The disruption of the epigenetic patterns and its impact on gene expression is recognized as a critical factor in the initiation and progression of cancer. Altered patterns of DNA methylation, histone modifications, and non-coding RNA expression are distinctive features of tumorigenesis. These dynamic shifts in the epigenetic landscape during oncogenic transformation are intricately linked to tumor heterogeneity, the sustained capacity for self-renewal, and the ability to undergo multi-lineage differentiation. The abnormal reprogramming of cancer stem cells presents a formidable challenge in cancer treatment and drug resistance. However, the reversible nature of epigenetic modifications holds significant potential for developing novel cancer treatments through the targeted inhibition of epigenetic modifiers. Utilizing this approach as a standalone therapy or combined with other anticancer treatments has yielded promising outcomes. In this review, we emphasize the central role of epigenetic dysregulation in cancer pathogenesis, epigenetic changes in the cancer genome, and the latest advancements in cancer therapy, particularly the potential of epigenetic factors as biomarkers for early detection and their application in current cancer treatment modalities.

Pleomorphic rhabdomyosarcoma (pRMS) is a rare and highly malignant mesenchymal tumor. Complete resection is the only curative treatment available, owing to the limited efficacy of chemotherapy and radiotherapy. Therefore, developing novel therapies for pRMS is important for improving clinical outcomes. Herein, a novel pRMS cell line, SMU-pRMS, was established for a detailed understanding of the biological characteristics of pRMS, thereby developing new therapies. A tissue sample from a surgically resected tumor of a 69-year-old patient was subjected to primary culture. The cell line was established and authenticated by evaluating the short tandem repeats of DNA microsatellites. Monolayer cultures of SMU-pRMS cells exhibited constant growth, spheroid formation, and invasiveness. These cells exhibited high chemosensitivity to eribulin. In addition, mice inoculated with SMU-pRMS cells developed tumors after 4 weeks. Therefore, the SMU-pRMS cell line is a useful tool for investigating pRMS development and evaluating novel therapeutic agents.

Treatments for solid tumors, the most common malignant neoplasms, are often confounded by tumor microenvironments that impede the achievement of uniform anti-tumor effects throughout the entire malignant mass, which contributes to recurrence and progression, negatively impacting clinical outcomes. Improved treatment methods for solid malignancies are therefore needed. Mesenchymal stromal cells (MSCs) have been investigated for treatments for various types of solid tumor cancers due to their ability to target tumor cells with similar cell surface protein profiles. MSC-derived exosomes (MSC-Exos) elicit many of the tumor cell responses produced by MSC with no potential for differentiation and reduced risks of adverse effects. We surveyed the literature and clinical trials registries to identify studies investigating MSC-Exo-based anti-cancer therapies for gastric cancer, colorectal cancer, breast cancer, lung cancer, brain cancer, pancreatic cancer, and urological malignancies, and summarize the results of relevant studies herein to provide a comprehensive description of the therapeutic effects and potential clinical applications of MSC-Exos for the treatment of solid tumor malignancies. We include a summary of relevant clinical trials performed to date in an attempt to assess the data available regarding MSC-Exo safety, and propose future efforts regarding the requirements for transitioning forward from phase-1, 2 trials.

To observe the effect of wheat-grain moxibustion plus chemotherapy on the activities of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling and expressions of Caspase-3 and Caspase-9 in mice with breast cancer, so as to explore its mechanisms underlying suppression of tumor growth.

Forty female BALB/c mice were randomly divided into blank control, model, chemotherapy, wheat-grain moxibustion (moxibustion) and moxibustion+chemotherapy groups, with 8 mice in each group. The breast cancer model was established by injection of 4T1 cell suspension (0.1 mL) into the subcutaneous fat pad of the mouse's right fourth nipple. After successful modeling, the mice of the chemotherapy group and moxibustion+chemotherapy group received injection of Adriamycin (2.5 mg/kg) into the mouse' leg or abdomen in the morning of Monday and Friday every week, 3 weeks altogether. For mice of the moxibustion and moxibustion+chemotherapy groups, wheat-grain moxibustion was applied to "Shenque" (CV8) and bilateral "Zusanli" (ST36) for 2 cones every time, once every other day for 21 days. The body weight, tumor weight and tumor volume were measured. The histopathological changes of the tumor were observed after H.E. staining. The terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to detect the apoptosis of tumor tissues in each group. The expression levels of PI3K, AKT, mTOR, phosphorylated (p)-PI3K, p-AKT, p-mTOR, Caspase-3, Cleaved Caspase-3, Caspase-9, and Cleaved Caspase-9 proteins in the tumor tissues were determined by Western blot.

Compared with the model group, the body weight in the chemotherapy group, the tumor weight, tumor volume, and the expression ratios of p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR in the chemotherapy, moxibustion and moxibustion+chemotherapy groups were significantly decreased (P<0.05), while the apoptosis rate of tumor tissue, the expression levels of Caspase-3, cleaved Caspase-3, Caspase-9 and cleaved Caspase-9 proteins in the chemotherapy, moxibustion and moxibustion+chemotherapy groups were considerably increased (P<0.05). The therapeutic effect of moxibustion + chemotherapy was significantly superior to that of simple chemotherapy and simple moxibustion in reducing the tumor volume and tumor mass, and in down-regulating the expression ratio of p-AKT/AKT (P<0.05), and in up-regulating the apoptosis rate and the expression levels of Caspase-3 and cleaved Caspase-3 proteins (P<0.05), and superior to that of simple moxibustion (not the simple chemotherapy) in up-regulating the expression levels of Caspase-9 and cleaved Caspase 9 protein (P<0.05). The therapeutic effect of simple moxibustion was evidently inferior to that of simple chemotherapy in reducing tumor volume and tumor mass, in down-regulating the expression ratios of p-PI3K/PI3K and p-mTOR/mTOR (P<0.05), and in increasing the apoptosis rate, and expression of Caspase-3, Caspase-9 and cleaved Caspase-9 proteins (P<0.05). H.E. staining showed that the tumor cells of tumor tissue grew diffusely and arranged densely in the model group, while in the chemotherapy, moxibustion and moxibustion+chemotherapy groups, the tumor tissue showed light staining of cytoplasm and nucleus, reduced nuclear division, nuclear debris, smaller density, and different degrees of tumor cell necrosis, and the degree of necrosis was increased in the moxibustion group, chemotherapy group and moxibustion+ chemotherapy group.

Moxibustion plus chemotherapy and simple moxibustion can inhibit tumor growth in breast cancer mice, which may be related to their functions in inhibiting the expression and phosphorylation of PI3K/AKT/mTOR signaling pathway related proteins in the tumor tissue, and then upregulating the expression of apoptosis related proteins Caspase-3 and Caspase-9.

Self-limiting sternal tumour of childhood (SELSTOC) is a rare, benign tumour, characterised by a rapidly growing pre- or parasternal mass in children up to 2 years of age. This review aimed to improve awareness among physicians and summarise the clinical features and outcomes of SELSTOC.

We conducted PubMed and Google Scholar searches to collect data on children diagnosed with SELSTOC from the earliest records until July 2024. Three new cases from two Belgian paediatric hospitals (ZAS Queen Paola Children's Hospital and University Hospital Brussels) were included. Data on demographics, clinical presentation, diagnostics, treatment and outcomes were analysed.

Forty-one children were included (3 new cases) with a mean age of 14.0 ± 8.3 months and with a male predominance (25 males, 16 females). Fever occurred in 33% (13/39), pain or tenderness in 55% (21/38), discolouration in 33% (11/33) and warmth in 4% (1/23). Ultrasound was used in 90% (37/41), typically showing a hypoechoic, heterogeneous, avascular mass with pre-, para- and retrosternal components ('dumbbell' shape). All lesions resolved spontaneously within weeks to months.

Greater clinical awareness of SELSTOC is essential to prevent unnecessary investigations and treatments, given its benign, self-limiting course.

Tilapia piscidin 4 (TP4) is a 25-amino-acid cationic antimicrobial peptide derived from Nile tilapia (Oreochromis niloticus). TP4 has demonstrated strong antimicrobial activity against a broad range of pathogens and exhibits additional biological functions, including wound healing and anticancer activity. In a previous study, recombinant TP4 peptide was produced in the Pichia pastoris KM71H expression system and purified by Ni-NTA affinity chromatography. The aim of this study was to evaluate and compare the cytotoxicity of recombinant TP4 against HT-29 colon cancer and HGF-1 healthy gingival fibroblast cells.The antimicrobial activity of TP4 was first assessed using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, confirming its efficacy. Subsequently, the cytotoxic effects of TP4 on HT-29 and HGF-1 cells were further analyzed using the MTT, lactate dehydrogenase (LDH), total antioxidant/oxidant status (TAS/TOS), and malondialdehyde (MDA) assays. TP4 disrupted the antioxidant balance in both cell types, with a significant increase in the oxidant levels and a marked decrease in the antioxidant levels in HT-29 cells. The IC₅₀ values of TP4 were determined to be 15 μg/mL for HT-29 cells and 25 μg/mL for HGF-1 cells. Apoptosis assays, including Annexin V & Dead Cell, RT-qPCR, and ELISA, revealed that TP4 induced apoptosis predominantly in HT-29 cells, as evidenced by the upregulation of BAX and CASP3 and the downregulation of the BCL-2. In conclusion, TP4 exhibited selective and potent apoptotic effects on HT-29 colon cancer cells, suggesting its potential as a novel therapeutic agent for colon cancer treatment.

Breast cancer is among the most prevalent malignancies, with lymph node metastasis strongly linked to worse prognostic outcomes. Despite this, the mechanisms underlying the formation of an immunosuppressive microenvironment that drives lymph node metastasis remain poorly understood. By profiling 118,127 cells from eight patients with breast cancer alongside their metastatic axillary lymph nodes through single-cell sequencing and spatial transcriptomics, this study uncovered the activation of the pentose phosphate pathway during the metastatic process. The expression level of G6PD in breast cancer tumor tissues was significantly higher than that in adjacent tissues. Furthermore, high G6PD expression was associated with poorer prognosis. G6PD was more highly expressed in metastatic lymph nodes, which exhibited an immunosuppressive microenvironment induced by CD4 Treg cells, and the expression of G6PD was positively correlated with immune cell infiltration by Treg cells. Clinical evaluation further demonstrated a significant correlation among G6PD expression, lymph node metastasis, and malignancy. Additionally, clinical drug response data revealed that patients resistant to chemotherapy also had higher G6PD expression. These findings establish G6PD as a molecular marker for predicting the risk of lymph node metastasis and prognosis in breast cancer. This study discovered elevated expression of G6PD in breast cancer, as well as the formation of an immunosuppressive microenvironment mediated by Treg cells in breast cancer lymph node metastatic tissues, emphasizing the critical role of G6PD in promoting lymph node metastasis by driving Treg cell infiltration.

BRAF immunohistochemistry (IHC) serves as a surrogate for BRAF p.V600E but shows variable performance across tumor types and institutions. This study evaluated BRAF IHC staining quality and interpretation in general pathology laboratories through a nationwide proficiency test (PT) in Taiwan, focusing on the most commonly encountered thyroid neoplasm and colorectal cancer. This PT was organized by the Taiwan Society of Pathology using a tissue microarray, containing six tumor cores with confirmed BRAF mutation status and one positive control. Participating laboratories performed BRAF IHC staining and interpretation independently, with results centrally reviewed for concordance, accuracy, and staining quality. Twenty-six pathology laboratories participated. Two laboratories failed the initial control check. Among the remaining 24, 17 (70.83%) demonstrated optimal staining, while 5 (20.83%) showed over-staining and 2 (8.33%) under-staining. No significant associations were found between staining quality and antibody clones, platforms, dilution folds, or assay types. Interpretation was highly concordant (100% agreement and accuracy) for tissues with 3 + or negative staining. However, discrepancies arose in tissues with 2 + intensity (50% positive, 41.67% negative, 8.33% equivocal) and 1 + intensity (83.33% disagreement with test results). The overall accuracy was 79.2%, with sensitivity at 58.3% and specificity at 100%. Under-calling was frequent in cases with 1 + staining (33 cores across 23 laboratories) and 2 + staining (3 cores across 3 laboratories). Our study highlights the importance of optimizing staining quality and reinforcing education on interpretation criteria. To minimize false-negative results, we recommend molecular confirmation for all cases exhibiting diffusely weak staining.

To propose a deep learning (DL) system for the preoperative diagnosis of follicular-like thyroid neoplasms (FNs) using routine ultrasound images.

Preoperative diagnosis of malignancy in nodules suspicious for an FN remains challenging. Ultrasound, fine-needle aspiration cytology, and intraoperative frozen section pathology cannot unambiguously distinguish between benign and malignant FNs, leading to unnecessary biopsies and operations in benign nodules.

This multicenter, retrospective study included 3634 patients who underwent ultrasound and received a definite diagnosis of FN from 11 centers, comprising thyroid follicular adenoma (n=1748), follicular carcinoma (n=299), and follicular variant of papillary thyroid carcinoma (n=1587). Four DL models including Inception-v3, ResNet50, Inception-ResNet-v2, and DenseNet161 were constructed on a training set (n=2587, 6178 images) and were verified on an internal validation set (n=648, 1633 images) and an external validation set (n=399, 847 images). The diagnostic efficacy of the DL models was evaluated against the ACR TI-RADS regarding the area under the curve (AUC), sensitivity, specificity, and unnecessary biopsy rate.

When externally validated, the four DL models yielded robust and comparable performance, with AUCs of 82.2%-85.2%, sensitivities of 69.6%-76.0%, and specificities of 84.1%-89.2%, which outperformed the ACR TI-RADS. Compared to ACR TI-RADS, the DL models showed a higher biopsy rate of malignancy (71.6% -79.9% vs 37.7%, P<0.001) and a significantly lower unnecessary FNAB rate (8.5% -12.8% vs 40.7%, P<0.001).

This study provides a noninvasive DL tool for accurate preoperative diagnosis of FNs, showing better performance than ACR TI-RADS and reducing unnecessary invasive interventions.

Despite elevated serum vitamin B12 levels, functional (i.e., metabolically manifest) vitamin B12 deficiency has been reported in a significant proportion of MPN patients. This study aimed to assess the prevalence of functional vitamin B12 deficiency and elevated serum vitamin B12 levels among Indian MPN patients.

This cross-sectional study evaluated serum vitamin B12, homocysteine, methyl malonic acid (MMA) and holotranscobalamin levels among 176 MPN patients. Serum vitamin B12 levels between 150 and 950 pg/mL were considered normal. Functional vitamin B12 deficiency was diagnosed based on combination of elevated serum MMA (> 0.4 nmol/mL) and homocysteine (> 15 µmol/L) levels and low serum holotranscobalamin levels (< 25 pmol/L), irrespective of serum vitamin B12 levels and clinical manifestations of deficiency.

Among patients enrolled (n = 176), 108 (61%) had chronic phase CML, 37 (21%) PV, 23 (13%) PMF and 8 (4%) ET. Nearly one-third were newly diagnosed to have MPNs and treatment naïve. Elevated serum vitamin B12 levels (> 950pg/mL) were seen in about a quarter (n = 45) of MPN patients. Half (n = 89) were detected to have functional vitamin B12 deficiency. No association was found between functional vitamin B12 deficiency and serum vitamin B12 levels and functional deficiency prevalence did not differ significantly between different types of MPNs and between newly diagnosed (treatment-naïve) and already treated MPNs.

About a quarter of MPN patients had elevated serum B12 levels and half had functional vitamin B12 deficiency. Functional deficiency was diagnosed independent of serum vitamin B12 levels. Hence, evaluation for functional deficiency should be carried out irrespective of serum vitamin B12 levels. Future studies should evaluate potential benefit of vitamin B12 replacement in MPN patients with functional vitamin B12 deficiency.