c‑Myc, a member of the MYC family, is an extensively studied proto‑oncogenic transcription factor that plays crucial roles in various biological processes of tumor cells, including proliferation, cell cycle regulation, DNA damage repair, metabolic reprogramming, differentiation and genomic maintenance. Furthermore, in cancer therapeutics, c‑Myc may serve as a key factor influencing targeted drug efficacy and tumor drug resistance. This review comprehensively summarizes the structural characteristics of c‑Myc and its roles and key molecular mechanisms across various malignancies, as well as current strategies for c‑Myc‑targeted therapies and related clinical trials. Additionally, the existing challenges in c‑Myc research are discussed and future research directions are being outlined. The synthesis aims to provide novel insights for fundamental research, offer new perspectives for precision cancer therapy in clinical practice and ultimately bring renewed hope for cancer treatment.

Inhibition of β-tubulin polymerization has been set as promising therapeutic strategy for cancer therapy. Accordingly, a new set of triaryl-tethered acetohydrazide-acryloyl derivatives were designed and synthesized. The antiproliferative influence was evaluated against liver Huh-7 cell line using MTT colorimetric method with Doxorubicin as a positive control. Compounds 3b, 4f, 4i, and 4j showed excellent cytotoxic activity against Huh-7 cell line. Among the investigated compounds, 2-(naphthalene-2-yloxy)acetohydrazide having 2-(4-methyl)-3-(3,4,5-trimethoxybenzamido)acryloyl moiety (compound 4i) was the most active one with an IC₅₀ value of 2.46 µM. In addition, all compounds were further evaluated in vitro for their β-tubulin polymerization inhibition activity. Results found that compound 4i showed high activity against β-tubulin polymerization with an IC₅₀ value of 2.29 µM, surpassing the activity of the reference Podophyllotoxin (IC₅₀ = 4.45 µM). Further studies revealed the ability of the promising compound 4i to induce apoptosis and halt the cellular cycle at G2/M phase. Furthermore, the apoptosis-inducing activity of naphthalene-tethered acryloyl moiety 4i was correlated to the downregulation of Bcl-2 as well as elevation of both Bax and caspase 9 as concluded from RT-PCR immunoassay measurements. Finally, molecular docking studies were also performed to explain the displayed inhibitory activities.

Glioblastoma (GBM) is recognized as one of the most treatment-resistant malignancies, owing to its reinforced DNA repair systems and limited drug accessibility across the blood-brain barrier. This study, identifies, daidzin (DZN), a naturally derived isoflavone, as a potent redox-active DNA intercalator that intrinsically combines physical intercalation with chemical reactivity to breach this resistance. Unlike traditional intercalators, DZN autonomously triggers destabilization of DNA helices by inducing torsional strain, thereby producing convergent strand and base lesions through photo-independent redox pathways involving deoxyribose cleavage and C8 guanine oxidation. Additionally, DZN demonstrates pronounced glioma-specific cytotoxicity by initiating 1O2-driven oxo-cation formation and concomitant H2O2 production. This redox burst results in DNA strand scission activating robust DDR signaling and oxidative base lesions, which cripple tumor survival. Enhanced membrane fluidity in glioma cells likely facilitates superior DZN permeability, intracellular accumulation, thereby allowing DZN to initiate this robust DNA damage responses, culminating in G1 arrest and apoptosis in GBM cells while sparing normal glia. In vivo, DZN markedly suppresses tumor growth and surpasses temozolomide efficacy, current clinical option for GBM treatment. This work, thus, establishes a previously unrecognized paradigm of DNA intercalation-driven redox chemistry, presenting DZN as a promising therapeutic capable of exploiting the genomic frailties to overcome therapeutic resistance in glioma.

Hepatosplenic T-cell lymphoma (HSTL) is a highly aggressive form of mature T-cell lymphoma, characterised by abnormal proliferation of cytotoxic T cells in the spleen, liver, and bone marrow. It accounts for <1.0% of all non-Hodgkin lymphomas.

We present a case of HSTL in a 32-year-old male who came with pancytopenia, abdominal distension, constitutional symptoms, and splenomegaly. Initial bone marrow examination was misdiagnosed as Myelodysplastic Syndrome (MDS) or Myelodysplastic Syndrome/Myeloproliferative Neoplasm (MDS/MPN). A repeated bone marrow examination showed CD3-positive neoplastic lymphoid cells in the bone marrow intrasinusoidally and immunophenotyping revealed predominance of gamma-delta (γδ) T-cells.

This case highlights the importance of including HSTL in the differential diagnosis when a patient exhibits splenomegaly and pancytopenia even though background dyspoiesis is prominent. This will enable an early diagnosis of this aggressive cancer.

Acute monocytic leukaemia (AML-M5) disease models are scarce. To address this, we reprogrammed THP-1 cells from a patient into AML-M5-specific induced pluripotent stem cells (AML-M5-iPSCs) and differentiated them into monocytic-like cells. Unexpectedly, reprogramming transgenes Oct3/4, Sox2 and c-Myc were reactivated in the AML-M5-iPSC genome. This study examined how transgene reactivation influences responses to doxorubicin in differentiated monocytic-like cells; MATERIALS AND METHODS: AML-M5-iPSCs were differentiated into monocytic-like cells using hM-CSF and IL-3. Cell morphology, phagocytotic activity and surface markers expression of monocytic-like and THP-1 cells were assessed and compared. Cytotoxicity and apoptotic effects of doxorubicin were investigated with CCK-SK assay and flow cytometry; RESULTS: Monocytic-like cells showed morphology, size, and phagocytosis comparable to THP-1 cells. However, they expressed lower surface markers CD4, CD117, CD33, CD64 and HLA-DR than THP-1 cells. Following 24h doxorubicin exposure, THP-1 cells exhibited an IC ₅₀ of 0.59 μM, while the IC ₅₀ for monocytic-like cells could not be determined. Upon similar treatment conditions, 92.47±3.90% of THP-1 cells underwent late apoptosis. In contrast, only 0.26±0.21% of monocytic-like cells entered late apoptosis, 37.23±1.52% underwent necrosis and 62.47±1.63% remained viable; CONCLUSION: Reactivation of Oct3/4, Sox2 and c-Myc in AML-M5-iPSCs induced lower surface marker expression and doxorubicin resistance in monocytic-like cells. Moreover, the apoptotic effect of doxorubicin had been switched to necrotic effect. Surprisingly, morphology and phagocytic function were unaffected. We postulate that transgene reactivation disrupts epigenetic stability and downstream apoptotic pathways. Further investigations are warranted to clarify mechanisms underlying transgene-mediated drug resistance in iPSC-derived disease models.

Calreticulin (CALR) mutations in essential thrombocythemia (ET) are associated with younger age, higher platelet counts, and lower thrombosis rates. The present study analyzes the demographic, laboratory, and clinical features of the CALR mutation and its prognostic impact.

The clinical impact of CALR mutations was assessed in 391 ET patients.

CALR-mutation patients were more commonly male than JAK2 V617F-positive and triple-negative patients. Age at diagnosis was similar across all groups, although patients with type 2 CALR mutations were younger than those with nontype 1/nontype 2 mutations. Compared with JAK2 V617F-positive patients, CALR-mutation patients had lower leukocyte counts (9.6 × 10⁹/L vs. 10.9 × 10⁹/L), lower hemoglobin (Hb) and hematocrit (Hct) levels, higher platelet counts (1078.5 × 10⁹/L vs. 858.1 × 10⁹/L), and lower total thrombosis rates (20.8% vs. 37.8%), while the CALR-mutated and triple-negative patients had lower venous thrombosis rates than in the JAK2 V617F-positive patients. The arterial thrombosis rate before and at the time of diagnosis was lower in the CALR-mutation patients than in the JAK2 V617F-positive patients, and the total venous thrombosis rate in patients aged <60 years at the time of diagnosis was lower in the CALR-mutation and triple-negative patients than in the JAK2 V617F-positive patients. Multivariable analysis revealed cardiovascular (CV) risk to be the only independent predictor of total thrombosis. Female gender, absence of CV risk, and platelet count ≥1000 × 10⁹/L were associated with a lower incidence of arterial thrombosis. Age <60 years was associated with lower risks of arterial and venous thrombosis. Overall, thrombosis-free, and leukemia-free survival were similar across all groups, while myelofibrosis-free survival was longer in the type 2 CALR-mutation group.

The CALR mutation was lower among females, and was associated with lower leukocyte counts, and Hb and Hct levels, and with higher platelet counts. In multivariable analysis, the apparent protective association of CALR with thrombosis was not independent.

Pineal region tumors are rare and biologically heterogeneous central nervous system neoplasms that occur predominantly in the pediatric population and are associated with significant morbidity and mortality. Among these, pineal parenchymal tumors encompass a spectrum of entities ranging from indolent pineocytomas to highly aggressive pineoblastomas. Recent advances in genomic, epigenomic, and transcriptomic profiling have fundamentally reshaped the understanding of these tumors, moving beyond purely histological classification toward molecularly defined subgroups with distinct biological behavior and clinical outcomes. This review provides a comprehensive overview of the current molecular landscape of pineal region tumors, with a particular focus on genetic predisposition, somatic driver alterations, DNA methylation profiles, and transcriptional programs across pineocytoma, pineal parenchymal tumor of intermediate differentiation (PPTID), pineoblastoma, papillary tumor of the pineal region (PTPR), and desmoplastic myxoid tumor, SMARCB1-mutant. Key oncogenic mechanisms involving microRNA biogenesis disruption, cell-cycle deregulation, MYC/FOXR2-driven transcriptional amplification, PI3K/AKT/mTOR pathway activation, and chromatin remodeling defects are discussed, highlighting their prognostic and therapeutic relevance. In particular, the molecular subdivision of pineoblastoma into distinct subgroups has revealed subgroup-specific vulnerabilities that may be exploitable through targeted therapies. Emerging translational approaches, including molecularly guided treatment strategies and rapid intraoperative sequencing technologies, are also addressed. Despite these advances, the rarity of pineal region tumors continues to limit large-scale clinical trials. Multicenter collaboration and systematic integration of molecular profiling into clinical practice will be essential to improve outcomes for affected children.

Anastomotic hemangioma (AH) is a rare benign vascular tumor primarily occurring in the genitourinary tract; however, only two cases have been reported in the thigh. In this report, a 42-year-old female patient presented to the hospital for examination due to "a subcutaneous mass on the lateral aspect of the left thigh discovered 9 months ago, which has been gradually enlarging." Subsequently, the lump was removed via local surgery. Histological examination reveals: At low magnification, the tumor was situated within the superficial subcutaneous fascia layer, presenting a loose lobular structure. Most of its margins were well - defined, while a small portion displayed expansile infiltrative changes. There were well - differentiated vascular lumens arranged in a communicating or anastomosing pattern, along with pseudopapillary structures. At high magnification, tumor cells were oval or short spindle - shaped, with vacuoles in the cytoplasm that contain red blood cells or homogeneously red - stained glassy globules. Moderate atypia was present, and mitotic activity was frequent, with hot spots averaging approximately 4/mm². PCR-GNAQ mutation detection result: detected a missense mutation at codon 209 in exon 5 (c.627A>T, p. Q209H). Follow-up revealed tumor recurrence 10 months after surgery. Given the rarity of AH occurring on skin surfaces, coupled with the high proliferative activity observed in this case and its recurrence following excision, we report the diagnostic and therapeutic process along with the clinical and pathological features of this AH case. This aims to enhance the understanding of this disease among clinicians and pathologists.

Breast cancer is the most prevalent malignancy in women, and the limited effectiveness of current treatments highlights the need for novel immune regulatory mechanisms to improve long-term survival. This study investigated the role of Vim in PGI₂ synthesis and its impact on tumor immune regulation. Multiomics profiling revealed molecular alterations following Vim deletion, which were validated in murine breast cancer models using RT-qPCR, Western blot, ELISA, and flow cytometry, with rescue experiments involving exogenous PGI₂. The findings showed that Vim deletion downregulated arachidonic acid metabolism, reduced PTGIS expression, and significantly lowered PGI₂ levels. Functional assays demonstrated that Vim deficiency enhanced T cell-mediated antitumor immunity, evidenced by an increased proportion of CD8⁺ T cells, upregulation of cytotoxic genes (Ifng, Gzmb, Tnf, and Klrd1), and activation of inflammation-related signaling pathways, as indicated by enhanced phosphorylation of ERK1/2 and p65. Both exogenous PGI₂ supplementation and ozagrel treatment reversed these effects. In conclusion, the Vim-PGI₂ axis is identified as a key regulator of CD8⁺ T cell immunity in breast cancer, representing a potential therapeutic target and a critical consideration in anticoagulant management during cancer immunotherapy.