Systematic screening of synthetic organochalcogen compounds with anticancer activity using human lung adenocarcinoma spheroids.

Lung adenocarcinoma stands as a leading global cause of cancer-related fatalities, with current therapeutic approaches remaining unsatisfactory. Given the association between elevated oxidative markers and the aggressive nature of cancer cells (including multidrug resistance and metastatic potential) that can predict poor outcome of lung adenocarcinoma patients, any compounds that interfere with their aberrant redox biology should be rationally explored as innovative intervention strategies. This study was designed to screen potential anticancer activities within nine newly synthesized organochalcogen - compounds characterized by the presence of oxygen, sulfur, or selenium elements in their structure and exhibiting antioxidant activity - and systematically evaluated their performance against cisplatin, the cornerstone therapeutic agent for lung adenocarcinoma. Our methodology involved the establishment of optimal conditions for generating single tumor spheroids using A549 human lung adenocarcinoma cell line. The initiation interval for spheroid formation was determined to be four days in vitro (DIV), and these single spheroids demonstrated sustained growth over a period of 20 DIV. Toxic dose-response curves were subsequently performed for each compound after 24 and 48 h of incubation at the 12th DIV. Our findings reveal that at least two of the synthetic organochalcogen compounds exhibited noteworthy anticancer activity, surpassing cisplatin in key parameters such as lower LD (Lethal Dose) 50, larger drug activity area, and maximum amplitude of effect, and are promising drugs for futures studies in the treatment of lung adenocarcinomas. Physicochemical descriptors and prediction ADME (absorption, distribution, metabolism, and excretion) parameters of selected compounds were obtained using SwissADME computational tool; Molinspiration server was used to calculate a biological activity score, and possible molecule targets were evaluated by prediction with the SwissTargetPrediction server. This research not only sheds light on novel avenues for therapeutic exploration but also underscores the potential of synthetic organochalcogen compounds as agents with superior efficacy compared to established treatments.

Bioscaffold developed with decellularized human amniotic membrane seeded with mesenchymal stromal cells: assessment of efficacy and safety profiles in a second-degree burn preclinical model.

Therapies to deep burn injuries remain a global challenge. Human amniotic membrane (hAM) is a biomaterial that has been increasingly explored by the field of regenerative medicine. A decellularized hAM (DhAM) can be used as scaffold for mesenchymal stromal cells (MSCs) to grow without the loss of their stemness potential, allowing its application as cell therapy for wound healing. In this work, we associated DhAM with adipose-derived MSCs (DhAM + AD-MSCs), as a therapy strategy for second-degree burns in a preclinical model. Animals with induced second-degree burns were divided into four groups: control, which consists of a non-adherent gauze; a synthetic commercial dressing as the positive control (Control+); DhAM; and DhAM plus rat AD-MSCs (DhAM + AD-MSCs), followed by detailed and long term analysis (5 weeks). The macroscopical analysis showed the healing improvement in the wound area after the DhAM + AD-MSC treatment. Histological analysis also showed no alteration in the animal organs and a regular epithelial progression in comparison to the control. This observation was also confirmed by the analysis of suprabasal layers in the neoepidermis with CK10, showing a stratified and differentiated epithelium, when compared to Control and Control+. A strong CD73 (ecto-5'-nucleotidase) labeling was observed in the first 2 weeks postburn in dermis and epidermis. The expression in dermis was stronger in the second week in the middle of the wound, when comparing the Control+ with DhAM + AD-MSCs (p= 0.0238). In the epidermis the expression of CD73 was increased in all regions when compared to the control. This data suggests the involvement of this protein on wound healing. A low CD11b labeling was observed in DhAM + AD-MSCs treatment group mainly in the last treatment week, in comparison to Control and Control+ (p< 0.0001), which indicates a reduction in the inflammatory process. MSCs through CD73 can release high concentrations of adenosine, an immunosuppressive molecule, suggesting that this could be the mechanism by which the inflammation was better modulated in the DhAM + AD-MSCs group. The results obtained with this preclinical model confirm the effectiveness and safety of this low-cost and highly available dressing for future clinical application as a therapy for burn treatments.

The Relevance of Ultrastructural Studies of Metastatic Cells from Women with Breast Cancer History.

The interaction between cancer cells and the surrounding microenvironment is determinant for metastasis success. In this study, the ultrastructural relevance of cells in the malignant pleural effusion (MPE) of women with breast cancer history was investigated. In MPE, it is possible to observe single cells and clusters. Women whose MPE presents carcinomas in aggregates have a better prognosis when compared to cases in which metastatic single cells are found. Samples were collected via fine-needle aspiration puncture (US-FNA). Subsequent to the material preparation and ultrathin cuts, they were observed using light and transmission electron microscopy (LM/TEM). LM and TEM images served as a basis for the creation of a digital sculpture using ZBrush® software. Clusters exhibited structural stability, en route vesicles allowing exocytosis of electron-dense fibrous elements, and cytoplasmic protrusions contributing to migratory and invasive skills. Single cells presented different necrotic phenotypes and many displayed leukocyte-like characteristics. Cluster cooperative relationships seem to be related to a long-term permanence in MPE. The absence of a collaborative network presumably triggers a more aggressive behavior of single cells. Its putative fusion with leukocytes can maximize the efficiency for transendothelial migration, increasing chances of metastatic success and, unfortunately, reducing survival of women with recidivism.

Effect of QTC-4-MeOBnE Treatment on Memory, Neurodegeneration, and Neurogenesis in a Streptozotocin-Induced Mouse Model of Alzheimer's Disease.

Growing evidence suggests that drugs targeting neurogenesis and myelinization could be novel therapeutic targets against Alzheimer's disease (AD). Intracerebroventricular (icv) injection of streptozotocin (STZ) induces neurodegeneration through multiple mechanisms ultimately resulting in reduced adult neurogenesis. Previously, the multitarget compound QTC-4-MeOBnE (1-(7-chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide) demonstrated beneficial effects in preclinical models of AD. Here we investigated its pharmacokinetics profile and the effect on memory impairments and neurodegeneration induced by STZ. Two icv injections of STZ resulted in significant cognitive and memory impairments, assessed by novel object recognition, Y-maze, social recognition, and step-down passive avoidance paradigms. These deficits were reversed in STZ-injected mice treated with QTC-4-MeOBnE. This effect was associated with reversion of neuronal loss in hippocampal dentate gyrus, reduced oxidative stress, and amelioration of synaptic function trough Na+/K+ ATPase and acetylcholinesterase activities. Furthermore, brains from QTC-4-MeOBnE-treated mice had a significant increase in adult neurogenesis and remyelination through Prox1/NeuroD1 and Wnt/ß-catenin pathways. Overall, our findings support the potential anti-AD effect of QTC-4-MeOBnE through multiple pathways, all of which have been involved in the onset and progression of the disease.

Hypermethioninemia induces memory deficits and morphological changes in hippocampus of young rats: implications on pathogenesis.

The aim of this study was to investigate the effect of the chronic administration of methionine (Met) and/or its metabolite, methionine sulfoxide (MetO), on the behavior and neurochemical parameters of young rats. Rats were treated with saline (control), Met (0.2-0.4 g/kg), MetO (0.05-0.1 g/kg), and/or a combination of Met + MetO, subcutaneously twice a day from postnatal day 6 (P6) to P28. The results showed that Met, MetO, and Met + MetO impaired short-term and spatial memories (P < 0.05), reduced rearing and grooming (P < 0.05), but did not alter locomotor activity (P > 0.05). Acetylcholinesterase activity was increased in the cerebral cortex, hippocampus, and striatum following Met and/or MetO (P < 0.05) treatment, while Na+, K+-ATPase activity was reduced in the hippocampus (P < 0.05). There was an increase in the level of thiobarbituric acid reactive substances (TBARS) in the cerebral cortex in Met-, MetO-, and Met + MetO-treated rats (P < 0.05). Met and/or MetO treatment reduced superoxide dismutase, catalase, and glutathione peroxidase activity, total thiol content, and nitrite levels, and increased reactive oxygen species and TBARS levels in the hippocampus and striatum (P < 0.05). Hippocampal brain-derived neurotrophic factor was reduced by MetO and Met + MetO compared with the control group. The number of NeuN-positive cells was decreased in the CA3 in Met + MetO group and in the dentate gyrus in the Met, MetO, and Met + MetO groups compared to control group (P < 0.05). Taken together, these findings further increase our understanding of changes in the brain in hypermethioninemia by elucidating behavioral alterations, biological mechanisms, and the vulnerability of brain function to high concentrations of Met and MetO.

Altered expression of COX-2 and TNF-α in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: hepatocellular carcinoma is a type of cancer related with inflammation, as 90% of cases develop in a chronic inflammation condition. Excess inflammation can affect tissue homeostasis. Cytokines and inflammatory mediators are immunological components that can influence the functioning of cells and tissues. In addition, the estrogen receptor appears to play an important role in hepatocarcinogenesis. The aim of the study was to evaluate the expression of inflammatory markers and ER in patients with hepatocellular carcinoma. METHODS: data from 143 patients of ISCMPA were analyzed. Immunohistochemistry was performed of cyclooxygenase-2 enzyme (COX-2), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α) and ER in paraffin-embedded hepatic tissue. The percentage of the stained area, intensity of staining and of the number of ER positive nuclei were evaluated using the ImageJ 1.50 software. RESULTS AND CONCLUSION: there was a significant difference between the groups in terms of the percentage of marked area (p = 0.040) for COX-2 and the intensity of staining of TNF-α (p = 0.030). No significant differences were observed in any of other parameters evaluated. In conclusion, COX-2 and TNF-α are possible markers that should be further studied to determine their immunohistochemical profile and role in HCC development.

A phytochemical study of the Cuphea glutinosa from Southern Brazil: Na+,K+-ATPase activity inhibition and antioxidant properties.

This study investigated the antioxidant activity of Cuphea glutinosa (CG) and its effect on Na+, K+-ATPase from cardiac muscle. The ethanolic extract showed higher antioxidant capacity compared to aqueous and ethyl acetate fraction. Ethyl acetate fraction showed ß-sitosterol-3-O-ß-glucoside, kaempferol, quercetin, isoquercetin, gallic acid methyl ester, and gallic acid. The ethanolic extract also reduced the Na+,K+-ATPase activity. CG presented a promising antioxidant activity and inhibitory effect on the Na+, K+-ATPase activity, supporting biochemical evidences the popular use of this plant in the treatment of heart failure.

Omega-3 fatty acids revert high-fat diet-induced neuroinflammation but not recognition memory impairment in rats.

Neuroinflammation is a consequence of overeating and may predispose to the development of cognitive decline and neurological disorders. This study aimed to evaluate the impact of omega-3 supplementation on memory and neuroinflammatory markers in rats fed a high-fat diet. Male Wistar rats were divided into four groups: standard diet (SD); standard diet + omega-3 (SD + O); high fat diet (HFD); and high fat diet + omega-3 (HFD + O). Diet administration was performed for 20 weeks and omega-3 supplementation started at the 16th week. HFD significantly increased body weight, while omega-3 supplementation did not modify the total weight gain. However, animals from the HFD + O group showed a lower level of visceral fat along with an improvement in insulin sensitivity following HFD. Thus, our results demonstrate a beneficial metabolic role of omega-3 following HFD. On the other hand, HFD animals presented an impairment in object recognition memory, which was not recovered by omega-3. In addition, there was an increase in GFAP-positive cells in the cerebral cortex of the HFD group, showing that omega-3 supplementation can be effective to decrease astrogliosis. However, no differences in GFAP number of cells were found in the hippocampus. We also demonstrated a significant increase in gene expression of pro-inflammatory cytokines IL-6 and TNF-α in cerebral cortex of the HFD group, reinforcing the anti-inflammatory role of this family of fatty acids. In summary, omega-3 supplementation was not sufficient to reverse the memory deficit caused by HFD, although it played an important role in reducing the neuroinflammatory profile. Therefore, omega-3 fatty acids may play an important role in the central nervous system, preventing the progression of neuroinflammation in obesity.

Intervention with the mother-infant relationship reduces cell proliferation in the Locus Coeruleus of female rat pups.

The Locus Coeruleus (LC) is a noradrenergic nucleus involved in several neuroendocrine and behavioral functions. During the neonatal period, the LC is critical for olfactory learning. Full development occurs during the early postnatal period. Environmental interventions after birth may affect neurogenesis. In rats, the neonatal handling procedure has been used as a model to analyze the effects of environmental intervention early in life. It has been related to several long-lasting behavioral and neuroendocrine changes. The present study analyzed the effects of handling on the number of neurons, cellular proliferation, and apoptosis in the LC of 11-day-old female rats. Wistar rat pups were submitted to brief maternal separation followed by handling (1 min per day from postnatal day [PND] 1 to 10). On PND 11, the LC was analyzed using immunohistochemistry for NeuN and BrdU, TUNEL staining, and electron microscopy. The intervention reduced the number of neurons in the LC but showed no significant change in the number of apoptotic cells, as measured by the TUNEL technique. However, the number of proliferating cells was significantly lower in the handled rat pups as compared with the nonhandled ones. This study demonstrates that the infant LC is sensitive to changes in maternal behavior. A seemingly mild environmental intervention during the neonatal period may reprogram the development of the LC, altering cell proliferation. (PsycINFO Database Record

The effect of taurine and enriched environment on behaviour, memory and hippocampus of diabetic rats.

Diabetes mellitus (DM) has been studied recently as a major cause of cognitive deficits, memory and neurodegenerative damage. Taurine and enriched environment have stood out for presenting neuroprotective and stimulating effects that deserve further study. In this paper, we examined the effects of taurine and enriched environment in the context of diabetes, evaluating effects on behaviour, memory, death and cellular activity. Eighty-eight Wistar rats were divided into 2 groups (E=enriched environment; C=standard housing). Some animals (24/group) underwent induction of diabetes, and within each group, some animals (half of diabetics (D) and half of non-diabetics (ND)/group) were treated for 30days with taurine (T). Untreated animals received saline (S). In total, there were eight subgroups: DTC, DSC, NDTC, NDSC, DTE, DSE, NDTE and NDSE. During the experiment, short-term memory was evaluated. After 30th day of experiment, the animals were euthanized and was made removal of brains used to immunohistochemistry procedures for GFAP and cleaved caspase-3. As a result, we observed that animals treated with taurine showed better performance in behavioural and memory tasks, and the enriched environment had positive effects, especially in non-diabetic animals. Furthermore, taurine and enriched environment seemed to be able to interfere with neuronal apoptosis and loss of glial cells, and in some instances, these two factors seemed to have synergistic effects. From these data, taurine and enriched environment may have important neurostimulant and neuroprotective effects.

Effect of Alcohol and Tobacco Smoke on Long-Term Memory and Cell Proliferation in the Hippocampus of Rats.

INTRODUCTION: Alcohol is frequently used in combination with tobacco and few studies explore interactions between these two drugs of abuse. Here, we evaluated the effect of chronic alcohol administration and concomitant exposure to tobacco smoke on long-term memory and on cell proliferation in the hippocampus of rats. METHODS: Forty male Wistar rats were assigned to four groups and treated with alcohol (2g/kg by gavage) and/or exposed to tobacco smoke (from six cigarettes, by inhalation) twice a day (at 9:00 AM and 2:00 PM) for 30 days. Long-term memory was evaluated in the inhibitory avoidance test and hippocampal cell proliferation was analyzed for bromodeoxyuridine immunohistochemistry. RESULTS: Our results showed that alcohol, tobacco smoke, or their combination improved the long-term memory evaluated by the memory index in rats. Moreover, alcohol and tobacco coadministration decreased bromodeoxyuridine-labeled cells by 60% when compared to the control group, while alcohol treatment decreased labeled cells by 40%. The tobacco group showed a nonsignificant 26% decrease in labeled cells compared to the control group. CONCLUSIONS: Chronic alcohol and tobacco coadministration improves the long-term memory in rats in the inhibitory avoidance test. However, coadministration decreases the cell proliferation in the hippocampus of rats, suggesting a deleterious effect by the combined use of these drugs of abuse.

The potential role of extracellular regulatory kinase in the survival of patients with early stage adenocarcinoma.

BACKGROUND: Lung cancer is among the most common types of neoplasias, and adenocarcinoma is the most frequent histological type. There is currently an extensive search for prognostic biomarkers of nonsmall cell lung cancer (NSCLC). METHODS: We analyzed the correlation of clinical data and patient survival with the levels of activated extracellular regulatory kinase (ERK) in histological samples of surgically resected early stage lung adenocarcinoma. We randomly selected 36 patients with stage I or II lung adenocarcinoma who underwent pulmonary lobectomy between 1998 and 2004. Patients were divided into the following two groups according to immunohistochemical profile: a group with <15% ERK-positive tumor cells and a group with ≥15% ERK-positive tumor cells. For data comparison, an enrichment analysis of a microarray database was performed (GSE29016, n=72). RESULTS: Activated ERK levels were ≥15% and <15% in 21 (58%) and 15 (42%) patients, respectively. There were no statistically significant differences in age, sex, smoking history, and body mass index (BMI) among the groups stratified by ERK levels. The survival rate was lower in the ERK ≥15% group than in the ERK <15% group (P=0.045). Enrichment analyses showed no correlation between variations in gene expression of ERK in patients with adenocarcinoma and survival rates in patients with stage I and combined stage II + III disease. CONCLUSIONS: Our findings suggest that high ERK positivity in cells from biological samples of lung adenocarcinoma is related with tumor aggressiveness and a poorer prognosis.

New therapy of skin repair combining adipose-derived mesenchymal stem cells with sodium carboxymethylcellulose scaffold in a pre-clinical rat model.

Lesions with great loss of skin and extensive burns are usually treated with heterologous skin grafts, which may lead rejection. Cell therapy with mesenchymal stem cells is arising as a new proposal to accelerate the healing process. We tested a new therapy consisting of sodium carboxymethylcellulose (CMC) as a biomaterial, in combination with adipose-derived stem cells (ADSCs), to treat skin lesions in an in vivo rat model. This biomaterial did not affect membrane viability and induced a small and transient genotoxicity, only at the highest concentration tested (40 mg/mL). In a rat wound model, CMC at 10 mg/mL associated with ADSCs increased the rate of cell proliferation of the granulation tissue and epithelium thickness when compared to untreated lesions (Sham), but did not increase collagen fibers nor alter the overall speed of wound closure. Taken together, the results show that the CMC is capable to allow the growth of ADSCs and is safe for this biological application up to the concentration of 20 mg/mL. These findings suggest that CMC is a promising biomaterial to be used in cell therapy.

Enriched environment prevents memory deficits in type 1 diabetic rats.

Studies have shown that an enriched environmental (EE) enhances hippocampal neurogenesis and dendritic branching in rodents, improving the performance in learning and memory task. Diabetes, however, is associated with memory deficits and decreasing in cell proliferation in the hippocampal dentate gyrus (DG), possibly related with higher glucocorticoid levels. Thus, our objective was to investigate the influence of EE on the memory deficits and cell proliferation of diabetic rats. For this, we reared rats for 2 months during early stages of life in standard environments (control rats) or EE. At adulthood, control and EE groups were divided and half of them induced to diabetes by a single injection of streptozotocin, 60 mg/kg, via i.p. Memory deficit was evaluated in these groups in the novel object-placement recognition task 11 days after diabetes induction. BrdU label cells were detected by immunohistochemistry after 3 days of administration to correlate cell proliferation in the DG area and performance in the memory task. Our results showed that EE decreased memory deficits in diabetic-induced rats (p < 0.05). Although cell proliferation in the DG was lower in the diabetic rats, enriched environment did not interfere in this parameter. These findings suggest that enriched environment is able to prevent or delay the development of memory deficits caused by diabetes in rats.

Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies.

The molecular mechanisms underlying the cellular lost found in the nigrostriatal pathway during the progression of Parkinson's disease (PD) are not completely understood. Human neuroblastoma cell line SH-SY5Y challenged with 6-hydroxydopamine (6-OHDA) has been widely used as an in vitro model for PD. Although this cell line differentiates to dopaminergic neuron-like cells in response to low serum and retinoic acid (RA) treatment, there are few studies investigating the differences between proliferative and RA-differentiated SH-SY5Y cells. Here we evaluate morphological and biochemical changes which occurs during the differentiation of SH-SY5Y cells, and their responsiveness to 6-OHDA toxicity. Exponentially growing SH-SY5Y cells were maintained with DMEM/F12 medium plus 10% of fetal bovine serum (FBS). Differentiation was triggered by the combination of 10 microM RA plus 1% of FBS during 4, 7 and 10 days in culture. We found that SH-SY5Y cells differentiated for 7 days show an increase immunocontent of several relevant neuronal markers with the concomitant decrease in non-differentiated cell marker. Moreover, cells became two-fold more sensitive to 6-OHDA toxicity during the differentiation process. Time course experiments showed loss of mitochondrial membrane potential triggered by 6-OHDA (mitochondrial dysfunction parameter), which firstly occurs in proliferative than neuron-like differentiated cells. This finding could be related to the increase in the immunocontent of the neuroprotective protein DJ-1 during differentiation. Our data suggest that SH-SY5Y cells differentiated by 7 days with the protocol described here represent a more suitable experimental model for studying the molecular and cellular mechanisms underlying the pathophysiology of PD.

Resveratrol and red wine function as antioxidants in the nervous system without cellular proliferative effects during experimental diabetes.

Chronic hyperglycemia increases oxidative stress status and has been associated with neurological complications in diabetic individuals. This study compared the antioxidant properties of red wine or resveratrol in different brain areas of diabetic and non-diabetic rats, and investigated the effect of them on hippocampal cell proliferation in hippocampal dentate gyrus of diabetic rats. Streptozotocin-induced diabetic and control rats were treated with red wine (4 mL/kg), resveratrol (20 mg/kg), or saline, by oral gavage, for 21 days. Lipid peroxidation (TBARS), catalase and superoxide dismutase were measured to evaluate the oxidative stress and the BrdU-positive cells were assessed to measure changes in cellular proliferation. In diabetic animals, resveratrol showed antioxidant property in the hippocampus and in the striatum, while red wine had an antioxidant effect only in the hippocampus. Neither red wine nor resveratrol reversed the lower hippocampal cell proliferation in diabetic rats. Daily doses of red wine or resveratrol have an antioxidant effect in rats depending on the brain area and the glycemic status.

Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters.

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5%), >20% of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40%) and 8 (20%) cases, respectively. P53 was positive in 18 (45%) cases, with 11 (61%) weakly positive and 7 (39%) strongly positive. HER2 was positive in 23 (57.5%) of the samples and did not show statistical association with survival (p=0.07).

Immunohistochemical expression of markers Ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters / Expressão imunoistoquímica dos marcadores Ki-67, neun, sinaptofisina, p53 e HER2 em meduloblastoma e sua correlação com os parâmetros clínico-patológicos

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5 percent), >20 percent of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40 percent) and 8 (20 percent) cases, respectively. P53 was positive in 18 (45 percent) cases, with 11 (61 percent) weakly positive and 7 (39 percent) strongly positive. HER2 was positive in 23 (57.5 percent) of the samples and did not show statistical association with survival (p=0.07).

Meduloblastoma (MB) é o tumor maligno encefálico mais freqüente na infância. dentre as alterações encontradas estão: a presença das oncoproteínas p53 e HER2, elevado índice mitótico e presença de diferenciação neuronal. o objetivo deste estudo foi determinar a expressão imunoistoquímica (IMQ) dos marcadores Ki-67, NeuN, sinaptofisina, HER2 e p53 em 40 amostras de MB, correlacionando-as com parâmetros clinicopatológicos e com a sobrevida. Vinte e nove pacientes (72,5 por cento) apresentaram 20 por cento ou mais das células positivas para Ki-67. os pacientes do sexo masculino apresentaram maior expressão do Ki-67 (p=0,02) e também menor sobrevida (p=0,002). NeuN e sinaptofisina foram negativos em 16 (40 por cento) e 8 (20 por cento) casos, respectivamente. P53 foi positivo em 18 (45 por cento) casos, sendo 11 (61 por cento) fracamente positivos e 7 (39 por cento) fortemente positivos. HER2 foi positivo em 23 (57,5 por cento) das amostras e não demonstrou associação estatística com a sobrevida (p=0.07).

Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.