Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the need for early detection and accurate lesion characterization. Traditional white-light imaging has limitations in detecting lesions, particularly those with flat morphology or minimal color contrast with the surrounding mucosa. It also struggles to distinguish neoplastic from non-neoplastic lesions. These limitations led to the development of image-enhanced endoscopy (IEE). Image-enhanced endoscopy modalities such as narrow-band imaging, blue laser imaging, linked color imaging, and texture and color enhancement imaging enhance mucosal surface and vascular pattern visualization, thereby improving lesion detection and characterization. In contrast, red dichromatic imaging is primarily designed to enhance the visibility of deep blood vessels, making it particularly useful during therapeutic endoscopies, such as identifying bleeding sources and monitoring post-treatment hemostasis. Although IEE enhances lesion detection and characterization, it remains limited in assessing submucosal invasion depth, which is a key factor in treatment decisions. Endoscopic submucosal dissection requires accurate prediction of invasion depth; however, IEE mainly reflects superficial features. Endoscopic ultrasound and artificial intelligence-assisted diagnostics have emerged as complementary techniques for improving depth assessment and lesion classification. Additionally, IEE plays a critical role in detecting ulcerative colitis-associated neoplasia (UCAN), which often presents with a flat morphology and indistinct borders. High-definition chromoendoscopy and IEE modalities enhance detection; however, inflammation-related changes limit diagnostic accuracy. Artificial intelligence and molecular biomarkers may improve UCAN diagnosis. This review examines the role of IEE in lesion detection and treatment selection, its limitations, and complementary techniques such as endoscopic ultrasound and artificial intelligence. We also explored pit pattern diagnosis using crystal violet staining and discussed emerging strategies to refine colorectal cancer screening and management.

Breast-conserving surgery (BCS) is the standard treatment for early-stage breast cancer, yet patients often experience significant psychological distress and physical symptoms during recovery. This study aimed to explore the relationships between antecedents, physical symptoms (pain and nausea), psychological distress, and coping strategies utilized by women recovering from BCS to improve management of postoperative challenges.

This repeated-measures descriptive study involved 75 women who underwent BCS with sentinel lymph node biopsy at a National Cancer Institute-designated center. Participants completed the National Comprehensive Cancer Network (NCCN) Distress Thermometer and Ways of Coping Instrument on Postoperative Day 1 (POD1) and POD14. Bivariate analyses, multiple linear regression, and structural equation modeling were conducted to evaluate associations between antecedents, coping strategies, and distress. Open-ended responses were qualitatively analyzed for thematic content.

Seeking social support (POD1 mean ​= ​1.25; POD14 mean ​= ​1.20) and planful problem-solving (POD1 mean ​= ​1.19; POD14 mean ​= ​1.04) were the most frequently used coping strategies, while accepting responsibility and confrontive coping were least utilized. Overall coping strategy use decreased between POD1 and POD14, likely reflecting recovery adaptation. Significant predictors of distress included escape-avoidance coping (β ​= ​0.415, P ​< ​0.001), social support (β ​= ​0.270, P ​= ​0.02), history of nausea (β ​= ​0.517, P ​< ​0.001), and age (β ​= ​0.293, P ​= ​0.007). Coping strategies did not mediate the relationship between antecedents and distress.

Adaptive coping strategies such as social support and planful problem-solving play a critical role in mitigating distress during BCS recovery. Interventions should emphasize fostering these strategies and addressing high-risk groups, such as younger patients and those with a history of nausea. Despite limitations, this study underscores the importance of supporting adaptive coping to improve postoperative outcomes and provides a basis for future research.

New regimens have emerged as third-line or later therapies for metastatic colorectal cancer (mCRC), including regorafenib dose optimization (ReDO), trifluridine/tipiracil and bevacizumab (TAS-BEV) combination therapy, and fruquintinib. We evaluated relative cost-effectiveness of these therapies in patients with mCRC from a US payer's perspective.

A partitioned survival model (PSM) was constructed to estimate total costs and quality-adjusted life years (QALYs). Clinical parameters were obtained from pivotal trials of the respective therapies and incremental cost-effectiveness ratios (ICERs) were estimated to assess relative cost-effectiveness of these treatments. Model robustness was assessed using deterministic (DSA) and probabilistic sensitivity analysis (PSA). Three scenario analyses were conducted: (1) assuming equal efficacy across treatments, (2) with prior exposure to anti-vascular endothelial growth factor (VEGF) therapy, and (3) alternative clinical inputs for fruquintinib from a different clinical trial.

Under the conventional willingness-to-pay (WTP) threshold in US ($150,000 per QALY gained), ReDO was cost-effective when compared with TAS-BEV and was dominant over fruquintinib. TAS-BEV was associated with an incremental QALY of 0.197 over ReDO, resulting in an ICER at $554,567 per QALY gained. The base case results were robust in DSA and PSA. Most influential parameters were treatment cost and effectiveness. In patients with prior anti-VEGF therapy, ReDO remained cost-effective compared to TAS-BEV and fruquintinib under the conventional WTP threshold.

Differences in trial populations may affect the comparability of the outcomes. Sensitivity and scenario analyses were conducted to address these limitations.

ReDO was cost-effective compared with TAS-BEV from the US payer's perspective despite a higher QALY gain associated with TAS-BEV. ReDO was dominant over fruquintinib, consistently having a higher QALY gain and lower cost.

To explore the mediating roles of depression and self-efficacy in the relationship between social support and body image in patients with breast cancer during chemotherapy.

A convenience sampling method was employed to survey 647 breast cancer chemotherapy patients. The survey included validated scales assessing social support, depression, self-efficacy, and body image. The chain mediation model was established using Mplus 8.3 software.

Social support was negatively correlated with depression (P < 0.001) and poor body image (P < 0.001) and positively correlated with self-efficacy (P < 0.001). Social support indirectly affected body image through three mediating pathways: depression (β = -0.084, P < 0.001), self-efficacy (β = -0.060, P < 0.01), and the depression-self-efficacy pathway (β = -0.058, P < 0.001). The indirect effect accounted for 55.96% of the total effect.

The results support our hypothesis. Enhancing social support, alleviating depression, and improving self-efficacy through psychological interventions are recommended to improve body image in breast cancer patients during chemotherapy.

This study aimed to describe treatment patterns and quantify the economic impact of recurrence in early-stage human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC).

Medicare beneficiaries with stages I-III HER2-negative BC and lumpectomy or partial/total mastectomy were identified from SEER-Medicare data (2010-2019). Perioperative therapies were reported in the neoadjuvant and adjuvant setting. Locoregional recurrence and distant metastasis were identified using a claims-based algorithm developed with clinical input and consisting of a diagnosis-based and treatment-based indicator. All-cause and BC-related healthcare resource utilization (HRU) per-patient-month and monthly healthcare costs were estimated from the recurrence date for patients with recurrence and from an imputed index date for patients without recurrence using frequency matching. HRU and costs were compared between groups stratified by hormone receptor-positive (HR+) or triple negative BC (TNBC) using multivariable regression models.

Of 28,655 patients, 8.5% experienced recurrence, 90.4% had HR+ disease, and 5.6% received neoadjuvant therapy. Relative to patients without recurrence, patients with recurrence had more advanced disease (stage II/III: 73.7% vs. 34.0%) and higher-grade tumors (Grade 3/4: 40.6% vs. 18.0%) at diagnosis. Recurrence in HR+/HER2-negative BC and TNBC was associated with higher rates of all-cause hospitalizations (incidence rate ratio [IRR]: 2.84 and 3.65), emergency department (ED) visits (IRR: 1.75 and 2.00), and outpatient visits (IRR: 1.46 and 1.55; all p < 0.001). Similarly, recurrence was associated with higher rates of BC-related HRU, particularly for ED visits in HR+/HER2-negative BC (IRR: 4.24; p < 0.001) and hospitalizations in TNBC (IRR: 11.71; p < 0.001). Patients with HR+/HER2-negative BC and TNBC recurrence incurred higher monthly all-cause (cost difference [CD]: $3988 and $4651) and BC-related healthcare costs (CD: $3743 and $5819).

Our findings highlight the considerable economic burden of recurrence in early-stage HER2-negative BC and underscore the unmet need for optimization of therapies that reduce recurrence in this population.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic Lactobacillus, particularly L. reuteri. Treatment with L. reuteri significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of L. reuteri, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal Lactobacillus abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of L. reuteri in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic Lactobacillus may offer a novel therapeutic strategy for PDAC.

Patients undergoing video-assisted thoracoscopic surgery (VATs) for lung cancer (LC) frequently experience prolonged symptoms that can significantly affect their quality of life (QoL).

This study employed a longitudinal observational design. The MDASI and QLQ-C30 were utilized to evaluate symptoms and QoL one day before surgery, as well as at 1 day, 2 weeks, and 1, 2, and 3 months post-surgery. Latent class growth modeling (LCGM) was employed to identify heterogeneous trajectories. By Logistic regression analysis, a score prediction model was developed based on predictive factors, which was internally validated utilizing 1000 bootstrap samples. The SHaply Additive Explanations (SHAP) was used to calculating the contribution of each factor.

205 participants participated in this study. The predominant postoperative complaints included fatigue, shortness of breath, pain, and coughing. Two distinct classes of symptom trajectories were identified: 'severe group' and 'mild group'. Four independent predictors of heterogeneous symptom trajectories were used to develop a scoring model. The area under the receiver operating characteristic curve for this model was 0.742 (95% CI: 0.651-0.832). And the calibration curves demonstrated strong concordance between anticipated probability and actual data (mean absolute error: 0.033). Furthermore, the decision curve analysis (DCA) indicated higher net benefit than other four single factors. SHAP highlighted WBC and surgical duration time as the most influential features.

We established a score model to predict the occurrence of severe symptom trajectories 3 months postoperatively, promoting recovery by advancing rehabilitation plan based on preoperative and surgical situation.

ClinicalTrials.gov (ChiCTR2100044776).

The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (m6A). Aberrant regulation of RBPs, such as HuR and YBX1, typically enhances tumour immune escape and impacts prognosis of GI tumour patients. Further, while targeting RBPs offers a promising strategy for improving immunotherapy in GI cancers, the mechanisms by which RBPs regulate the TIME in these tumours remain poorly understood, and the therapeutic application is still in its early stages. This review summarizes current advances in exploring the roles of RBPs in regulating genes expression and their effect on the TIME of GI tumours, then providing theoretical insights for RBP-targeted cancer therapies.

Including racial and ethnic minorities in clinical trials is essential for advancing health equity. Despite progress, trials often do not mirror patient population demographics.

The National Library of Medicine's Clinical Trials database was queried for phase III trials of lung, colorectal, breast, and prostate cancers. A reference population was identified from the Surveillance, Epidemiology, and End Result (SEER) database, covering 48% of the US population.

Among 181 trials, race and ethnicity data were included in 86.7% and 60.2% of trials, respectively, with improving reporting over time. Participants were predominantly White (76.3%), followed by Asian/Pacific Islander (14.1%), Black/African American (4.5%), and American Indian/Alaska Native (0.6%). Hispanic/Latino constituted 6.4% of participants. The proportion of non-White groups increased from 19.4% in trials started before 2011 to 26.2% after 2015. Compared with SEER data, the percentages were lower for Asian/Pacific Islander across all cancers, Black/African American in breast and prostate cancers, American Indian or Alaska Native in colorectal, breast, and prostate cancers in US solely trials.

Reporting and enrollment of racial and ethnic minorities in trials remain inadequate but improving. To enhance diversity, real-world data are warranted to identify recruitment goals by better assessing the geographic distribution within the patient population.

Xuetongsu (XTS, Schisanlactone E) is one of the main active compounds and considered as the star molecule isolated from Kadsura heteroclita (Roxb.) Craib. In order to improve XTS anti-tumour bioactivities, a series of novel XTS derivatives were designed and synthesised by introducing an amide bond at the parent. Anti-proliferative assays on four different human tumour cell lines (BGC-823, HepG-2, HCT-116, and MCF-7) showed that the anti-tumour activities of most derivatives increased greatly compared to the parent XTS, and especially, compounds A-7, A-14, and A-18 exhibited multiple anti-tumour effects. Among them, compound A-7 has the best biological activities on the four tumour cell lines with the IC50 values ranging from 13.86 to 20.71 μM, which could significantly increase the fraction of apoptotic cells according to flow cytometry experience. Further study demonstrated that A-7 could induce apoptosis on HepG-2 cells through influencing the key apoptotic related proteins, such as Bcl-2, Bax, and cleaved Caspase-3.

Mitochondria and angiogenesis play key roles in multiple myeloma (MM) development, but their interrelated genes affecting MM prognosis are under-studied.

We analyzed TCGA_MMRF and GSE4581 datasets to identify four genes - CCNB1, CDC25C, HSP90AA1, and PARP1 - that significantly correlate with MM prognosis, with high expression indicating poor outcomes.

A prognostic signature based on these genes stratified patients into high- and low-risk groups, with the latter showing better survival. The signature was validated as an independent prognostic factor. Biological function analysis revealed differences in cell cycle processes between risk groups, and immune microenvironment analysis showed distinct immune cell infiltration patterns.

This mitochondria- and angiogenesis-related prognostic signature could enhance MM prognosis assessment and offer new therapeutic insights.

Proline-rich transmembrane protein 4 (PRRT4) has been infrequently studied, with limited literature suggesting its potential as a prognostic marker for gastric cancer. This study aims to investigate the prognostic value of the PRRT4 gene in pan-cancer.

We acquired and analyzed data from several platforms, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), Cancer Cell Line Encyclopedia (CCLE), cBioPortal, HPA, and TIMER 2.0. In addition, we have further analyzed the data using multivariate analyzes and RT-qPCR. In vitro experiments were performed to detect the proliferation and apoptosis of AML cells before and after PRRT4 knockdown.

PRRT4 exhibited low expression in 10 types of cancers and high expression in 3 types, and this expression was significantly correlated with tumor stage, age, and gender across various cancer types. PRRT4, identified as a potential independent prognostic factor for overall survival (OS) in several cancers including LAML, PAAD, SKCM, STAD, THYM, and UVM, and exhibited a high frequency of mutation in UCEC. Moreover, PRRT4 was found to be correlated with DNA methylation and immune infiltration in various cancers. Ultimately, in the multivariate analysis model, PRRT4 was discerned as an independent prognostic biomarker for AML, predicated on the statistics based from our institution. After PRRT4 knockdown, the proliferation ability of THP1 cells was significantly enhanced, and the apoptosis ratio was significantly decreased.

PRRT4 may serve as a potential therapeutic target and prognostic marker for various malignancies.

Bone metastasis is common for breast cancer and associated with poor prognosis. Currently, radiotherapy (RT) serves as the standard treatment for patients exhibiting symptoms of bone metastasis to alleviate pain. Whether earlier application of RT will better control bone metastasis remains unclear.

We utilized a mouse model of breast cancer bone metastasis by intra-femoral injection of 4T1-luc breast tumor cells. The bone metastasis was treated by RT using various doses, timings, and modalities. Tumor growth was assessed through bioluminescence imaging, and lung metastases was quantified following lung tissue fixation. Flow cytometry was employed to analyze alterations in immune cell populations.

Single high-dose RT suppressed tumor growth of bone metastases, but caused severe side effects. Conversely, fractionated RT mitigated tumor growth in bone metastases with fewer adverse effects. Fractioned RT initiated at the early stage of bone metastasis effectively inhibited tumor growth in the bone, suppressed secondary lung metastases, and prolonged mouse survival. In line with the known pro- and anti-metastatic effects of neutrophils and T cells in breast cancer, respectively, earlier fractioned RT consistently decreased the proportions of neutrophils while increased the proportions of T cells in both the bone and the lung tissues.

The data suggest that fractionated RT can inhibit the progression of early stage of bone metastasis and reduce secondary lung metastasis, leading to favorable outcomes. Therefore, these findings provide preclinical evidence to support the application of fractionated RT to treat patients with bone metastasis as earlier as possible.

Lysine-specific demethylase 1 (LSD1) is abnormally overexpressed in various tumour tissues of patients and has been an attractive anticancer target. In this work, a potent LSD1 inhibitor (compound 14) was designed and synthesised by the molecular hybridisation strategy. It displays the potent antiproliferative activity against HepG2, HEP3B, HUH6, and HUH7 cells with IC50 values of 0.93, 2.09, 1.43, and 4.37 μM, respectively. Furthermore, compound 14 is a selective and reversible LSD1 inhibitor with an IC50 value of 0.18 μM and increases the methylation levels of H3K4me1/2. Molecular docking studies showed that it formed hydrogen bonds, hydrophilic interactions and hydrophobic interactions with residues of LSD1. Anticancer mechanisms demonstrated that it suppresses migration and epithelial-mesenchymal transition process in HepG2 cells. Importantly, it exhibits potent anti-liver cancer effects in vivo without obvious toxic effects. These interesting findings suggested that compound 14, a novel LSD1 inhibitor, may be a promising therapeutic agent to treat liver cancer.

Most high-grade serous ovarian cancers (OC) do not respond to current immunotherapies. To identify potential new actionable tumor antigens in OC, we performed immunopeptidomics on a human OC cell line expressing the HLA-A02:01 haplotype, which is commonly expressed across many racial and ethnic groups. From this dataset, we identified TTLL8, POTEE, and PKMYT1 peptides as candidate tumor antigens with low expression in normal tissues and upregulated expression in OC. Using tissue microarrays, we assessed the protein expression of TTLL8 and POTEE and their association with patient outcomes in a large cohort of OC patients. TTLL8 was found to be expressed in 56.7% of OC and was associated with a worse overall prognosis. POTEE was expressed in 97.2% of OC patients and had no significant association with survival. In patient TILs, increases in cytokine production and tetramer-positive populations identified antigen-specific CD8 T cell responses, which were dependent on antigen presentation by HLA class I. Antigen-specific T cells triggered cancer cell killing of antigen-pulsed OC cells. These findings suggest that TTLL8, POTEE, and PKMYT1 are potential targets for the development of antigen-targeted immunotherapy in OC.

For years, xanthophylls have been recognized for their potential in medicine. Evidence supports the role of diets rich in algae, fruits, and vegetables in preventing cancer. Due to the complexity of the human body, numerous mechanisms could explain the health benefits of xanthophylls. Various studies have explored their effects on specific diseases. However, the impact of certain xanthophylls, such as crocetin, crocin, and fucoxanthin, on aggressive breast cancer remains unclear. To address this, we examined their effects on human breast adenocarcinoma (MDA-MB-231 cells) using Raman spectroscopy and imaging. Our findings revealed that crocetin enhances cancer cell viability by increasing lipid and protein levels, suggesting it does not directly inhibit tumour growth. Crocin redirected cellular metabolism towards lipid accumulation, shown by increased Raman signals at 1444 cm-1 in lipid droplets/endoplasmic reticulum. Fucoxanthin demonstrated the greatest potential, reducing lipid and protein levels (Raman bands at 1254, 1444, 1654 cm-1), thereby inhibiting adenocarcinoma progression.

Bladder cancer (BCa) is the most prevalent cancer of the urinary system in adults; the prognosis is dismal for BCa treated with gemcitabine (GEM) owing to intrinsic or acquired chemoresistance. This study investigated the potential of Qici Sanling decoction (QCSL), an herbal Chinese medicine, to augment the efficacy of GEM in treating GEM-resistant BCa via network pharmacology and RNA sequencing. We screened 103 active components of QCSL and their 226 targets from the TCMSP database and identified 3985 targets of GEM-resistant BCa via transcriptome sequencing. On the basis of the 69 common targets, a proteinprotein interaction (PPI) network was constructed to identify the top 7 targets. Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were conducted to uncover key pathways. CCK-8 assays, Western blotting, flow cytometry, colony formation, and EdU assays were used to assess the apoptosis and proliferation of GEM-resistant T24 and J82 cells treated with QCSL. The BCa gene set was among the top enriched gene sets in the DO analysis; GO analysis revealed enrichment of 2020 terms linked to GEM resistance, and KEGG analysis revealed 161 enriched signalling pathways. Molecular docking indicated that PTGS2 has high affinity for targets of QCSL components. In vitro experiments demonstrated that cells treated with both QCSL and GEM had significantly reduced viability, increased levels of apoptosis, and decreased proliferative capacity. Thus, QCSL enhances the therapeutic effects of GEM in BCa by promoting cell apoptosis and inhibiting cell proliferation. These findings have significant clinical implications, highlighting a potential combined treatment strategy for GEM-resistant BCa to improve patient outcomes.

The incidence and mortality rates of malignant tumors are increasing annually, with gliomas and brain metastases linked to a poor prognosis. Hyperbaric oxygen therapy is a promising treatment modality for both gliomas and brain metastases. It can alleviate tumor hypoxia and enhance radiosensitivity. When combined with other treatments for gliomas, this therapy has the potential to enhance survival rates. This review addresses the progress in research on the use of hyperbaric oxygen therapy combined with radiotherapy. For brain metastases, the combination of hyperbaric oxygen therapy and stereotactic radiosurgery is both feasible and advantagenous. This combination not only offers protection against radiation-induced brain injury but also supports the recovery of neurological and motor functions. The incidence of adverse reactions to hyperbaric oxygen therapy is relatively low, and it is safe and manageable. Future efforts should be made to investigate the mechanisms by which hyperbaric oxygen therapy combined with radiotherapy treats gliomas and brain metastases, optimize protection of the combined treatment against brain injury, minimizing adverse reactions, conducting multidisciplinary research and clinical trials, and training healthcare providers to facilitate broader clinical application.

The detection of specific protein biomarkers holds significant potential for the early diagnosis of colorectal cancer (CRC). However, the accurate quantification of low-abundance proteins in serum presents a major challenge due to factors such as limited sensitivity and the complexity of the required methodologies. In this work, we established a universal CRISPR/Cas biosensing platform by integrating novel photosensitive nanoprobes (DA/PL@Cu NPs) and CRISPR/Cas12 system (DPC-Cas) for the highly sensitive, specific and user-friendly detection of angiopoietin-like protein 2 (ANGPTL2). The DA/PL@Cu NPs serve as a critical component in the transduction of protein recognition information into nucleic acid amplification events to produce Cas12a activators. The DPC-Cas biosensor integrates DA/PL@Cu NPs-assisted amplification with Cas12a self-amplification, enabling ultrasensitive detection of ANGPTL2 at concentrations as low as 20.00 pg/mL. The proposed DPC-Cas biosensor successfully detected ANGPTL2 in serum, demonstrating significant potential for the early diagnosis of CRC.

Ferroptosis, a non-apoptotic programmed cell death modality, has been recognized as an emerging therapeutic target for cancer treatment, particularly with the rapid advancements in bionanotechnology. However, the insufficient intracellular Fe2+ ions and low reactive oxygen species (ROS) production severely restrict the efficacy of ferroptosis at tumor sites. Herein, a pH-responsive multifunctional nanoplatform (p-COF@GOx-FeS@HA/ART) was constructed to achieve efficient tumor ferroptosis through self-supplied Fe2+ ions and amplified ROS. In this system, the large specific surface area and mesoporous structure enabled the porphyrin-based covalent organic frameworks (p-COFs) to act as scaffolds and drug carriers for enhancing the catalytic activity of glucose oxidase-stabilized ferrous sulfide nanodots (GOx@FeS) and encapsulation of artesunate (ART). By oxidizing glucose (Glu) in tumor cells, GOx not only consumed Glu for starvation therapy but also promoted intracellular acidity and supplied hydrogen peroxide (H2O2) in the tumor microenvironment (TME), which facilitated the FeS-mediated chemodynamic therapy (CDT) as well as the release of hydrogen sulfide (H2S) for accelerating the ROS generation. Moreover, the lowered acidic TME could simultaneously trigger the release of ART and Fe2+ ions, thus exacerbating ART-mediated ferroptosis. Due to its photothermal and photodynamic behavior, the nanoplatform under laser irradiation could generate ROS storms in tumor cells for high-performance ferroptosis therapy, which was demonstrated both in cancer cells and tumor-bearing mice. This work provides a promising strategy for the simple construction of a multifunctional nanoplatform with TME-responsive and self-triggered ferroptosis, showing great potential in cascade amplification of ferroptosis therapy.

Epoxide hydrolase-4 (EPHX4) belongs to the epoxide hydrolase enzyme family, but its biological function remains unclear, especially its potential involvement in the development of pancreatic tumours. This research sought to examine the function of EPHX4 in pancreatic adenocarcinoma (PAAD).

The expression of EPHX4 across cancers was examined through The Cancer Genome Atlas (TCGA). Bioinformatics was employed, leveraging multiple databases to investigate EPHX4 gene expression in pancreatic cancer and its association with survival prognosis, functional enrichment, immune infiltration, tumour mutation load, and drug sensitivity, among other variables. To evaluate EPHX4 expression in PAAD cells, Western blotting and reverse transcription quantitative PCR were used. A series of in vitro functional experiments was performed to assess the proliferation, migration, and invasion of PAAD cells.

EPHX4 expression was markedly elevated in a number of malignancies, including PAAD, and was associated with patient sex, clinical stage, and metastasis to the lymph nodes. High EPHX4 expression was significantly associated with a worse outcome in PAAD patients. According to functional and enrichment studies, EPHX4 is involved in many signalling pathways linked to cancer. The study of immune infiltration revealed that EPHX4 was connected to the existence of a variety of immune cells inside the tumour. Our study revealed that EPHX4 knockdown significantly decreased PAAD cell migration, proliferation, and invasion.

EPHX4 is highly expressed in PAAD and independently predicts poor survival. Functional experiments demonstrate its tumor-promoting effects. Its involvement in multiple cancer-related signaling pathways and immune regulation mechanisms highlights the dual prognostic and therapeutic potential of EPHX4 in PAAD.

Honokiol (HK) is a polyphenol isolated from the Magnolia genus, a component of traditional Chinese herbal medicine, which can effectively suppress the growth of various tumors, including ovarian cancer. However, its low water solubility and lack of tumor-targeting ability have greatly hindered the clinical application of HK. Herein, a glutathione (GSH)-sensitive HK polyprodrug was prepared using HK as the backbone. An EpCAM-specific aptamer and poly(ethylene glycol) (PEG) were then conjugated to the HK polyprodrug, and the resulting polyprodrug was assembled into nanoparticles (NPs) in water. The HK polyprodrug-formed NPs achieved high drug loading and GSH-responsive drug release. Moreover, after optimization, HK polyprodrug NPs (A/P-PHK NP40), formed by aptamer-modified and PEG-modified prodrug at a feed molar ratio of 2: 3, exhibited the highest ability to target EpCAM-overexpressing ovarian cancer cells. A/P-PHK NP40 also demonstrated a greater cell growth inhibition effect in ovarian cancer cells compared to free HK and control HK NPs. All in all, this work reported a novel strategy for HK delivery based on microenvironment responsiveness polyprodrug, which provided a potential method for ovarian cancer targeting therapy.

Intraductal papillary mucinous neoplasm (IPMN) is the most common type of pancreatic cyst often incidentally detected in asymptomatic patients. The current consensus guidelines, largely based on imaging features, have high sensitivity but low specificity in differentiating benign from malignant IPMNs, leading to unnecessary surgeries. Discovering biomarkers is thus warranted to improve the preoperative risk stratification of IPMN. Pancreatic cyst fluid samples were obtained from patients with pathologically confirmed low-grade (n = 73) or high-grade/invasive (n = 18) IPMN. Global proteome quantitation was performed using liquid chromatography-tandem mass spectrometry. Differentially expressed proteins (DEPs) between the two groups were analyzed using Wilcoxon rank-sum test. 152 upregulated and 74 downregulated DEPs were discovered by comparing low-grade IPMN with high-grade/invasive IPMN (all p < 0.05). The enriched upstream regulators of these DEPs included let-7, miR-122, IL15, and FLT1 (p = 6.76 × 10-5 - 5.97 × 10-3). Five discriminatory biomarkers with the largest LASSO coefficients and each with AUCs of >0.75 (FAHD2A, TCEAL3, TWF1, MMUT, and NTPCR) were identified. The combined five-protein model achieved a bootstrap-corrected AUC of 0.94. A combined analysis of TCGA and GTEx databases showed TWF1 overexpression in pancreatic cancer (p = 2.22 × 10-16) that was associated with poor prognosis (p = 0.0063). The present study identified several cyst fluid proteins (particularly TWF1) that are predictive of malignant pancreatic cyst lesions. If validated in other patient populations, these biomarkers may enhance the accuracy of the preoperative detection of high-risk IPMN and thereby improve patient outcomes.

Prazosin (Prz), an antagonist of alpha-1 adrenergic receptors, is conventionally employed in the treatment of hypertension. Our study pioneers the exploration of Prz in oncology, examining its impact on cellular autophagy and its potential to trigger antitumor immune responses. We have developed a novel Prz-loaded liposome hybrid nanovesicle (Prz@LINV) system, integrating tumor-derived nanovesicles (TNV) with liposomes (LIP) to facilitate targeted Prz delivery to tumor sites. This formulation enhances Prz bioavailability and markedly inhibits tumor cell autophagy, leading to immunogenic cell death (ICD) and the activation of antitumor immune responses. Furthermore, Prz@LINV modulates dendritic cells (DCs), augmenting their antigen cross-presentation capacity and thereby potentiating antitumor immunity. These effects were validated in a colorectal cancer mouse model, demonstrating the good biocompatibility of Prz@LINV and its significant inhibition in tumor growth, along with the enhancement of antitumor immune responses. Our findings elucidate a novel mechanism by which Prz inhibits autophagy and enhances the antitumor immune response, providing a foundation for the development of innovative immunotherapeutic strategies. The efficacy of Prz@LINV suggests that Prz may emerge as a pivotal component in future immunotherapeutic regimens, offering patients more potent therapeutic options.

Resistance to Nelarabine, the primary FDA-approved therapy for relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL), is a major obstacle in this high-risk pediatric malignancy. To identify alternative therapies, we have developed two nelarabine-resistant T-ALL cell models and utilized the Connectivity Map (CMap) database to screen for compounds reversing resistance-associated expression profiles., Among the inhibitors screened, gemcitabine emerged as a lead candidate by inhibiting cell proliferation, inducing apoptosis, and suppressing DNA replication in resistant T-ALL cells. RNA sequencing revealed global transcriptomic changes in cells treated with gemcitabine, which were further validated by qRT-PCR. Critically, gemcitabine effectively controlled bone marrow tumor growth in an NSG mouse model with good tolerability. These findings highlight the potential of gemcitabine as a promising therapeutic strategy to overcome nelarabine-resistance in T-ALL.

The Notch signaling pathway is a fundamental and highly conserved cell-to-cell communication system vital for embryonic development and tissue maintenance. However, its dysregulation has been associated with the initiation, progression, and chemoresistance of various cancers. In this comprehensive review, we will take an in-depth look at the multiple roles of the Notch family in cancer pathogenesis, immune response, and resistance to chemotherapy. We delve into the complicated mechanisms by which Notch signaling promotes tumor growth and development, including its influence on TME remodeling and immune evasion strategies. We will also be discussing recent studies that shed light on the connection between cancer stemness and chemoresistance mediated through the activation of Notch signaling pathways. Elucidation of the interplay between the Notch pathway and major constituents of the TME, including immune cells and cancer-associated fibroblasts, is necessary for the development of targeted therapies against Notch-driven tumors. We further discuss the potential of targeting Notch signaling alone or in combination with standard chemotherapy and immunotherapy as a potent strategy to overcome chemoresistance and improve patient outcomes. We conclude by discussing the challenges and future prospects of using Notch signaling as a therapeutic target in cancer treatment, focusing on how precision medicine and combination approaches are important.

The pH-responsive anticancer peptides (ACPs) have been regarded as a new generation of prospective antitumor candidates due to their selectivity. However, the successful utilizations have been hampered by their narrow therapeutic index, poor stability and long sequence. Here, a new type of short pH-responsive ACPs was constructed by smart intramolecular charge shielding in histidine-rich peptide LH. This design would not depend on the introduction of additional anionic binding peptide, which might be an effective method for appreciably shortening the sequence of pH-responsive ACPs while improving their safety and stability. As expected, 2E-K stood out from the acquired peptides as it exhibited a considerable pH-dependent antitumor activity concomitant with remarkably improved therapeutic selectivity (14.5-fold increase) and extended serum half-life (3.6-fold enhancement) compared to LH. Experimental results showed that acid-activated 2E-K could efficiently induce tumor cell death by rapid membrane damage. Notably, the in vivo experiments further confirmed its excellent antitumor efficacy and low toxicity when compared with PTX, which demonstrating its superiority for in vivo application. In conclusion, our work opened a new avenue for developing short pH-responsive ACPs as promising alternative drugs in cancer treatment.

Prostate-specific membrane antigen (PSMA)-PET/CT has shown considerable promise in the evaluation of prostate cancer bone metastases; however, data utilizing a histopathologic reference standard in this setting are limited. We therefore sought to evaluate the diagnostic performance of PSMA-PET/CT using a consistent histopathologic gold standard in the form of bone biopsy.

In this single-center, retrospective study, we identified 80 patients with prostate cancer who underwent CT-guided bone biopsy of a tracer-avid osseous lesion on PSMA-PET/CT performed with 18F-piflufolastat. Concordance between PET/CT and histopathology and the positive predictive value of PSMA-PET/CT were determined. Factors predictive of positive biopsies were also evaluated.

PSMA-PET/CT and bone biopsy results were concordant in 55/80 patients (69%), and the positive predictive value of PSMA-PET/CT for osseous metastasis of prostate cancer was 66% (53/80). Positive predictive values for spine, pelvis, and rib biopsies were 82% (23/28), 72% (18/25), and 26% (5/19), respectively. Peak SUV and its ratio to liver mean SUV were significantly higher in biopsy-positive lesions compared to biopsy-negative lesions. A threshold peak SUV to liver mean SUV ratio of 1.7 had a sensitivity of 61% and a specificity of 92% for a histopathologic diagnosis of metastatic prostate cancer.

PSMA-PET/CT has a moderately high histopathologic concordance and positive predictive value for the diagnosis of osseous metastatic disease in prostate cancer. Peak SUV is useful for distinguishing biopsy-positive from biopsy-negative lesions. In keeping with prior investigations, a majority of biopsied rib lesions were negative for metastatic prostate cancer.

The gut microbiota exhibits intricate connections with the body's immune system and holds significant implications for various diseases and cancers. Currently, accumulating evidence suggests a correlation between the composition of the gut microbiota and the development, treatment, and prognosis of melanoma. However, the underlying pathogenesis remains incompletely elucidated. In this comprehensive review, we present an in-depth review of the role played by gut microbiota in melanoma tumorigenesis, growth, metastasis, treatment response, and prognosis. Furthermore, we discuss the potential utility of gut microbiota as a promising prognostic marker. Lastly, we summarize three routes through which gut microbiota influences melanoma: immunity, aging, and the endocrine system. By modulating innate and adaptive immunity in patients with melanoma across different age groups and genders, the gut microbiota plays a crucial role in anti-tumor immune regulation from tumorigenesis to prognosis management, thereby impacting tumor growth and metastasis. This review also addresses current study limitations while highlighting future research prospects.

Patients with cancer undergoing chemotherapy with an anthracycline-based regimen are at increased risk of cardiotoxicity, predisposing to heart failure, arrhythmias and death. Whether carvedilol may confer benefit to prevent anthracycline-induced cardiotoxicity remains to be determined.

CARDIOTOX is a double-blind, placebo controlled randomized clinical trial that plan to enroll 1,018 patients across 25 study sites in Brazil. Patients with active cancer scheduled to undergo an anthracycline-based chemotherapy regimen are eligible. Patients with prior HF or cardiomyopathy are excluded. Patients are randomized in 1:1 ratio to carvedilol (starting dose 6.25mg BID up titrated to 25mg BID or maximum tolerated dose) or placebo, stratified by site and use of renin-angiotensin blockers at baseline. Study drug is administered through the duration of chemotherapy and up to 30 days after the last dose of anthracycline. Patients are scheduled to undergo echocardiographic evaluations at baseline and at 3, 6, and 12 months. The study primary endpoint is the composite of new left ventricle ejection fraction (LVEF) reduction by at least 10% leading to an LVEF <50%, cardiovascular death, myocardial infarction, urgent care visit or hospitalization for heart failure, or clinically significant arrhythmias at 12 months. Echocardiographic images will be analyzed by a central core lab, clinical outcomes will be adjudicated, and safety endpoints include serious adverse events and adverse events of special interest (symptomatic bradycardia, hypotension, syncope and bronchospasm).

The CARDIOTOX trial is the largest trial to date analyzing the potential role of beta-blockers as prophylactic therapy to prevent cardiotoxicity induced by anthracyclines.

Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox).

gov ID NCT04939883. https://clinicaltrials.gov/study/NCT04939883.

Brain and nervous system neoplasms account for 25 % of childhood cancer cases. In these instances, radiotherapy treatments increase survival rates, but the high radiosensitivity of pediatric patients raises concerns about the potential adverse effects of radiation. Thus, dose delivery precision becomes crucial in treatment planning, and stereotactic radiosurgeries, such as those performed with Gamma Knife equipment, are the leading-edge techniques in precision radiotherapy. This study aims to evaluate conversion coefficients for equivalent doses (CC[HT]) for out-of-field organs using pediatric mesh-type reference computational phantoms aged 1-, 5 -, 10-, and 15-years during stereotactic radiosurgery through computational simulations with the MCNP 6.3.0 code. Higher CC[HT] values were found for organs closer to the target organ of the treatment, such as the eyes, salivary glands, and thyroid, which received an average of 33.6 %, 6.4 %, and 2.6 % of the treatment dose, respectively. As the age of the pediatric phantom increased, CC[HT] values in organs farther from the target region decreased due to the increase in body length. We also determined the conversion coefficients for effective doses CC[E] and observed higher CC[E] values for the computational phantom with the lowest BMI. Thus, computational simulations showed to be meaningful tool for estimating out-of-field CC[HT] values in pediatric patients and CC[E] values, given the challenges of performing organ-level dosimetry.

Docetaxel (DTX) is used in the first-line chemotherapy for advanced castration-resistant prostate cancer (CRPC), but resistance remains a major clinical challenge. Circular RNAs (circRNAs) play critical roles in DTX resistance. This study aimed to investigate the mechanism of a novel circRNA, circQKI, in DTX resistance and its regulatory network in CRPC.

DTX-resistant cell lines (PC3/DR and 22RV1/DR) were established, and circQKI's circular structure was validated by Sanger sequencing. CircQKI expression was modulated via siRNA knockdown and overexpression plasmids. Cell viability, apoptosis, and colony formation were assessed by CCK-8, flow cytometry, and clonogenic assays. The interaction between circQKI and miR-188-3p was verified by dual-luciferase reporter, RIP, and RNA pull-down. Autophagy activation was analyzed via Western blot and TEM. Subcutaneous xenograft models evaluated in vivo drug resistance. M6A modification was investigated through m6A RIP-PCR, METTL3/IGF2BP2 knockdown, and stability assays.

CircQKI was significantly upregulated in resistant cells and promoted DTX resistance by sponging miR-188-3p, thereby enhancing Beclin-1 expression and autophagy activation. Inhibiting Beclin-1 or co-treatment with chloroquine (CQ) partially restored DTX sensitivity. Mechanistically, METTL3-mediated m6A modification stabilized circQKI via IGF2BP2 recognition, leading to its accumulation in resistant cells. In vivo studies confirmed that circQKI overexpression reduced tumor sensitivity to DTX by enhancing autophagy.

circQKI drives DTX resistance via the miR-188-3p/Beclin-1 axis and autophagy activation, with its expression regulated by METTL3-dependent m6A modification and IGF2BP2. Targeting circQKI or autophagy pathways may offer novel therapeutic strategies to overcome DTX resistance in prostate cancer.

Prostate cancer is the most common cancer and remains a leading cause of cancer-related deaths among men worldwide. Androgen deprivation therapy continues to be the cornerstone of treatment for prostate cancer. However, the efficacy of this treatments is often limited, leading to the emergence of drug resistance and tumor recurrence. TAK-901, an inhibitor of Aurora kinase B, has been shown to inhibit tumor growth both in vitro and in vivo models. To date, the effect of TAK-901 on prostate cancer and the underlying mechanism remain unknown. In this study, we found that TAK-901 could inhibit proliferation, colony formation and migration, while also inducing apoptosis in prostate cancer cells. We further demonstrated that TAK-901 activates the CHK1 signaling pathway, leading to G2/M-phase arrest in these cells. Additionally, we identified EPHA2 as a novel therapeutic target of TAK-901. By mutating the binding sites between EPHA2 and TAK-901, we discovered that these mutations could reverse the anti-proliferative effects of TAK-901 in prostate cancer models. Our study is the first to reveal that TAK-901 induces apoptosis in prostate cancer cells and inhibits cell growth by targeting EPHA2. These findings provide valuable insights into the underlying mechanisms of TAK-901 and may develop its therapeutic applications in prostate cancer.

Lung cancer, which has the highest morbidity and mortality rates worldwide, involves intricate interactions with the nervous system. Research indicates that the nervous system not only plays a role in the origin of lung cancer, but also engages in complex interactions with cancer cells through neurons, neurotransmitters, and various neuroactive molecules during tumor proliferation, invasion, and metastasis, especially in brain metastases. Cancer and its therapies can remodel the nervous system. Despite advancements in immunotherapy and targeted therapies in recent years, drug resistance of lung cancer cells after treatment limits improvements in patient survival and prognosis. The emergence of neuroscience has created new opportunities for the treatment of lung cancer. However, it also presents challenges. This review emphasizes that a deeper understanding of the interactions between the nervous system and lung cancer, along with the identification of new therapeutic targets, may lead to significant advancements or even a revolution in treatment strategies for patients with lung cancer.

This bibliometric analysis aims to explore scientific data on Artificial Intelligence (AI) and Head and Neck Cancer (HNC).

AI-related HNC articles from the Web of Science Core Collection were searched. VosViewer and Biblioshiny/Bibiometrix for R Studio were used for data synthesis. This analysis covered key characteristics such as sources, authors, affiliations, countries, citations and top cited articles, keyword analysis, and trending topics.

A total of 1,019 papers from 1995 to 2024 were included. Among them, 71.6% were original research articles, 7.6% were reviews, and 20.8% took other forms. The fifty most cited documents highlighted radiology as the most explored specialty, with an emphasis on deep learning models for segmentation. The publications have been increasing, with an annual growth rate of 94.4% after 2016. Among the 20 most productive countries, 14 are high-income economies. The keywords of strong citation revealed 2 main clusters: radiomics and radiotherapy. The most frequently keywords include machine learning, deep learning, artificial intelligence, and head and neck cancer, with recent emphasis on diagnosis, survival prediction, and histopathology.

There has been an increase in the use of AI in HNC research since 2016 and indicated a notable disparity in publication quantity between high-income and low/middle-income countries. Future research should prioritize clinical validation and standardization to facilitate the integration of AI in HNC management, particularly in underrepresented regions.

BAF complexes (BAFs), ATP-dependent regulators of chromatin structure, play a significant role in cancer progression. This pan-cancer study aimed to decode the potential of specific BAFs in the pathology, immunity, and therapy of targeted cancers.

Data were retrieved from The Cancer Genome Atlas, Gene Expression Omnibus, and IMvigor210 databases and were analyzed for expression patterns, prognostic value, mutational signatures, biological pathways, tumor immune microenvironment (TIME) remodeling, and therapeutic resistance of BAFs. Experimental validation was also conducted.

BAFs exhibit abnormal expression in various human cancers. The BAFs model and nomogram (based on multiple variables) were developed as prognostic tools. BAFs regulate the TIME and influence the response to anti-PD-L1 therapy, particularly through ACTL6A, as observed in RNA sequencing and single-cell RNA sequencing datasets (high-resolution gene expression data at the single-cell level). ACTLA6 is a major adverse gene in the prognostic model. Patients with high ACTL6A expression showed significantly worse overall survival (hazard ratio = 1.32, 95 % CI: 1.26-1.39, p < 0.001). ACTL6A expression escalates with breast cancer (BRCA) malignancy, particularly in triple-negative BRCA (TNBC), and correlates with immune checkpoint expression while playing a crucial role in promoting cancer metastasis in TNBC.

Our findings first emphasize the significance of a novel BAFs model for patient prognosis and corroborate the considerable role of BAFs as immune-related biomarkers in pan-cancer progression. ACTL6A has a dual role as an immune-related biomarker and potential therapeutic target in TNBC, deepening our comprehension of its function as an oncogene.