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World Journal of Gastrointestinal... Feb 2024Early adenocarcinoma mixed with a neuroendocrine carcinoma (NEC) component arising in the gastroesophageal junctional (GEJ) region is rare and even rarer in young...
BACKGROUND
Early adenocarcinoma mixed with a neuroendocrine carcinoma (NEC) component arising in the gastroesophageal junctional (GEJ) region is rare and even rarer in young patients. Here, we report such a case in a 29-year-old Chinese man.
CASE SUMMARY
This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation. Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line, without Barrett's esophagus or involvement of the gastric cardia. The nodule was completely resected by endoscopic submucosal dissection (ESD). Pathological examination confirmed diagnosis of intramucosal adenocarcinoma mixed with an NEC component, measuring 1.5 cm. Immunohistochemically, both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%; NEC was positive for synaptophysin and chromogranin. Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the gene in the DNA repair pathway and a germline mutation of the gene, a common gastric cancer driver gene, in addition to pathogenic somatic mutations in and genes. The patient was alive without evidence of the disease 36 mo after ESD.
CONCLUSION
Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.
PubMed: 38425401
DOI: 10.4251/wjgo.v16.i2.563 -
Cureus Jan 2024Esophageal neuroendocrine carcinomas (E-NECs) are rare malignant tumors with unknown etiology and pathogenesis. The aggressive nature of E-NECs coupled with a tendency...
Esophageal neuroendocrine carcinomas (E-NECs) are rare malignant tumors with unknown etiology and pathogenesis. The aggressive nature of E-NECs coupled with a tendency to metastasize and no available treatment guidelines lead to poor prognosis. Here, we report a case of a 65-year-old, previously healthy female who presented with difficulty in swallowing solids, burning sensation over the epigastric region, weight loss (>10%), and altered bowel habits for the last three months. Contrast-enhanced CT (CECT) thorax revealed asymmetric mid-esophageal wall thickening with lymphadenopathy and metastasis in both hepatic lobes. Esophageal endoscopy revealed a large circumferential ulcero-proliferative mass and umbilicated lesions. A histopathological examination revealed small cells with scant cytoplasm and pleomorphic, hyperchromatic nuclei with prominent nuclear molding, and extensive necrosis. Immunohistochemistry revealed positivity for synaptophysin, chromogranin A, and CD56. Ki-67 index was 53%. These findings suggested poorly differentiated, small cell type, high-grade E-NEC. Chemotherapy with cisplatin (30mg/m) + irinotecan (60mg/m) was initiated. However, following two chemotherapy cycles, the patient succumbed.
PubMed: 38410310
DOI: 10.7759/cureus.53027 -
Foods (Basel, Switzerland) Feb 2024Alzheimer's disease (AD) is the most common neurodegenerative disease that results in memory impairment. (L.) Correa () is used as a traditional medicine. leaves have...
Alzheimer's disease (AD) is the most common neurodegenerative disease that results in memory impairment. (L.) Correa () is used as a traditional medicine. leaves have the potential to inhibit acetylcholinesterase activity. This study used scopolamine to induce AD in rats. The aim of this study was to investigate the effects of leaf extract using this model. Motor and memory functions were tested by the motor activity and Morris water maze (MWM) tests, respectively. The density of the synaptophysin and dendritic spines in the CA1 were detected by immunofluorescence and Golgi impregnation, respectively. The hippocampal histology was reviewed by H&E staining. After the treatment, the latency times in the MWM tests of the AD groups reduced, while the motor activities showed no difference. The density of the synaptophysin of the AD groups increased after the treatments, and that of the dendritic spines also increased in all AD groups post-treatment. The hippocampal tissue also recovered. leaf extract can improve cognitive impairment in AD models by maintaining the presynaptic vesicle proteins and dendritic spines in a dose-dependent manner.
PubMed: 38397604
DOI: 10.3390/foods13040627 -
CNS Neuroscience & Therapeutics Feb 2024Alleviating neurological dysfunction caused by acute ischemic stroke (AIS) remains intractable. Given Annexin A6 (ANXA6)'s potential in promoting axon branching and...
AIMS
Alleviating neurological dysfunction caused by acute ischemic stroke (AIS) remains intractable. Given Annexin A6 (ANXA6)'s potential in promoting axon branching and repairing cell membranes, the study aimed to explore ANXA6's potential in alleviating AIS-induced neurological dysfunction.
METHODS
A mouse middle cerebral artery occlusion model was established. Brain and plasma ANXA6 levels were detected at different timepoints post ischemia/reperfusion (I/R). We overexpressed and down-regulated brain ANXA6 and evaluated infarction volume, neurological function, and synaptic plasticity-related proteins post I/R. Plasma ANXA6 levels were measured in patients with AIS and healthy controls, investigating ANXA6 expression's clinical significance.
RESULTS
Brain ANXA6 levels initially decreased, gradually returning to normal post I/R; plasma ANXA6 levels showed an opposite trend. ANXA6 overexpression significantly decreased the modified neurological severity score (p = 0.0109) 1 day post I/R and the infarction area at 1 day (p = 0.0008) and 7 day (p = 0.0013) post I/R, and vice versa. ANXA6 positively influenced synaptic plasticity, upregulating synaptophysin (p = 0.006), myelin basic protein (p = 0.010), neuroligin (p = 0.078), and tropomyosin-related kinase B (p = 0.150). Plasma ANXA6 levels were higher in patients with AIS (1.969 [1.228-3.086]) compared to healthy controls (1.249 [0.757-2.226]) (p < 0.001), that served as an independent risk factor for poor AIS outcomes (2.120 [1.563-3.023], p < 0.001).
CONCLUSIONS
This study is the first to suggest that ANXA6 enhances synaptic plasticity and protects against transient cerebral ischemia.
Topics: Animals; Humans; Mice; Annexin A6; Infarction; Ischemic Stroke; Neuronal Plasticity; Reperfusion Injury
PubMed: 38380783
DOI: 10.1111/cns.14639 -
BMC Cancer Feb 2024Glioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this...
BACKGROUND
Glioblastoma (GBM) is an aggressive brain tumor that exhibits resistance to current treatment, making the identification of novel therapeutic targets essential. In this context, cellular prion protein (PrP) stands out as a potential candidate for new therapies. Encoded by the PRNP gene, PrP can present increased expression levels in GBM, impacting cell proliferation, growth, migration, invasion and stemness. Nevertheless, the exact molecular mechanisms through which PRNP/PrP modulates key aspects of GBM biology remain elusive.
METHODS
To elucidate the implications of PRNP/PrP in the biology of this cancer, we analyzed publicly available RNA sequencing (RNA-seq) data of patient-derived GBMs from four independent studies. First, we ranked samples profiled by bulk RNA-seq as PRNP and PRNP and compared their transcriptomic landscape. Then, we analyzed PRNP and PRNP GBM cells profiled by single-cell RNA-seq to further understand the molecular context within which PRNP/PrP might function in this tumor. We explored an additional proteomics dataset, applying similar comparative approaches, to corroborate our findings.
RESULTS
Functional profiling revealed that vesicular dynamics signatures are strongly correlated with PRNP/PrP levels in GBM. We found a panel of 73 genes, enriched in vesicle-related pathways, whose expression levels are increased in PRNP/PRNP cells across all RNA-seq datasets. Vesicle-associated genes, ANXA1, RAB31, DSTN and SYPL1, were found to be upregulated in vitro in an in-house collection of patient-derived GBM. Moreover, proteome analysis of patient-derived samples reinforces the findings of enhanced vesicle biogenesis, processing and trafficking in PRNP/PRNP GBM cells.
CONCLUSIONS
Together, our findings shed light on a novel role for PrP as a potential modulator of vesicle biology in GBM, which is pivotal for intercellular communication and cancer maintenance. We also introduce GBMdiscovery, a novel user-friendly tool that allows the investigation of specific genes in GBM biology.
Topics: Humans; Gene Expression; Gene Expression Profiling; Glioblastoma; Prion Proteins; Prions; rab GTP-Binding Proteins; Synaptophysin
PubMed: 38347462
DOI: 10.1186/s12885-024-11914-6 -
Case Reports in Oncology 2024Spindle cell sarcomas are rare breast lesions which are difficult to diagnose due to resemblance with other breast lesions. Histopathological examination and...
INTRODUCTION
Spindle cell sarcomas are rare breast lesions which are difficult to diagnose due to resemblance with other breast lesions. Histopathological examination and immunohistochemical staining are essential for diagnosis.
CASE PRESENTATION
We present a rare case of a 15-year-old female presenting with high-grade rapidly progressive spindle cell sarcoma of the breast, differentiated as phyllodes tumor, with axillary lymph node involvement. Her lesion, on the left breast, measured 16.9 × 10.1 × 13.7 cm. Histology revealed malignant neoplasm arranged in sheets and individual neoplastic cells with an epithelioid to spindled morphology with scant cytoplasm and irregular nuclear membranes. Immunohistochemistry showed weakly positive focal CD-99, and negative WT-1, Myogenin, Desmin, p63, Cytokeratin, Synaptophysin, and CD-34 markers. She was successfully managed with modified radical mastectomy and discharged with regular follow-up advised.
CONCLUSION
Spindle cell sarcomas have a very aggressive course and prompt diagnosis, and management is mandatory for better patient outcomes. Modified radical mastectomy is the mainstay of treatment.
PubMed: 38333631
DOI: 10.1159/000536125 -
Diagnostic Pathology Feb 2024NUT carcinoma is a rare cancer associated with a poor prognosis. Because of its rarity, its diagnosis is challenging and is usually made by excluding other diagnoses....
Neuroendocrine and squamous cell phenotypes of NUT carcinoma are potential diagnostic pitfalls that discriminating it from mimickers, such as small cell and squamous cell carcinoma.
INTRODUCTION
NUT carcinoma is a rare cancer associated with a poor prognosis. Because of its rarity, its diagnosis is challenging and is usually made by excluding other diagnoses. Immunohistochemical analysis is a reliable technique that contributes to a correct diagnosis, but overestimating the expression of neuroendocrine (NE) markers may result in an incorrect diagnosis. In this study, we established the immunohistochemical phenotypes of NUT carcinoma compared with tumors that mimic its phenotype to identify potential diagnostic pitfalls.
METHODS
Eight cases of NUT carcinoma were examined along with eight basaloid squamous cell carcinomas and thirteen cases of small cell carcinoma using an immunohistochemical panel consisting of various antibodies.
RESULTS
Of the eight NUT carcinomas, three patients had a smoking history. All the cases examined for INSM1 were positive (6/6, 100%), although the staining was somewhat weak. Among the NE markers, synaptophysin was variably positive in two NUT carcinomas (2/6, 33%); however, all cases were negative for ASCL1, chromogranin A, and CD56. Moreover, the squamous cell markers, p40 and CK5/6, were weakly expressed in 4/6 (67%) and 3/6 (50%) of the NUT carcinomas, respectively.
CONCLUSIONS
For tumors with an ambiguous morphology, applying the neuroendocrine phenotype of NUT carcinoma may be misleading; particularly, when distinguishing it from small-cell carcinoma. Similarly, null or weak expression of squamous cell markers may be observed in NUT carcinoma, but this differs from squamous cell carcinoma, which consistently demonstrates strong positivity for squamous cell markers.
Topics: Humans; Biomarkers, Tumor; Synaptophysin; Carcinoma, Squamous Cell; Small Cell Lung Carcinoma; Lung Neoplasms; Epithelial Cells; Phenotype; Carcinoma, Neuroendocrine; Repressor Proteins
PubMed: 38326851
DOI: 10.1186/s13000-024-01448-7 -
Brain, Behavior, & Immunity - Health Mar 2024Brain infection by the parasite is thought to impair learning and memory, although the underlying mechanisms remain largely unknown. Recent studies suggest that...
Brain infection by the parasite is thought to impair learning and memory, although the underlying mechanisms remain largely unknown. Recent studies suggest that perineuronal nets (PNNs) and their key regulator, matrix metalloproteinase-9 (MMP-9), have essential roles in synaptic plasticity associated with learning and memory. We investigated their roles in a chronic toxoplasmosis model using female mice. In mice with a high parasite burden of chronic infection, we found that MMP-9 expression was increased in the peripheral circulation and the brain. A correlation was found between the serum levels of MMP-9 and antibodies to the matrix antigen MAG1, a surrogate marker for tissue cysts in the brain. MMP-9 elevation was accompanied by increased expression of its endogenous regulators, TIMP-1 and NGAL. An increase in the levels of GSK-3α/β was observed, alongside a decrease in inhibitory GSK-3α/β (Ser-21/Ser-9) phosphorylation. MMP-9 expression was notably associated with the loss of PNNs but increased expression of the synaptic vesicle protein synaptophysin. There was a trend toward a negative correlation between MMP-9 and aggrecan expression, a critical PNN component. Together, these results suggest that chronic infection can cause an increase in MMP-9 expression, resulting in the degradation of PNNs, which provides a possible mechanism for -associated deficits in learning and memory.
PubMed: 38323226
DOI: 10.1016/j.bbih.2024.100728 -
BMC Veterinary Research Feb 2024The red-eared slider (Trachemys scripta elegans) is renowned for its remarkable adaptations, yet much of its complex biology remains unknown. In this pioneering study,...
The tongue of the red-eared slider (Trachemys scripta elegans): morphological characterization through gross, light, scanning electron, and immunofluorescence microscopic examination.
The red-eared slider (Trachemys scripta elegans) is renowned for its remarkable adaptations, yet much of its complex biology remains unknown. In this pioneering study, we utilized a combination of gross anatomy, scanning electron microscopy (SEM), light microscopy, and immunofluorescence techniques to examine the tongue's omnivorous adaptation in this species. This research bridges a critical knowledge gap, enhancing our understanding of this intriguing reptile. Gross examination revealed a unique arrowhead-shaped tongue with a median lingual fissure and puzzle-piece-shaped tongue papillae. SEM unveiled rectangular filiform, conical, and fungiform papillae, with taste pores predominantly on the dorsal surface and mucous cells on the lateral surface of the papillae. Histologically, the tongue's apex featured short rectangular filiform and fungiform papillae, while the body exhibited varying filiform shapes and multiple taste buds on fungiform papillae. The tongue's root contained lymphatic tissue with numerous lymphocytes surrounding the central crypt, alongside lingual skeletal musculature, blood and lymph vessels, and Raffin corpuscles in the submucosa. The lingual striated muscle bundles had different orientations, and the lingual hyaline cartilage displayed a bluish coloration of the ground substance, along with a characteristic isogenous group of chondrocytes. Our research represents the first comprehensive application of immunofluorescence techniques to investigate the cellular intricacies of the red-eared slider's tongue by employing seven distinct antibodies, revealing a wide array of compelling and significant findings. Vimentin revealed the presence of taste bud cells, while synaptophysin provided insights into taste bud and nerve bundle characteristics. CD34 and PDGFRα illuminated lingual stromal cells, and SOX9 and PDGFRα shed light on chondrocytes within the tongue's cartilage. CD20 mapped B-cell lymphocyte distribution in the lingual tonsil, while alpha smooth actin (α-SMA) exposed the intricate myofibroblast and smooth muscle network surrounding the lingual blood vessels and salivary glands. In conclusion, our comprehensive study advances our knowledge of the red-eared slider's tongue anatomy and physiology, addressing a significant research gap. These findings not only contribute to the field of turtle biology but also deepen our appreciation for the species' remarkable adaptations in their specific ecological niches.
Topics: Animals; Turtles; Electrons; Receptor, Platelet-Derived Growth Factor alpha; Tongue; Microscopy, Electron, Scanning
PubMed: 38310245
DOI: 10.1186/s12917-024-03879-2 -
Lung Cancer (Amsterdam, Netherlands) Mar 2024Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized distinct clinicopathological entity according to the fifth edition of the 2021...
BACKGROUND
Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized distinct clinicopathological entity according to the fifth edition of the 2021 World Health Organization Classification (WHO) for thoracic tumors. Thoracic SMARCA4-UTs are diagnostically challenging to diagnose, especially on small biopsies.
METHODS
We identified 35 thoracic SMARCA4-UTs from the Department of Pathology of West China Hospital, Sichuan University, between January 2017 and December 2022. In the present study, we summarized the clinicopathological features, prognostic significance and immunotherapy efficacy of thoracic SMARCA4-UTs.
RESULTS
All 35 patients were male, and 88.6 % were smokers. The left upper lobe (25.7 %) and mediastinum (20.0 %) were the most affected sites. 17.1 % of the patients received surgical treatment. 30.4 % of the patients were stage III, and 69.6 % were stage IV. Solid architecture (100 %), rhabdoid morphology (51.4 %) and necrosis (42.9 %) were the common histological features. Immunohistochemical staining revealed CD34 and synaptophysin positivity in most patients (76.9 % and 65.2 %, respectively). Patients had unfavorable outcomes. Patients who received immunotherapy had better OS and PFS than those who did not (p = 0.007 and p = 0.02, respectively). Five patients were evaluated for immunotherapy efficacy, and four of those patients were negative expression of PD-L1. Cases 1-4 presented TIL counts ranging from 20 to 1000/HPF. Case 5 presented TIL counts of 5-10/HPF. Mutations in SMARCA4 were confirmed in cases 4 and 5, and the TMB was 5.98 and 5.03 mutations/Mb, respectively. Case 1 achieved a CR, cases 2-4 achieved a PR, and case 5 had a PD. Five patients who received immunotherapy were all alive, with OS ranging from 10.7 to 33.6 months.
CONCLUSIONS
Thoracic SMARCA4-UTs exhibited an aggressive clinical course, presented solid architecture with or without necrosis and/or rhabdoid morphology, and frequently expressed CD34 and synaptophysin. Some thoracic SMARCA4-UTs appear to be associated with responsiveness to immunotherapy, suggesting the need for validation in larger series.
Topics: Humans; Male; Biomarkers, Tumor; DNA Helicases; Lung Neoplasms; Necrosis; Nuclear Proteins; Prognosis; Sarcoma; Synaptophysin; Transcription Factors
PubMed: 38306886
DOI: 10.1016/j.lungcan.2024.107471