and overall survival.

Overexpression of cyclooxygenase-2 is associated with a favorable prognostic phenotype in breast carcinoma.

OBJECTIVES: Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIalpha (topoIIalpha) and peroxisome proliferator-activated receptor (PPARgamma) proteins, as well as its effect on patients' survival. METHODS: We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIalpha and PPARgamma proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis. RESULTS: Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p < 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIalpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARgamma was parallel (p < 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival. CONCLUSIONS: The current data suggest that increased expression of COX-2 may be related to breast carcinomas with less aggressive phenotype. This suggestion is further supported by the positive correlation between COX-2 and PPARgamma, since the latter is considered to be indicative of a less malignant phenotype of tumor cells.

Effect of different ERK2 protein localizations on prognosis of patients with invasive breast carcinoma.

Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK1/2, which have been implicated in the pathogenesis of cancer. We examined 151 cases of invasive breast carcinoma by immunohistochemistry and compared the ERK2 expression with clinicopathological parameters, MMP-11 immunoexpression and patients' survival. ERK2 immunoexpression was detected in the cytoplasm and nucleus of cancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p = 0.039), whereas cytoplasmic ERK2 was positively correlated with MMP-11 in fibroblasts (p = 0.032) and more often expressed in lobular than ductal carcinomas (p = 0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p = 0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p < 0.0001 and p = 0.002, respectively). These findings suggest that the different subcellular localizations of ERK2 seem to be related to different, possibly contradictory, effects on patient survival.

Hormone-replacement therapy use, but not race, impacts the resting and exercise-induced GH response in postmenopausal women.

OBJECTIVE: This study examined the effect of hormone-replacement therapy (HRT) use on the incremental GH response to aerobic exercise in postmenopausal women and established whether racial differences in the GH response were seen at rest and in response to exercise. METHODS: 13 white (n = 6, HRT; n = 7, no HRT) and seven black women (no HRT) were studied on two occasions, a control day and an exercise day (30 min at 70% VO(2)max on a cycle ergometer). Blood was sampled every 10 min for a 4-h period and analyzed for GH using an ultrasensitive chemiluminescent assay. RESULTS: The mean 4-h GH concentration was higher on both study days in the HRT women than the non-HRT users. The integrated GH concentrations were greater in the HRT women both at rest and in response to exercise (rest, 352 +/- 53 min microg l(-1); exercise, 711 +/- 57 min microg l(-1); P < 0.01) than in the non-HRT women (rest, 157 +/- 87 min microg l(-1); exercise, 248 +/- 94 min microg l(-1)). The incremental GH response was greater in the HRT users than in the non-HRT women (358 +/- 130 versus 90.8 +/- 94 min microg l(-1), respectively; P < 0.05). GH-production rate during the 4-h period was greater in the HRT women than in the non-HRT women (P < 0.01), due to an increase in the GH mass secreted/pulse (P < 0.05), with no change in GH pulse number or GH half-life. No racial differences in the mean 4-h GH concentrations or integrated GH concentrations were found at rest or in response to exercise. CONCLUSION: HRT use resulted in a greater incremental exercise response compared with non-HRT users, due to changes in the secretory pulse characteristics in the HRT users. This study also demonstrated that no racial differences exist at rest and in response to exercise in the morning hours.

PPARgamma expression in breast cancer: clinical value and correlation with ERbeta.

AIMS: To examine the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in invasive breast carcinoma in relation to known clinicopathological features, ERbeta, and relapse-free and overall patient survival. PPARgamma is a ligand-activated transcriptional factor that regulates the transcription of various target genes and has been implicated in human breast cancer. METHODS AND RESULTS: We performed immunohistochemistry to detect PPARgamma, ERalpha, PR and ERbeta in 170 infiltrative breast carcinomas. The results were subjected to statistical analysis. PPARgamma was detected in the cytoplasm of 58% of breast carcinoma samples. PPARgamma did not differ with regard to any of the clinicopathological parameters except for histological grade, to which it was found to be inversely correlated (P = 0.019), and ERbeta, to which it was positively related (P = 0.016). As regards relapse-free survival, in univariate statistical analysis PPARgamma was found to exert a marginally favourable impact on all the patients (P = 0.076), but a strong one on patients with ductal carcinoma (P = 0.027), whereas Cox's regression analysis depicted PPARgamma to be an independent prognosticator for patients with ductal carcinoma (P = 0.039). No association was found between PPARgamma expression and overall survival. CONCLUSION: These results indicate the favourable impact of PPARgamma expression on disease-free survival of patients with ductal breast carcinoma and its possible cooperation with ERbeta in exerting that favourable effect.

Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes.

This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise (D+E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women (body mass index, 34.6 +/- 1.9 kg/m(2)) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone (EX), and D+E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution (magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured pre- and postintervention. Body weight ( approximately 4.5 kg) and percent body fat ( approximately 5%) were decreased (P < 0.05) with the D and D+E intervention, whereas only percent body fat ( approximately 2.3%) decreased with EX. Total abdominal fat and sc adipose tissue (SAT) were reduced with the D and D+E interventions (P < 0.05), whereas visceral adipose tissue (VAT) decreased with the D+E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT (P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels (P < 0.05). In conclusion, modest weight loss, through either D or D+E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes.