H3 G34-mutant diffuse hemispheric gliomas are rare, aggressive primary brain tumors predominantly affecting young patients. We investigated the prognostic value of anatomic staging (AS)-a system previously validated in adult-type diffuse gliomas-in this molecularly distinct tumor type.

Methylthioadenosine phosphorylase (MTAP) loss is a common genomic event in cancer and is associated with an immunologically cold phenotype. Recent research has highlighted a synthetic lethality of MTAP loss when combined with PMRT5 or MAT2A inhibition. Although contemporary somatic genomic testing now routinely includes MTAP status, the clinicogenomic characteristics of MTAP loss in cholangiocarcinoma (CCA) remain largely undefined. In this study, we examine the genomic profiles, clinical features, and survival outcomes of MTAP loss CCA.

Although prostate cancer is generally associated with favorable outcomes, metastatic disease remains incurable. Additionally, a subset of individuals with high-risk or metastatic disease are likely to harbor at least one germline variant in known prostate cancer association genes. Because of differences in cohort selection and sequencing strategies, the prevalence of germline variants in global populations is unclear.

The rising incidence of early-onset colorectal cancer (EOCRC) presents a growing challenge to traditional approaches in screening, treatment, and survivorship. EOCRC is increasingly recognized as a biologically distinct entity, driven by complex inter-related biological, genetic, behavioral, and socioenvironmental factors. This chapter reviews the molecular and clinical features that distinguish EOCRC, with attention to emerging precision oncology strategies, including germline testing, tumor genomic profiling, and biomarker-directed therapies. In metastatic disease, recent advances in targeting BRAF V600E, KRAS G12C, HER2 amplification, and microsatellite instability-high (MSI-H)/mismatch repair deficiency tumors have reshaped therapeutic paradigms. Tumor sidedness and metastatic site patterns are now recognized as predictive and prognostic factors. In localized disease, neoadjuvant immunotherapy for MSI-H tumors and nonoperative management are redefining standard care, with special relevance to younger patients seeking fertility preservation or organ-sparing approaches. The chapter also addresses key gaps in EOCRC care, including underutilization of fertility preservation counseling and limited guidance for cancer management during pregnancy. A multidisciplinary, lifecycle-based framework is essential to optimize outcomes and improve quality of life for this unique and growing patient population.

A 57-year-old woman presented with a 1-year history of left shoulder pain with an atraumatic mass overlying the left clavicle. Magnetic resonance imaging showed an enhancing, spiculated mass adherent to the clavicle. Preoperative needle biopsy confirmed the diagnosis of granular cell tumor (GrCT). The patient underwent mass resection and was symptom free without evidence of recurrence during her most recent evaluation, 29 months postoperatively.

Epstein-Barr virus-associated gastric cancer (EBVaGC) represents a distinct molecular subtype of gastric cancer. EBV encodes various viral RNAs, including BamHI-A rightward transcripts (BARTs), which are implicated in the carcinogenic processes of EBVaGC. This study aims to explore the function and underlying mechanisms of EBV-miR-BART5-5p in gastric cancer, providing a basis for the identification of more effective biomarkers for EBVaGC.

Accurate nuclei segmentation and classification in histology images are critical for cancer detection but remain challenging due to color inconsistency, blurry boundaries, and overlapping nuclei. Manual segmentation is time-consuming and labor-intensive, highlighting the need for efficient and scalable automated solutions. This study proposes a deep learning framework that combines segmentation and classification to enhance nuclei evaluation in histopathology images. The framework follows a two-stage approach: first, a SegNet model segments the nuclei regions, and then a DenseNet121 model classifies the segmented instances. Hyperparameter optimization using the Hyperband method enhances the performance of both models. To protect data privacy, the framework employs a FedAvg-based federated learning scheme, enabling decentralized training without exposing sensitive data. For efficient deployment on edge devices, full integer quantization is applied to reduce computational overhead while maintaining accuracy. Experimental results show that the SegNet model achieves 91.4% Mean Pixel Accuracy (MPA), 63% Mean Intersection over Union (MIoU), and 90.6% Frequency-Weighted IoU (FWIoU). The DenseNet121 classifier achieves 83% accuracy and a 67% Matthews Correlation Coefficient (MCC), surpassing state-of-the-art models. Post-quantization, both models exhibit performance gains of 1.3% and 1.0%, respectively. The proposed framework demonstrates high accuracy and efficiency, highlighting its potential for real-world clinical deployment in cancer diagnosis.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Personalized medicine based on genetic mutations is required to improve its prognosis. The PI3K/AKT pathway plays a crucial role in cancer progression. While PI3K inhibitors have been developed for several malignancies, none have been clinically applied to PDAC. PIK3CA encodes the catalytic subunit of Class IA PI3K, and an activating mutation such as E545K and H1047R is oncogenic. In this study, we developed a novel pancreatic cancer mouse model with PIK3CAH1047R mutation, designated Ptf1acre/+; Rosa26-LSL-PIK3CAH1047R:p53loxP/loxP (PPC) mice. At 150 days of age, PPC mice developed PDAC and AKT was activated in their tumor epithelial cells. We established a pancreatic cancer cell line from PPC mice, and alpelisib, an inhibitor of PI3K p110α, inhibited the proliferation of PPC cells in vitro. Furthermore, PPC cells were subcutaneously transplanted into NOD/SCID mice, and alpelisib significantly reduced the tumor burden of PPC cells. Western blotting upon treatment with alpelisib revealed compensatory activation of ERK in PPC cells. Combination treatment with alpelisib and the MEK inhibitor PD98059 significantly inhibited cell proliferation. These data indicate that PIK3CA mutation may be oncogenic in PDAC and that PI3K inhibitors can be effective against such tumors. Dual inhibition of the PI3K/AKT and MEK/ERK pathways may enhance therapeutic effects in PI3K/AKT-activated pancreatic tumors.

MiR-122 is a liver-abundant miRNA, which is thought to harbor antitumorigenic activity. Elevated transforming growth factor-β (TGF-β) in hepatocellular carcinoma (HCC) microenvironment is a potent inducer for tumor metastasis. However, the involvement of miR-122 in regulation of TGF-β signaling and its implication in TGF-β-related HCC metastasis remains obscure. In this study, we demonstrated that miR-122 significantly enhanced the activities of the TGF-β pathway reporter, the levels of phosphorylation of Smad2 and Smad3, and the expression of mesenchymal markers (N-cadherin and vimentin) in HCC cells. Notably, miR-122 significantly promoted the migration and invasion in vitro and pulmonary metastasis of HCC cells in vivo. Mechanism investigations revealed that miR-122 directly suppressed the expression of RBM47, which was a novel RNA binding protein. RBM47 decreased the level of αv integrin (ITGAV) by promoting the degradation of mRNA via interacting with the AU-rich elements in its 3'UTR. Subsequently, the elevated ITGAV induced by miR-122 promoted activation of the latent TGF-β, thereby boosted the TGF-β signaling and then promoted cell motility. Taken together, miR-122 could promote metastasis of hepatoma cells by regulating RBM47-ITGAV-TGF-β signaling. These findings provide new insight into the regulatory network of miR-122, the complexity and robustness of TGF-β pathway and the mechanisms of HCC metastasis.

Identifying mitosis is crucial for cancer diagnosis, but accurate detection remains difficult because of class imbalance and complex morphological variations in histopathological images. To overcome this challenge, we propose a Customized Deep Learning (CDL) model, which integrates advanced deep-learning techniques for better mitosis detection. The CDL model utilizes transfer learning to counter the effects of class imbalance and speed up convergence, while skip connections are also employed to improve the localization of mitosis. Furthermore, we have established an innovative selection mechanism by the hybrid of Jellyfish Search Optimizer (JSO) and Walrus Optimization Algorithm (WOA) to maximize the momentum of the model. The proposed approach is rigorously evaluated on multiple publicly available mitosis detection datasets, including Mitosis WSI CCMCT Training Set, Mitosis-AIC, Mitosis Detection, and Mitosis and Non-Mitosis datasets. To tackle these issues, we hereby bring forth a specifically tailored Custom Deep Learning model, that assimilates hybrid CNN architecture into transfer learning and feature selection for improved mitotic detection. The CDL model comprises a Transfer Learning-based Mitosis Detection module under which extracted features from pre-trained deep networks are used to bolster feature extraction and alleviate class imbalance through skip connections to better localize mitosis. The robust assessment on a benchmark dataset displays the outstanding efficacy of the CDL model, reaching an excellent F1 score of 0.994 and accuracy of 98.8% thus proving its strength for the detection of mitotic figures. This proposed methodology can greatly empower pathologists for accurate appraisal of cancer diagnosis and prognosis. Future lines of exploration will include fusion methodologies and time efficiency for real-time applications, as well as extending CDL to various histopathological analyses.

Metastasis is one of the important factors leading to poor prognosis in patients with colon cancer. However, the molecular mechanism contributing to this cellular behaviour remains largely unknown. Here, RNA-seq analysis suggested that Fibronectin 1 (FN1) was significantly increased in metastatic colon cancer, which was associated with poor prognosis. FN1 enhanced colon cancer cell migration, invasion, and epithelial to mesenchymal transition (EMT) in vitro and promoted liver and lung metastasis of colon cancer in nude mice through RAP1B. Mechanistically, FN1 could interact with RAP1B by suppressing the interaction between RAP1B and the E3 ligase PARK2, relieving RAP1B ubiquitination modification and improving RAP1B protein stability. Furthermore, FN1-RAP1B activated Akt signalling pathway, leading to the phosphorylation and activation of CREB. Interestingly, CREB was found directly bound to the FN1 and TIMP1 promoter, respectively and increased FN1 and TIMP1 transcription, thereby establishing a positive regulatory feedback loop. Overall, our results elucidated that FN1 promotes colon cancer migration, invasion, and metastasis. FN1 may be used as the potential therapeutic target for colon cancer metastasis.

Multidisciplinary treatment is the standard of care for patients with cancer of the rectum. Neoadjuvant therapy decisions rely on the local carcinoma stage's magnetic resonance imaging assessment. However, the reliability of magnetic resonance imaging in evaluating mesorectal lymphadenopathy remains highly questionable.

Colorectal cancer is a common and often fatal malignancy, and predicting survival can help guide treatment decisions. This study aimed to investigate the impact of clinicopathological characteristics and nutritional status on survival in patients with metastatic colorectal cancer receiving first-line treatment with 5-fluorouracil in combination with monoclonal antibodies (bevacizumab, cetuximab, or panitumumab).

The Nottingham Prognostic Index, Ki-67 Prognostic Index, and combination of platelet count and lymphocyte-to-monocyte ratio have shown prognostic significance in breast cancer. This aim of the study was to compare combination of platelet count and lymphocyte-to-monocyte ratio with Nottingham Prognostic Index and Ki-67 Prognostic Index in early-stage breast cancer.

There are no published data on the occurrence of neoplasia in wild great apes of any species. The aim of this study was to utilize postmortem and histopathology reports collected from wild human-habituated mountain gorillas (Gorilla beringei beringei) and Grauer's gorillas (Gorilla beringei graueri) to determine both the incidence and types of spontaneous neoplasms and proliferative lesions that occur in these species. Pathology records of 194 mountain gorillas and 12 Grauer's gorillas necropsied from 1985 to 2020 were examined for all cases of neoplasia or hyperplastic/proliferative disease. Slides and/or scanned images were reviewed to confirm morphologic diagnoses. Data were collected on comorbidities that may have contributed to neoplastic/proliferative transformation. A total of nine malignant neoplasms were identified: large cell anaplastic B-cell lymphoma, gastric adenocarcinoma (two cases), gastric carcinoid, oral mucocutaneous malignant melanoma, gastric carcinoma in situ (two cases), squamous cell carcinoma of the lip, and renal adenocarcinoma. Benign lesions included pheochromocytoma, adrenocortical adenoma (two cases), parathyroid adenoma, mandibular fibroma with gingival hyperplasia, and uterine hemangioma. Proliferative gastritis was commonly identified secondary to gastrointestinal parasitism (n = 35); chronic inflammation from nematodiasis may have led to neoplastic transformation of hyperplastic mucosal epithelium. Other hyperplastic lesions included nodular hyperplasia of the adrenal cortex (n = 9), adrenal medulla (n = 7) and thyroid glands (n = 3), pulmonary reactive lymphoid hyperplasia in infants and juveniles (n = 16), as well as nodular splenic siderofibrosis (n = 5) that may be associated with parasite migration. These findings demonstrate that free-ranging mountain and Grauer's gorillas in a natural environment develop neoplasia and proliferative disease.

Activation of the transcription factor forkhead box O1 (FOXO1) contributes to multiple pathological processes. The FOXO1 inhibitor AS1842856 demonstrated strong therapeutic effects in preclinical models of common diseases such as diabetes and anthracycline-induced heart failure. We have previously identified FOXO1 as a B-cell acute lymphoblastic leukemia (B-ALL) dependency and demonstrated in in vivo B-ALL models that AS1842856 increased the survival of animals and decreased B-ALL tumor load in all critical organ compartments, but most efficiently in the central nervous system. Here, we interrogated the underlying molecular mechanisms by comparison of the transcriptomic effects of AS1842856 and Foxo1 knockout (Foxo1-KO) in a B-ALL mouse model. Despite the significant similarity in sets of regulated genes, we identified glycogen synthase kinase (GSK) 3B inhibition as a signature enriched only in AS1842856-treated cells. Using an in vitro kinase assay and an unbiased kinome screen, we identified AS1842856 as a direct GSK3 inhibitor that ultimately stabilizes CTNNB1. CTNNB1-KO partially protected B-ALL cell lines from the cytotoxic effect of AS1842856. At the same time, using a chemical protein degradation model, we found that FOXO1 indeed contributes to the cytotoxic effect of AS1842856. We conclude that AS1842856 targets 2 B-lymphoid vulnerabilities: GSK3 and FOXO1. The unique mode of action, low toxicity, and ability to penetrate the blood-brain barrier warrant further investigation of the therapeutic potential of AS1842856 in B-ALL.

Urea transporters (UTs) UT-As (encoded by Slc14A2) and UT-B (encoded by Slc14A1), are important members of the solute carrier family. They are a group of membrane channel proteins that are selectively permeable to urea. Slc14A1 is considered the key gene determining the Kidd blood group system, and its variants can lead to the loss of Jk antigens, resulting in transfusion-related complications. Additionally, studies have shown that Slc14A1 is closely associated with cancer development and progression, with its expression level and promoter methylation status potentially serving as biomarkers for cancer progression and prognosis. Recent research suggests that UT-B functional deficiency may cause neurodegenerative diseases by accumulating urea in the brain, thereby affecting neuronal function and viability. Mutations of Slc14A2 are linked to hypertension and metabolic syndrome, due to its essential role in maintaining urea homeostasis. This chapter aims to introduce the clinical significance of UT-B and UT-A and highlight their potential roles as diagnostic and therapeutic targets.

Oral squamous cell carcinoma (OSCC) is an aggressive epithelial malignancy with limited therapeutic options and high recurrence rates. C-Phycocyanin, a phycobiliprotein derived from Spirulina platensis, exhibits promising anticancer properties by modulating various molecular pathways. This study aimed to investigate the cytotoxic and pro-apoptotic effects of C-Phycocyanin on human oral cancer cells (KB) and compare its safety profile on normal endothelial cells (HUVECs). Cell viability was assessed using the MTT assay in both KB and HUVEC cell lines following treatment with different concentrations of C-Phycocyanin. Apoptotic features were evaluated by DAPI nuclear staining and quantified using Annexin V/PI-based flow cytometry. The expression of apoptosis-related genes (P53, Bax, Bcl-2) and signaling molecules involved in the Akt/PTEN and MAPK (ERK2) pathways was analyzed by semi-quantitative RT-PCR. C-Phycocyanin significantly inhibited the viability of KB cells in a dose-dependent manner while exerting minimal cytotoxic effects on HUVEC cells. DAPI staining revealed nuclear fragmentation and chromatin condensation in KB cells. Flow cytometry confirmed apoptosis induction. RT-PCR analysis showed upregulation of P53 and Bax and downregulation of Bcl-2, suggesting activation of the intrinsic apoptotic pathway. In addition, C-Phycocyanin inhibited Akt and upregulated PTEN and MAPK (ERK2) pathway components. C-Phycocyanin effectively induces apoptosis in oral cancer cells by modulating key molecular pathways, with minimal toxicity on normal cells. These results support its potential as a natural and selective therapeutic agent for OSCC, meriting further in vivo validation.

Glioblastoma, an aggressive primary brain malignancy associated with poor survival rate and limited curative interventions, posing significant challenges in clinical management. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is known to regulate various cellular processes including energy homeostasis and immune modulation under normal physiological conditions as well as promoting metastasis in several cancer types. This review delves into the intricate involvement of CAMKK2 in the virulence of glioblastoma. Several studies have suggested that CAMKK2 can be a potential biomarker and therapeutic target for glioblastoma. Differential expression of CAMKK2 across glioma grades highlights its potential utility in disease stratification. Specifically, elevated CAMKK2 expression in high-grade gliomas is associated with increased metastatic potential. Furthermore, CAMKK2 ha been implicated in promoting resistance to immune checkpoint blockade therapy, underscoring its protumorigenic role. Given its involvement in tumor progression metastasis, modulation of the tumor microenvironment, and therapy resistance, CAMKK2 represents a promising candidate for the development of novel glioblastoma treatment strategies.

Robotic-assisted partial nephrectomy has emerged as the standard surgical procedure for managing localized kidney cancers, with bleeding risk being a primary clinical consideration. This investigation seeks to establish simple predictive indicators for hemorrhage-related adverse events.