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.

Chronic atrophic gastritis (CAG) is a critical precancerous condition with limited therapeutic options to halt its progression toward gastric cancer. Targeting dysregulated metabolism and inflammation-driven transformation represents a promising yet underexplored strategy. Herein, through systematic screening of Jianwei Xiaoyan Granule (JWXYG)-derived compounds via molecular docking and surface plasmon resonance (SPR), we identified hederagenin as a potent and novel mechanistic target of rapamycin (mTOR) binder (Kd = 1.30 μM). In a rat CAG model, hederagenin administration resulted in marked histological and biochemical improvements. Histopathological evaluation revealed that hederagenin effectively restored gastric mucosal architecture, significantly attenuated characteristic glandular atrophy, and reduced the extent of intestinal metaplasia, a key precancerous lesion. Concurrently, serum analysis demonstrated that hederagenin treatment normalized critical biomarker levels, including a significant reduction in gastrin-17 (G-17) and the pro-inflammatory cytokine interleukin-6 (IL-6), alongside a notable increase in the levels of pepsinogen I (PG I) and pepsinogen II (PG II). Functionally, hederagenin exhibited potent anti-tumor properties in vitro by significantly suppressing the proliferation, migration, and invasion capabilities of premalignant gastric epithelial cells. Mechanistically, transcriptomic analyses revealed that hederagenin targeted cancer-associated metabolic reprogramming through the mTOR/hypoxia-inducible factor-1α (mTOR/HIF-1α) signaling axis. Experimental validation further confirmed that hederagenin significantly suppressed the mTOR/HIF-1α pathway. Additionally, it downregulated the expression of key rate-limiting glycolytic enzymes, including hexokinase II (HK II), pyruvate kinase M2 (PKM2), enolase 1 (ENO1), and lactate dehydrogenase A (LDHA), thereby attenuating glycolytic flux, a hallmark metabolic adaptation in precancerous lesions. Importantly, mTOR knockdown abolished hederagenin-mediated LDHA suppression and compromised its therapeutic efficacy, validating mTOR as an essential target. Our findings demonstrated that hederagenin could inhibit inflammation-cancer transformation in CAG via regulation of glycolysis through the mTOR/HIF-1α pathway, which provided new candidate compounds for regulating the transformation of CAG into cancer.

Organoid technology is rapidly refining our understanding of organ development, physiology, and disease. The generation of patient-derived organoid cultures is paving the way for effective personalized treatments, defined based on specific genetic and molecular criteria. Moreover, the possibility of testing in vitro the response of tumor cells to the most appropriate therapeutic regimes helps to anticipate the emergence of resistance, to define the molecular mechanisms involved and, in turn, to tailor treatment through a bed-to-bench-to-bed co-clinical strategy. In addition, the creation of organoid biobank provides an opportunity to reduce the reliance on animal models, while expanding the scale and relevance of patient/human material derived analyses, ultimately accelerating the preclinical-to-clinical workflow. Prostate cancer (PCa) is one of the most common cancers in men world-wide, second only to lung cancer. Although not particularly aggressive, PCa lethality remains a clinical issue. The paucity of innovative molecular targeted therapies and the ineligibility for immunological strategies limit the clinical intervention to mainly surgery or radiotherapy for organ confined tumors, and systemic hormone therapy in the case of advanced metastatic disease. Initially effective in most patients, tumor almost inevitably relapses with palliative care remaining the only option. In this review we provide a historical and conceptual overview of organoid technology, we discuss its application in prostate cancer and outline future prospective for the development of an organoid based platform aimed at risk stratification, risk factor studies, therapeutic prediction, and personalized medicine.

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.

Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and drives one of the leading causes of cancer mortality worldwide. Immune checkpoint blockade targeting PD-1/PD-L1 has improved patient outcomes, but sustained tumor control is still limited. Tumor-associated macrophages (TAMs), the dominant myeloid population in the tumor microenvironment (TME), contribute to immune escape and immunotherapy resistance. Here, we identified tumor-intrinsic SERPINE1 as a critical driver of macrophage remodeling. SERPINE1 expression was strongly elevated in tissue microarrays, paired patient samples, and NSCLC cell lines. SERPINE1 knockdown limited tumor growth in immunocompetent mice, while growth differences were markedly reduced in immunodeficient mice, supporting immune involvement. Macrophage depletion attenuated the antitumor phenotype, indicating a macrophage-dependent mechanism. SERPINE1 silencing reduced TAM recruitment, decreased M2-like TAMs, and increased M1-like TAMs. Mechanistically, SERPINE1 inhibition reduced STAT3 phosphorylation and CCL2 production, a crucial chemokine involved in macrophage chemotaxis and polarization. Finally, in vivo experiments revealed that genetic targeting of SERPINE1 enhanced the efficacy of anti-PD-1 treatment, reduced tumor progression, and prolonged the survival of tumor-bearing mice. In conclusion, SERPINE1 inhibition restricts macrophage infiltration and shifts macrophage polarization away from M2-like phenotypes, enabling stronger tumor control when combined with anti-PD-1 therapy. These findings suggest the potential of targeting SERPINE1 as a strategy to enhance the efficacy of immunotherapy in NSCLC.

Main pancreatic duct (MPD) dilation is an imaging finding that encompasses a broad spectrum of benign and malignant etiologies. Differentiating between these conditions is critical for appropriate patient management, and radiologists play a central role in this diagnostic process. CT and MR, particularly with MR cholangiopancreatography (MRCP), are crucial for assessing ductal morphology, parenchymal changes, and associated lesions. Thin-slice dual-phase CT provides excellent spatial resolution and is particularly effective for evaluating pancreatic ductal adenocarcinoma (PDAC), vascular invasion, and metastatic disease. Conversely, MR offers superior soft-tissue contrast and ductal delineation, allowing detailed assessment of subtle strictures, cystic lesions, and intraductal abnormalities. Benign causes of MPD dilation include chronic pancreatitis with ductal calculi, post-inflammatory strictures, low-grade main-duct intraductal papillary mucinous neoplasms (IPMNs), and focal autoimmune pancreatitis. These entities often show gradual ductal narrowing, multiple strictures, or smooth contour irregularities without abrupt cutoff. In contrast, malignant etiologies - such as PDAC, high-grade IPMN, ampullary carcinoma, pancreatic neuroendocrine carcinoma (NET), and metastases - typically present with abrupt ductal truncation, associated mass effect, and upstream atrophy. Recognition of imaging patterns such as the "double duct sign," enhancing mural nodules, or restricted diffusion improves diagnostic confidence. Technical optimization of CT and MR protocols, awareness of artifacts, and correlation with clinical data are essential to avoid misinterpretation. Radiologists must integrate morphological, functional, and clinical information to ensure accurate characterization of MPD dilation and guide optimal management.

To describe the gross and microscopic histopathological changes observed in human liver tissue resected after pre-surgical portal vein embolization (PVE) performed exclusively with ethylene-vinyl alcohol copolymer (EVOH).

The escalating demand for efficient therapeutic development necessitates innovative strategies to accelerate drug discovery. This study employs an active fragment assembly (AFA) strategy to create a series of linear indoxadiazole compounds that serve as viable inhibitors for KRAS protein. Preliminary assessments indicate that compound 10b exhibits significant inhibitory activity in pancreatic cancer cells harboring KRASG12C and KRASG12D mutations (ASPC-1, PANC-1 and Miapac-2) and excellent selectivity between cancerous and non-cancerous cells. Mechanistic studies reveal that 10b effectively downregulates the levels of phosphorylated Raf1, AKT, and ERK in the ASPC-1 and Miapac-2 cancer cell lines. Additionally, molecular docking studies demonstrate a robust binding affinity of compound 10b with both KRASG12C and KRASG12D proteins. These findings provided unique pathways for investigating multi-target inhibitors aimed at mutated KRAS proteins, thereby advancing the development of innovative molecular therapies for cancers associated with KRAS mutations.

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.