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Diagnostics (Basel, Switzerland) Nov 2021Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than... (Review)
Review
Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1's reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears).
PubMed: 34943408
DOI: 10.3390/diagnostics11122172 -
The Prostate Sep 2020Most prostate cancers express androgen receptor (AR), and our previous studies have focused on identifying transcription factors that modify AR function. We have shown...
BACKGROUND
Most prostate cancers express androgen receptor (AR), and our previous studies have focused on identifying transcription factors that modify AR function. We have shown that nuclear factor I/B (NFIB) regulates AR activity in androgen-dependent prostate cancer cells in vitro. However, the status of NFIB in prostate cancer was unknown.
METHODS
We immunostained a tissue microarray including normal, hyperplastic, prostatic intraepithelial neoplasia, primary prostatic adenocarcinoma, and castration-resistant prostate cancer tissue samples for NFIB, AR, and synaptophysin, a marker of neuroendocrine differentiation. We interrogated publically available data sets in cBioPortal to correlate NFIB expression and AR and neuroendocrine prostate cancer (NEPCa) activity scores. We analyzed prostate cancer cell lines for NFIB expression via Western blot analysis and used nuclear and cytoplasmic fractionation to assess where NFIB is localized. We performed co-immunoprecipitation studies to determine if NFIB and AR interact.
RESULTS
NFIB increased in the nucleus and cytoplasm of prostate cancer samples versus matched normal controls, independent of Gleason score. Similarly, cytoplasmic AR and synaptophysin increased in primary prostate cancer. We observed strong NFIB staining in primary small cell prostate cancer. The ratio of cytoplasmic-to-nuclear NFIB staining was predictive of earlier biochemical recurrence in prostate cancer, once adjusted for tumor margin status. Cytoplasmic AR was an independent predictor of biochemical recurrence. There was no statistically significant difference between NFIB and synaptophysin expression in primary and castration-resistant prostate cancer, but cytoplasmic AR expression was increased in castration-resistant samples. In primary prostate cancer, nuclear NFIB expression correlated with cytoplasmic NFIB and nuclear AR, while cytoplasmic NFIB correlated with synaptophysin, and nuclear and cytoplasmic AR. In castration-resistant prostate cancer samples, NFIB expression correlated positively with an AR activity score, and negatively with the NEPCa score. In prostate cancer cell lines, NFIB exists in several isoforms. We observed NFIB predominantly in the nuclear fraction of prostate cancer cells with increased cytoplasmic expression seen in castration-resistant cell lines. We observed an interaction between AR and NFIB through co-immunoprecipitation experiments.
CONCLUSION
We have described the expression pattern of NFIB in primary and castration-resistant prostate cancer and its positive correlation with AR. We have also demonstrated AR interacts with NFIB.
Topics: Cell Line, Tumor; Gene Expression; Humans; Immunohistochemistry; Male; NFI Transcription Factors; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Tissue Array Analysis; Transcriptome
PubMed: 32692871
DOI: 10.1002/pros.24019 -
Oncology Letters Dec 2023SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4)-deficient non-small cell lung cancer (dNSCLC) is a rare...
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4)-deficient non-small cell lung cancer (dNSCLC) is a rare malignant tumor that originates in the lungs. It occurs more frequently in male smokers, and the epidermal growth factor receptor () gene is often mutation-free. In the present study, the case of a 60-year-old, non-smoking female patient diagnosed with SMARCA4-dNSCLC is reported. Biopsy of the tumor showed solid flaky, nest-like infiltrating growth. Immunohistochemistry revealed the following: SMARCA4/BRG1(-), SMARCB1/INI-1(+), cytokeratin7 (+), cytokeratin 5.2 (+), CK5/6(+) and calretinin(+). The Ki-67 positivity index was 75%, and the thyroid transcription factor-1, NapsinA, p40, nuclear protein in testis, CD34, Sal-like protein 4, SRY-box transcription factor 2 and synaptophysin were negative. Molecular analysis showed mutations in both and . The pathological diagnosis was SMARCA4-dNSCLC with an gene mutation. The present case report could be used for broadening the pathological diagnosis of SMARCA4-dNSCLC and for selecting appropriate treatment approaches.
PubMed: 37927421
DOI: 10.3892/ol.2023.14100 -
Brain Research Mar 2022Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of...
Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of neurons in the neocortical white matter in TLE patients than in controls. The aim of this work was to investigate whether white matter neurons are part of the neuronal circuitry. Therefore, we studied the distribution and density of synapses in surgically resected neocortical tissue of pharmacotherapy-resistant TLE patients. Neocortical white matter of temporal lobe from non-epileptic patients were used as controls. Synapses and neurons were visualized with immunohistochemistry using antibodies against synaptophysin and NeuN, respectively. The presence of synaptophysin in presynaptic terminals was verified by electron microscopy. Quantification of immunostaining was performed and the data of the patients' cognitive tests as well as clinical records were compared to the density of neurons and synapses. Synaptophysin density in the white matter of TLE patients was significantly higher than in controls. In TLE, a significant correlation was found between synaptophysin immunodensity and density of white matter neurons. Neuronal as well as synaptophysin density significantly correlated with scores of verbal memory of TLE patients. Neurosurgical outcome of TLE patients did not significantly correlate with histological data, although, higher neuronal and synaptophysin densities were observed in patients with favorable post-surgical outcome. Our results suggest that white matter neurons in TLE patients receive substantial synaptic input and indicate that white matter neurons may be integrated in epileptic neuronal networks responsible for the development or maintenance of seizures.
Topics: Drug Resistant Epilepsy; Epilepsy, Temporal Lobe; Humans; Neocortex; Nerve Net; Neurons; Synapses; Synaptophysin; Verbal Learning; White Matter
PubMed: 35041843
DOI: 10.1016/j.brainres.2022.147787 -
Neurobiology of Stress Nov 2023Maternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism...
Maternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism spectrum disorders, bipolar disorder and depression. These disorders are characterized by changes in microglial cells, which play a notable role in synaptic pruning, and synaptic deficits. Here, we investigated the effect of prenatal infection and social adversity during adolescence - either alone or in combination - on behavior, microglia, and synaptic density. Male offspring of pregnant rats injected with poly I:C, mimicking prenatal infection, were exposed to repeated social defeat during adolescence. We found that maternal infection during pregnancy prevented the reduction in social behavior and increase in anxiety induced by social adversity during adolescence. Furthermore, maternal infection and social adversity, alone or in combination, induced hyperlocomotion in adulthood. Longitudinal in vivo imaging with [C]PBR28 positron emission tomography revealed that prenatal infection alone and social adversity during adolescence alone induced a transient increase in translocator protein TSPO density, an indicator of glial reactivity, whereas their combination induced a long-lasting increase that remained until adulthood. Furthermore, only the combination of prenatal infection and social adversity during adolescence induced an increase in microglial cell density in the frontal cortex. Prenatal infection increased proinflammatory cytokine IL-1β protein levels in hippocampus and social adversity reduced anti-inflammatory cytokine IL-10 protein levels in hippocampus during adulthood. This reduction in IL-10 was prevented if rats were previously exposed to prenatal infection. Adult offspring exposed to prenatal infection or adolescent social adversity had a higher synaptic density in the frontal cortex, but not hippocampus, as evaluated by synaptophysin density. Interestingly, such an increase in synaptic density was not observed in rats exposed to the combination of prenatal infection and social adversity, perhaps due to the long-lasting increase in microglial density, which may lead to an increase in microglial synaptic pruning. These findings suggest that changes in microglia activity and cytokine release induced by prenatal infection and social adversity during adolescence may be related to a reduced synaptic pruning, resulting in a higher synaptic density and behavioral changes in adulthood.
PubMed: 37920548
DOI: 10.1016/j.ynstr.2023.100580 -
Scientific Reports May 2021Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4)...
Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.
Topics: Adenosine Triphosphate; Animals; Astrocytes; Cells, Cultured; Cerebral Cortex; Electron Transport Complex I; Hippocampus; Male; Mice; Mice, Knockout; Mitochondria; Nerve Tissue Proteins; Neurites; Neurons; Organ Specificity; Synaptophysin
PubMed: 34040028
DOI: 10.1038/s41598-021-90127-4 -
Basic and Clinical Neuroscience 2022The model for screening antidepressant-like activity in pre-clinical drug studies include, rat forced swimming test (FST). The reports on N-acetylcysteine (NAC) as an...
INTRODUCTION
The model for screening antidepressant-like activity in pre-clinical drug studies include, rat forced swimming test (FST). The reports on N-acetylcysteine (NAC) as an antioxidant supplement in stress related disorder is well documented. This study was aimed at potential antidepressant mechanism of N-Acetyl Cysteine (NAC), a glutamate precursor on FST animal model for screening antidepressant drugs using fluoxetine, a selective serotonin reuptake inhibitors (SSRIs) as standard antidepressant drug.
METHODS
Thirty adult male Wistar rats used for this study were randomly divided into six groups each with five (n=5) rats. The control group (A) received 1 ml of normal saline daily, group B served as the FST model, group C received 200mg/kg/day of NAC, group D received 20mg/kg/day of fluoxetine, group E the FST model treated with 200mg/kg/day of NAC, and F is the FST model treated with 20mg/kg/day of fluoxetine. Drugs were given orally. The effects of NAC on brain weights, the FST paradigms, sucrose preference test (SPT) for anhedonia were assessed and data analyzed using ANOVA where Tukey post-hoc test for statistical significance was set at (p < 0.05). The brains fixed in 4% paraformaldehyde, were processed and the paraffin embedded tissue were serially sectioned at 5 μm thick to be stained using Haematoxylin and Eosin (H and E) stain, immuno-histochemistry for synaptophysin (p38) and astrocytes (GFAP) activities in the prefrontal cortex (PFC).
RESULTS
Findings showed that NAC prevented FST-induced anxiety-like behaviors demonstrated by an increased SPT (that alleviates anhedonia), mobility time, and reduced immobility time. NAC caused an increase in brain weights and prevented FST-induced neurodegeneration, the proliferation of reactive astrocytes, and diminished synaptophysin immunoreactivity in the PFC similar to that seen in fluoxetine a standard anti-depressant drug.
CONCLUSION
NAC treatment significantly exhibits its neuroprotective mechanism via inhibiting the proliferation of reactive astrocytes, which protects neurons and synapses from oxidative tissue damage induced by FST, hence an increase in synaptophysin activity that culminates in increased neural activity, increased SPT, and reduced immobility time.
PubMed: 37323955
DOI: 10.32598/bcn.2023.2356.2 -
ACG Case Reports Journal Mar 2021Pancreatic ganglioneuromas occur mostly in children and rarely in young adults, with no cases reported in adults older than 60 years. An 86-year-old-woman, with active...
Pancreatic ganglioneuromas occur mostly in children and rarely in young adults, with no cases reported in adults older than 60 years. An 86-year-old-woman, with active advanced multiple myeloma, presented with epigastric pain for 2 days. Abdominal and pelvic computed tomography demonstrated a distended gallbladder, mildly dilated biliary tree, and a 13 × 8-mm hypodense mass in pancreatic body, without extrapancreatic invasion at endoscopic ultrasound. Fine-needle endoscopic ultrasound-guided core biopsy revealed characteristic histopathology of ganglioneuroma, as confirmed by immunohistochemical positivity for S100, SOX-10, and synaptophysin. This demonstrates novel finding of pancreatic ganglioneuroma occurring in the elderly. Lesion inclusion in the differential diagnosis may mandate tissue for pathologic diagnosis and complete lesion resection.
PubMed: 33763500
DOI: 10.14309/crj.0000000000000546 -
European Review For Medical and... Mar 2021Pancreatic neuroendocrine tumors (pNETs) are neuroendocrine tumors primarily found in the pancreas and upper small intestine. There are ten different pNETs: nine of...
Pancreatic neuroendocrine tumors (pNETs) are neuroendocrine tumors primarily found in the pancreas and upper small intestine. There are ten different pNETs: nine of these are associated with a specific functional syndrome, while one is not associated with a specific hormonal syndrome, and it is called non-functional. Up to 90% of pNETs are classified as non-functional. Immunohistochemistry is essential to define the diagnosis. However, to have a correct and reliable diagnosis, the pathologist must have adequately collected and treated tissue samples, thus the surgeon himself should be aware of some fundamental notions about tissue collection and fixation. Although several common biomarkers have been described to date, Chromogranin A and synaptophysin are currently considered the most specific immunohistochemical markers for NETs. Nearly 100% of pNETs are positive for both synaptophysin and Chromogranin A. Therefore, CgA and synaptophysin are effective for well-differentiated NETs but are less helpful in the diagnosis of poorly differentiated NECs, due to dedifferentiation, and then, degranulation of tumor cells. The Neuronal Specific Enolase (NSE) results to be an adequate marker in these cases. Considering the specific markers, many studies reported that endocrine pancreatic neoplasms are able to produce many different polypeptides and amines. Through immunohistochemical techniques, it is possible to define the diagnosis of pNET, which allows the clinicians to direct the patient to an effective therapeutic procedure. But to have a correct and reliable diagnosis, the tissue samples have to be adequately collected and treated.
Topics: Biomarkers, Tumor; Chromogranin A; Humans; Immunohistochemistry; Male; Neuroendocrine Tumors; Pancreatic Neoplasms; Surgeons; Synaptophysin
PubMed: 33829441
DOI: 10.26355/eurrev_202103_25418 -
Turkish Journal of Urology Jul 2022The aim of the study is to identify whether crossing vessel is a cause or an associated finding in Pelvi Ureteric Junction Obstruction.
OBJECTIVE
The aim of the study is to identify whether crossing vessel is a cause or an associated finding in Pelvi Ureteric Junction Obstruction.
MATERIAL AND METHODS
This is a prospective study of a total of 128 patients who underwent laparoscopic pyeloplasty from January 2016 to June 2020. All patients who underwent laparoscopic pyeloplasty and pelvi ureteric junction segments were sent for histopathological examination. The presence of crossing vessels is documented intraoperative and patients were divided into two groups, group 1 having pelvi ureteric junction obstruction with crossing vessel, and group 2, pelvi ureteric junction obstruction without crossing vessels. Histopathological examination findings of pelvi ureteric junction segment including inflammation, fibrosis, muscle hypertrophy, muscle disarray, and synaptophysin were recorded. Unpaired Student t-test was used for comparing differences between continuous normally distributed data from 2 samples and non-parametric tests were applied for continuous data.
RESULTS
Of the total 128 patients, crossing vessels were identified in 42 (32.8%), and 86 (67.2%) were without crossing vessels. The demographic profile of patients between the 2 groups was comparable. On histopathological examination, moderate-to-severe chronic inflammation was seen in 23.8% and 44.2% (P > .05) in group 1 and group 2, respectively; fibrosis and muscular hypertrophy were higher in group 2 but statistically insignificant (P > .05), and muscle disarray was higher in group 1 but statistically insignificant (P > .05). Synaptophysin was positive in 4.8% and 4.7% in group 1 and group 2, respectively.
CONCLUSION
The differences in histopathological examination between the 2 groups were not statistically significant. However, in patients with crossing vessels, there was a higher degree of inflammation, which may lead to early pelvi ureteric junction obstruction.
PubMed: 35913445
DOI: 10.5152/tud.2022.22012