Colorectal cancer (CRC) remains difficult to treat because redox adaptation, metabolic plasticity, mucin-associated delivery barriers, immune exclusion, and microbiota-dependent signaling jointly limit conventional therapy. Engineered nanozymes provide a reaction-centered strategy for exploiting these CRC-specific vulnerabilities. This review critically compares metal, metal-oxide, carbon-based, porous-framework, and single-atom nanozymes with respect to catalytic mechanism, enzyme-mimicking activity, substrate dependence, controllability, biosafety, and translational suitability. We examine how acidity, hydrogen peroxide, hypoxia, glutathione enrichment, metabolic dysregulation, mucin barriers, and the gut microbiota influence catalytic performance. We further evaluate evidence for chemotherapy sensitization, chemodynamic, photothermal, photodynamic, sonodynamic, immunotherapeutic, and multimodal treatment, emphasizing both mechanistic synergy and limitations of the available preclinical models. Major translational barriers include non-standardized catalytic assays, heterogeneous intratumoral substrates, off-target reactive oxygen species toxicity, uncertain degradation and long-term fate, microbiome disruption, manufacturing reproducibility, and limited validation in orthotopic, immunocompetent, organoid, and patient-derived systems. We therefore position CRC nanozyme therapy as a disease-oriented catalytic medicine platform whose clinical value will depend on biomarker-guided selection, programmable activation, and degradable, locally controllable designs.

Gestational gigantomastia is a very rare disorder characterised by massive, bilateral breast enlargement during pregnancy. Clinically, it is characterised by rapid breast enlargement associated with severe mastodynia, back and shoulder pain, and erythema of the skin. In its most severe forms, it can lead to ulceration, necrosis, haemorrhage, or septicaemia. The underlying pathophysiology is not completely understood, but is thought to be multifactorial, involving hormonal hypersensitivity and autoimmune mechanisms. Histopathological confirmation is necessary for definitive diagnosis because its clinical presentation can closely mimic that of inflammatory breast carcinoma or other malignant neoplasms. We report a case of a 28-year-old primigravida who presented at 24 weeks of gestation with progressive bilateral breast enlargement that reached its maximal extent at 36 weeks and caused significant functional impairment. On clinical examination, there was symmetrical breast hypertrophy with diffuse erythema and a marked peau d'orange appearance. Breast ultrasound revealed glandular hypertrophy with ductal ectasia and marked oedema. No suspicious focal lesions were seen. Hormonal and immunological workup was normal, and skin and glandular biopsy showed benign hyperplasia without atypia. Throughout the pregnancy, conservative management with analgesics and postural support was continued until an uncomplicated vaginal delivery at 39 weeks of gestation. Cabergoline was then administered to suppress lactation. Given the absence of spontaneous regression of the breasts, a multidisciplinary decision was taken to perform a bilateral reduction mammoplasty at 12 months postpartum. This case demonstrates the phenotypic variability of gestational gigantomastia that may present without any preceding breast pathology. In severe cases, surgical treatment (reduction mammoplasty or bilateral mastectomy with delayed reconstruction) is the mainstay of treatment, and bromocriptine is the best-established medical alternative, but with variable success. Coordinated multidisciplinary care is essential to optimise patient outcomes and minimise life-threatening complications.

Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma is a rare and aggressive peripheral T-cell lymphoma typically diagnosed at advanced stages. Although venovenous extracorporeal membrane oxygenation (VV-ECMO) has been associated with poor outcomes in patients with active hematological malignancies, emerging evidence points to a potential benefit for carefully selected patients with severe acute respiratory failure due to cancer. We describe the clinical case of a 19-year-old male who initially presented with pleuritic chest pain and fever. Following a four-day hospitalization, he was discharged home with a diagnosis of acute pericarditis. Because of worsening symptoms with acute respiratory failure and newly developed lymphadenopathies, he was readmitted a few days later and diagnosed with nosocomial pneumonia. Despite treatment with broad-spectrum antibiotics, his condition worsened, necessitating mechanical ventilation and VV-ECMO to manage refractory hypoxemia. Subsequent investigation revealed the diagnosis of ALK-positive anaplastic large cell lymphoma with pulmonary involvement. Treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone (CHOEP) chemotherapy led to significant clinical improvement, allowing successful VV-ECMO weaning. However, the disease relapsed shortly after with a comparable severity of respiratory failure, leading to a second VV-ECMO run combined with urgent BRESHAP (brentuximab vedotin, etoposide, methylprednisolone (Solu-Medrol), high-dose cytarabine (Ara-C), and cisplatin) chemotherapy. This strategy resulted in another successful VV-ECMO weaning. Although complete remission was achieved, stem cell transplantation was delayed due to pulmonary sequelae, and the patient declined further treatment. A second relapse occurred, and the patient died 12 months after diagnosis. This case report explores the potential utility of VV-ECMO as a bridge to recovery in carefully selected patients with treatable hematologic malignancies.

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor of the central nervous system. The typical form demonstrates relatively low-grade histologic features, whereas an anaplastic variant shows more aggressive behavior, including increased mitotic activity and necrotic changes. These tumors are often associated with alterations involving key growth signaling pathways and cell cycle regulatory genes, with molecular features that may resemble those seen in other high-grade astrocytic neoplasms. We describe an unusual example of an anaplastic pleomorphic xanthoastrocytoma showing focal piloid differentiation. The patient presented with acute neurologic symptoms, and imaging demonstrated a large, enhancing, well-circumscribed cerebral lesion with limited surrounding edema. Histologic evaluation revealed a highly cellular astrocytic neoplasm composed of spindle-shaped cells with marked pleomorphism, including scattered multinucleated forms, brisk mitotic activity, and necrotic areas. At the periphery, regions with elongated bipolar glial cells and occasional cytoplasmic inclusions suggestive of piloid morphology were identified. Molecular analysis demonstrated an activating alteration in the mitogen-activated protein kinase (MAPK) pathway along with additional genomic abnormalities, while mutations commonly associated with diffuse gliomas were not detected. The presence of piloid features within an otherwise anaplastic tumor is rare and may be relevant to the relatively favorable outcome observed during extended follow-up.

Improvements in access to early-detection research on cancer are still urgently needed to ensure that new research on early-stage cancer detection benefits all groups in society. To achieve this, cancer early detection (ED) studies must include participants from all walks of life. There are unique aspects to cancer early detection research that may deter potential research participants and complicate efforts to involve people from underrepresented backgrounds that require a review on its own merit. For instance, a unique risk for cancer ED research is overdiagnosis and overtreatment, in which a tumor is uncovered and treated that would not have led to the patient's death if left undiscovered and untreated. This potential 'side effect' of cancer ED research participation is particularly problematic for those without adequate access to healthcare and insurance.

We conducted a targeted scoping review to identify empirically tested approaches to improve participation of underrepresented groups in cancer early detection research. Searches were conducted in PubMed and PsycINFO using terms related to cancer, research participation, and underserved populations in the title and/or abstract. Eligible studies were peer-reviewed, published between 2002 and April 2022, conducted in high-income countries, focused on adults without a cancer diagnosis, and reported on their evaluation of an intervention designed to improve recruitment or participation of minoritized groups in cancer early detection research. Data were extracted on study characteristics, barriers to participation, intervention strategies, and outcomes of the recruitment and engagement intervention that was assessed. We analyzed data extracted using narrative synthesis to identify cross-cutting themes across barriers to participating, and recruitment or engagement approaches.

This review identified themes in the 38 included studies that aimed to recruit and involve participants from underserved groups in cancer ED research so that future studies may learn from or further test these varied strategies. We narratively grouped the review in terms of the barriers identified, and the approaches that have been designed to improve participation. These included rethinking recruitment locations and partnerships with local communities, designing educational interventions, combining research with community needs, increasing cultural competence of research teams, and overcoming practical barriers in study design.

This scoping literature review highlights various tools, empirically tested, that research teams can employ to improve participation rates of groups underrepresented in cancer ED research. Combinations of these methods could help overcome the perceived barriers to participation in cancer research that mainly affect people without a cancer diagnosis from these minoritized groups. Not only would these methods increase the generalizability and representativeness of studies; the highlighted approaches also contribute to a more significant shift in research culture toward less extractive and more trusting relationships between researchers and the public.

To evaluate the clinical efficacy and safety of flumatinib in the treatment of chronic myelocytic leukemia (CML) by using propensity score matching (PSM) to balance baseline confounding factors.

A retrospective cohort of 201 patients with CML treated between January 2019 and January 2025 was selected for this study. Patients were stratified into imatinib and flumatinib groups based on their treatment regimens. PSM was employed to control for confounding variables, enabling a comparative analysis of early treatment responses and long-term survival outcomes, including overall survival (OS), between the two tyrosine kinase inhibitor therapies, as well as further analysis of long-term prognosis.

Through PSM, a total of 61 patient pairs were successfully matched. In the flumatinib group, the rates of complete hematologic response (CHR) and early molecular response (EMR) at 3 months of first-line treatment were 96.72% and 83.61%, respectively, with the EMR rate being significantly higher than achieved with imatinib treatment (P < 0.001). For flumatinib, the rates of cumulative major molecular response (MMR) at 6, 9, and 12 months of first-line therapy were 34.43%, 50.82%, and 59.02%, respectively, all exceeding those observed with imatinib (P < 0.05). The molecular response 4 (MR⁴) rates for flumatinib at 9 and 12 months of first-line treatment were 19.67% and 27.87%, respectively, also higher than those for imatinib (P < 0.05). Additionally, the cumulative complete cytogenetic response (CCyR) rates for flumatinib at 3, 6, and 12 months of first-line treatment were 67.21%, 85.25%, and 91.28%, respectively, consistently outperforming imatinib (P < 0.05). Generalized estimating equation analysis revealed that patients in the flumatinib group had a significantly higher probability of achieving MMR than those in the imatinib group (Wald χ ² = 16.280, P < 0.001, odds ratio [OR] = 2.130, 95% CI: 1.570-2.890). The time effect indicated that the probability of achieving MMR increased with the extension of treatment duration in both groups (Wald χ ² = 48.720, P < 0.001). In addition, a statistically significant group-by-time interaction effect was observed (Wald χ ² = 8.940, P = 0.003). During the treatment period, the highest incidence of diarrhea was observed in the flumatinib group (26.23%), while thrombocytopenia was most prevalent in the imatinib group (31.15%). Furthermore, the imatinib group exhibited higher incidences of rash and edema compared to the flumatinib group (P < 0.05). No significant differences were observed in the incidence of other adverse events between the groups (P > 0.05). The median follow-up duration was 43 (37, 52) months. By the end of the follow-up, a total of 7 patients had died, with 4 deaths (6.56% [4/61]) in the imatinib group and 3 deaths (4.92% [3/61]) in the flumatinib group. The comparison of OS between the two groups revealed no statistically significant difference (log-rank P = 0.955).

Compared with imatinib, flumatinib demonstrates superior short-term efficacy and safety profile in the treatment of CML. Despite the lack of significant improvement in long-term OS, flumatinib can still serve as an effective first-line therapeutic option for patients with CML.

Talquetamab, a first-in-class G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, demonstrates substantial clinical activity in relapsed/refractory multiple myeloma (RRMM). However, immune dysfunction associated with advanced disease, extensive prior therapies, and bispecific antibody-mediated immune modulation may increase susceptibility to infections. This systematic review and meta-analysis aimed to characterize infection risk associated with talquetamab, with separate evaluation of monotherapy and combination therapy settings.

PubMed, Embase, Web of Science Core Collection, and Cochrane Library databases were searched from inception to July 1, 2026. Studies reporting infection outcomes among RRMM patients treated with talquetamab-containing regimens were eligible. Outcomes included any-grade infections, grade ≥3 infections, infection-related mortality, reported pathogens, and preventive strategies when available. Because talquetamab monotherapy and combination regimens represent clinically distinct treatment strategies, quantitative analyses were restricted to monotherapy cohorts, whereas combination therapy studies were summarized descriptively. A random-effects model was used to estimate pooled infection incidence. Methodological quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Series.

Six studies were included in the qualitative synthesis, including four talquetamab monotherapy cohorts and two talquetamab-based combination therapy cohorts. Quantitative meta-analysis included four monotherapy cohorts comprising 735 patients for any-grade infections and three cohorts comprising 584 patients for grade ≥3 infections. The pooled incidence of any-grade infections was 51% (95% CI, 34%-67%; I² = 94.2%), while the pooled incidence of grade ≥3 infections was 22% (95% CI, 17%-28%; I² = 59.6%). Given the limited number of available studies and substantial heterogeneity, these pooled estimates should be interpreted as exploratory and hypothesis-generating. Combination therapy cohorts, including talquetamab plus teclistamab and talquetamab-based regimens from MonumenTAL-3, demonstrated substantial infection burdens and were characterized descriptively rather than quantitatively. Infection-related mortality ranged from 0% to 3.2%. Frequently reported infections included viral infections (particularly SARS-CoV-2 and cytomegalovirus), bacterial pneumonia, and opportunistic infections such as Pneumocystis jirovecii pneumonia.

Talquetamab monotherapy in heavily pretreated RRMM patients is associated with a clinically meaningful risk of infections, including severe infections. The substantial heterogeneity observed across studies likely reflects differences in patient characteristics, prior therapies, treatment settings, infection definitions, and supportive care strategies. Combination bispecific antibody regimens may represent a potentially higher infection burden requiring enhanced infection surveillance and preventive approaches. Further prospective studies are warranted to better define infection risk factors and optimal prevention and management strategies during talquetamab therapy.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261357352, identifier CRD420261357352.

Metastasis is the primary cause of treatment failure and adverse prognosis in hepatocellular carcinoma (HCC), and the molecular basis of HCC metastasis remains poorly defined. This work investigated the potential mechanisms underlying HCC metastasis through integrated multi-omics analysis of metabolomics and proteomics.

This retrospective study included 105 individuals with HCC, with comparative analysis between metastatic and non-metastatic cases. We further evaluated the effects of metastasis on serum metabolomics and proteomics in HCC patients.

Widespread disturbances in amino acid metabolism were identified via untargeted metabolomics in HCC patients with metastasis, closely governing inflammation-related metabolic remodeling and oxidative stress responses. Specifically, we identified 91 and 59 distinct differential metabolites capable of indicating HCC metastasis, with the screening criteria set as log₂ fold change > 1.5, adjusted P value < 0.05, and VIP > 1.5 in positive and negative modes, respectively. The alanine, aspartate and glutamate metabolism pathway correlated with HCC-associated lung metastasis, while the gluconeogenesis pathway was linked to HCC-associated bone metastasis. Compared with HCC (non-metastatic hepatocellular carcinoma), the key molecular alterations in the multi-omics network of HCC_M (HCC with metastasis) are implicated in inflammatory metabolic reprogramming, oxidative stress response, gluconeogenesis, glycolysis, and the tricarboxylic acid (TCA) cycle. Twenty-five proteins, including PKM2, PERCK, ALDH2, CPS1, GLS1, GLUD1, GOT1, and SLC38A2, were identified as potential biomarkers for HCC metastasis.

By integrating untargeted metabolomic and proteomic profiling, we identified distinct metabolic and proteomic changes linked to HCC metastasis. This work also characterized the pathological characteristics and core pathways underlying HCC metastasis, while identifying potential therapeutic candidates.

With the widespread application of neoadjuvant immunochemotherapy (nICT) in locally advanced resectable esophageal squamous cell carcinoma (ESCC), determining the optimal postoperative adjuvant treatment strategy has become a critical clinical issue. This study aimed to evaluate the efficacy of different adjuvant treatment patterns and identify beneficial populations.

This was a multicenter real-world study involving 612 ESCC patients from six national centers who underwent R0 resection after nICT. Patients were divided into three groups based on postoperative treatment patterns: Clinical Observation (CO group, n=337), Postoperative Adjuvant Chemotherapy (POCT group, n=80), and Postoperative Adjuvant Chemoimmunotherapy (POICT group, n=195). Study endpoints included overall survival (OS), disease-free survival (DFS), and recurrence patterns.

Multivariate analysis of the whole cohort showed that both POCT and POICT reduced the risk of death (HR = 0.51, P = 0.007; HR = 0.49, P<0.001) and disease progression (HR = 0.48, P = 0.003; HR = 0.48, P<0.001) compared with CO. Subgroup analysis indicated that among patients without pathological complete response (non-pCR), both POCT and POICT significantly improved OS and DFS (P<0.05), with no statistical difference between the two groups. In pCR patients, only POICT showed an OS benefit (P = 0.014). Patients with postoperative pathological stage III benefited in both OS and DFS (P<0.05) from POCT and POICT. After propensity score matching (PSM), the 3-year OS (74.7% vs 79.8%) and DFS (63.1% vs 67.2%) rates between the POCT and POICT groups showed no significant difference (P>0.05). Postoperative adjuvant therapy was an independent factor affecting OS in patients with more advanced yT, yN, and yTNM stages, and an independent prognostic factor for DFS in patients with yN2 stage and advanced yTNM stages. Failure pattern analysis revealed no statistically significant differences in the cumulative incidence of locoregional recurrence or distant metastasis between the POCT and POICT groups (χ²=0.279, 2.828; P = 0.597, 0.093).

For ESCC patients receiving nICT, postoperative adjuvant treatment can provide survival benefits, particularly more pronounced in non-pCR patients and those with advanced postoperative pathological stages. Adding immunotherapy to chemotherapy did not significantly further improve survival outcomes in the overall PSM-matched population; however, in pCR patients, POICT showed OS benefit while POCT did not, suggesting potential differential efficacy according to pathological response.

The tumor microenvironment has emerged as an important determinant of response to immune checkpoint inhibitors (ICIs), with increasing attention directed toward stromal components such as cancer-associated fibroblasts (CAFs). Experimental evidence suggests that renin-angiotensin system (RAS) signaling may participate in stromal remodeling and immune regulation, raising interest in whether RAS inhibitors could influence immunotherapy outcomes. However, clinical findings remain inconsistent and the extent to which reported associations reflect biological effects rather than study-level bias remains uncertain. This study aimed to systematically evaluate the association between concomitant RAS inhibitor use and survival outcomes in lung cancer patients receiving ICIs while interpreting the findings within a tumor microenvironment-oriented conceptual framework.

PubMed and Embase were searched from database inception through February 2026. Eligible studies included lung cancer patients receiving ICIs and reported hazard ratios (HRs) for overall survival (OS) and/or progression-free survival (PFS) according to concomitant RAS inhibitor exposure. Random-effects meta-analyses were performed to pool effect estimates. Publication bias and potential small-study effects were evaluated using Egger's regression and explored using Precision-Effect Test and Precision-Effect Estimate with Standard Error (PET-PEESE).

Thirteen eligible publications involving 46,618 patients were included. Conventional random-effects analyses suggested improved OS (HR 0.74, 95% CI 0.64-0.86) and PFS (HR 0.81, 95% CI 0.68-0.96) among RAS inhibitor users. However, substantial funnel plot asymmetry and significant Egger's test results for OS indicated possible small-study effects. Exploratory PET-PEESE analyses attenuated the observed associations toward the null (adjusted OS HR 0.99, 95% CI 0.96-1.02; adjusted PFS HR 1.04, 95% CI 0.85-1.27). Subgroup analyses suggested possible heterogeneity across histological and regional categories, although these findings should be interpreted cautiously.

Current evidence does not indicate a consistent survival advantage associated with concomitant RAS inhibitor use in unselected lung cancer populations treated with ICIs. The discrepancy between conventional pooling and exploratory bias-adjusted analyses suggests that the observed survival advantage may be partially attributable to small-study effects and residual confounding rather than a reproducible treatment-enhancing effect. Rather than supporting routine clinical use of RAS inhibitors to enhance immunotherapy efficacy, these findings support further biomarker-informed investigation into stromal and tumor microenvironment contexts that may contribute to differential treatment responses.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261369330.