Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. Many traditional treatments for this type of cancer, including chemotherapy and surgery, have significant side effects that limit their effectiveness. Therefore, developing new therapeutic agents with fewer side effects and higher efficacy is crucial. C-Phycocyanin (C-PC), found in Spirulina platensis, exhibits antitumor properties; however, the molecular mechanisms underlying its action remain unclear. This study aims to determine the anti-cancer activity of C-PC extracted from Spirulina platensis on the MKN45 gastric cancer cell line and its impact on the expression of the Gli1 gene from the Sonic hedgehog (Shh) signaling pathway and Bcl-2 as a target gene of Gli1. This research was conducted as an interventional laboratory study at the Gene Fan Telma laboratory and North Research Center of the Pasteur Institute of Iran. The anti-cancer effects of C-PC extracted from Spirulina platensis were investigated. Cytotoxic and antiproliferative activities were evaluated using the MTT assay with various concentrations of C-PC and different incubation times. Real-time PCR was employed to assess the expression levels of Gli1 and Bcl-2 genes. The HF2FF cell line (normal human fibroblasts) was used as a control to evaluate C-PC's selectivity and safety profile. The results indicated that C-PC is a natural compound with therapeutic potential for various cancers, particularly gastric cancer. C-PC significantly affects the MKN45 gastric cancer cell line by reducing proliferation and inducing apoptosis by downregulating the anti-apoptotic gene Bcl-2. Furthermore, C-PC did not affect Bcl-2 expression in normal cells, underscoring its potential for cancer therapy use to minimize unwanted side effects. The results indicate that C-PC selectively triggers apoptosis in MKN45 gastric cancer cells and may enhance the treatment of gastric cancer by partially modifying the expression of anti-apoptotic genes. In conclusion, C-PC effectively inhibits the growth and proliferation of MKN45 gastric cancer cells while promoting apoptosis by downregulating Bcl-2 gene expression. Furthermore, C-PC demonstrates a protective role by increasing Bcl-2 expression in normal cells, thereby improving treatment efficacy and minimizing undesirable side effects. In conclusion, it can be inferred that C-PC may influence the proliferation rate of gastric cancer cell lines by partially altering anti-apoptotic gene expression.

Spinal cord astrocytoma (SCA) is the most common type of spinal glioma in children and the second most common in adults. The standard treatment involves surgical resection, with adjuvant radiotherapy and chemotherapy being considered depending on the degree of malignancy. However, for malignant SCA, especially diffuse midline gliomas (DMG) with H3 K27M alterations, the relationship between resection extent and patient prognosis remains a topic of debate. The primary goal of surgery is to maximize tumor removal while minimizing damage to spinal cord function. Due to the complexity of spinal structures and the diffuse nature of these tumors, complete resection is often challenging. The choice of surgical strategy significantly impacts long-term survival and quality of life, highlighting the importance of in-depth studies on surgical approaches and tumor biology. This review provides an overview of recent advancements in understanding the role of surgical resection extent in malignant SCA, with a focus on the underlying biological factors, aiming to guide clinicians in practice. Additionally, we emphasize the importance of comprehensive treatment, including postoperative radiotherapy, chemotherapy, and novel therapies, to improve survival rates and overall clinical outcomes.

T-cell engagers (TCEs), the most extensively studied class of bispecific antibodies, redirect effector T cells to tumor cells to induce immune synapse formation, T-cell activation, and subsequent tumor cell killing. However, their therapeutic efficacy in solid tumors is limited by immunosuppressive mechanisms within the tumor microenvironment (TME). To address this challenge, we engineered an enhanced PSMA/CD3 bispecific antibody by incorporating the extracellular domain of CD80, which provides a co-stimulatory signal to counteract T-cell inhibition in prostate cancer. This trifunctional antibody is designated as TriTE-N13.

We engineered the fully humanized fusion antibody TriTE-N13 using gene editing and eukaryotic expression systems. In vitro, we evaluated its ability to activate and proliferate T cells, as well as its cytotoxicity against PSMA⁺ tumor cells in both 2D co-culture and 3D spheroid models. Additionally, we assessed the in vivo antitumor efficacy and safety of TriTE-N13 using human immune-reconstituted mouse models bearing prostate cancer xenografts.

In vitro, TriTE-N13 demonstrated robust activation of human T cells and high-affinity binding to both human PSMA and CD3 antigens. Furthermore, TriTE-N13 effectively mediated T-cell-dependent cytotoxicity against PSMA-positive prostate cancer cells. In vivo studies revealed that TriTE-N13 achieved significantly greater tumor volume reduction compared to conventional bispecific TCEs, particularly in established large tumors.

Our findings indicate that incorporating CD80 as a co-stimulatory signal substantially enhances the antitumor efficacy of TCEs against solid tumors. These results position TriTE-N13 as a promising immunotherapeutic candidate for advanced prostate cancer treatment.

Portal vein tumor thrombus (PVTT) develops in up to half of patients with hepatocellular carcinoma (HCC) and historically signifies advanced-stage disease with limited treatment options and poor prognosis. Systemic therapy has been the standard treatment for HCC with PVTT, but this review highlights the potential of image-guided locoregional therapies including transarterial chemoembolization (TACE), transarterial embolization (TAE) radioembolization (TARE), hepatic arterial infusion chemotherapy (HAIC), and ablative or radiotherapeutic approaches to improve outcomes in this challenging context. We will summarize current evidence and clinical experience demonstrating that these modalities can achieve meaningful tumor control and extend survival, especially when tailored to tumor burden and PVTT extent or combined with systemic treatments. These findings underscore that aggressive locoregional treatment can be a valuable component of multidisciplinary management for advanced HCC, offering select patients an improved prognosis despite PVTT.

We present the first documented case of gastric-type endocervical adenocarcinoma in situ in a mosaic STK11 pathogenic variant carrier, who delivered a child with classic Peutz-Jeghers syndrome (PJS). A 53-year-old woman presented with persistent watery vaginal discharge for 2 years. Histopathology confirmed gastric-type endocervical adenocarcinoma in situ. Familial genetic investigation was initiated after her son's diagnosis of PJS with an apparent de novo STK11 germline variant [NM_000455.4:c.842del (p.Pro281Argfs*6)]. Comprehensive STK11 screening via Sanger sequencing of peripheral blood from both parents showed no pathogenic variants. Following multidisciplinary tumor board review, ultra-deep next-generation sequencing was performed on multiple tissue specimens. Molecular analysis revealed low-level mosaicism for the familial STK11 variant in cervical tissue with no detectable mutations in blood, saliva, urine, or ovarian stroma. This case demonstrates three key clinical insights: (1) parental mosaicism may underlie apparent de novo PJS cases, (2) tissue-specific STK11 mosaicism can manifest as localized neoplastic transformation without classic PJS manifestations, and (3) ultra-deep sequencing may be considered in genetic counseling paradigms for parents of children with "de novo" cancer predisposition syndromes. These findings highlight the importance of considering mosaic phenomena in tumor prevention for hereditary cancer syndrome families.

Clear cell renal cell carcinoma (ccRCC) is characterized by frequent mutations in chromatin-modifying genes, notably PBRM1 and SETD2, which play critical roles in tumorigenesis and disease progression. These mutations affect chromatin remodeling and histone methylation, influencing cellular functions such as tumor suppression, genomic integrity, and cell cycleregulation. Despite their prevalence, the distinct biological impacts and clinical implications of PBRM1 and SETD2 mutations remain incompletely understood. This review aims to elucidate the functional similarities and differences between PBRM1 and SETD2 mutations in ccRCC, investigate their roles in tumor progression and metastasis, and assess the potential clinical and therapeutic implications of these genetic alterations in the context of precision oncology. A comprehensive literature review was conducted, analyzing genomic, transcriptomic, and clinical data from ccRCC cohorts. Functional studies of PBRM1 and SETD2 mutations were examined alongside gene set enrichment analyses (GSEA), histopathologic observations, and molecular profiling of primary and metastatic tumor sites. Recent advances in therapeutic strategies targeting these mutations were also reviewed. PBRM1 mutations occur early in ccRCC development, altering chromatin accessibility and acting as tumor co-initiators, while SETD2 mutations arise later, exacerbating genomic instability and promoting metastasis. Both genes share tumor suppressor functions but differ in their genetic interactions and pathways. Co-mutation of PBRM1 and SETD2 correlates with increased tumor aggressiveness, poor prognosis, and higher metastatic potential. Emerging therapeutic approaches, including targeted molecular therapies and immunotherapies, show promise in addressing these mutation-driven pathways. PBRM1 and SETD2 mutations critically influence the molecular pathogenesis and clinical outcomes of ccRCC. Understanding their distinct and cooperative roles can enhance molecular profiling and guide personalized treatment strategies. Further research is warranted to develop targeted therapies that exploit the vulnerabilities associated with these chromatin-modifying gene mutations, ultimately improving prognosis and therapeutic response in ccRCC patients.

MiR-106a and miR-20a (miR-17 family members) are frequently dysregulated in carcinogenesis, but their prognostic significance in acute myeloid leukemia (AML) remains unclear.

We analyzed miR-106a and miR-20a expression in bone marrow from 115 AML patients and 45 healthy controls using qRT-PCR. Additionally, we utilized TCGA data (n=188) to assess the association of these miRNAs with clinical factors and outcomes. Prognostic analysis evaluated the impact of miR-106a and miR-20a on overall survival (OS) and event-free survival (EFS). Differentially expressed genes (DEGs) were identified using Limma. GO and KEGG pathway analyses were performed by DAVID. GSEA and PPI were constructed using ClusterProfiler and STRING database.

MiR-106a and miR-20a elevated in AML versus healthy controls. In chemotherapy group, miR-106a^high or miR-20a^high predicted poor OS and EFS, with dual-high expression conferring the worst outcome. In allo-HSCT group, miR-106a^high or miR-20a^high predicted poor OS but similar EFS, with dual-high cases showing the worst OS. In the miR-106a^high or miR-20a^high group, allo-HSCT prolonged OS (but not EFS) versus chemotherapy. In the miR-106a^low or miR-20a^low group, there were no obvious differences in OS or EFS between the chemotherapy and allo-HSCT regimens. Multivariable analyses confirmed miR-106a/miR-20a signature as an independent prognostic marker. Moreover, we identified 706 signature-associated DEGs. Bioinformatic analysis illuminated the involvement of miR-106a and miR-20a in regulating diverse biological processes and signaling pathways.

MiR-106a and miR-20a are promising AML prognostic biomarkers for adverse outcome. The combined signature improves risk stratification and guides therapy selection (e.g., ⁣allo-HSCT for high-risk cases).

Background: The validity of using hospital discharge abstract database (DAD) diagnostic codes to identify insulinoma remains unverified. Objective: The study aimed to develop case-finding algorithms to identify insulinomas using ICD-10 codes from hospital DAD, evaluate their performance and investigate causes of misidentification. Method: This study utilised a 12-year retrospective dataset from a large medical centre in China to test four ICD algorithms for identifying insulinoma patients with hospital DAD. Algorithm performance was evaluated against electronic medical records, using sensitivity, specificity and predictive values as metrics. Results: This study involved 4929 patients with pancreatic tumours, including 610 insulinoma patients, resulting in 5760 hospitalisations. Algorithm variant 1, which uses the code M8151, achieved a sensitivity of 69% and a specificity of 99.7%. The most comprehensive algorithm, variant 4, demonstrated a sensitivity of 84.8% and a specificity of 99.5%. Both algorithm variants 1 and 4 showed higher sensitivity in patients admitted to the endocrinology department and in those lacking pathological evidence (p < 0.001). The use of "pancreatic neuroendocrine tumour" instead of "insulinoma" in pathology reports and inadequate documentation of hypoglycaemia were the main contributors to coding inaccuracies. Conclusion: Owing to the complexity and variability of insulinoma documentation, a single morphology code was not ideal for identifying insulinoma in the hospital DAD. Enhanced, comprehensive algorithms are expected to better recognise confirmed cases. Implications for health information management practice: A multidisciplinary approach with improved pathology reporting, hypoglycaemia statements and precise tumour site-specific coding is crucial for improving the sensitivity of coded data in the hospital DAD for the identification of insulinoma.

This study investigated the incorporation of C5, a pan-HDAC inhibitor, into a norbornene-derived block copolymer with pH-sensitive hydrolysis (PNEG-b-P(Nor-PABA-C5)) to generate NPs for prostate cancer treatment. Amphiphilic PNEG-b-P(Nor-PABA-C5) formed NPs in aqueous environments, with hydrophobic Nor-PABA-C5 monomers in the core and hydrophilic PNEG monomers on the surface. DLS analysis showed a particle size of 122 ± 12 nm with a PDI of 0.35, confirmed by SEM and TEM. TEM imaging revealed spherical morphology, enabling the NPs to transport hydrophobic pan-HDACi drugs to PC-3 tumour sites and facilitate release through hydrolysis under acidic conditions. The NPs exhibited pH-hydrolysis characteristics, with enhanced drug release (61 ± 1.7%) at pH 6.2 compared to pH 7.4 (35 ± 0.8%). MTT assay confirmed antiproliferative effect. Analysis of FITC/(PNEG-b-P(Nor-PABA-C5)) cellular uptake showed increased absorption in prostate tumours. Live/dead cell assays showed loss of viability, with increased red fluorescence and morphological disruption at higher concentrations over 48 and 72 h.

Duplication cysts are congenital anomalies that arise during early embryonic development. They occur in the small intestine, oesophagus, stomach, and colon. Oesophageal duplication cyst (ODC) is rare among newborns, but even rarer in adults. We report the case of a 55-year-old male with the presenting complaints of haematemesis, dysphagia, and significant weight loss for the past eight months. Clinical examination was unremarkable, except that the patient had pallor. Computed tomography scan confirmed the presence of ODC. Subtotal oesophagectomy with gastric pull-up and sub-aortic oesophagogastrostomy was completed. Histopathology was consistent with foregut duplication cyst. Post-operative period was complicated by left basal atelectasis, and the patient was discharged without long-term sequelae. Adult ODC can be regarded as a diagnosis of exclusion after ruling out oesophageal malignancy, high-grade oesophageal varices, mediastinal masses, and submucosal lesions. Complete surgical excision with restoration of gut continuity is optimal management in complicated, large (>5cm) ODC.