The in vitro mouse lymphoma assay cell (MLA) is one of the most widely practiced assays in genetic toxicology. MLA detects forward mutations at the thymidine kinase (Tk) locus of the L5178Y (Tk+/- 3.7.2C) cell line derived from a mouse thymic lymphoma. This assay is capable of detecting a wide range of genetic events including point mutations, deletions (intragenic) and multilocus, chromosomal rearrangements, mitotic recombination and non-disjunction. There are two equally accepted versions of the assay, one using soft agar cloning and the second method using liquid media cloning in 96-microwell plates. There are two morphologically distinct types of mutant colonies recovered in the MLA: small and large colony mutants. The induction of small colony mutants is associated with chemicals inducing gross chromosomal aberrations whereas the induction of large mutant colonies is generally associated with chemicals inducing point mutations. The source and karyotype of the cell line as well as the culture conditions are important variables that could influence the assay performance. The assay when performed according to the standards recommended by the International Workshops on Genotoxicity Testing (IWGT) and the Organization of Economic Cooperation and Development Test Guideline 490 is capable of providing valuable genotoxicity hazard information as part of the overall safety assessment process of various classes of test substances.

Breast cancer (BC) is the second leading cause of cancer-related deaths among women, primarily due to late-stage detection and therapy resistance. Therefore, identifying novel therapeutic targets is critical for improving BC outcomes. Long non-coding RNAs (lncRNAs) have recently emerged as promising candidates for cancer prognosis and treatment, owing to their ability to modulate oncogenic signaling pathways. Among them, the tumor-suppressive lncRNA Nkx2-2as has shown inhibitory effects in certain cancers; however, its role in BC remains poorly understood. To the best of our current knowledge, the relationship between Nkx2-2as and the Wnt/β-catenin signaling pathway in BC has not been previously characterized. To address this, we used computational tools including lncHUB2, RPISeq, GeneMANIA, TCGA and ENCORI to predict functional interactions of Nkx2-2as, which guided our focus toward its involvement in the Wnt/β-catenin signaling pathway, a key driver in BC progression. We hypothesized that Nkx2-2as may act as a pharmacologically actionable molecule in this context. To test this, MCF-7 breast cancer cells were transfected with either Nkx2-2as siRNA or an Nkx2-2as-pcDNA3.1 overexpression vector, individually and in combination. Overexpression of Nkx2-2as led to a significant reduction in proliferation (~ 85%), suppression of migration, and increased apoptosis. Conversely, silencing Nkx2-2as enhanced tumorigenic properties. Mechanistic analyses revealed that Nkx2-2as downregulates oncogenic targets such as β-catenin, TCF7 and MYC, while upregulating tumor suppressors AXIN2 and BTG2, the latter being a known inhibitor of β-catenin. Western blot analysis confirmed the transcriptional trends, showing decreased β-catenin and MYC and elevated BTG2 protein levels upon Nkx2-2as overexpression. These findings indicate that Nkx2-2as acts as a negative regulator of Wnt/β-catenin signaling through BTG2 activation, suggesting its potential role as a tumor suppressor and a candidate for RNA-based therapeutic strategies in BC. Targeting the Nkx2-2as/BTG2 axis may provide a conceptual framework for future studies aimed at developing RNA-based interventions to enhance chemosensitivity and overcome therapy resistance in BC.

Accurate brain tumor classification is crucial for advancing diagnostic precision and streamlining treatment strategies. This chapter presents a brain tumor image classification methodology leveraging deep learning techniques, specifically convolutional neural networks (CNNs). Our method exploits CNNs to autonomously extract salient features from medical imaging data, enabling the differentiation of tumor types, including gliomas, meningiomas, and metastatic tumors. The architecture of our CNN comprises several convolutional layers, pooling layers, and fully connected layers designed to capture and interpret complex patterns in brain tumor imagery effectively. We enhance the model's performance through comprehensive data augmentation and rigorous hyperparameter tuning, achieving significant improvements in classification accuracy. Extensive experimental evaluations demonstrate the efficacy of our approach, underscoring its potential to significantly enhance diagnostic processes by providing accurate, automated tumor classification. The advancements detailed herein contribute to the broader application of machine learning in medical imaging, promising substantial impacts on patient care and treatment optimization.

Lipidomics identifies and analyzes the composition of intact lipid molecules within biological systems. Techniques including mass spectrometry enhance lipid coverage; however, the loss of ion connectivity and the generation of large datasets complicate precise feature annotation. Given the complexity of lipidomic data, advanced computational methodologies are essential for precise analysis. Herein, we efficiently explored lipidome alterations in human neuroblastoma SK-N-SH cells exposed to amyloid-beta, a peptide that appears to play a crucial role in the pathology of Alzheimer's disease. The derived datasets were analyzed using the R programming language, employing tools such as lipidr for lipid species identification and significance and ggplot2 for data visualization. Our results revealed significant changes in phospholipid levels under amyloid-beta exposure with emphasis on PE 16:0-18:1, PC 18:2-16:1, and PC 20:2-18:0, highlighting the complex and multifaceted interactions of lipid markers in the pathophysiology of Alzheimer's disease and providing deeper insights into their potential roles in disease progression.

Infantile hemangiomas (IHs) are the most prevalent noncancerous childhood tumors, affecting up to 10% of infants. IHs develop de novo and following excessive proliferation in the first 4-9 months; they typically degenerate spontaneously in 4-7 years. While treatment is not usually required, 10-15% of cases necessitate clinical or surgical intervention due to functional impairments. Here, we present a complicated capillary IH case, from a clinical and genetic perspective.

Gorlin syndrome (GS) or basal cell nevus syndrome type 1 (BCNS1) is a rare genetic disease belonging to the spectrum of genodermatoses. Here, we present a case with BCNS1 that was caused by haploinsufficiency of PTCH1 gene, which is associated with BCNS1.

Afatinib, an irreversible ErbB family inhibitor, is approved for the treatment of non-small cell lung cancer (NSCLC) with both common and selected uncommon EGFR mutations. Evidence in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) is scarce, especially with pharmacokinetic (PK) data. Here, we report the case of a patient with metastatic NSCLC harboring an EGFR G719C mutation who was successfully treated with afatinib during regular hemodialysis. Afatinib was initiated at 20 mg once daily under fasting conditions and later escalated to 30 mg once daily. PK sampling was conducted on two consecutive HD days at each dose level. At 20 mg, the trough concentration (Ctrough) was 4.02 ng/mL, with peak concentrations (Cmax) of 6.09 and 8.75 ng/mL, both lower than reported values in patients with normal renal function. At 30 mg, Ctrough increased to 26.3 ng/mL, while Cmax values of 48.2 and 55.5 ng/mL were comparable to steady-state exposures in patients with preserved renal function. Notably, no adverse events were observed, and the patient has maintained a partial response for over eight months. This case suggests that afatinib can be administered without major dose modification in HD patients, with PK data indicating minimal impact of dialysis and underscoring the importance of accumulating real-world evidence in this underrepresented population.

The systemic study of thymic mucosa-associated lymphoid tissue (MALT) lymphoma remains lacking. The objective of this study was to characterize the clinical features and outcomes of patients with thymic MALT lymphoma.

This phase 1 study aimed to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary efficacy of rucaparib (RUB), a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, combined with liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU) in metastatic gastrointestinal (GI) cancers. RUB targets DNA repair pathways, showing efficacy in tumors with homologous recombination deficiency, such as BRCA mutations. Preclinical data suggest synergy with irinotecan, but overlapping toxicities pose challenges.

Afatinib, an irreversible pan-ERBB family inhibitor, has demonstrated promising efficacy in non-small cell lung cancer (NSCLC) patients with uncommon EGFR activating mutations. However, besides the acquisition of the secondary T790M mutation, other resistance mechanisms to afatinib remain to be explored.

Lung adenocarcinoma (LUAC) patients with micropapillary (MP) and/or solid (S) generally demonstrate a poorer survival prognosis. In the diagnosis and treatment of stage IA LUAC, precisely establishing personalized treatment strategies for patients is crucial for both clinical practice and scientific investigation. Our study aims to develop a novel prediction model based on machine learning (ML) to predict the probability of MP/S patterns in stage IA LUAC patients.

Synchronous bilateral breast cancer (SBBC) presents significant radiotherapy planning challenges due to complex target volumes near critical organs. This study evaluated RapidArc Dynamic (RAD), a novel technique integrating dynamic arcs with static angle modulated ports (STAMPs) via simultaneous GPU-accelerated optimization, against conventional volumetric modulated arc therapy (VMAT) for SBBC treatment planning and delivery efficiency.

The metastasis of laryngeal squamous cell carcinoma (LSCC) is not only caused by the tumor itself but is also closely related to cancer-associated fibroblasts (CAFs). The epithelial-mesenchymal transition (EMT) serves as a key event during its metastasis. However, the specific mechanisms underlying LSCC metastasis remain uncertain.

A solid pseudopapillary tumor of the pancreas is one of the rare pancreatic tumors. It usually occurs in young women. The common clinical presentation of this tumor is nonspecific abdominal pain and an abdominal mass. Since it has low malignancy potential, with complete surgical resection, the outcome is excellent.

Multifocal micronodular pneumocyte hyperplasia as first manifestation of tuberous sclerosis complex has rarely been reported.

Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia rarely transforms into diffuse large B-cell lymphoma, and there have been no reports of cases proving clonal identity when presenting as primary central nervous system lymphoma. There are many unclear aspects regarding the mechanism by which lymphoplasmacytic lymphoma/Waldenström macroglobulinemia infiltrates the central nervous system and transforms, as well as the treatment methods for the transformed lymphoma.

Myofibroblastic sarcoma (MFS) is a rare malignant tumor of the myofibroblasts (mammary MFS being even rarer but more aggressive). Only 12 cases of mammary MFS have been reported before this. We report a rare case of a 32-year-old lady who had been operated on twice for phyllodes tumor and who came with another recurrence at the same site. Preoperative work-up was suggestive of recurrent phyllodes tumor. Wide local excision with 1 cm margin with type 1 oncoplastic reconstruction was done, considering her age and marital status. Final histology was suggestive of MFS, and margins were clear. Immunostaining was positive for vimentin and weakly positive for smooth muscle actin (SMA). In the existing literature, there exists no clarity on the underlying lesion or cell origin of MFS. One case report highlighted old fibroadenoma and another attributed radiation preceding the MFS. We report a rare case of MFS in a setting of recurrent breast phyllodes in a young unmarried woman.

Histiocytic sarcoma (HS), a rare malignant neoplasm of hematolymphoid origin, belongs to the World Health Organization (WHO) classification of histiocytic and dendritic cell neoplasms. This rare aggressive malignancy occurs predominantly in adults and accounts for less than 1% of all hematolymphoid neoplasms. It arises from the monocytic/macrophage lineage and shares the histomorphologic and immunohistochemical features of mature tissue histiocytes. Its predominant presentation is extranodal, involving the intestinal tract, skin, and soft tissue, and it rarely presents with lymphadenopathy. The diagnosis of HS is entirely based on identifying the histiocytic lineage and the exclusion of other poorly differentiated malignancies with large pleomorphic cells like high-grade lymphomas, carcinoma, melanoma, germ cell tumors, and sarcomas. Herein, we report a case of a 61-year-old female patient who noticed a left supraclavicular swelling of 3 weeks duration, and the biopsy revealed a nodal HS. The clinicopathologic, histomorphologic, immunohistochemical, and molecular features of the disease will be further discussed.

Ewing sarcoma is a highly malignant neoplasm of bone or soft tissues that is predominantly seen in adolescents and young adults. Patients with recurrent and metastasis have poor survival despite aggressive treatment. In Ewing sarcoma, EWS-FLI-1 translocation has been identified as a biomarker for Poly-ADP ribose Polymerase inhibitor (PARPi) sensitivity and olaparib has been shown to enhance the antitumor activity of chemotherapy agents like temozolomide, irinotecan, and trabectedin. We tried the combination of olaparib and temozolomide in an adult patient of Ewing sarcoma who had metastatic disease, and after 4 months of treatment, he showed excellent response to treatment.

Glomus tympanicum is a hypervascular, benign neoplasm with a slow rate of growth. The incidence of this pathology is higher in females than in males and mainly occurs in the fifth to sixth decade of life. Pulsatile tinnitus and hearing loss are the main clinical features. We present the case of a 70-year-old female patient who was admitted to the otolaryngology service with a 1-month history of epistaxis and equilibrium disorder that caused a ground-level fall.