Intraoperative microwave ablation (MWA) can be used simultaneously with liver resection in patients with colorectal liver metastases (CLM) with curative intent. It is uncertain whether this treatment concept is limited by the number of intraoperative MWAs or the number of CLMs. This study was performed to investigate whether the number of CLMs and intraoperative MWAs is associated with overall survival (OS) and recurrence-free survival (RFS).

This review summarizes the latest advancements in electrochemical biosensors for the detection of circulating tumor cells (CTCs). As a core component of liquid biopsy, CTCs are highly valuable for tumor diagnosis and treatment. However, conventional detection methods often fail to meet clinical requirements due to limitations such as low sensitivity and heavy reliance on biomarkers. Electrochemical sensors address these challenges by immobilizing biorecognition elements on electrode interfaces, converting CTCs binding events into quantifiable electrical signals. This approach enables high-sensitivity detection (at the single-cell level), rapid response, and portability. The review systematically explores two key optimization strategies: (1) surface modification for antifouling (e.g., zwitterionic materials, polyethylene glycol layers) and (2) signal transduction strategies (e.g., aptamer-mediated nucleic acid amplification, nanomaterial-based signal amplification), which significantly enhance detection specificity and sensitivity. Furthermore, the review evaluates the clinical utility of this technology in early diagnosis and treatment monitoring, while also discussing challenges such as standardization and clinical translation. This review provides theoretical and technical insights for the development of systematically exploring next-generation high-performance liquid biopsy platforms for cancer.

Retinoblastoma (RB) is typically associated with highly penetrant pathogenic sequence variants (PSVs) in the RB1 gene; however, some families exhibit low penetrance RB (LPRB). We aimed to determine the penetrance rate and identify genetic and clinical characteristics of LPRB. To that end two cohorts were analyzed: 250 genetically confirmed LPRB cases identified through systematic literature review and 78 classical germline RB (CGRB) from three international centers- Thailand, Korea, and Israel. Penetrance rate was estimated as the proportion of affected individuals among RB1 PSV carriers. Multivariate models assessed parent-of-origin effects and predictors of penetrance. PSVs were annotated with Combined Annotation Dependent Depletion (CADD) scores and mapped to pRB structural domains. LPRB penetrance ranged from 50% (125/250, non-age-adjusted, CI [43.8%-56.2%]) to 64% (125/196, age-adjusted, CI [56.8%-70.2%]). Paternal inheritance of RB1 PSV was associated with a significantly increased risk of LPRB in offspring (OR = 6.24; P < 0.0001). Clinically, LPRB were significantly more likely than CGRB to present with unilateral disease (OR = 9.3, P < 0.0001), diagnosed at an older age (13 Vs 6.5 months, P = 0.01), and affect males (OR = 2.4, P = 0.03). LPRB-associated PSVs showed lower CADD scores (OR = 1.5; P = 0.0008), indicating lower predicted pathogenicity, and were enriched in pRB's N- or C-terminal domains (OR = 3.2; P = 0.007), consistent with hypomorphic effects. In conclusion, LPRB shows a 50-64% penetrance rate, more likely to be paternally inherited, have unilateral presentation, and associated with hypomorphic RB1 PSVs in the terminal pRB regions. These findings support retitling 'low penetrance RB' to 'medium penetrance RB'.

Cancer biology is a constantly evolving field of study due to the dynamic and complex nature of biological systems. The unique role of in vitro assays in cell biology has led to numerous transformations in our understanding of the functional and structural details of the cells and tissues that comprise these systems. However, the traditional monolayer assays have been reported to fall short of the in vivo physiology of cells. This has led to the development of 3D cell models, such as spheroids and organoids, that aim to recapitulate the intricate structural and functional behaviour of in vivo tumours. This review describes passive methods of spheroid formation (scaffold-free and scaffold-based) and the limitations that have driven the development of engineered active design methods to increase the physiological relevance of the model. Traditional assays need to be modified to evaluate these models, accounting for their architecture, density, and microenvironment gradients. Current developments in performing 3D cell assays include increased reagent concentration and incubation periods; however, many protocols still require single-cell analysis. We present a review of assay developments that maintain the spatial and contextual information that makes the 3D models physiologically relevant. Additionally, we introduce the advances in microscopy techniques that provide deeper visualisation of these models.

Background and objectives Diffuse large B-cell lymphoma presents a significant challenge due to its high rate of treatment failure in 40% of patients. In this study we screened microRNAs as biomarkers in chemotherapy non-responding patients, to allow their early prognostication. Methods In the exploratory phase, whole transcriptome microRNA profiling was conducted on 10 diffuse large B-cell lymphoma cases. Three patients achieved complete remission, while seven had refractory or relapsed disease. The differentially expressed miRNAs were validated in 41 retrospective, treatment-naive diffuse large B-cell lymphoma biopsies, including the original 10 cases. Additionally, 33 cases with paired biopsy and plasma samples were prospectively evaluated using qRT-PCR to correlate miRNA expression with clinical outcomes. Functional validation to identify downstream pathways was done by knocking down identified miRNAs in JM-1 cells by semi-quantitative proteomics. Results miR-193b-5p, miR-1307-5p, and miR-671-5p expression were downregulated in refractory/relapsed diffuse large B-cell lymphoma biopsies. Plasma miRNA levels did not reflect prognosis. In vitro proteomics showed their impact on key oncogenic pathways, revealing significant enrichment of replication and transcription-related proteins. Interpretation and conclusions The expression of miR-193b-5p, miR-1307-5p, and miR-671-5p miRNAs in diffuse large B-cell lymphoma tissues may serve as predictive biomarkers.

Background and objectives Ovarian carcinoma is one of the most lethal carcinomas among females. Its high prevalence and shorter 5-year survival rate is due to the fact that most of the cases are diagnosed at later stages. This highlights the importance of early diagnosis through reliable biomarkers. We studied the diagnostic role of SOX9 protein in ovarian carcinoma and its diagnostic ability. The primary objective was to compare the level and clinical relevance of SOX9 protein in the tissues of patients with ovarian carcinoma with non-malignant ovarian tissues. Methods Tissue levels of SOX9 protein were estimated in the study and control groups (60 each group). SOX9 levels were compared between the study vs. control groups and also between high grade and low-grade ovarian cancer. SK-OV3 ovarian adenocarcinoma cell line was used as supportive evidence to prove the presence of SOX9 in malignant ovarian cells. Results Levels of SOX 9 protein (3.9±2.7 ng/mL) were high in tissue of ovarian cancer patients when compared to non-malignant (1.5 ±1.1 ng/mL) ovarian tissues. Higher levels of SOX 9 protein were found in tissues of ovarian cancer patients when compared to non-malignant ovarian tissues. The mean of SOX 9 levels in tissues of high-grade serous carcinoma was 3.5±2.5 ng/mL as compared to 1.0±0.9 ng/mL in low-grade serous carcinoma. Interpretation and conclusions SOX9 appears to be an important player in the molecular tumourigenesis of ovarian cancer, particularly in high grade tumours.

Background and objectives Radiotherapy for advanced cervical cancer (CaCx) often results in unintended genitourinary toxicities, notably bladder damage. Predicting such radiation-induced toxicity remains challenging. γ-H2AX, a marker of DNA double-strand breaks (DSBs), offers promise as a predictive biomarker for radiosensitivity. This study aimed to evaluate γ-H2AX foci kinetics in peripheral blood lymphocytes (PBLs) as a surrogate for DNA damage response and a predictor of bladder toxicity in CaCx patients undergoing pelvic radiotherapy. Methods In this prospective study, 43 FIGO stage IIIB CaCx patients were enrolled. Stage I (n=31) assessed γ-H2AX induction post-CT simulation (2-6 mGy); Stage II (n=34) evaluated γ-H2AX kinetics across three radiotherapy fractions (FR1, FR13, FR25) during external beam radiotherapy (50 Gy in 25 fractions ± cisplatin). Blood samples were collected at baseline, 1-, 4-, and 24-h post-irradiation. γ-H2AX foci were quantified via flow cytometry. Bladder toxicity was graded usingRadiation Therapy Oncology Group (RTOG) criteria. Results CT and radiotherapy both induced significant γ-H2AX foci, peaking at 1 h. Patients without bladder toxicity showed higher foci induction and faster decay (1→4h: 48.9% vs. 39.4%; 1→24h: 43.6% vs. 12.8%) across all fractions. Persistent foci at 24 h correlated with increased toxicity risk, indicating deficient DNA repair capacity. Interpretation and conclusions γ-H2AX foci kinetics effectively reflect in vivo DNA repair efficiency and predict radiation-induced bladder toxicity. This minimally invasive biomarker may guide personalized radiotherapy, enabling early identification of high-risk patients and potential use of radioprotectors or treatment modifications.

Background and objectives Genomic studies are essential for identifying mutations that may influence key aspects of breast tumours, such as susceptibility, aggressiveness, and response to treatment. There are deficient molecular and genomic data from Indian breast cancer patients. Methods mRNA from primary breast cancer samples were subjected to next-generation transcriptome (mRNA) sequencing on an Illumina platform, in duplicates and triplicates to generate 30-60 M reads/sample. PAM50, and absolute intrinsic molecular subtyping (AIMS) gene expression-based classifiers were used for intrinsic subtyping. Variants were called using, GATK, MuTect2, VarScan2, and VarDict, followed by filtering for somatic and non-synonymous changes. Germline variants were excluded using public databases. ClinVar annotations prioritised pathogenic variants, and the STRING algorithm was used for network analysis. Results A total of 207 RNA-Seq datasets from 97 breast cancer patients were analysed. There was good concordance between the immunohistochemical receptor and AIMS classification for all subtypes, but there was discordance between immunohistochemical and PAM50 subtypes within the ER-positive/HER2-positive subgroup, wherein only 38.5% (n= 5) were classified as HER2-like by gene expression classification. Variant analysis identified 145 high-confidence somatic mutations, with TP53 (n=46, 47%) and PIK3CA (n=33, 34%) being the most frequent. Additional actionable mutations in BRCA1, BRCA2, FGFR2, PTEN, AKT1, and mTOR pathways were identified. At least one actionable mutation was found in 52% of patients. Fusion transcript analysis identified 91 recurrent fusions, including novel partners with ERBB2, MED1, and CDK12, suggesting the possibility of unique molecular events. Interpretation and conclusions This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.

Hyperandrogenism and elevated thioredoxin-interacting protein (TXNIP) are potential causes of infertility in women with polycystic ovary syndrome (PCOS). Epigenetic regulation of TXNIP mediates oxidative stress and inflammatory activation. However, the precise mechanisms including epigenetic regulation in PCOS are poorly understood. In this study, aberrant TXNIP in dehydroepiandrosterone (DHEA)-induced rat PCOS ovaries and dihydrotestosterone (DHT)-induced PCOS primary granulosa cells (GCs) coincided with a marked increase of DNA methyltransferases (DNMTs); this aberrant TXNIP triggers the release of pro-fibrotic factors, such as collagen I, α-SMA, and TGF-β, from GCs. Administration of the DNMT inhibitor 5-Aza downregulated TXNIP expression and improved the aberrant expression of the pro-fibrotic factors in PCOS-like ovaries and DHT-treated GCs. Furthermore, MG132, a proteasome inhibitor, attenuated the inhibitory effect of 5-Aza on DHT-induced TXNIP upregulation. Our data suggest that DNMT activation, by suppressing proteasome activity, contributes to increases in TXNIP expression, resulting in ovarian fibrosis and GC dysfunction in PCOS-like ovaries after exposure to hyperandrogenism.

Cervical cancer continues to be a major cause of female cancer deaths globally, with dysregulation of the PTEN/PI3K/AKT pathway contributing to disease progression and treatment resistance. Baicalein, a bioactive flavonoid, exhibits anti-cancer properties through incompletely understood mechanisms.

The tumor microenvironment (TME) significantly influences cancer progression, metastasis, and therapeutic resistance. Among the diverse cellular constituents of the TME, tumor-associated macrophages (TAMs) are critical players that support tumor growth, facilitate angiogenesis, and suppress anti-tumor immune responses. Metabolic reprogramming of TAMs has emerged as a pivotal mechanism driving their immunosuppressive and pro-tumourigenic functions. This extensive review delves into the intricate metabolic pathways involved in TAM reprogramming, the underlying molecular mechanisms, and the impact of these metabolic alterations on the TME. We also explore potential therapeutic strategies targeting TAM metabolism to reprogram the TME and enhance cancer immunotherapy efficacy.

Glioblastoma (GBM) is an aggressive CNS malignancy with extensive tumor growth and invasion. Highly proliferating cells require an increased intracellular iron concentration to maintain cell metabolism. We assessed the expression of transferrin receptor 1 (TFR1), the principal iron transporter, in GBM and ascertained its clinicopathological significance, implication in pathobiology, and therapeutic potential. Ninety-four cases of adult-type hemispheric GBM were included, along with 60 cases of IDH-mutant astrocytic and oligodendroglial tumors (grade 2-4) for comparison. The protein and mRNA expression were assessed by immunohistochemistry and qRT-PCR, respectively. We used U87MG and LN229 cell lines for in vitro analysis. TFR1 expression was significantly higher in GBM than in other IDH-mutant/lower-grade diffuse gliomas at mRNA and protein level. The non-tumor brain was negative on immunohistochemistry, and strong immunoreactivity was present only in GBM, indicating its diagnostic significance. SiRNA-mediated knockdown of TFR1 was associated with reduced cell survival, proliferation, migration, invasion, and increased apoptosis in vitro. Ferroptosis induction by RSL3/FIN56 led to increased TFR1 expression and ROS generation. The pro-ferroptotic effect of these drugs could be reversed by TFR1 knockdown. Hence, TFR1 appears to be crucially implicated in the cell survival and proliferation and ferroptosis sensitivity of malignant cells. Temozolomide in combination with siRNA-mediated gene silencing showed a significantly higher antitumor effect than the drug or silencing alone. This may be one of the important therapeutic vulnerabilities of GBM. High TFR1 expression was associated with shorter overall survival in all gliomas together but not in GBM separately.

Geraniol (GI), an acyclic monoterpene alcohol, exhibits diverse anti-cancer activities. However, its potential effects against gastric cancer remain poorly understood.

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.