The standard treatment for early-stage (cT2-3N0) rectal adenocarcinoma is upfront Total Mesorectal Excision (TME), but the desire for organ preservation has seen the increasing use of neoadjuvant therapy in these patients. Owing to its likely higher complete response rate, Total Neoadjuvant Therapy (TNT) is an attractive but understudied option. This study aimed to determine outcomes in patients with early-stage rectal cancer undergoing TNT.

Immune exclusion inhibits antitumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. In triple-negative breast cancer (TNBC), an aggressive and generally immune-rich subtype, an immune-cold microenvironment predicts poor prognosis due to a limited response to chemotherapy and immune checkpoint inhibitors. This study aimed to identify mechanisms regulating immune infiltration in TNBC.

Low-grade epilepsy-associated tumors are the second common cause of drug-resistant epilepsy, mostly occurring in young adults. The IDH-wild type tumors ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNET) account for the majority of these tumors. Only DNETs have a specific imaging profile of multilobulated cysts oriented in a ball-like fashion or perpendicular to the cortical surface. GG with a predominant neuronal or glial population are more heterogenous and cannot be clearly separated from pilocytic astrocytomas (PAs), pleomorphic xanthoastrocytomas, angiocentric gliomas, and polymorphous low-grade neuroepithelial tumors of the young, respectively.

A male in his late fifties, a chronic smoker, presented to his primary care physician with multiple painless subcutaneous swellings over the torso, which were misdiagnosed as a cutaneous infection for more than a month. Later, he developed haemoptysis for which he presented to our tertiary care subspecialty unit. Further evaluation with imaging revealed a left lung mass with adrenal and gastric lesions, raising suspicion of a lung malignancy with metastasis. A biopsy from a chest wall swelling confirmed primary lung small cell carcinoma with positive synaptophysin expression. Despite timely whole-brain radiotherapy and chemotherapy, his condition deteriorated rapidly, and he succumbed within weeks. This case highlights the rare presentation of small-cell lung carcinoma with cutaneous metastases, which is associated with poor prognosis.

Mucoepidermoid carcinoma originates from the submucosal glands of the tracheobronchial tree. It is structurally homologous with exocrine salivary glands.It is a rare tumour, consisting of 0.1% to 0.2% of primary lung malignancies.Complete surgical resection is the treatment of choice and is associated with an excellent prognosis. Here we present a case where a boy in his teenage years came with a dry cough and haemoptysis.Contrast-enhanced CT confirmed the presence of a polypoidal enhancing space-occupying lesion arising from the right anterolateral aspect of the carina, protruding into the right main bronchus, causing near complete narrowing. The initial biopsy suggested a benign polyp, which led to complete excision of the polyp using an electro-cautery snare. The repeat histopathology suggested a low-grade muco-epidermoid carcinoma, which further required surgical sleeve resection of the distal trachea.

The authors describe the case of a right eye sub-conjunctival lesion, initially misdiagnosed and treated as anterior scleritis, in a female patient in her early twenties. The lesion showed nearly complete clinical resolution on initial treatment with oral steroids. The lesion recurred, however, after discontinuing oral steroids, and at the subsequent visit, the lesion was more widespread and elevated. Anterior-segment optical coherence tomography showed a sub-conjunctival lesion, and CT scan of the orbits showed an isodense periocular lesion moulding around the globe. Crush artefacts prevented accurate histopathological interpretation of the initial incisional biopsy. The patient developed right eye chemosis, proptosis and extraocular motility limitation. Repeat incisional biopsy revealed myeloid sarcoma based on immunohistochemistry. Bone marrow and peripheral blood smears were normal. A whole-body positron emission tomography-computed tomography scan showed hypermetabolic activity in the right periocular area alone. The patient was treated with intravenous chemotherapy, leading to complete tumour resolution.

Tumor tissue engineering, integrating organoid, microfluidic, and biofabrication technologies, has opened new avenues for cancer research. Leveraging advanced bioengineering and biomaterials, these 3D models capture tumor architecture, cellular heterogeneity, biomechanics, and biochemical characteristics for disease modeling. Despite recognition that tissue organization influences malignancy and drug resistance, clinically oriented 3D approaches are rare, largely due to tumor microenvironment complexity, cellular plasticity, and interpatient heterogeneity. With a primary emphasis on gastrointestinal malignancies, we outline the capabilities and remaining limitations of organoid-based cancer models, including developmentally defined stem cell-derived systems that enable controlled early-stage modeling when premalignant material is scarce. We discuss patient-derived organoids as clinical avatars for therapy response prediction and summarize recent clinical trials that delineate key bottlenecks hindering routine implementation. Finally, we outline how innovations in biomaterial design, biofabrication, and microfluidics, benchmarking against patient data, and artificial intelligence are converging to better reconstruct tumor complexity, improve experimental tractability, and accelerate translation.

Ferroptosis is an iron-dependent form of cell death converging on lipid peroxidation first identified by examining compounds with enhanced lethality to KRAS mutant cells. Despite over 90% of pancreatic ductal adenocarcinoma (PDAC) tumors harboring KRAS mutations, PDAC exhibits relative resistance to ferroptosis compared with other tumor types, and the mechanisms behind this resistance remain unclear. Here, we report that exposure to pancreatic tumor interstitial fluid in synergy with hypoxia induced robust protection against ferroptosis in a manner dependent on the hypoxia-inducible transcription factor 2 (HIF-2). HIF-2 upregulates the expression of both components of the system Xc- cystine transporter and transsulfuration pathway enzymes CBS and CTH to increase intracellular cysteine levels, enabling anti-ferroptotic glutathione production. HIF-2 also induces the Parkin mitophagy factor and suppresses mitochondrial function and reactive oxygen species (ROS) generation. Altogether, our findings uncover an unforeseen role of the HIF-2 transcription factor as a coordinator of anti-ferroptotic mechanisms in pancreatic cancer.

The development of colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations, leading to the inactivation of tumor suppressor genes and activation of oncogenes. Aquaporin 1 (AQP1) has been shown to promote tumor angiogenesis; however, its specific role in CRC proliferation and migration remains unclear. This study aims to investigate the functions of miR-210-5p and AQP1 in CRC cell proliferation and migration. Using online datasets from the Cancer Genome Atlas (TCGA) and ten clinical samples, we examined AQP1 expression in CRC. Bioinformatic analysis was conducted to identify miRNAs potentially regulating AQP1. The effects of miR-210-5p and AQP1 on invasion and migration were further assessed in vivo in xenograft Balb/c nu/nu mice. Results showed that dysregulated AQP1 expression in CRC was correlated with advanced clinical stage and venous invasion. miR-210-5p was predicted to bind AQP1 and may target its expression. In vitro experiments revealed that miR-210-5p inhibits CRC proliferation and invasion by downregulating AQP1, which subsequently reduces the expression of vascular endothelial growth factor (VEGR), Wnt-7a, Matrix metallopeptidase 2 (MMP2), MMP9, and β-catenin. Targeting AQP1 led to suppressed proliferation and migration of CRC cells. In summary, AQP1 is upregulated in CRC and regulated by miR-210-5p. Downregulation of AQP1 by miR-210-5p attenuates CRC proliferation and migration through decreasing VEGR, Wnt-7a, MMP2, MMP9, and β-catenin expression.

Matrine (MAT), a commonly employed Chinese botanical, has a long-standing history of application in the treatment of inflammation and cancer. Nevertheless, the precise molecular mechanism underlying MAT's impact on thymoma remains unresolved. Consequently, the objective of this investigation was to assess the influence of MAT on thymomas and ascertain the potential mechanisms through which it modulates the Wnt3a/β-catenin pathway. Thy0517 cells were treated with different doses of MAT to construct a thymoma cell therapy model in vitro, and given Wnt3a/β-catenin pathway agonist Laduviglusib for follow-up experiments. The effect of different doses of MAT on the proliferation, colony formation ability, apoptosis, migration, invasion, and stemness of Thy0517 cells was determined by MTT, colony formation assay, flow cytometry, wound healing assay, Transwell assay, and spheroid formation assay, respectively. Genes and proteins were evaluated by RT-qPCR and/or Western blot. High-dose MAT significantly inhibited the proliferation, migration, invasion, and stemness of Thy0517 cells, which also proved the anti-tumor effect of MAT. The suppressive impact of MAT on cellular function could potentially be augmented through the blockade of the Wnt3a/β-catenin pathway, thereby providing additional evidence for the pivotal role of MAT as a signaling pathway in governing the migratory and invasive capabilities of thymoma cells. We found that MAT has anti-tumor effects, inhibiting the proliferation, migration, invasion, and stemness of thymoma cells by regulating the Wnt3a/β-catenin pathway.

Cellular senescence is a stable and irreversible state of proliferative arrest triggered by diverse stressors, inclh3uding DNA damage, oncogenic signaling, oxidative stress, and metabolic imbalance. Once regarded as a culture artifact, senescence is now recognized as a fundamental biological program that governs tissue homeostasis, development, aging, and disease. Based on its origin, senescence can be divided into two principal categories: damage-induced, encompassing replicative, oncogene-induced, and therapy-induced forms, and developmentally programmed, which orchestrates tissue patterning and remodeling during embryogenesis. These processes converge on the activation of p53/p21 and p16/RB tumor suppressor axes, sustained DNA damage response (DDR), and the establishment of the senescence-associated secretory phenotype (SASP). Acute senescence serves beneficial roles in tumor suppression, wound healing, and embryonic morphogenesis by transiently activating SASP-mediated immune clearance. However, persistent senescence becomes detrimental, promoting chronic inflammation, tissue dysfunction, and cancer progression. Within the tumor microenvironment, chronic SASP signaling driven by nuclear factor kB (NF-κB), CCAAT/enhancer-binding protein beta (C/EBPβ), and Signal Transducer and Activator of Transcription 3 (STAT3) fosters epithelial-to-mesenchymal transition (EMT), invasion, and therapy resistance. Therapy-induced senescence (TIS) often leads to polyploidization and the emergence of polyploid giant cancer cells (PGCCs) that can escape arrest, regenerate proliferative progeny, and drive tumor relapses. Thus, senescence represents a biological paradox: a protective, transient process that maintains tissue integrity but, when unresolved, transforms into a driver of aging and malignancy. Understanding the molecular determinants, distinguishing beneficial from pathological senescence is crucial for developing targeted senotherapies.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma worldwide and in Saudi Arabia. However, regional data on clinical characteristics and outcomes remain limited.

Breast cancer mortality rates are disproportionately high in low- and middle-income countries. The primary reasons for high mortality rates are delays to diagnosis and treatment leading to late-stage presentation. Mujeres Avanzando a la Sobrevida is a prospective cohort study of two cancer centers in Honduras which aimed to map the current landscape of breast cancer in Honduras and understand delays in diagnosis and treatment.

Patient navigation programs have been associated with accelerated access to treatments and improved follow-up care in multiple diseases. Metastatic breast cancer reflects a complex scenario in low- and middle-income countries (LMICs) because of multiple barriers, including a challenging administrative burden associated with multiple diagnostic assessments.

Yan Leyfman, MD, reflected on resilience and hope in the face of cancer, recounting a 37-year-old diagnosed with stage IV colorectal cancer followed by HIV.

Soft tissue sarcomas (STS) are rare but aggressive tumors. Although surgery and radiotherapy are standard treatments for localized STS, the role of adjuvant chemotherapy, particularly doxorubicin, in high-grade STS is debated.

Immunotherapy combined with chemotherapy is a standard treatment for advanced non-small cell lung cancer (NSCLC). However, the comparative efficacy and safety of cost-efficient modified PD-1 inhibitors remain incompletely characterized. This study aimed to determine the optimal choice for the 3 most commonly used modified PD-1 inhibitors-tislelizumab, sintilimab, and camrelizumab-combined with chemotherapy in locally advanced or metastatic NSCLC.

Cellular water content governs the concentration of all biomolecules inside a cell, thereby influencing the physical and functional properties of the cell. However, measurements of water content in physiologically relevant cell culture models remain largely unavailable, particularly in three-dimensional (3D) models such as tumor spheroids and organoids. Here, we achieve such measurements using an industrial-grade capillary steel tube. The steel tube functions as a mechanical resonator that inertially senses the buoyant mass of particles. For microgram-scale particles ≥ 400 micrometers in diameter, we achieve <1% precision error in buoyant mass with a 5-minute acquisition interval. By sequentially measuring the buoyant mass of individual, patient-derived glioblastoma tumor spheroids derived from patients with glioblastoma in media of different densities and cell permeabilities, we determine the absolute and fractional (volume/volume) water content of the spheroids, along with their dry mass, volume, and density properties. We achieve ~0.5% precision error in fractional water content with a throughput of three spheroids per hour. This enables us to detect both interspheroid heterogeneity in fractional water content and acute responses to kinase inhibition. Overall, we establish a simple and accessible technique for quantifying water content in living 3D cell culture models, opening previously unexplored avenues for studying biophysical regulation in multicellular systems.

Metabolic dysfunction-associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma remain major clinical challenges. Chronic endoplasmic reticulum (ER) stress, induced by sustained high-fat diet (HFD) intake, promotes hepatic inflammation, lipid accumulation, and hepatocellular dysfunction during MASH pathogenesis. While transcriptional responses are well characterized, the posttranscriptional mechanisms underlying hepatocyte adaptation to chronic ER stress remain poorly understood. Using an integrative approach combining transcriptomics, ribosome profiling, cytoplasmic polyadenylation analysis, and cis-regulatory mapping, we define the posttranscriptional landscape induced by chronic HFD exposure. To delineate the specific role of chronic ER stress, we use a hepatocyte-specific knockout of a key regulator of translational control under prolonged ER stress. We show that ~70% of HFD-induced gene expression changes are modulated at the translational level. A distinct subset of mRNAs, enriched in suboptimal codons and bearing short poly(A) tails under normal diet, becomes selectively activated upon HFD-induced poly(A) tail elongation. These transcripts, associated with cell cycle, immune response, fibrosis, and tissue remodeling, correlate with MASH severity in both murine models and human samples. Their regulation is mediated by cis-elements in the 3' UTR that coordinate polyadenylation and deadenylation. Loss of this adaptive response exacerbates liver damage and tumor burden in HFD-fed mice.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a dense desmoplastic stroma and an immunosuppressive tumor microenvironment that contribute to therapeutic resistance. Here, we identify plasminogen activator inhibitor 1 (PAI1) as a stroma-derived mediator of immune evasion and tumor progression in PDAC. PAI1 is predominantly produced and secreted by cancer-associated fibroblasts, and its genetic ablation in the stromal compartment impairs tumor growth. Mechanistically, hypoxia induces PAI1 expression in fibroblasts, which in turn shifts macrophages toward immunosuppressive phenotypes and suppresses CD8+ T cell infiltration and function. We further show that tissue plasminogen activator (tPA), a direct PAI1 target, is also secreted by fibroblasts and supports antitumor CD8+ T cell responses. Notably, elimination of stromal tPA promotes immunosuppressive macrophage phenotypes, reduces CD8+ T cell infiltration, and accelerates PDAC progression. These findings define a previously unrecognized PAI1-tPA regulatory axis within the tumor stroma that modulates antitumor immunity. Targeting this pathway may provide a therapeutic opportunity to overcome stroma-driven immune suppression in PDAC.