Gastrointestinal (GI) cancers remain a major global health concern characterized by aggressive progression, poor prognosis, and resistance to traditional treatment modalities. Despite significant advancements, conventional treatments like surgery, chemotherapy, and radiotherapy often cause systemic toxicity, lack tumor specificity, multidrug resistance, and risk of relapse, emphasizing the need for safer and more targeted interventions. In response to these challenges, extensive research has focused on natural compounds for GI cancer treatment, with many phytochemicals demonstrating low toxicity and the ability to modulate multiple cancer-related pathways. Among natural compounds, isorhamnetin, a methylated flavonol and quercetin derivative found in various dietary sources, has emerged as a highly promising anticancer agent. Through modulation of various key oncogenic pathways such as PI3K/Akt, MAPK, NF-κB, and Wnt/β-catenin, isorhamnetin exerts pro-apoptotic, antiproliferative, anti-angiogenic, and anti-metastatic effects in various GI cancers. Isorhamnetin's chemopreventive efficacy is further underscored by its anti-inflammatory and antioxidant properties, which are essential in reducing chronic inflammation and oxidative stress commonly involved in GI tumor development. However, its efficacy and clinical translation remain hindered due to pharmacokinetic constraints such as low water solubility and rapid metabolism. Recent emerging nanotechnological approaches aim to address these challenges by enhancing their bioavailability and targeted delivery. This manuscript emphasizes the anticancer potential of isorhamnetin in GI malignancies, with a particular focus on its molecular mechanisms of action, chemopreventive properties, and recent progress in nanoformulation-based strategies.

Artificial intelligence has diverse applications, especially in perioperative surgery. Intraoperative recognition of anatomical structures affects surgical decision-making, surgical progress, and outcomes. Nerve-sparing robot-assisted radical prostatectomy is performed to preserve postoperative function; however, recognition of the layers that need to be preserved still depends largely on surgeon experience. Therefore, we developed a convolutional neural network-based deep-learning model to assist in recognition of the prostatic capsule.

In proton therapy of low-grade glioma (LGG) patients, contrast-enhancing brain lesions (CEBLs) on magnetic resonance imaging are considered predictive of late radiation-induced lesions. From the observation that CEBLs tend to concentrate in regions of increased dose-averaged linear energy transfer (LETd) and proximal to the ventricular system, the probability of lesion origin (POLO) model has been established as a multivariate logistic regression model for the voxel-wise probability prediction of the CEBL origin.

Metastatic pheochromocytomas and paragangliomas (mPPGLs) are uncommon, heterogeneous neuroendocrine tumors lacking standardized systemic treatment pathways. Evidence on treatment response predictors and outcome-based stratification remains limited. We conducted a retrospective study of 49 patients with mPPGLs treated between 2010 and 2024 at two Spanish referral centers. We evaluated clinical characteristics, systemic treatment patterns, radiologic responses (per RECIST), and survival outcomes. Patients were stratified into five clinical evolution patterns based on treatment response and disease trajectory. The most common indications for initiating systemic therapy were radiologic progression (59.5%) and high tumor burden (31%). First-line treatments included somatostatin analogues (SSAs, 40.5%), radionuclide therapies (33.3%: 177Lu 9.5% and 131I-MIBG 23.8%), and chemotherapy (23.8%). Partial response rates were higher with chemotherapy, 131I-MIBG, and 177Lu compared with SSAs. Tumor burden at treatment initiation appeared to be more closely associated with radiologic response than radiologic progression. Progression-free survival (PFS) appeared to differ according to first-line treatment type, with longer PFS observed in patients receiving radionuclide therapies. The median overall survival from systemic treatment initiation was 48 months. Five clinical evolution patterns were identified, highlighting disease heterogeneity. Radiologic progression remains the main trigger for systemic treatment in mPPGLs; however, initial tumor burden appears to be a stronger predictor of treatment response. Our proposed five-pattern clinical classification may contribute to prognostication and therapeutic individualization. Prospective studies are a key unmet need to determine the optimal timing and sequencing of systemic therapies in mPPGL.

Accurate delineation of the prostate and intraprostatic gross tumor volume (GTV) on multiparametric MRI (mpMRI) is critical for radiation therapy planning, particularly for focal dose escalation strategies. However, interpretation of mpMRI can be challenging and prone to inter-observer variability, especially among radiation oncologists (ROs) who may have limited training in prostate MRI interpretation. In addition, because many patients do not undergo diagnostic mpMRI before treatment, radiologist input is often absent during treatment planning, which can compromise accurate GTV delineation.

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.

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.