Salivary gland neoplasms are rare, comprising less than 5% of pediatric head and neck tumors, with mucoepidermoid carcinoma (MEC) being the most common malignant type. MEC in the parotid gland is exceedingly rare in children. Histologically, MEC tumors consist of squamous cells, mucus-secreting cells, and lymphoid infiltration, reflecting their complex cellular composition. This case report presents a 9-year-old female with a one-year history of progressive, painless swelling in the left cheek, accompanied by facial nerve palsy. Imaging studies revealed a heterogeneously enhancing mass in the left parotid gland with features suggestive of malignancy. Surgical resection was performed, and histopathologic examination confirmed MEC with perineural invasion. The patient subsequently received adjuvant radiotherapy and chemotherapy. Post-surgery, she demonstrated good healing, and with no significant complications from the adjuvant therapy. Literature review described in this case report provides insights into the prevalence, diagnostic approaches, histopathological characteristics, treatment modalities, and prognostic factors for MEC, offering a comprehensive understanding of this uncommon pediatric malignancy.

N⁶-methyladenosine (m⁶A) modifications play a vital role in hepatocellular carcinoma (HCC) progression. However, the function of m⁶A reader proteins in HCC remains poorly understood. Here, we elucidate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in HCC. In here, we analyzed IGF2BP2 expression in HCC using bioinformatics and clinical samples. The functional role of the IGF2BP2-RELB regulatory axis in HCC progression was assessed through cytological assays and a xenograft HCC mouse model. RNA sequencing, Western blotting, Actinomycin-D assays, and RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays were performed to investigate the regulatory mechanisms of IGF2BP2 on RELB expression. We found high expression of IGF2BP2 in HCC was positively correlated with poor prognosis. Gain- and loss-of-function assays demonstrated that IGF2BP2 was essential for HCC cell proliferation and migration. IGF2BP2 directly bound to RELB mRNA and enhanced its stability via the KH3/4 domain. Upregulated RELB promoted nuclear translocation of the RELB:p52 dimer, leading to activation of the NF-κB signaling pathway. Furthermore, inhibition of IGF2BP2 and RELB suppressed HCC tumor progression both in vitro and in vivo. Our study demonstrates that IGF2BP2 plays a critical role in HCC progression by stabilizing RELB mRNA and activating the NF-κB signaling pathway. The results suggest that IGF2BP2 may be a potential therapeutic strategy for HCC.

Population-level descriptions of long-term childhood cancer survivors are fundamental to survivorship care and research but seldom available. Accordingly, we aimed to describe long-term childhood cancer survivors at the population-level and project future prevalence. In this register-based study we calculated the absolute number and prevalence proportions of all individuals diagnosed with a childhood cancer (aged 0-14 years, 1958-2018) in Sweden who survived ≥ 5 years post-diagnosis and were alive and residing in Sweden on December 31st, 2023. We also described the clinical and sociodemographic characteristics of this population and presented the observed prevalence over time (1990-2023) and projected prevalence under different mortality assumptions (2024-2040). On December 31st, 2023, there were 8645 long-term childhood cancer survivors in Sweden, equivalent to nearly 1 in 1000 inhabitants (921 persons per million). Leukemias (28.3%) and central nervous system tumors (27.0%) were the most common childhood cancer diagnoses, although the distribution of cancer type varied by attained age. Disease burden in the preceding five years was heterogeneous: approximately 25-30% of the survivors had no recent diagnoses or prescriptions, while a similar proportion experienced substantial morbidity. Most adult survivors were employed (72.0%) and relatively few received sickness benefits (9.7%). From 1990 to 2023, the long-term survivor population tripled in size. Projected mean annual growth was between 1.6% and 2.2%, with the population increasing to approximately 11,400 - 12,600 individuals by 2040. As this heterogeneous population continues growing, our comprehensive description can help plan survivorship care and provide a benchmark for prevalence estimates in settings with less complete data.

Oxaliplatin-induced peripheral neuropathy (OIPN) is a frequent, dose-limiting toxicity in colorectal cancer and markedly impairs quality of life. This study aimed to evaluate the protective role of ketotifen in preventing OIPN, considering its mast-cell stabilizing, histamine H1 receptor-blocking, anti-inflammatory, and analgesic properties demonstrated in preclinical models.

In this randomized controlled trial, 64 patients with stage III colorectal cancer were assigned to two groups. The control group (n = 32) received the standard mFOLFOX-6 regimen for 12 cycles, whereas the ketotifen group (n = 32) received the same regimen plus ketotifen 2 mg orally once daily. Neuropathy prevention was assessed through serum biomarkers (neurotensin, superoxide dismutase, interleukin-6), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0), the 12-item neurotoxicity questionnaire (Ntx-12), and the Brief Pain Inventory-Short Form (BPI-SF).

After 12 cycles, the ketotifen group showed a significant reduction in interleukin-6 and neurotensin levels (p < 0.0001), a lower incidence of grade 2-3 neuropathy (p = 0.001), reduced pain severity (p < 0.0001), and better Ntx-12 scores (p < 0.0001) compared with controls. Ketotifen was well tolerated and improved quality of sleep and appetite (p < 0.0001), addressing additional patient-reported challenges.

This trial indicates that ketotifen may offer a promising approach for preventing OIPN. Larger placebo-controlled, double-blind, multicenter trials are needed to confirm these findings.

NCT05624138.

1-11-2022.

36030/11/22.

Celiac plexus block (CPB) is an established interventional technique for the management of severe upper abdominal pain, particularly in patients with chronic pancreatitis (CP) and pancreatic cancer (PC). Pain in these conditions is complex, involving visceral and neuropathic mechanisms and, in CP, additional contributions from neuropathic remodeling, central sensitization, and altered descending modulation play a role.

CPB provides targeted neural blockade to disrupt nociceptive transmission from the upper abdominal viscera, thereby improving analgesia, reducing opioid requirements, and enhancing quality of life. This chapter emphasizes the role of CPB in treating pain resulting from CP and PC, with a specific focus on therapeutic timing, procedural approaches, technical considerations, efficacy, durability of pain relief, side effects, and recent advances. Current evidence suggests that CPB is highly effective in PC pain but provides only modest and short-lived benefit in CP, where it should be reserved for carefully selected refractory cases. Future directions include advanced imaging modalities, improved neurolytic agents, and integration of CPB into multimodal, mechanism-based strategies for comprehensive pain control.

Meningiomas are mainly benign brain tumors, but they can evolve to higher grades. The phenomena of these changes are not well-known. Therefore, more basic research is needed. This study attempted to assess the lipidome profile in meningiomas harboring different NF2 mutation statuses (wildtype and mutated). Solid-phase microextraction (SPME) probes were used to sample and extract the metabolites and reduce the invasiveness of lipidomic analysis.

This study aimed to select the set of lipids distinguishing meningiomas with different genotypes using two chromatography methods (hydrophilic interaction chromatography (HILIC) and reversed-phase chromatography (RPLC) in two ionization modes.

Brain tumors were obtained during neurosurgical procedures. Then, sampling using SPME fibers was performed directly after the lesion excision. After collecting the whole batch of samples, desorption using an isopropanol-methanol solution was performed. Subsequently, instrumental analysis was carried out using liquid chromatography coupled with high-resolution mass spectrometry. The remaining part of the lesion was stored as paraffin tissue blocks, and then genetic testing was performed to determine the presence of mutations in the NF2 gene.

Genetic profiling of meningiomas revealed that most lesions had a mutation in the NF2 gene. A wide range of analytes was extracted from the studied tumors using SPME probes. A set of 34 lipids was selected as crucial metabolites in tumor differentiation. A combination of analytes detected in more than one analysis mode demonstrated higher sensitivity and specificity compared to the individual models and increased the differentiation of mutant and wildtype samples.

SPME coupled liquid chromatography and mass spectrometry, can be successfully applied to the screening of lipids in meningiomas with different NF mutation statuses.

Triple-negative breast cancer (TNBC) is an aggressive and molecularly heterogeneous subtype of breast cancer characterized by limited targeted treatment options, frequent chemoresistance, and a strong propensity for metastasis, particularly to the central nervous system (CNS). These challenges highlight the need for multi-targeted therapeutic strategies. The tumor-targeting peptide p28, which exhibits antitumor activity and potential blood-brain barrier (BBB) penetration, represents a promising candidate for enhancing therapeutic efficacy in TNBC through distinct mechanisms of action. In this study the effects of p28, five standard chemotherapeutic agents, and their low-dose combinations with p28 were systematically evaluated in TNBC models in vitro and in vivo. Cellular responses, including BBB permeability, viability, proliferation, apoptosis, cell cycle distribution, oxidative stress, DNA damage, and metastatic potential, were assessed. Integrated transcriptomic and systems biology analyses were performed to identify dysregulated pathways, and selected targets were subsequently evaluated at the transcript and protein levels. In xenograft models, tumor growth, apoptosis, metastasis-related features, histopathology, toxicity, and overall survival were comprehensively assessed. p28 reduced TNBC cell viability while sparing normal cells, demonstrated favorable BBB permeability, and significantly enhanced the antitumor activity of chemotherapeutic agents at reduced doses. These combinations showed synergistic effects, resulting in markedly enhanced tumor suppression, increased apoptosis, reduced invasion and metastasis, reduced toxicity, and prolonged survival. Collectively, these findings support p28 as a promising preclinical combination strategy in TNBC, distinguished by its synergistic interaction with chemotherapy, and justify further investigation of its therapeutic potential in metastatic breast cancer.

Hypocellular bone marrow failure (BMF) may be acquired due to immune-mediated disease, the prototype being immune aplastic anemia (IAA), or inherited, due to germline defects in genes important for hematopoietic stem cells' function and maintenance (inherited bone marrow failure syndromes [IBMFS]). Proper diagnosis of the underlying etiology of hypocellular bone marrow failure, particularly distinguishing immune AA, myelodysplastic syndrome (MDS) (most relevant in this setting, hypoplastic MDS [MDS-h]), and the IBMFS, is important given the differences in clinical management. Clonal hematopoiesis (CH), in this context comprising somatic mutations or chromosomal abnormalities, is incorporated into standard algorithms for classification, risk stratification, and treatment decisions for hematologic malignancies, but the clinical significance in BMF is not well established. Disease-specific clonal signatures have been reported across the BMF spectrum, and here we show how distinct patterns of CH can aid in distinguishing different etiologies of hypocellular BMF. Additionally, detection of somatic alterations in many BMF disorders can estimate risk for secondary myeloid neoplasms, guide surveillance and, in some instances, allow for early therapeutic intervention.

Ovarian cancer (OV) is one of the deadliest gynecological malignancies, and its high heterogeneity significantly impacts treatment efficacy. Against this background, the molecular mechanisms underlying the pathogenesis of this lethal disease have attracted extensive research attention. However, the pathogenic mechanisms of OV remain incompletely understood. Therefore, this study systematically investigates the pathogenesis of OV. This study collected 20 paired clinical samples comprising OV tissues and benign ovarian tissues to investigate RASSF2 expression. The biological effects of RASSF2 were investigated using both in vitro and in vivo models, including assessments of proliferation and migration. The impact of RASSF2 on PTEN protein stability was examined through co-immunoprecipitation and cycloheximide (CHX) chase assays. Additionally, chromatin immunoprecipitation (ChIP) was performed to investigate the SETDB1/RASSF2 interaction and H3K9me3 modifications on the chromatin of RASSF2. OV tissues exhibited significantly lower RASSF2 expression compared to normal tissues, and this reduction was associated with poorer patient survival. Overexpression of RASSF2 inhibited the proliferation and migration of OV cells. Additionally, RASSF2 inhibited OV growth in vivo. Mechanistically, RASSF2 stabilized PTEN expression to inhibit the activation of PI3K/AKT pathway. In addition, SETDB1 drove OV progression by increasing H3K9me3 enrichment at the RASSF2 promoter to negatively regulate RASSF2 expression. H3K9me3‑modified RASSF2 promotes ovarian cancer metastasis by regulating PTEN expression, which may offer a potential therapeutic target to counteract distant dissemination of OV.

The pharmaceutical and nutraceutical industries are seeking structurally and pharmacologically novel anticancer molecules, as well as onco-protective nutraceuticals. One approach to achieving this goal is to study traditional pharmacopoeias, particularly those from regions where cancers are less common. Certain ethnic groups in Sabah (East Malaysia) appear to have a low incidence of cancer, and the study of their pharmacopeia could lead to the discovery of original anticancer molecules or nutraceuticals.

This review presents a selection of 64 plants used for medicinal food in Sabah their potential for clinical uses.

The data for this focused narrative review were gathered from Google Scholar, PubMed, ScienceDirect, Web of Science, PubMed, the Internet Archive, and Google books. For each plant the search string included the binomial denomination and the words "cytotoxic" or "tumors." of the binomial denomination of each plant and "cytotoxic" and "tumors" was employed. Each result was examined and articles that did not contain information relevant to the topic or coming from non-peer-reviewed journals were excluded.

Eight plant species, of which Helminthostachys zeylanica (L.) Hook., Pycnarrhena tumefacta Miers, Myrmecodia platytyrea Becc., and Mangifera pajang Kosterm, demonstrate activities in vitro and in vivo, which call for further research. Others constitute a source of cytotoxic natural products that warrant further investigation.

There is currently a need to find oncopreventive nutraceuticals as well as original natural products for developing anticancer drugs. Such products could potentially be found among the medicinal and edible plants of Sabah. Further studies are needed.