Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, necessitating novel biomarkers for early intervention. Although FAM111B - a gene implicated in DNA repair and cell cycle control - exhibits dysregulation in multiple malignancies, its CRC-specific relevance is underexplored.

The extracellular matrix protein Tenascin-C (TNC) is known to promote the development of pancreatic cancer. The current study investigated the effect and mechanism of Triptolide (TP), a monomer component extracted from the traditional Chinese herb Tripterygium wilfordii, on TNC expression and TNC-mediated malignant behaviors in human pancreatic cancer.

The chromosomal abnormality (CA) in newly diagnosed multiple myeloma (NDMM) suggests the involvement in disease initiation and progression. Fluorescence in situ hybridization (FISH) provides high-sensitivity detection of these aberrations. To elucidate the clinicopathological impact of CAs, we integrated bone marrow (BM) morphology, FISH, flow cytometry (FCM), and PET/CT to analyze their interrelationships in a cohort of 156 NDMM patients.

Colorectal cancer (CRC) is a major cause of cancer-related death and is driven by epigenetic alterations. KDM1A, a key histone demethylase, has a poorly defined role in CRC. This study investigates its molecular mechanisms using bioinformatic and experimental analyses to better understand its impact on tumor progression.

Ovarian cancer, although ranking lower in overall incidence among cancers in the United States, is the most lethal gynecologic malignancy, with a 5-year survival rate of 50.9% despite advances in therapies. Two of the largest challenges in management are the lack of effective screening and the vague symptoms of the disease. Most ovarian cancers are diagnosed after metastasis has occurred. Genetic variants, such as BRCA1 and BRCA2, are strong risk factors, accounting for 10% to 15% of all ovarian cancers. Physicians should consider ovarian cancer in patients with pelvic pain or rapidly increasing abdominal girth. Initial workup includes a bimanual examination palpating for pelvic mass, an abdominal examination for ascites, transvaginal ultrasonography, and a cancer antigen 125 level. Referral to gynecologic oncology is appropriate for patients with findings concerning for malignancy on ultrasonography or with ascites or findings of metastasis. For patients with elevated cancer antigen 125 levels, referral is also warranted. Although there have not been significant advances in early detection, survival rates have improved because of better management and treatment. Family physicians play an important role by providing long-term continuous relationships with patients that may improve recognition of the disease and by providing support during treatment.

Eighty years have passed since the atomic bombings (A-bombing) of Hiroshima and Nagasaki in August 1945. Survivors represent an unparalleled and irreplaceable human cohort for comprehensively studying the long-term carcinogenic effects of radiation exposure. This review provides a pathological perspective on A-bomb radiation-related solid cancers. Key findings underscore the persistent nature of radiation-induced carcinogenesis: an increased risk of solid cancers has been evident for over 10 years post-bombing and continues to persist. Epidemiological data consistently demonstrate a linear dose-response relationship, with the risk of all solid cancers increasing by ∼40%-50% per Gy, notably without an apparent threshold. The phenomenon of multiple primary cancers is significantly affected by A-bomb radiation, suggesting a systemic predisposition. At a molecular level, evidence points to long-lasting genomic instability, characterized by constitutive activation of the DNA damage response in non-neoplastic epidermis of proximally exposed survivors. This persistent genomic disruption is a critical contributing factor to tumorigenesis. Furthermore, radiation-associated cancers exhibit distinct molecular features. For instance, specific gene fusions are prevalent in thyroid cancer, while HER2 and c-MYC co-amplifications are observed in breast cancer, and gene expression alterations are noted in gastric cancer, often differing from sporadic cases. Research into biomarkers, such as cdkn1a in a rat model of thyroid carcinogenesis, shows promise for identifying radiation effects from the early pre-cancerous phase. This comprehensive analysis highlights the profound and enduring impact of A-bomb radiation on human carcinogenesis. The insights derived from this unique cohort are profoundly relevant for understanding and mitigating global radiation health risks.

RNA interference (RNAi) therapeutics represent breakthrough discoveries, but their use in cancer remains limited due to hepatocyte-specific targeting. Cancer metastasis is regulated by complex crosstalk between tumor cells and niche-derived factors. However, the molecular mechanisms enabling metastatic seeding and outgrowth in the liver remain incompletely understood, representing a major clinical challenge. We identified neuropeptide Y (NPY) as a promotor of liver metastasis. Hepatocyte-derived NPY attracts metastatic tumor cells to the liver niche. Subsequent microenvironment activation induces TGFβ, promoting a vicious cycle of perimetastatic NPY secretion and liver metastasis. Concomitantly, cancer cells upregulate the NPY-5 receptor (Y5R) which is correlated with liver metastasis. NPY-Y5R crosstalk drives chemotactic migration via cAMP and ERK signaling. Moreover, NPY-Y5R activation dephosphorylates checkpoint kinase 2 to promote clonogenicity and proliferation of cancer cells. Lipid nanoparticles (LNPs) are a promising drug delivery vehicle for siRNAs. LNPs carrying siRNA pools targeting NPY were designed, and preclinical studies provided evidence for efficacy for the treatment of liver metastasis. Our findings transform the limitation of hepatocyte specificity of RNA interference into a therapeutic advantage, introducing a paradigm for the treatment of hepatic metastases.

Brain metastasis (BrM) resulting from thyroid cancer remains poorly characterized despite its significant impact on patient outcomes. The current study aims to combine clinical features with genomic sequencing data to identify potential prognostic variables in thyroid cancer BrM.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by the BCR::ABL1 fusion gene resulting from the translocation t(9;22). This type of leukemia represents a biologically and clinically distinct subset of ALL, known for its aggressive nature and comparatively poor prognosis among hematologic malignancies. Although the advent of tyrosine kinase inhibitors (TKIs) has converted the therapeutic view and fulfilled short-term outcomes, resistant responses remain limited, and disease relapse, often due to BCR::ABL1 kinase domain mutations or activation of alternative signaling pathways, continues to impede long-term success. Recent findings emphasizes the essential involvement of microRNAs in leukemogenesis, TKI resistance, and the advancement of Ph+ ALL. Importantly, miR-17∼92 cluster members (such as miR-17, miR-18a, miR-20a) can prompt apoptosis by direct suppression of BCL2 in BCR::ABL1 positive cells. Moreover, epigenetic silencing of miR-203 enhances BCR::ABL1 expression, further contributing to TKI resistance. These small regulatory RNAs consequently act for promising candidates both as therapeutic targets and as prognostic biomarkers, with the potential to fill treatment gaps that persist even in the TKI era.

This study aimed to investigate the feasibility of using engineered NK-92 cell-derived exosomes to deliver miR-124 to breast cancer cell lines and to assess the anti-tumor effects of these exosomes in breast cancer cell lines. In this study, the NK-92 cell line was genetically engineered to overexpress miR-124. Subsequently, exosomes were isolated from the modified cell line. The effects of these NK-92-miR-124 exosomes were assessed on the proliferation, apoptosis, and migration of three different subtypes of breast cancer cell lines (MCF-7, MDA-MB-231, and SK-BR-3) using MTT assays, Annexin V/PI staining, and scratch tests, respectively. Finally, the results from all experiments were compared with the outcomes obtained from the treatment of breast cancer cell lines with NK-92 exosomes. All comparisons were made under the same experimental conditions. Our findings demonstrated that miR-124 was effectively delivered to breast cancer cell lines via engineered NK-92-derived exosomes. Furthermore, these NK-92-miR-124-loaded exosomes exhibited notable anti-tumor effects, such as reducing cell proliferation and migration across all three breast cancer cell lines. Additionally, they significantly enhanced apoptosis in MCF-7 and MDA-MB-231 breast cancer cell lines compared to NK-92-derived exosomes. Our study demonstrated that engineered NK-92-derived exosomes can effectively deliver miR-124 to breast cancer cells, leading to reduced migration and enhanced apoptosis. However, the anti-tumor effects varied among different breast cancer cell lines.

Leiomyomas are benign smooth muscle tumors that commonly present in the uterus, soft tissue, skin, and gastrointestinal tract but in rare cases can also arise within the eye. Notably, intraocular leiomyomas often show slightly different histopathologic and immunohistochemical features, referred to as mesectodermal morphology, given their presumed neural crest origin. Genetic and cytogenetic alterations of intraocular leiomyomas, as well as their association with various clinical and histopathologic features, have not been previously studied.

Nucleophosmin 1 (NPM1)mut acute myeloid leukaemia (AML) patients may experience different disease evolutions after achieving complete remission. Essential thrombocythaemia (ET) may arise in ≈3% of NPM1mutAML patients achieving molecular remission after treatment. The presence of JAK2V617F mutation within the persisting clonal haematopoietic background of NPM1mutAML favours the development of ET among other myeloid malignancies during NPM1wtAML remission.

Gastric Signet Ring Cell Carcinoma (GSRCC) is an increasingly recognized subtype of gastric cancer, particularly prevalent in South Asian populations and regions within India. This carcinoma is distinguished by its abundant cytoplasmic mucinous cells and aggressive clinical behavior, often affecting younger individuals and leading to a poor prognosis due to its advanced-stage presentation and resistance to standard treatments. A critical factor in its progression is the tumor's uniquely immunosuppressive and stromal-rich microenvironment, characterized by dysfunctional immune infiltrates, activation of cancer-associated fibroblasts, extracellular matrix remodeling, and complement cascade dysfunction. Recent research has highlighted the significance of key biomarkers, including MSMB, AGR2, CLDN18.2, and notably GRIN2D, which play roles in tumor angiogenesis, immune evasion, and metabolic reprogramming. The interaction of these elements contributes to therapeutic resistance and immune escape, thereby reducing the effectiveness of chemotherapy and checkpoint inhibitor immunotherapies. Innovative strategies that integrate stromal-targeting agents, complement modulators, anti-CLDN18.2 antibodies, and novel GRIN2D-targeted therapies, along with precision molecular profiling, offer potential for enhancing patient outcomes. Tailored approaches that incorporate early detection and dynamic biomarker monitoring may ultimately transform GSRCC management toward personalized, evidence-based therapies and prevention.

Lysyl oxidase-like 3 (LOXL3) is a key member of the lysyl oxidase (LOX) family and belongs to the copper-dependent amine oxidase family. Its traditional core function is to catalyze the cross-linking of collagen and elastin in the extracellular matrix (ECM), thereby maintaining the structural integrity and normal physiological functions of the ECM. In recent years, studies on cancer molecular mechanisms have confirmed that LOXL3 exhibits abnormal expression in a variety of cancers: in common malignant tumors such as melanoma, liver cancer, gastric cancer, colorectal cancer, and breast cancer, its expression level is significantly higher than that in the corresponding normal tissues. Meanwhile, numerous prognostic analyses have demonstrated that high LOXL3 expression is an independent risk factor for poor prognosis in cancer patients. Such patients usually have shorter progression-free survival (PFS) and overall survival (OS), suggesting that LOXL3 may serve as a potential biomarker for evaluating cancer prognosis. At the functional and mechanistic level, the role of LOXL3 is not limited to ECM remodeling. It can directly affect key biological behaviors of cancer cells, including proliferation, invasion, metastatic potential, and sensitivity to chemotherapeutic drugs, by regulating a variety of intracellular signaling pathways. This article reviews the specific roles and potential molecular mechanisms of LOXL3 in cancer, covering its associations with key cancer pathological processes such as epithelial-mesenchymal transition, maintenance of genomic stability, and regulation of the tumor microenvironment. It focuses on clarifying the specific molecular pathways through which LOXL3 promotes pro-tumor activities in different tumors, as well as the regulatory effects of these pro-tumor activities on patients' relevant prognosis.

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.

Meningiomas are the most common primary brain tumors in adults and have the potential for recurrence. Although most recurrent meningiomas retain their initial World Health Organization grade, a subset undergoes malignant transformation (MT). The molecular mechanisms underlying this transformation remain poorly understood. We aimed to characterize distinct recurrence subtypes-MT and grade 1-retained recurrence (GR)-using sequential multi-omic analyses. In this study, we reviewed meningioma patients with paired histological evaluations. Among these, 10 patients experienced MT and 25 showed GR. Patients with MT exhibited significantly higher Ki-67 proliferation indices and shorter overall survival. Comprehensive molecular profiling, including matched sequential recurrences, was performed on samples from six patients each with MT and GR meningiomas. Compared to GR tumors, MT tumors demonstrated a marked increase in tumor mutation burden and copy number alterations, with deletion of cyclin-dependent kinase inhibitor 2A emerging as a key acquired event. MT cases also showed selective upregulation of cell cycle-related genes, including Forkhead box M1, a feature absent in GR tumors. Notably, even prior to recurrence, MT tumors displayed distinct global DNA methylation patterns, particularly in regions targeted by the polycomb repressive complex 2 and H3K27me3 marks. Our findings suggest that molecular signatures evolve during MT and that certain intermediate aggressive meningiomas may progress toward malignancy. This study underscores the importance of DNA methylation and transcriptomic profiling in understanding tumor progression and recurrence. While molecular profiling holds promise for prognostication, further research is needed to identify key drivers of MT and clarify their roles in meningioma pathogenesis.

Esophageal squamous cell carcinoma (ESCC) is characterized by poor prognosis. tRNA-derived fragments (tRFs), a novel class of non-coding RNAs generated by tRNA cleavage, have emerged as key regulators of cancer development. However, the functional landscape of tRFs remains underexplored in ESCC. We here identified tRF-24-RPM8309M2S (tRF-24), a 5' tRF derived from mature tRNALeuAAG/TAG, which promotes the malignant progression of ESCC and offers a promising therapeutic target.

Ubiquitin-specific proteases (USPs) play a critical role in the development of various cancers. The study aimed to elucidated the pathogenic molecular mechanisms and analyze its clinical significance in esophageal squamous cell carcinoma (ESCC).

Chemotherapy incorporating the proteasome inhibitor bortezomib (BTZ) has improved outcomes for patients with multiple myeloma (MM); however, resistance to chemotherapy and disease relapse remain significant challenges, closely associated with cellular senescence. This study investigated the key drivers of myeloma cell senescence and its role in MM progression.

Juvenile Polyposis Syndrome (JPS) is a hereditary gastrointestinal polyposis condition characterized by the development of multiple juvenile-type hamartomatous polyps. Approximately half of individuals meeting clinical diagnostic criteria for JPS have an identifiable germline pathogenic variant in SMAD4 or BMPR1A, while the remaining individuals have non-informative genetic results. For pediatric cases, the proportion of children with an identifiable causative variant is likely much lower, with one study noting only 22% of pediatric patients having informative genetic testing. This qualitative study utilized surveys and interviews to explore the impact of non-informative germline genetic results for JPS on parents' understanding of their child's diagnosis and prognosis, as well as recurrence risk and familial screening uptake. Coding reliability thematic analysis of transcripts was completed through open inductive coding. Common parental experiences emerging from interviews with eight parents of seven children with JPS included emotional turmoil throughout the diagnostic process, prognostic unpredictability, and limited familial screening uptake. While the majority of participants (n = 7/8, 87.5%) correctly recalled their child's genetic testing results, those that did not receive genetic counseling (n = 3/8, 37.5%) described feeling confused and uninformed in the pre- and post-test setting. A majority of participants (n = 6/8, 75%) questioned the permanence, natural history, and severity of their child's JPS, while those with more time to cope felt greater clarity and less concern. Such parental perceptions were noted to be heavily influenced by differences in polyp burden over time, genetic testing results, and initial acceptance of the clinical diagnosis. The desire for a genetic diagnosis to increase clarity in their child's long-term management recommendations was noted by some participants (n = 2/8, 25%). Our findings highlight the importance of timely and clear education surrounding prognosis, early incorporation of a genetic counselor in the diagnostic process, and providing follow-up appointments to address misconceptions and resolve uncertainty.