BACKGROUND: Hematogenous tumor spread of malignant meningiomas occurs very rarely but is associated with very poor prognosis.
METHODS: We report an unusual case of a patient with a malignant meningioma who developed multiple metastases in bones, lungs and liver after initial complete resection of the primary tumor. After partial hepatic resection, specimens were histologically analyzed, and a complete loss of E-cadherin adhesion molecules was found. No oncogenic target mutations were found. The patient received a combination of conventional radiotherapy and peptide receptor radionuclide therapy (PRRT). Due to aggressive tumor behavior and rapid spread of metastases, the patient deceased after initiation of treatment.
CONCLUSIONS: E-cadherin downregulation is associated with a higher probability of tumor invasion and distant metastasis formation in malignant meningioma. Up to now, the efficacy of systemic therapy, including PRRT, is very limited in malignant meningioma patients.

暂无摘要。

BACKGROUND: Pericardial effusions are one of the most common cardiac diseases in dogs. Common causes of haemorrhagic pericardial effusions include neoplasia, such as hemangiosarcoma, mesothelioma, chemodectoma, and ectopic thyroid tumours, and benign idiopathic pericardial effusion. Distinguishing among reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma in body effusions is a diagnostic challenge. Therefore, the author aimed to discover whether the observed cells were reactive mesothelial, mesothelioma, or adenocarcinoma cells through immunocytochemistry using five markers (cytokeratin, vimentin, desmin, E-cadherin, and calretinin) in a canine patient.
METHODS: A 2.1 kg, spayed female, 10-year-old Yorkshire Terrier dog presented to a local hospital with dyspnoea and was evaluated for pericardial effusion. The presence of pericardial fluid was confirmed, and she was referred to our hospital for further evaluation. In cytological evaluation, cells shed individually or in clusters were observed, along with numerous non-degenerative neutrophils and macrophages. The cells showed binucleation, anisocytosis, anisokaryosis, abnormal nucleoli, abundant basophilic cytoplasm, high nuclear-cytoplasmic ratio, and coarse chromatin. Large atypical multinucleate cells were also observed. Erythrophagia was observed, indicating chronic haemorrhage. Immunocytochemistry using pericardial fluid was positive for cytokeratin, vimentin, desmin, E-cadherin, and calretinin. Therefore, malignant mesothelioma was diagnosed.
CONCLUSIONS: Immunocytochemistry is a very useful diagnostic technique because it can determine whether several fluorescent markers are simultaneously expressed in the same cell. Further, E-cadherin and calretinin can be used for the differential diagnosis of reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma in dogs.

Variations in the protocadherin gene FAT1 have recently been associated with a syndrome that includes coloboma, facial dysmorphism, renal failure, syndactyly, and other developmental defects.
Detailed medical and family history, physical examination, and molecular analysis.
This non-dysmorphic, intellectually normal 51-year-old woman presented with bilateral colobomata and renal failure of unclear etiology, and asymmetric sensorineural hearing loss. Family history was notable for multiple family members with various forms of cancer. Whole exome sequencing revealed a homozygous frame shift variant in FAT1, predicted to truncate the FAT1 protein at the furthest position in the protein structure published to date in a patient with coloboma.
This case provides further evidence of the pleiotropic effects of FAT1 in optic fissure closure and kidney function. Also, because this variant is in the last exon, it would be anticipated to escape nonsense-mediated decay, opening the possibility that the protein is made and expressed, but not completely functional, as its intracellular domain is truncated.

Microcystin-leucine-arginine (MC-LR) is positively linked with multiple cancers in humans. However, the association between MC-LR and the risk and prognosis of prostate cancer has not been conducted in epidemiological studies. No reported studies have linked MC-LR exposure to the poor prognosis of prostate cancer by conducting experimental studies. The content of MC-LR was detected in most of the aquatic food in wet markets and supermarkets in Nanjing and posed a health risk for consumers. MC-LR levels in both prostate cancer tissues and serum were significantly higher than controls. The adjusted odds ratio (OR) for prostate cancer risk by serum MC-LR was 1.75 (95%CI: 1.21-2.52) in the whole subjects, and a positive correlation between MC-LR and advanced tumor stage was observed. Survival curve analysis indicated patients with higher MC-LR levels in tissues exhibited poorer overall survival. Human, animal, and cell studies confirmed that MC-LR exposure increases the expression of estrogen receptor-α (ERα) and promotes epithelial-mesenchymal transition (EMT) in prostate cancer. Moreover, MC-LR-induced decreased E-cadherin levels, increased vimentin levels, and increased migratory and invasive capacities of prostate cancer cells were markedly suppressed upon ERα knockdown. MC-LR-induced xenograft tumor growth and lung metastasis in BALB/c nude mice can be effectively alleviated with ERα knockdown. Our data demonstrated that MC-LR upregulated vimentin and downregulated E-cadherin through activating ERα, promoting migration and invasion of prostate cancer cells. Our findings highlight the role of MC-LR in prostate cancer, providing new perspectives to understand MC-LR-induced prostatic toxicity.

BACKGROUND: While 15 to 20% of cancers are associated with microbial infection, the relationship between oral microorganisms and oral squamous cell carcinoma (OSCC) remains unclear. The location of bacteria in a tumor is closely related to its carcinogenic mechanism. The aim of this study was to analyse bacterial diversity in clinical OSCC tissue samples and tumor distant normal tissues, locate target bacteria, and search for proteins that may interact with target bacteria.
METHODS: The 16S rDNA method was used to analyse bacterial diversity in clinical OSCC tissue samples and tumor distant normal tissues. Correlations between Fusobacterium abundance and clinicopathological characteristics were analysed using the χ2 test. The position of target bacteria was analysed by fluorescence in situ hybridization (FISH), and the expression of CK, CD31, CD45, CD68, cyclin D1, β-catenin, E-cadherin, NF-κB, and HIF-1α was analysed by immunohistochemistry (IHC) in OSCC tumor tissues and tumor distant normal tissues.
RESULTS: The 16S rDNA results showed that the detected amount of Fusobacterium in OSCC tumor tissues was significantly larger than that in tumor distant normal tissues. High expression of Fusobacterium was significantly correlated with the lifestyle-related oral risk habits, including smoking (p=0.036) and alcohol consumption (p=0.022), but did not correlate with patient sex, age, tumor laterality, tumor size, grade or TNM stage. Fusobacterium nucleatum was enriched in tumor stroma, where CD31+ blood vessels and inflammatory cells (including CD45+ leukocytes and CD68+ macrophages) were densely distributed. Cyclin D1 was mainly expressed in the nucleus of tumor cells. β-catenin was expressed in the tumor cell membrane and was positively expressed in tumor interstitial vascular endothelial cells. E-cadherin was mainly expressed in tumor cell membranes. NF-κB was positively expressed in the cytoplasm of tumor cells, tumor interstitial cells and myo-fibrocytes. HIF-1α was mainly expressed in the cytoplasm of tumor interstitial cells. HIF-1α was highly expressed where Fusobacterium nucleatum was densely distributed.
CONCLUSIONS: According to our study, the detected amount of Fusobacterium in OSCC tumor tissues was significantly larger than that in tumor distant normal tissues, and Fusobacterium nucleatum might aggravate inflammation and hypoxia by interacting with NF-κB and HIF-1α in OSCC.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder primarily responsible for deaf-blindness. Patients with subtype Usher syndrome type 1 (USH1) typically experience congenital sensorineural hearing loss, abnormal vestibular function, and retinitis pigmentosa (RP). Here we present a case of Usher syndrome type 1F (USH1F) with a novel homozygous variant in the calcium-dependent cell-cell adhesion protocadherin-15 (PCDH15) gene.
METHODS: Ophthalmic examinations were evaluated over a course of 10 years and the disease-causing variant was identified by whole exome sequencing (WES). Initial and follow-up examination of color fundus photos after 10 years revealed an increase in bone spicule pigment deposits in both eyes. A parafoveal hyper-AF ring in both eyes was shown in fundus autofluorescence (FAF) with a progressive diameter-wise constriction observed over 8 years. Outer nuclear layer (ONL) loss was observed in parafoveal and perifoveal regions of both eyes on spectral domain-optical coherence tomography (SD-OCT). Full-field electroretinography (ffERG) showed extinguished global retinal function. WES identified a novel two-base-pair deletion, c.60_61del (p.Phe21Ter), in the PCDH15 gene, confirming the diagnosis of USH1F.
CONCLUSIONS: We report a novel homozygous PCDH15 pathogenic variant expected to lead to nonsense-mediated decay (NMD) of PCDH15 mRNA. The patient exhibits a loss of function with USH1F, experiencing congenital hearing loss and syndromic RP.

Pathogenic variants in the Cadherin 3 (CDH3) gene are responsible for the occurrence of Hypotrichosis with Juvenile Macular Dystrophy (HJMD) and Ectodermal Dysplasia, Ectrodactyly and Macular Dystrophy Syndrome (EEMS), both of which are rare autosomal recessive disorders characterized by hypotrichosis and progressive macular dystrophy. The CDH3 gene encodes for P-cadherin, a calcium-binding protein that is essential for cell-cell adhesion, which is expressed in the retinal pigment epithelial cells and hair follicles.
Fundus examination of both eyes was done in addition to clinical investigation. Genomic DNA was extracted from a whole-blood sample and whole-exome sequencing (WES) was performed to identify the underlying etiology.All identified variants were evaluated for their pathogenicity and causality.
We present the first case of HJMD in a 23-year-old female patient from Jordan. The patient presented to our ophthalmology clinic with poor vision in both eyes. Gross examination revealed sparse scalp hair along with macular dystrophy on fundus exam in both eyes. HJMD was suspected and whole-exome sequencing (WES) confirmed the diagnosis with the identification of a homozygous frameshift deletion (p.Gly277AlafsTer20) localised in exon 7 of the CDH3 gene.
Blindness due to progressive macular degeneration is a common manifestation in numerous syndromic recessive disorders such as HJMD. Ophthalmologists should consider the importance of systemic manifestations and genetic testing for the confirmation of diagnosis.

Cancer is a major health problem worldwide and the second leading cause of death following cardiovascular diseases. Breast cancer is the leading cause of mortality and morbidity among women and one of the most common malignant neoplasms prompt to metastatic disease. In the present review, the mechanisms of the major cell adhesion molecules involved in tumor invasion are discussed, focusing on the case of breast cancer. A non-systematic updated revision of the literature was performed in order to assemble information regarding the expression of the adhesion cell molecules associated with metastasis.

BACKGROUND: 22q13.3 deletion syndrome is a well-known syndrome characterized by typical clinical findings including neonatal hypotonia, absent or severely delayed speech, intellectual disability, and other various features, and detection of a heterozygous deletion of chromosome 22q13.3 with the involvement of at least part of SHANK3. It is reported that 10% to 29% of patients with 22q13.3 deletion syndrome present lymphedema. Protein-losing enteropathy (PLE) has never been reported in 22q13.3 deletion syndrome.
UNASSIGNED: The patient presented to our institution for refractory hypoalbuminemia and chronic lymphedema in both legs.
METHODS: The patient manifested intellectual disability, absent speech, tooth grinding, dysmorphic face, and abnormal hands and toenails. Copy-number variation sequencing confirmed the maternal deletion in 22q13.31-q13.33 (chr22:46285592-51244566, hg19). The patient was genetically diagnosed with 22q13.3 deletion syndrome.
METHODS: Low-fat diets and medium-chain triglycerides supplements were prescribed. The patient was recommended to wear compression garments and elevate legs.
RESULTS: The symptom of diarrhea was resolved, but hypoalbuminemia persisted. Lower extremities lymphedema was gradually becoming severe.
CONCLUSIONS: Primary lymphedema and PLE can occur simultaneously in a patient with 22q13.3 deletion syndrome. The 2 phenotypes could share the same genetic etiology of congenital lymphatic abnormalities. CELSR1 deletion may play a role in lymphatic dysplasia. The case also provides additional proof of the pathogenic effect of CELSR1 on hereditary lymphedema.