A tumor association to be aware: endometrial cancer and colon cancer in relation to lynch syndrome

lynch syndrome (LS) is an autosomal dominant genetic disorder with incomplete penetration caused by a germline mutation in one of the genes of the deoxyribonucleic acid (DNA) mismatch repair system (MMR) namely: mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MHS6), post-meiotic segregation increased 1 homolog 2 (PMS2) or the EpCAM (Epithelial CellAdhesionMolecule) gene, which causes the inactivation of MSH2. Patients with this syndrome have a high relative risk of developing cancers at a young age, led by colorectal cancer (CRC) and endometrial cancer in females. The diagnosis is suspected when the patient’s personal and family history meets the Amsterdam or Bethesda criteria. It is guided by immunohistochemistry (IHC) and/or molecular biology that show loss of expression of one or more proteins of the MMR system and microsatellite instability on tumor DNA. In case of positive IHC and/or molecular biology, the patient should be referred to an oncogenetic consultation for a definitive diagnosis. We present the case of a 49-year-old patient who presented an anaemic syndrome in metrorrhagia. After a clinical, imaging, biological and anatomopathological examination, the diagnosis of LS was made.

Human oral microbiome dysbiosis as a novel tool for detecting noninvasive biomarkers for colorectal cancer.

23 Background: The oral microbiome may play an important role in colorectal carcinogenesis. However, few studies have investigated the association between oral microbiome and the development of colorectal cancer (CRC). We aimed to investigate whether oral health–colorectal tumor association has an underlying microbial basis, in the quest for novel non-invasive biomarkers for CRC. Methods: We collected oral swab samples from 161 patients with CRC, 34 patients with colorectal adenoma (CRA), and 58 healthy volunteers. The oral microbiota was assessed using 16S rRNA sequencing. The oral microbiome was characterized, microbial markers were identified, and colorectal tumor (CRA and CRC) classifiers were constructed and validated. Results: Oral microbial composition and diversity were significantly different among the three groups; the CRA group had the highest diversity. Analysis of the functional potential of oral microbiota demonstrated that the pathway involving cell motility was overrepresented in the CRA and CRC groups relative to that in the healthy controls. Moreover, a random forest model was constructed based on oral microbial markers, which could distinguish the colorectal tumor groups from the healthy controls and achieve a powerful classification potential in the discovery and validation cohorts. Conclusions: This study suggests a potential association between oral microbiome dysbiosis and colorectal cancer. Oral microbiota-based biomarkers may be helpful in predicting the risk of developing CRA and CRC.

Surgical Strategies and Clinical Outcome of Large to Giant Sphenoid Wing Meningiomas: A Case Series Study

Large to giant sphenoid wing meningiomas (SWMs) remain surgically challenging due to frequent vascular encasement and a tendency for tumoral invasion of the cavernous sinus and optic canal. We aimed to study the quality of resection, postoperative clinical evolution, and recurrence rate of large SWMs. This retrospective study enrolled 21 patients who underwent surgery between January 2014 and December 2019 for SWMs > 5 cm in diameter (average 6.3 cm). Tumor association with cerebral edema, extension into the cavernous sinus or optic canal, degree of encasement of the major intracranial arteries, and tumor resection grade were recorded. Cognitive decline was the most common symptom (65% of patients), followed by visual decline (52%). Infiltration of the cavernous sinus and optical canal were identified in five and six patients, respectively. Varying degrees of arterial encasement were seen. Gross total resection was achieved in 67% of patients. Long-term follow-up revealed improvement in 17 patients (81%), deterioration in two patients (9.5%), and one death (4.7%) directly related to the surgical procedure. Seven patients displayed postoperative tumor progression and two required reintervention 3 years post initial surgery. Tumor size, vascular encasement, and skull base invasion mean that, despite technological advancements, surgical results are dependent on surgical strategy and skill. Appropriate microsurgical techniques can adequately solve arterial encasement but tumor progression remains an issue.

Clinically based score predicting cryptogenic NORSE at the early stage of status epilepticus

ObjectiveTo determine whether a clinically based score predicts cryptogenic new-onset refractory status epilepticus (C-NORSE) at the early stage of status epilepticus (SE) with prominent motor symptoms (SE-M) of unclear etiology.MethodsThe score (range 0–6) included 6 clinical features: highly refractoriness to antiseizure drugs, previously healthy individual, presence of prodromal fever, absence of prodromal psychobehavioral or memory alterations, absence of dyskinesias, and symmetric brain MRI abnormalities (the first 2 mandatory). We retrospectively assessed the usefulness of a high scale score (≥5) in predicting C-NORSE in 83 patients with SE-M of unclear etiology, who underwent testing for neuronal surface antibodies (NS-Abs) between January 2007, and December 2019.ResultsThirty-one (37.3%) patients had a high score. Patients with a high score had more frequent prodromal fever (28/31 vs 24/52), mechanical ventilatory support (31/31 vs 36/52), and symmetric MRI abnormalities (26/31 vs 12/52), had less frequent involuntary movements (2/31 vs 30/52), and had absent prodromal psychobehavioral alterations (0/31 vs 27/52), CSF oligoclonal band detection (0/27 vs 11/38), tumor association (0/31 vs 13/52), or NS-Abs (0/31 vs 29/52) than those with a low score (<5). Thirty-three patients (median age, 27 years; 18 [54.5%] female) were finally regarded as C-NORSE. The sensitivity and specificity of a high score for predicting C-NORSE were 93.9% (95% CI 0.87–0.94) and 100% (95% CI 0.95–1.00), respectively.ConclusionsPatients with a high score in the indicated scale are more likely to have C-NORSE, making it a useful diagnostic tool at the early stage of SE-M before antibody test results become available.

Identification of Novel Hub Genes Through Expression Profiles Analysis in Adrenocortical Carcinoma

Background: Adrenocortical carcinoma (ACC) is a heterogeneous and rare malignant tumor associated with a poor prognosis. The molecular mechanisms of ACC remain elusive and more accurate biomarkers for the prediction of prognosis are needed.Methods: In this study, integrative profiling analyses were performed to identify novel hub genes in ACC to provide promising targets for future investigation. Three gene expression profiling datasets in the GEO database were used for the identification of overlapped differentially expressed genes (DEGs) following the criteria of adj.P.Value<0.05 and |log2 FC|>0.5 in ACC. Novel hub genes were screened out following a series of processes: the retrieval of DEGs with no known associations with ACC on Pubmed, then the cross-validation of expression values and significant associations with overall survival in the GEPIA2 and starBase databases, and finally the prediction of gene-tumor association in the GeneCards database.Results: Four novel hub genes were identified and two of them, TPX2 and RACGAP1, were positively correlated with the staging. Interestingly, co-expression analysis revealed that the association between TPX2 and RACGAP1 was the strongest and that the expression of HOXA5 was almost completely independent of that of RACGAP1 and TPX2. Furthermore, the PPI network consisting of four novel genes and seed genes in ACC revealed that HOXA5, TPX2, and RACGAP1 were all associated with TP53. Conclusions: This study identified four novel hub genes (TPX2, RACHAP1, HXOA5 and FMO2) that may play crucial roles in the tumorigenesis and the prediction of prognosis of ACC.

Sciellin stimulates gallbladder cancer proliferation and tumor-association thrombosis via formation of neutrophil extracellular traps

Background：Apart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallblader cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin （SCEL） in GBC cell proliferation and the development of venous thromboembolism. Methods: The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methodsResults: SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. Conclusions: The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis , thus serving as a potential therapeutic target.

A parallel and cascade control system: magnetofection of miR125b for synergistic tumor-association macrophage polarization regulation and tumor cell suppression in breast cancer treatment

A parallel and cascade controllable magnetofection system for synergistic tumor-association macrophage repolarization and tumor cell suppression in breast cancer treatment.