Search Results (911)

Background/Objectives: The management and prognosis of ALK-rearranged non-small-cell lung cancer have substantially improved over the past decade. However, challenges remain in timely molecular identification, prediction of treatment response, and understanding resistance mechanisms. This systematic review evaluates and synthesizes the evidence on artificial intelligence (AI) approaches leveraging imaging, pathology, molecular, and clinical data in this setting. Methods: A systematic search was conducted for peer-reviewed studies published between 2020 and 2025. Eligible studies involved human subjects and applied AI, machine learning, or deep learning methods to predict ALK status or treatment-related outcomes using imaging, pathology, molecular, or multimodal data. Study selection followed the PRISMA 2020 guidelines. Data were extracted on study design, data modality, AI methodology, clinical objectives, and performance metrics. Bibliometric co-occurrence analysis was performed to characterize thematic patterns and temporal trends. Results: Thirteen studies met the inclusion criteria, most of which were retrospective and single-center. AI approaches were applied to radiologic, pathologic, molecular, or multimodal data. Models predicting ALK status reported area under the curve values ranging from 0.73 to 0.99, while prognostic and treatment-response models reported moderate to high discriminative performance. Bibliometric analysis identified two dominant research themes focused on molecular characterization and computational methodology, with a recent shift toward treatment-specific and integrative analyses. External validation and clinical implementation remained limited across studies. Conclusions: AI shows promising potential to support diagnosis, prognostication, and treatment assessment in ALK-rearranged lung cancer. However, methodological heterogeneity, limited external validation, and a lack of prospective studies currently constrain clinical translation. Full article

Background/Aim: Anastomotic stricture following choledochojejunostomy (CJS) is largely driven by fibrotic remodeling at the anastomotic site, a process mediated by transforming growth factor-β (TGF-β) signaling. This problem is particularly relevant in emergency biliary surgery, where CJS is frequently performed under suboptimal conditions and anastomotic leakage is common, predisposing to exaggerated fibrosis and late strictures. This study aimed to evaluate the effect of the TGF-β type I receptor (ALK5) inhibitor EW-7197 (vactosertib) on histopathological parameters of anastomotic healing, with a particular focus on fibrosis, in a rat CJS model. Materials and Methods: Twenty-four male Wistar Albino rats were randomized into three groups (n = 8 each): control (G1), CJS only (G2), and CJS plus EW-7197 (G3). EW-7197 was administered as a single intraperitoneal dose (20 mg/kg) immediately after completion of the anastomosis. On postoperative day 21, choledochojejunal anastomotic tissues were harvested and evaluated histologically using hematoxylin–eosin and Masson’s trichrome staining. Edema, hyperemia, inflammation, and fibrosis were graded using a semi-quantitative scoring system, and intergroup comparisons were performed using non-parametric statistical tests. Results: Compared with surgery alone, EW-7197 treatment resulted in a statistically significant reduction in fibrosis severity at the anastomotic site (p < 0.001) and a significant attenuation of hyperemia (p = 0.007). Edema scores showed a downward trend in the EW-7197-treated group but did not reach statistical significance, while inflammation scores did not differ significantly between the surgical groups. Conclusions: In this experimental rat choledochojejunostomy model, administration of the selective ALK5 inhibitor EW-7197 significantly reduced histopathological fibrosis and hyperemia at the anastomotic site on postoperative day 21 without affecting inflammation severity. These findings support the role of the TGF-β/Smad pathway in bilioenteric anastomotic fibrotic remodeling. However, further studies including molecular validation and functional assessments are required to clarify the translational relevance of these results. Full article

Background/Objectives: Adenine derivatives are promising anticancer scaffolds, but their cellular mechanisms remain unclear. This study aimed to synthesize adenine–hydrazone hybrids and evaluate their cytotoxic effects in human lung adenocarcinoma (A549) cells. Methods: A series of adenine–hydrazone compounds (3a–r) was synthesized and tested for cytotoxicity in A549 and MRC-5 cells. Selected compounds were further analyzed for LDH release, oxidative stress markers, ROS production, mitochondrial membrane potential, cell-cycle distribution, apoptosis, and in silico docking against VEGFR2, ALK5, and EGFR. Results: Compounds with electron-withdrawing or donor–acceptor substituents showed the highest cytotoxicity, while halogenated and methoxy analogs were moderately active. Among the synthesized derivatives, 4F-substituted derivatives (3c) showed more activity than 2F- and 3F-substituted ones (3a and 3b). 4F- and 3Br-substituted derivatives (3f) showed more activity than only 4F-substituted ones (3c). 4-Nitro-substituted derivative (3i) showed more activity than 4F- (3c), 4Cl- (3d) and 4OMe- (3h) derivatives. Trimethoxy-substituted derivative (3l) showed more activity than di- and mono-substituted methoxy derivatives (3g, 3h, 3j and 3k). Among the salicyl aldehydederivatives (3m–r), 4-N(et)₂-substituted derivative (3r) showed more activity than non-substituted (3m), 5Br-(3n), 5Cl-(3o), 5Me (3p) and 3OCH₃ (3q) derivatives. Treatment induced oxidative stress, mitochondrial depolarization, Sub-G1 cell-cycle accumulation, and apoptosis. Docking studies indicated strong binding to VEGFR2 and ALK5, suggesting dual inhibition as a potential mechanism. Conclusions: Adenine–hydrazone derivatives exert substituent-dependent anticancer effects by inducing redox imbalance-associated mitochondrial dysfunction and regulated cell death. These results highlight their potential as lead structures for lung cancer therapy. Full article

Oligoprogressive disease (OPD) in non-small-cell lung cancer (NSCLC) is a clinical entity with peculiar behavior and treatment. OPD patients, during systemic therapy, may receive local ablative treatment (LAT) with survival benefit. The importance of OPD and the role of LAT has been comprehensively assessed in the setting of EGFR mutant and ALK-rearranged NSCLC during tyrosine kinase inhibitor (TKI) treatment, but it is still almost unexplored in the context of NSCLC harboring actionable oncogenic drivers other than EGFR and ALK. The aim of our review is to collect and discuss the available data about standard treatment in this latter setting, with special consideration given to the role of LAT in case of OPD in systemic treatment. Through a comprehensive PubMed and ClinicalTrials.gov search, we identified the available data and ongoing clinical trials addressing these aims. To date, only limited evidence supports the use of LAT in OPD involving NSCLC driven by these molecular alterations, mainly deriving from case reports and retrospective series. This highlights an unmet clinical need that warrants systematic and multicentric data collection to generate more robust evidence. Full article

Background: An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor, sometimes with urinary bladder involvement (though this is extremely uncommon). Due to its rarity, the exact etiology and optimal treatment strategy remain unclear. Methods: A review of the existing literature on IMT of the urinary bladder was performed. Results: We report a case of a 32-year-old female presenting with frequent urination, hematuria with clots, and lower abdominal pain for one month. Initially misdiagnosed as acute cystitis, the symptoms persisted despite antibiotic therapy. Laboratory findings revealed severe anemia, and imaging studies identified a large bladder mass. Transurethral resection of the bladder tumor (TURB) was performed, and a 96 g mass was removed. Histopathological examination confirmed IMT of the urinary bladder (IMTUB) with positive immunohistochemical staining for ALK, vimentin, and actin. Follow-up at 30 months showed no recurrence, with annual cystoscopy and CT scans confirming remission. Conclusions: IMTUB should be considered in young patients presenting with hematuria and lower urinary tract symptoms. Early diagnosis through cystoscopy, imaging, and histopathological confirmation is essential for appropriate management. TURB remains the gold standard for treatment, with ALK inhibitors providing additional therapeutic options in select cases. Long-term follow-up is necessary due to the unknown malignant potential of IMTUB. Full article

Rhabdomyosarcoma is a small round-cell soft tissue tumor that occurs mainly in pediatric and adolescent/young adult (AYA) patients but also rarely in adults. Multidisciplinary treatments including multidrug therapy and local therapy (surgery and/or radiation) are the current standard of care, and treatment strategies are determined according to the estimated risk based on the patient’s age, site of onset, and histologic type, as well as the disease stage. New treatment developments in recent years have been based on risk; lower cumulative doses of alkylating agents to reduce late toxicity for low-risk patients are being studied, and long-term maintenance therapy or the addition of new drugs inhibitors to standard multidisciplinary therapy for intermediate- to high-risk patients have been investigated. For high-risk and metastatic patients, novel molecular targeted drug candidates are being evaluated. The target candidates for rhabdomyosarcoma have included the RAS-signaling pathway, ALK, NTRK, FGFR, and MSI-High. In addition, fusion genes (e.g., PAX3/7-FOXO1), which play an important role in diagnostic and prognostic factors, are also being investigated as potential therapeutic targets as their underlying backgrounds are gradually becoming clear. This review summarizes the overall picture of the development of novel therapies for rhabdomyosarcoma and discusses the direction that should be taken in the future. Full article

Background: Congenital renal masses in neonates are most commonly congenital mesoblastic nephroma or, less frequently, or Wilms tumor. We describe a neonate with an apparent primary renal tumor that proved to be adrenal neuroblastoma infiltrating the kidney, highlighting diagnostic pitfalls in this subgroup of patients. Methods: We retrospectively reviewed the diagnostic work-up, histopathology, genomic profiling, treatment, and outcome of a term neonate in whom a renal mass was detected incidentally on ultrasound. Results: Ultrasound and MRI showed a 2 cm solid lesion centered in the upper pole of the left kidney, interpreted as nephroblastomatosis/early Wilms tumor. Left nephrectomy with adrenalectomy revealed stroma-poor, undifferentiated neuroblastoma with regional node involvement and multiple segmental chromosomal aberrations, including 1p and 3p loss, but no MYCN or ALK alterations. Initial management consisted of surgery alone with close surveillance. Within weeks, early disseminated relapse with bone and soft-tissue metastases occurred, necessitating escalation to high-risk, COJEC-based chemotherapy; resection of residual mass; and modified consolidation without high-dose chemotherapy or radiotherapy. The child remains in complete remission with preserved renal function. Conclusions: Neuroblastoma should be considered in the differential diagnosis of congenital “renal” masses. Imaging-driven provisional diagnoses may be misleading, and genomic risk profiling may help lower the threshold for systemic therapy in selected cases. Full article

T-cell malignancies represent a complex spectrum of clinically and biologically heterogeneous diseases. Effective translational research and drug development are critically dependent on preclinical models that faithfully recapitulate this diversity. This review analyzes the current preclinical landscape, identifying a profound disparity between the clinical spectrum of T-cell neoplasms and the available in vitro tools. We demonstrate that the existing armamentarium of cell lines is heavily skewed, with an abundance of models for T-cell lymphoblastic leukemia/lymphoma (T-ALL), cutaneous T-cell lymphoma (CTCL), and anaplastic large cell lymphoma (ALCL). This skew is a direct result of a biological selection bias, as these entities are often driven by potent, TME-independent oncogenes (e.g., NOTCH1 mutations, NPM1-ALK fusions) conducive to immortalization. Conversely, the majority of peripheral T-cell lymphoma (PTCL) subtypes, which are frequently TME-dependent and clinically aggressive, remain “preclinical orphans” with few or no authenticated models. This “preclinical void” constitutes a major bottleneck, impeding mechanistic studies and therapeutic progress. We discuss the limitations of 2D cultures and highlight the necessity of adopting advanced platforms, such as patient-derived xenografts (PDX) and 3D organoid systems. These “avatar” models preserve vital tumor heterogeneity and microenvironmental context, offering superior predictive value. The systematic development and integration of these next-generation models are essential to bridge the translational gap and advance precision medicine for all patients with T-cell malignancies. Full article

Targeted therapies have revolutionized treatment paradigms for a variety of cancer types; however, challenges including primary and acquired resistance persist, and there remains a high demand for novel treatment options. HER3 (ErbB3), a member of the human epidermal growth factor receptor family of receptor tyrosine kinases, is a target of HER3-DXd, an antibody–drug conjugate currently under clinical investigation. As was previously reported, the cytotoxic activity of HER3-DXd in preclinical models is primarily mediated by the antitumor activity of the released payload. Therefore, we investigated the impact of HER3 expression changes on payload release after HER3-DXd treatment using HER3-positive human cancer cell lines and their xenograft models. In vitro studies showed that the amount of payload released from cells after HER3-DXd treatment was associated with baseline HER3 expression levels, HER3 internalization rate, and turnover rate. In female CAnN.Cg-Foxn1nu/CrlCrlj mouse models, dose and dosing interval influenced membrane HER3 expression levels and tumor payload concentrations. Furthermore, membrane HER3 was upregulated by tyrosine kinase inhibitor treatment in non-small-cell lung cancer cell lines harboring specific driver mutations, including EGFR-activating mutations, ROS1 fusions, and ALK fusions. The increase in HER3 expression induced by osimertinib treatment was associated with increased payload release in PC-9 cells. Our results indicate that HER3 dynamics, as well as baseline HER3 expression, modulate payload release from HER3-DXd and support combination strategies to potentiate the antitumor activity of HER3-DXd. Full article

Background/Objectives: Next-generation sequencing (NGS) has become the standard of care for identifying actionable genomic alterations in non-small cell lung cancer (NSCLC). This study aims to describe the clinicopathological characteristics and genomic landscape of a non-selected cohort of NSCLC patients from the Canary Islands (Spain), analyzed during the first two years of our Molecular Diagnosis Unit’s operation. Methods: We conducted an observational, retrospective study including 448 tumors from 446 patients diagnosed between March 2023 and March 2025. Genomic profiling was performed using amplicon-based NGS panels (Oncomine™ Focus and Precision Assays) on semiconductor sequencing platforms to detect single-nucleotide variants (SNVs), indels, copy number alterations (CNAs), and gene fusions from DNA and RNA. Results: Actionable alterations were identified in 55.1% of tumors. The most prevalent alterations were found in TP53 (29.5%), KRAS (27.2%), and EGFR (14.1%), with KRAS G12C being the most frequent variant. Stratified analysis revealed a high prevalence of ALK fusions in patients < 50 years (33.3%). Crucially, and in stark contrast with traditional exclusion criteria, 54.0% of EGFR mutations and 50.0% of ALK fusions were detected in patients with a history of smoking. Concomitant alterations were observed in 34.8% of cases, with TP53 being the most common co-mutation partner. Conclusions: Our real-world data confirm the feasibility and clinical value of routine NGS testing for NSCLC. The findings highlight specific genomic patterns in this population and demonstrate that smoking status should not preclude comprehensive molecular testing for canonical drivers. Full article

Pulmonary arterial hypertension (PAH) and cancer share high mortality and complex prognoses. Due to PAH’s rarity, these parallels may be underrecognized by healthcare stakeholders. This study explored similarities between PAH and cancer across epidemiological, clinical, therapeutic, and healthcare resource utilization (HCRU) considerations. A four-step approach was employed: (1) inclusion/exclusion criteria were applied to identify potential PAH cancer analogs; (2) characteristics for comparison were categorized as epidemiologic, clinical, therapeutic landscape, and HCRU; (3) a targeted literature review extracted data on disease characteristics; (4) a similarity ranking was calculated as the absolute difference between each cancer’s and PAH’s characteristics. Fourteen cancers met the inclusion criteria. Well-differentiated thyroid cancer (WDTC) had the highest number (5) of characteristics closest to PAH. WDTC and medullary thyroid cancer were most similar to PAH in epidemiology; gastrointestinal stromal tumor was most similar in clinical and HCRU characteristics, and anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer and renal cell carcinoma were most similar in therapeutic landscape. Although no single cancer fully mirrors PAH, the identification of multiple analogs underscores PAH’s multidimensional complexity and confirms its overlap with oncological conditions. Cancer analogs could serve as a valuable framework for enhancing recognition of PAH’s clinical, therapeutic, and HRCU implications among healthcare stakeholders. Full article

This study focused on the links between soil physicochemical properties and the gut microbiota of goitered gazelles (Gazella subgutturosa) in the hyper-arid Qaidam Basin. By integrating 16S rRNA gene sequencing, soil physicochemical analysis (11 soil indicators), and microbial source tracking (FEAST) on samples of feces (n = 58), soil (n = 35), and water (n = 35) collected from six typical regions. We systematically revealed the mechanisms by which soil properties influence the gut microbiome of wildlife in an arid desert ecosystem based on source tracking and Multiple Regression on distance Matrices (MRM) analysis. The results showed that soil total phosphorus (TP) was significantly positively correlated with the α-diversity of gut microbiota (coefficient = 0.4/0.23/0.332; p < 0.05), while soil organic carbon (SOC) was significantly negatively correlated (coefficient = −0.44/−0.436; p < 0.05), indicating that soil nutrients indirectly predict host microbial diversity by regulating vegetation productivity and forage quality. β-diversity analysis further demonstrated that spatial heterogeneity in soil pH (coefficient = 0.3083; p < 0.05) and TP (coefficient = 0.227; p < 0.05) significantly drove the structural differentiation of gut microbial communities. Source-tracking results based on FEAST revealed significant regional differences in the proportional contribution of environmental microorganisms to the gut microbiota, with individuals in resource-poor habitats (ALK region) exhibiting higher input from soil microbes (8.0672% ± 6.9291%; p < 0.05). In conclusion, this study clarifies the ecological mechanism by which soil physicochemical properties regulate the diversity and composition of herbivore gut microbiota through a “soil–plant–food–gut microbiota” cascading pathway, providing important empirical evidence for understanding animal–microbe–environment interactions and adaptive evolution in extreme environments. Full article

Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of malignancy and the leading cause of cancer-related fatalities. In clinical practice, metastatic sites are identified on a case-by-case basis. ALK rearrangements are detected in 3–5% of NSCLC cases and are known to have a tendency (tropism) to metastasize to the brain. Methods: Data from 81 ALK-positive and 91 ALK-negative metastatic NSCLC patients were retrospectively analyzed. Systemic markers, including HALP score, NLR, PLR, LMR, and LDH, were calculated from blood tests at the time of metastasis. Optimal cut-off values were determined using ROC analysis. Survival outcomes and prognostic factors were assessed using Kaplan–Meier and Cox regression analyses. Results: ALK-positive patients were significantly associated with female gender (p = 0.002), non-smoking status (p = 0.001), adenocarcinoma histology (p = 0.001), and a higher incidence of brain metastases (p = 0.001). In univariate analysis, age, time to metastasis, liver metastasis, and NLR were prognostic for survival. Crucially, multivariate analysis identified liver metastasis as an independent predictor of poor prognosis (HR = 1.618; 95% CI: 1.050–2.494; p = 0.029), indicating a 61.8% increased risk of death or progression. While inflammation markers (NLR, HALP, PLR, LMR) did not predict metastasis to specific sites, elevated LDH levels were significantly associated with liver metastasis (p = 0.007). Conclusion: ALK-positive NSCLC demonstrates a marked CNS tropism; however, liver metastasis remains a more critical adverse prognostic factor than brain metastasis in real-world settings. While routine inflammation markers showed limited utility in predicting site-specific metastasis, LDH levels correlated significantly with liver involvement. Aggressive management strategies are warranted for ALK-positive patients presenting with liver metastases. Full article

Surgical resection remains the cornerstone of curative-intent treatment for both oncogene and non-oncogene addicted early-stage non-small cell lung cancer, with neoadjuvant/adjuvant chemotherapy providing only a modest benefit in terms of disease-free survival and overall survival. Currently, in non-small-cell lung cancer without actionable molecular alterations, the addition of neoadjuvant or perioperative immunotherapy to chemotherapy has become the standard of care for resectable disease, with significant improvements in the rates of complete pathological response, major pathological response, and event-free survival. In terms of oncogene-addicted non-small-cell lung cancer, adjuvant treatment of completely resected disease with the third-generation EGFR inhibitor osimertinib in patients harboring activating EGFR mutations or the second-generation ALK inhibitor alectinib in patients with an ALK fusion/translocation has brought about a paradigm shift by significantly improving event-free survival and, in the case of osimertinib, overall survival. A glimpse into the future management of patients with early-stage disease and a common EGFR mutation or an ALK fusion/translocation may reveal a perioperative use of the respective targeted treatment. Data for the rest of the actionable molecular alterations remain limited, and those tumors are usually treated with algorithms used for non-oncogene-addicted non-small-cell lung cancer. This review aims to summarize all existing evidence about the current management of patients with early-stage non-small-cell lung cancer and actionable molecular alterations and to examine the future directions in this rapidly evolving field. Full article

Petroleum contamination poses a serious threat to human health and ecosystems worldwide, and microbially driven natural attenuation is an effective approach for accelerating hydrocarbon removal. Species of the genus Rhodococcus are recognized for their ability to degrade long chain petroleum hydrocarbons. However, their physiological traits and degradation mechanisms under alkaline conditions remain insufficiently understood. In this study, soil samples were collected from the Dagang oilfield in Tianjin, China, and Rhodococcus sp. A17 was isolated as an active indigenous strain for genomic and physiological characterization under high pH petroleum degradation conditions. The results showed that strain A17 grew optimally at 30 °C, pH 9.0, and 2% salinity. Petroleum hydrocarbon degradation reached 67.8% within 72 h, with a degradation half life of 34.2 h. Genome sequencing identified 18 oxygenase related genes involved in alkane degradation, including alkB, cytochrome P450 monooxygenases, and the long chain alkane monooxygenase ladA, together with four antibiotic resistance genes. Metabolite analysis suggested that alkane degradation might proceed via terminal and subterminal oxidation pathways. Overall, these findings indicate that Rhodococcus sp. A17 exhibits multiple adaptive traits that support its potential application in the bioremediation of petroleum contaminated alkaline environments. Full article