This article discusses a rare case of coexistent meningiomas and Primary familial brain calcification (PFBC). PFBC is a neurodegenerative disease characterized by brain calcifications and a variety of neuropsychiatric symptoms and signs, with pathogenic variants in specific genes. The study explores the potential link between PFBC and meningiomas, highlighting shared features like intralesional calcifications and common genes such as MEA6. The article also revisits PFBC patients developing other brain tumors, particularly gliomas, emphasizing the intersection of oncogenes like PDGFB and PDGFRB in both calcifications and tumor progression. In recent investigations, attention has extended beyond brain tumors to breast cancer metastasis, unveiling a noteworthy connection. These findings suggest a broader connection between brain calcifications and tumors, encouraging a reevaluation of therapeutic approaches for PFBC.

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In the past decade, SETBP1 has attracted a lot of interest on that the same gene with different type or level (germline or somatic) of variants could provoke different pathologic consequences such as Schinzel-Giedon syndrome, SETBP1 Haploinsufficiency Disorder (SETBP1-HD) and myeloid malignancies. Whole exome sequencing was conducted to detect the etiology of a pregnant woman with mental retardation. As a new oncogene and potential marker of myeloid malignancies, somatic SETBP1 variants in other cancers were rarely studied. We performed a pan-cancer analysis of SETBP1 gene in different cancers for the first time.
A novel heterozygous mutation of the SETBP1 gene (c.1724_1727del, p.D575Vfs*4) was found in the patient and the fetus and the mutation was predicted to result in a truncated protein. Reduced SETBP1 expression was associated with SETBP1-HD. The pan-cancer analysis of SETBP1 showed that SETBP1 overexpression should be given special attention in Bladder Urothelial Carcinoma (BLCA) and Stomach adenocarcinoma (STAD).
The de novo SETBP1 mutation was the genetic cause of SETBP1-HD in the family. BLCA and STAD might be related to SETBP1 overexpression.

The transcription factor nuclear factor-κB (NF-κB) is a critical regulator of the immune response, inflammation, cell growth, and survival. Canonical and non-canonical pathways, two NF-κB pathways, are activated through diverse stimulators and receptors. NF-κB activity is dysregulated in various inflammation-related diseases and cancers. It was found that the persistent NF-κB activity has a major role in proliferation, apoptosis inhibition, metastasis, and cell cycle disruption in cancer cells and also the survival of cancer stem cells (CSCs) within the tumors. Therefore, suppression of the NF-κB pathway could be a promising therapeutic target for cancer therapy. Different biological inhibitors (e.g., peptides, small molecules, antisense oligonucleotides (ASOs), and antibodies (Abs)) have been demonstrated to inhibit the NF-κB pathway. Low stability in the circulation system, weak availability, and poor cellular uptake of some inhibitors limit their therapeutic applications. To address these drawbacks nanocarrier systems are often formulated and applied in drug delivery as an effective therapeutic approach. Targeted nanosystems (i.e., small molecules, peptides, Abs and Aptamers (Aps) conjugated nanocarriers), as well as smart responsive nanocarriers, can improve the efficiency of therapeutics while reducing the off-target toxicity. This review describes the NF-κB signaling pathways and mechanisms of their over-activation in tumor initiation and progression. The NF-κB inhibitors and their clinical applications are also discussed. It also overviews different nanocarriers used as robust vehicles for the delivery of NF-κB inhibitors and anti-tumor agents to improve the bioavailability of drugs and selective targeting of cancer cells to repress NF-κB activity in tumor cells.

Since the pandemic\'s onset, a growing population of individuals has recovered from SARS-CoV-2 infection and its long-term effects in some of the convalescents are gradually being reported. Although the precise etiopathogenesis of post-acute COVID-19 sequelae (PACS) remains elusive, the mainly accepted rationale is that SARS-CoV-2 exerts long-lasting immunomodulatory effects, promotes chronic low-grade inflammation, and causes irreversible tissue damage. So far, several viruses have been causally linked to human oncogenesis, whereas chronic inflammation and immune escape are thought to be the leading oncogenic mechanisms. Excessive cytokine release, impaired T-cell responses, aberrant activation of regulatory signaling pathways (e.g., JAK-STAT, MAPK, NF-kB), and tissue damage, hallmarks of COVID-19 disease course, are also present in the tumor microenvironment. Therefore, the intersection of COVID-19 and cancer is partially recognized and the long-term effects of the virus on oncogenesis and cancer progression have not been explored yet. Herein, we present an up-to-date review of the current literature regarding COVID-19 and cancer cross-talk, as well as the oncogenic pathways stimulated by SARS-CoV-2.

Colon adenocarcinoma is one of the tumors with the highest mortality rate, and tumorigenesis or development of colon adenocarcinoma is the major reason leading to patient death. However, the molecular mechanism and biomarker to predict tumor progression are currently unclear. With the goal of understanding the molecular mechanism and tumor progression, we utilized the TCGA database to identify differentially expressed genes. After identifying the differentially expressed genes among colon adenocarcinoma tissues with different expression levels of LGR4 and normal tissue, protein-protein interaction, gene ontology, pathway enrichment, gene set enrichment analysis, and immune cell infiltration analysis were conducted. Here, the top 10 hub genes, i.e., ALB, F2, APOA2, CYP1A1, SPRR2B, APOA1, APOB, CYP3A4, SST, and GCG, were identified, and relative correlation analysis was conducted. Kaplan-Meier analysis revealed that higher expression of LGR4 correlates with overall survival of colon adenocarcinoma patients, although expression levels of LGR4 in normal tissues are higher than in tumor tissues. Further functional analysis demonstrated that higher expression of LGR4 in colon adenocarcinoma may be linked to up-regulate metabolism-related pathways, for example, the cholesterol biosynthesis pathway. These results were confirmed by gene set enrichment analysis. Immune cell infiltration analysis clearly showed that the infiltration percentage of T cells was significantly higher than other immune cells, and TIMER analysis revealed a positive correlation between T-cell infiltration and LGR4 expression. Finally, COAD cancer cells, Caco-2, were employed to be incubated with squalene and 25-hydroxycholesterol-3-sulfate, and relative experimental results confirmed that the cholesterol biosynthesis pathway involved in modulating the proliferation of COAD tumorigenesis. Our investigation revealed that LGR4 can be an emerging diagnostic and prognostic biomarker for colon adenocarcinoma by affecting metabolism-related pathways.

Asymmetric cell division (ACD) gives rise to two daughter cells with different fates after mitosis and is a fundamental process for generating cell diversity and for the maintenance of the stem cell population. The cancer stem cell (CSC) theory suggests that CSCs with dysregulated self-renewal and asymmetric cell division serve as a source of intra-tumoral heterogeneity. This heterogeneity complicates the diagnosis and treatment of cancer patients, because CSCs can give rise to aggressive clones that are metastatic and insensitive to multiple drugs, or to dormant tumor cells that are difficult to detect. Here, we review the regulatory mechanisms and biological significance of asymmetric division in tumor cells, with a focus on ACD-induced tumor heterogeneity in early tumorigenesis and cancer progression. We will also discuss how dissecting the relationship between ACD and cancer may help us find new approaches for combatting this heterogeneity.

Recent developments have given more credence into the brain-gut-microbiota axis and its role in the development of tumor genesis. The microbiota have multiple functions including maintenance of the epithelial barrier, immune response, digestion, cortisol regulation, and control of neurotransmitters and their metabolism [e.g., serotonin, dopamine, noradrenaline and gamma-Aminobutyric Acid (GABA)]. Changes in gut microbiota can interfere with homeostasis leading to dysbiosis microbiota, which is linked to colorectal cancer. Microbiota composition can cause pronounced effect on medical interventions including medications, chemotherapy, and radiation. Altered primary immune system is associated with microbiota disassociation and development of colorectal cancer. This article reviews the current research in brain-gut axis with focus on microbiota and its role in the development of gastrointestinal cancers. We conducted a literature review on PubMed, Cochrane, and Science direct using English language. We begin by reviewing the brain-gut axis and its function and then discuss its effect on the development of gastrointestinal cancers. We reviewed 70 manuscripts and found association between microbiota dysfunction and development of colorectal cancers predisposing to psychiatric manifestations. Lasting disturbances in the microbiota can lead to systemic inflammation with implications on disease development or treatment modifications. These disruptions of the intestinal flora can play an important role in the pathogenesis of cancers. Most psychological reactions to cancer are similar across cancer types but each cancer when examined individually has its own unique features associated with it. Correlation between fear of recurrence and the level of pathological distress is viewed as an indicator of overall adjustment to cancer survival.

Accurate regulation of cell cycle is important for normal tissue development and homeostasis. RCC2 (Regulator of Chromosome Condensation 2) play a role as chromosomal passenger complex (CPC) implicated in all cell cycle phases. RCC2 was initially identified as Ran guanine exchange factor (GEF) for small G proteins. Therefore, RCC2 plays a key role in oncogenesis of most cancers. RCC2 is implicated in Colorectal Cancer (CRC), Lung Adenocarcinoma (LUAD), breast cancer, and ovarian cancer. Expression level of RCC2 protein determines regulation of tumor cell proliferation, invasion, metastasis, and radio-chemotherapeutic resistance. In this review, we explored proteins that interact with RCC2 to modulate tumor development and cancer therapeutic resistance by regulation of cell cycle process through various signaling pathways.

BACKGROUND: Primary rectal choriocarcinoma is an extremely rare malignancy. The association of these neoplasms in patients with inflammatory bowel disease (IBD) has not been reported.
METHODS: A 34-year-old female with history of Ulcerative Colitis (UC) gave birth to a male fetus. She had postpartum bleeding and high level of beta-human chorionic gonadotropin (βhCG) was detected. Although initial investigations failed to confirm molar pregnancy, abnormal uterine bleeding and high βhCG level necessitate chemotherapy administration. She did not respond to chemotherapy sessions accordingly. Meanwhile, the patient experienced rectorrhagia and colonoscopy revealed a firm submucosal polypoid lesion 8-10 cm from the anal verge. The multidisciplinary team candidate the patient for total proctocolectomy and ileal pouch anal anastomosis. Although postoperative course was uneventful and βhCG level dropped but it showed a rising pattern in follow ups. Chemotherapy was planned but there was not suitable response. Unfortunately, the patient passed away 20 months after the initial diagnosis.
CONCLUSIONS: Pathology report indicated the coexistence of moderately differentiated tubular adenocarcinoma and choriocarcinoma. We assume previous history of UC might have put her at higher susceptibility to develop carcinoma and this poorly differentiated carcinoma has led to choriocarcinoma. Considering the fact that in most cases of colorectal choriocarcinoma, choriocarcinomatous differentiation was found alongside colonic adenocarcinoma made dedifferentiation theory to be the most acceptable explanation.
CONCLUSIONS: The adenocarcinoma of the colon and rectum in the setting of IBD may become so dedifferentiated that gain some characteristics of germ cell tumors.