SUMMARYThis study systematically explored the role of NEDD8 in pediatric acute myeloid leukemia (AML) through patient sample analysis, database mining, and in vitro experiments. Our results demonstrated that NEDD8 was significantly overexpressed in newly diagnosed pediatric AML patients and was associated with poor survival outcomes. Functional enrichment analysis of the TARGET database further revealed a strong correlation between NEDD8 and cancer-related pathways. In vitro experiments showed that NEDD8 knockdown significantly inhibited the proliferation of AML cells (THP-1 and MV4-11) and induced cell cycle arrest. Collectively, these findings highlight the critical role of NEDD8 in pediatric AML pathogenesis and suggest its potential as both a prognostic biomarker and a therapeutic target.

This study aimed to validate the Korean version of the Cancer Fatigue Scale (CFS-K) as a reliable tool for assessing cancer-related fatigue (CRF) for cancer survivors.

A total of 208 cancer survivors who completed active treatment participated in evaluating the reliability, construct validity, and factor structure of the CFS-K through confirmatory factor analysis (CFA). Correlations with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACT-F) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) scales were analyzed to assess construct validity.

The CFS-K demonstrated strong psychometric properties, with high internal consistency (Cronbach's α ​= ​0.875) and CFA validated a three-factor structure (physical, cognitive, and affective fatigue) with acceptable model fit indices (normed χ2 ​= ​2.62, CFI ​= ​0.899, TLI ​= ​0.878, RMSEA ​= ​0.088, SRMR ​= ​0.069). The standardized factor loadings for all items exceeded 0.5. Construct validity was confirmed through strong correlations with FACT-F (r ​= ​0.43-0.73) and significant correlations with EORTC QLQ-C30 subscales. Cancer survivors reported significantly higher fatigue levels across all subscales than controls.

The CFS-K is a reliable and valid tool for assessing multidimensional CRF in cancer survivors.

Chemotherapy combined with immunotherapy is a highly promising approach for treating tumors. However, chemotherapeutic drugs often fail to accumulate effectively at the tumor site after systemic administration and they lack sufficient immunogenicity to activate adaptive immunity, making an effective T-cell immune response within the tumor microenvironment difficult to achieve. Here, this work developed drug-loaded nanobubbles (DTX-R837@NBs) that encapsulate the chemotherapy drug docetaxel and the immune adjuvant R837 via a thin-film hydration method. Ultrasound-targeted nanobubble destruction promoted drug accumulation within tumor tissues and damaged tumor cells through the cavitation effect, inducing immunogenic cell death and releasing damage-associated molecular patterns to augment dendritic cell maturation. Notably, DTX-R837@NBs exhibited excellent contrast-enhanced ultrasound imaging capabilities, enabling the seamless integration of diagnosis and treatment. In combination with immune checkpoint blockade targeting programmed cell death protein 1 (PD-1), the generated immunological responses attacked residual tumor cells and ameliorated the immunosuppressive tumor microenvironment, inhibiting distant tumor growth and metastasis. Moreover, this strategy exhibited robust immune memory effects, effectively protecting the host and preventing tumor recurrence upon rechallenge. Overall, ultrasound-mediated DTX-R837@NBs combined with anti-PD-1 immune checkpoint blockade therapy exhibits robust antitumor efficiency, represent a promising strategy for overcoming immunotherapy resistance in cold tumors, and warrant further investigation for clinical translation.

Colorectal cancer is a highly prevalent and deadly malignancy worldwide. Current treatment strategies, including surgery, chemotherapy, and targeted therapy, still face limitations due to recurrence and metastasis. By conducting a weighted gene coexpression network analysis on gene expression data from The Cancer Genome Atlas, we pinpointed critical genes linked to M2 macrophages and tumor metastasis. Among these, FOXC1 emerged as a significant prognostic indicator within our predictive model. Clinical sample analysis further confirmed that FOXC1 is upregulated in colorectal cancer tissues and associated with an unfavorable patient outcome. Both in vivo and in vitro experimental results revealed that FOXC1 promotes CRC cell migration, invasion and proliferation by regulating the expression of Snail and TGF-β/Smad2/3 pathways, thereby facilitating the epithelial-mesenchymal transition process. Additionally, FOXC1 recruits M2 macrophages to the tumor microenvironment by regulating CXCL2 expression through Snail. The TGF-β factor secreted by M2 macrophages further activates the TGF-β/Smad2/3 pathway, forming a positive feedback loop. In these processes, FOXC1 plays a critical regulatory role. In summary, this study highlights the critical significance of FOXC1 in CRC progression and indicates its viability as a therapeutic target, offering a novel theoretical foundation for the development of future CRC treatment strategies.

Breast cancer is the most prevalent and lethal malignancy among females, with a critical need for safer and less invasive treatments. Photodynamic therapy (PDT) can effectively eliminate tumor cells with minimal side effects. Furthermore, the combination of PDT and immunotherapy using nanoparticles has shown promise in treating both primary and distant metastatic tumor cells. Therefore, this study proposes applying the PDT-immunotherapy combination to breast cancer treatment. However, the low immunogenicity characteristic of "cold" tumors in part of breast cancer significantly diminishes therapeutic efficacy. To address this challenge, here, a nano-gel system (designated as HCSC-gel) is constructed, which co-delivers a mitochondria-targeted photosensitizer and a STING agonist, capable of robustly activating "cold" tumor immunity. This system is further enhanced by collagenase (CN) to improve therapeutic outcomes. Upon injection into the primary tumor site, HCSC-gel rapidly forms a gel matrix, releasing CN to degrade the tumor extracellular matrix and facilitate the penetration of photosensitizers, STING agonists, and oxygen into the tumor tissue. Under laser irradiation, PDT and STING-mediated immune responses are activated, reversing the low immunogenicity of breast cancer and effectively treating both primary and metastatic lesions. This HCSC-gel nano hydrogel delivery platform is anticipated to provide novel insights for the clinical management of breast cancer and other low immunogenic "cold" tumors, offering significant benefits to patients.

The imperative need for early cancer detection, which is crucial for improved survival rates in many severe cancers such as lung cancer, remains challenging due to the lack of reliable early-diagnosis technologies and robust biomarkers. To address this gap, innovative screening platforms are essential to unveil the chemical signatures of lung cancer and its treatments. It is established that the oxidative tumor environment induces alterations in host metabolic processes and influences endogenous volatile synthesis. Despite efforts, consensus on unique volatile markers for cancer detection has been elusive, partly due to genetic variation leading to metabolic heterogeneity in humans and the lack of standardized procedures for analytical analyses.

In this study, we utilized advanced secondary electrospray ionization (SESI) technique coupled with a high-resolution mass spectrometer (HRMS) to non-invasively monitor lung cancer volatiles in a pre-clinical mouse model in real time. Our findings revealed 651 dysregulated volatile features upon cancer onset and identified 36 features correlated with tumor size. Endogenous tracing of glucose metabolism highlighted the γ-glutamyl cycle as a downstream pathway implicated in lung cancer, driven by an imbalance in glutathione metabolism due to reactive oxygen species (ROS) accumulation. Notably, our study unveiled unique volatile changes associated with gemcitabine and cisplatin treatment, which significantly abrogated tumor growth in vivo. Furthermore, we identified 5-oxoproline as a volatile metabolite indicative of lung cancer response to treatment.

In conclusion, our SESI-HRMS based analysis of pre-clinical model systematically explores the volatile signatures of lung cancer, and provides a novel non-invasive platform that possess great potential for the real-time, confident, and sensitive detection and monitoring of lung cancer.

The treatment of metastatic melanoma has long posed a complex challenge within clinical practice. Previous studies have found that EMT transcription factors are essential in the development of various cancers through their induction of EMT. Here, we demonstrate that Snail2 expression is dramatically increased in melanoma and is associated with an adverse prognosis. Elevated Snail2 in melanoma cells enhanced migratory and invasive capabilities in vitro and in vivo. Furthermore, RNA-Seq analysis revealed a significant reduction of IGFBP3 expression in melanoma cells overexpressing Snail2. IGFBP3 might mitigate the Snail2's ability to promote melanoma metastasis via the PI3K-AKT pathway. Moreover, Snail2 and HDAC3 collaborate to suppress IGFBP3 transcription through H3K4 deacetylation and H4K5 delactylation. Additionally, the combination of HDAC3 and p-GSK-3β inhibitors significantly improved the treatment outcomes for lung metastasis in melanoma in vivo. The results of our study indicate that Snail2, HDAC3, and IGFBP3 play significant roles in melanoma progression and represent promising therapeutic targets.

Exercise can improve the symptoms of chemotherapy-induced peripheral neuropathy. Traditional pairwise meta-analyses of exercise interventions can only identify the difference in effect between an exercise intervention and usual care. It is necessary to conduct network meta-analyses to establish evidence on the comparative effectiveness of all relevant exercise intervention strategies.

To evaluate the comparative effectiveness of all known exercise interventions for chemotherapy-induced peripheral neuropathy, rank the best exercise intervention and explore the influencing factors of exercise intervention.

Systematic review and network meta-analysis.

A comprehensive search was conducted in 14 databases. Risk of bias assessment, quality of evidence, sensitivity analysis, subgroup analysis and meta-regression were performed on the included studies. A network meta-analysis was used to identify the optimal exercise intervention.

Twenty-four eligible studies were included, and a total of 19 interventions were identified. Regular physical training combined with sensorimotor exercise, sensorimotor exercise, aerobic combined with resistance and balance training, aerobic exercise and resistance training had statistically significant differences in reducing CIPN symptoms with SMD and 95 % CI were - 1.06 (-1.77, -0.36), -0.61 (-1.08, -0.14), -1.88 (-2.81, -0.94), 0.94 (0.39, 1.49) and - 1.31 (-1.87, -0.74). For pain, the most effective interventions included hand-foot exercises, aerobic combined with resistance training, muscular strength combined with balance exercises, SMD and 95 % CI were - 1.99 (-2.85, -1.13), -1.13 (-1.58, -0.67) and - 1.04 (-1.66, -0.41). Endurance combined with strength training, endurance combined with resistance and balance training, regular physical training combined with sensorimotor exercise and balance training were found to be effective in treating balance with SMD and 95 % CI were 1.61 (0.74, 2.48), 1.10 (0.31, 1.88), 0.92 (0.23, 1.61), and 1.40 (0.59, 2.21). Nerve gliding exercises, aerobic combined with resistance and flexibility exercises, endurance combined with strength training, aerobic combined with resistance training and balance training were found to be effective in treating muscular strength with SMD and 95 % CI were 1.09 (0.48, 1.70), 0.94 (0.29, 1.60), 1.13 (0.32, 1.94), 0.75 (0.51, 1.00) and 1.00 (0.23, 1.76). Subgroup analysis showed that frequency of exercise, duration of exercise, exercise time per session, type of exercise supervision, types of cancer, types of chemotherapy drugs and age had a significant effect on CIPN patients.

This network meta-analysis found that multimodal exercise, consisting of aerobic, balance, resistance and sensorimotor training, was the most effective intervention for CIPN in adults. Healthcare professionals should consider the effects of patient characteristics and different exercise doses on CIPN patients.

CRD42024500334.

Fear of cancer recurrence (FCR) is a pervasive concern among lymphoma survivors and their family caregivers, influencing psychological and physical health. Given the substantial burden of FCR, identifying its predictors is crucial for targeted interventions that could enhance palliative care. We aimed to evaluate the prevalence of FCR in lymphoma survivors and their caregivers, as well as associated factors METHODS: A total of 118 patients with lymphoma, along with their family caregivers, were recruited from Hacettepe University Cancer Institute between March 2024 and May 2024. Psychological assessments were conducted using the Depression Anxiety Stress Scales (DASS-21), the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) and the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) RESULTS: High levels of FCR were experienced by 50.8% (n = 60) of lymphoma survivors and 57.6% (n = 68) of their caregivers. There was a positive correlation between the FCR of the survivors and caregivers (r = 0.349, p < 0.001). Poor overall quality of life (QoL) (aOR: 4.279, 95% CI: 1.738-10.531, p = 0.002), recent diagnosis (< 3 year) (aOR: 5.135, 95% CI: 1.852-14.238, p = 0.002), survivors' anxiety (aOR: 2.540, 95% CI: 1.014-6.363, p = 0.002) and caregivers' FCR (aOR: 2.970, 95% CI: 1.119-7.879, p = 0.029) were associated with high levels of FCR in lymphoma survivors.

We observed high FCR levels in over half the survivors with lymphoma and a higher FCR risk in patients with anxiety, poor QoL and caregiver FCR. These findings highlight the critical need for developing comprehensive care plans and interventions targeting FCR in patients with lymphoma.

To establish a model for prediction of recurrence of non-small cell lung cancer (NSCLC) based on clinical data and computed tomography (CT) imaging characteristics.

A total of 695 patients with surgically resected NSCLC confirmed by pathology at three centers were retrospectively investigated. 626 patients from center 1 were randomly divided into two sets in a ratio of 7:3 (training set, n = 438; testing set, n = 188), 69 patients from center 2 and 3 were assigned in the external validation set. Univariate and binary logistic regression analyses of clinical and CT imaging features determined the independent risk factors used to construct the model. The receiver-operating characteristic curve nomogram and decision curves analysis were used to evaluate the predictive ability of the model.

The mean patient age was 63.3 ± 10.1 years, and 44.7 % (311/695) were male. The univariate and binary logistic regression analyses identified four independent risk factors (age, tumor markers, consolidation/tumor ratio, and pleural effusion), which were used to construct the prediction model. In the training set, the model had an area under the curve of 0.857, an accuracy of 71.7 %, a sensitivity of 88.1 %, and a specificity of 70.0 %; in the testing set, the respective values were 0.867, 75.5 %, 94.4 %, and 73.5 %; in the external validation set, the respective values were 0.852, 79.7 %, 83.3 %, 78.9 %.

A prediction model based on clinical data and CT imaging characteristics showed excellent efficiency in prediction of recurrence of NSCLC. Clinical use of this model could be useful for selection of appropriate treatment options.

Treatment-related side effects are common among women treated for early breast cancer and their effective management is essential to maintain quality of life, ensure treatment adherence, and optimise survival outcomes. This study aimed to investigate patient-reported experiences and preferences about information regarding side effects received during breast cancer care.

An international multi-stakeholder expert group conducted an online patient survey assessing comprehensiveness, timing, and delivery modality of information regarding treatment-related side effects among patients undergoing primary therapy (surgery, radiation, and [neo]adjuvant chemotherapy) and endocrine therapy for early breast cancer. Descriptive analyses were performed.

From June-August 2023, 608 respondents from Brazil, France, Germany, Italy, Japan, and Spain completed the survey: 57.5 % were <50 years old, and all were or had been on endocrine therapy. Fatigue was the most reported side effect (47.0 % for primary and 42.3 % for endocrine therapy). A variable proportion of patients (14.4%-46.8 % across side effects) reported receiving information only after having experienced the side effect. Up to 43.6 % of respondents reported receiving insufficient or no information on side effects from their healthcare providers. Most patients reported preference for proactive communication from healthcare providers about side effects and prevention strategies. Respondents valued direct interactions with physicians and nurses and capitalised on a relevant role for peer-support, however utility of smartphone and web-based platforms to record and manage symptoms was acknowledged.

The survey underscores critical needs and offers insight informing the provision of comprehensive and timely information on treatment-related side effects across the cancer survivorship continuum.

non-small cell lung cancer (NSCLC) is the most prevalent malignancy worldwide despite versatile screening programs. Therapy-related adverse events can be predicted with various tools including frailty. Frailty predictive power is less well studied in operable NSCLC.

Retrospective analysis performed in NSCLC patients undergoing surgery in which ability of two preoperative frailty indexes mFI-5 and mFI-11 to predict the postoperative burden of adverse events was compared against conventional risk assessment tools such as American Society of Anesthesiologists (ASA), or the Revised Cardiac Risk Index (Lee score). Adverse events burden was categorized as any adverse event, any patient-related adverse event, any surgery-related adverse event, any administrative adverse event.

In a sample of 98 patients with surgery for NSCLC, mFI-5 was the best predictor of adverse events burden (OR 36.34, p = 0.006 for any adverse event, 45.2, p = 0.002 for any patient- related adverse event, 23.1, p = 0.01 for any surgery-related adverse event, 12.26, p = 0.03 for any administrative adverse event.

Despite its sporadic use in this setting, preoperative frailty might be a more versatile predictor for postoperative adverse events in patients undergoing open surgery for NSCLC. Further studies with more complex approach for frailty are needed.

Photodynamic therapy (PDT) has witnessed remarkable progress in recent years owing to its specific properties. Given that the antioxidation system of tumor microenvironment (TME) adversely affects treatment outcomes, powerful TME modulators can significantly resolve the limitation of PDT. Herein, we developed a PEG-modified Cu2+-doped hollow mesoporous carbon nanozyme (CHC-PEG) and loaded insoluble photosensitizer IR780 into its pores and cavities to construct the multifunctional nano-system IR780/CHCP. CHC-PEG nanozyme could perform photothermal therapy (PTT) effect and protect IR780 from aggregation-caused quenching (ACQ) effect, while exerting peroxidase (POD)-mimetic activity and the ability of consuming glutathione (GSH) to achieve oxidative stress-augmented PDT effect. When exposed to near-infrared (NIR) light, IR780 was stimulated to produce singlet oxygen (1O2) and CHC-PEG could increase the temperature of TME to exert stronger POD-mimetic activity for producing more hydroxyl radicals (OH), therefore the IR780/CHCP nano-system exhibited remarkable tumor growth inhibition. Benefited by the enhanced synergistic effect, IR780/CHCP exhibited remarkable in vivo tumor growth inhibition, with the tumor inhibition rate of 93 %, and had no significant effect on major organs. Above all, IR780/CHCP could resist the antioxidant system in TME to enhance the level of oxidative stress, thereby enabling effective anti-tumor therapy. This study introduced a novel strategy to effectively promote the synergistic PTT/PDT effect by the enhanced oxidative stress.

To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories.

Recently diagnosed nonmetastatic breast cancer survivors (n = 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up. Multivariable, multinomial logistic regression was used to identify baseline predictors of depression trajectories.

Survivors had three distinct trajectories: stable (84.6%), emerging depressive symptoms (10.3%), and recovery from high depressive symptoms at baseline that improved slowly over time (5.1%). Compared to stable survivors, those in the emerging (OR = 1.16; 95% CI = 1.08-1.23) or recovery (OR = 1.26; 95% CI = 1.15-1.38) groups reported greater baseline anxiety. Greater baseline deficit accumulation (frailty composite measure) was associated with emerging depressive symptoms (OR = 3.71; 95% CI = 1.90-7.26). Less social support at baseline (OR = 0.38; 95% CI = 0.15-0.99), but greater improvement in emotional (F = 4.13; p = 0.0006) and tangible (F = 2.86; p = 0.01) social support over time, was associated with recovery from depressive symptoms.

Fifteen percent of older breast cancer survivors experienced emerging or recovery depressive symptom trajectories. Baseline anxiety, deficit accumulation, and lower social support were associated with worse outcomes.

Our results emphasize the importance of depression screening throughout the course of cancer care to facilitate early intervention. Factors associated with depressive symptoms, including lower levels of social support proximal to diagnosis, could serve as intervention levers.

This study investigated the long-term prognosis and clinical course of patients who survived for more than 5 years after hepatocellular carcinoma (HCC) diagnosis.

This retrospective cohort study used data from the Korean National Health Insurance Service database. A total of 35,348 subjects newly diagnosed with HCC between January 2008 and December 2010 were followed up until December 2018.

A total of 11,514 (32.6%) survived for 5 years after diagnosis of HCC among 35,348 patients diagnosed with HCC. Long-term survivors (≥ 5 years) had a higher proportion of females, younger age, more frequent aetiology of hepatitis B virus, less frequent liver cirrhosis, diabetes mellitus and hypertension, and received curative treatment more frequently than nonsurvivors (< 5 years). The additional 1-, 3- and 5-year cumulative survival probabilities were 90.7%, 77.6% and 68.4% respectively. Patients who underwent curative treatment as the first treatment for HCC showed a higher additional 5-year cumulative survival probabilities than those treated with noncurative therapy (74.5% vs. 64.2%). Among the long-term survivors, 44.4% underwent HCC retreatment 5 years after HCC diagnosis. The additional 5-year cumulative survival probability was 54.9% in the HCC retreatment group. The overall 5- and 10-year cumulative probabilities of second primary malignancies in long-term survivors were 15.36% and 27.54% respectively. The most frequent second primary malignancy was prostate cancer, followed by colorectal and pancreatic cancers.

Our study highlights that a significant proportion of patients with HCC achieve long-term survival beyond 5 years, with favourable outcomes associated with curative treatments.

This study explores the molecular mechanism by which sentrin/SUMO-specific protease 1 (SENP1) promotes cisplatin (Cis) resistance and tumor stem cell characteristics in colon adenocarcinoma (COAD) through deSUMOylation-mediated modification of octamer-binding transcription factor 4 (OCT4). By analyzing single-cell and transcriptome sequencing datasets, we identified key genes and regulatory pathways in both resistant and sensitive COAD cells. Malignant cells were isolated and evaluated for stemness using the infercnv package, and differential genes between Cis-resistant and -sensitive groups were identified. Machine learning algorithms highlighted essential genes, and databases predicted interaction sites between OCT4 and SENP1. In vitro experiments using enriched HCT116 stem cells revealed that SENP1 and OCT4 expression significantly elevated CD44 and CD133 levels, enhancing stemness. Functional assays showed that SENP1's deSUMOylation of OCT4 intensified Cis resistance, migration, and invasion in cisplatin-resistant cell line 116 (Cis-116) cells. In vivo, SENP1 knockdown reduced tumor growth and stem cell markers, whereas OCT4 overexpression escalated tumor metastasis and structural damage. These findings demonstrate that SENP1's modulation of OCT4 is central to COAD's resistance and stem cell properties, offering a novel target for COAD therapy.NEW & NOTEWORTHY This study uncovers the critical role of SENP1 in regulating OCT4 through deSUMOylation, driving Cis resistance and tumor stemness in COAD. Targeting this pathway may provide novel therapeutic strategies for COAD management.

Lung adenocarcinoma (LUAD) is a prevalent malignant tumor of the respiratory system, with high incidence and mortality rates. Cellular senescence (CS) widely affects the tumor microenvironment (TME) and tumor growth, and is related to the invasion and immune escape of tumor cells. This study aims to develop a robust CS-related signature of LUAD.

Using the GSE140797, GSE42458, GSE75037, and GSE85841 datasets, in combination with cellular senescence databases, 75 LUAD CS-related differentially expressed genes (LUAD-CSDEGs) were identified through the weighted gene co-expression network analysis (WGCNA) method. Subsequently, we developed a novel machine learning framework that incorporated 12 machine learning algorithms and their 113 combinations to construct a LUAD CS-related signature (LUAD-CSRS), which were assessed in both training and validation cohorts. A LUAD-CSRS-integrated nomogram was constructed to provide a quantitative tool for predicting prognosis in clinical practice. Finally, the difference of immune infiltration and response to immunotherapy in patients with high and low risk of LUAD were evaluated.

Based on a 113-combination machine learning framework, we finally identified a LUAD-CSRS containing eight genes: RECQL4, TIMP1, ANLN, SFN, MDK, KIF2C, AGR2, ITGB4. We also confirmed that it was significantly associated with survival, immune cell infiltration, prognosis, and response to immunotherapy in LUAD patients. Additionally, we found it is related to the activation of immune responses and may be involved in regulating the balance between immune cells in the TME.

In summary, our study constructed a novel LUAD-CSRS, which is not only expected to be a powerful tool for assisting diagnosis and prognosis evaluation of LUAD, but also may provide guidance for personalized immunotherapy programs.

Immunotherapy combined with anti-angiogenesis has become a useful strategy in cancer treatment. Ivonescimab, the first approved bispecific antibody targeting both immune checkpoint inhibition and anti-angiogenesis, represents a breakthrough over the conventional dual-drug combination approach. The emerging clinical evidence demonstrates promising efficacy and manageable safety profile of ivonescimab in the treatment of non-small cell lung cancer (NSCLC), suggesting its potential role as a cornerstone in the next generation of cancer immunotherapy.

This review presents the pharmacological characteristics of ivonescimab, revisits relevant clinical trials and key data, and provides an in-depth analysis. Additionally, the potential of ivonescimab in NSCLC treatment is discussed, along with its clinical prospects.

The available clinical data demonstrate that simultaneously targeting both immune checkpoint inhibition and angiogenesis pathways through a single bispecific antibody represents a significant therapeutic advancement in NSCLC treatment. Ivonescimab's innovative dual-targeting mechanism, supported by promising efficacy data from the HARMONi trials and its manageable safety profile, appears to be fundamental to its potential to challenge current standards of care. As the first approved bispecific antibody with this unique mechanism of action, ivonescimab may not only transform current treatment paradigms but also pioneer a new direction in cancer immunotherapy.

Asian, Native Hawaiian, and Pacific Islanders (ANHPI) have a higher prevalence of type II diabetes compared to the non-Hispanic White (NHW) population. However, the incidence of type II diabetes among ANHPI lung cancer survivors is unknown. The aim of this study is to investigate the risk of newly diagnosed type II diabetes among older ANHPI lung cancer survivors compared to older NHW lung cancer survivors.

We identified 3920 ANHPI and 11,760 NHW lung cancer survivors diagnosed from 2000 to 2017 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of type II diabetes, adjusting for potential confounding factors.

Older ANHPI lung cancer survivors had an increased risk of incident type II diabetes compared to older NHW lung cancer survivors > 1 year after cancer diagnosis. For specific ANHPI subgroups, increased risks of type II diabetes were observed among Asian Indian and Pakistani (HR, 5.14; 95% CI 2.10, 12.60) compared to NHW patients, followed by Native Hawaiian and Pacific Islander (NHPI) (HR, 4.38; 95% CI 1.22, 15.74), Vietnamese (HR, 2.32; 95% CI 1.29, 4.18), Korean (HR, 2.26; 95% CI 1.13, 4.54), Filipino (HR, 1.78; 95% CI 1.00, 3.16), and Chinese (HR, 1.75; 95% CI 1.10, 2.79) lung cancer survivors.

Older ANHPI lung cancer survivors had a higher risk of type II diabetes compared to older NHW lung cancer survivors. Further research is needed to examine the underlying causes of health disparities in diabetes risk among ANHPI lung cancer survivors.

These findings suggest that increasing surveillance on type II diabetes and monitoring body weight for older ANHPI lung cancer patients may be beneficial.

Patients with premenopausal breast cancer (preBC) usually have long-term survivorship. However, less is known about the risk pattern of subsequent primary cancer (SPC) and noncancer diseases among them. Here, this study aimed to evaluate the risk of developing SPCs and mortality among preBC survivors. In this population-based, retrospective cohort study, 5-year preBC survivors diagnosed at age 20-59 years during 1992-2014, in the 11 Surveillance, Epidemiology and End Result registries were included. Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) were estimated for SPCs and mortality by cause, respectively. Among 181,947 survivors (mean age at diagnosis, 49.1 years; 65.9% White), there were 12,503 SPC cases, 4,280 SPC-related deaths, and 10,591 noncancer-related deaths. SPC risk was increased compared with the general population (SIR 1.06, [95% CI, 1.04-1.08]). The elevated risk was primarily associated with soft tissue cancer, bones/joints cancer, and acute non-lymphocytic leukemia (SIRs 2.01 [95% CI, 1.73-2.33], 1.78 [95% CI, 1.21-2.53], and 1.68 [95% CI, 1.46-1.93], respectively). Young-onset, Asian survivors, those with hormone receptor-negative BC, and initially treated with chemo-radiotherapy were at high-risk. The risk of dying from SPCs was also increased (SMR 1.07, [95% CI, 1.04-1.10]) and featured with similarly vulnerable subpopulations. Survivors of non-White ethnicity had a higher risk of dying from noncancer diseases. This study highlighted the excess risk of developing and dying from SPCs among preBC survivors, suggesting that targeted healthcare is warranted. Strategies for SPCs and noncancer comorbidity management are in great demand to achieve better long-term survivorship among preBC patients.

Gallium-based metallic drugs and agents have been widely applied for the diagnosis and treatment of diseases such as non-Hodgkin's lymphoma (NHL), but there are few reports on the potential Ga(III)-binding proteins and the related cytotoxic mechanisms for Ga(III). Herein, by using human urinary bladder cancer T24 cells as a model, we identify and report that tubulin is a Ga(III)-binding protein target in T24 cells. Our analyses, including the employment of a series of methods based on immobilized metal affinity chromatography (IMAC), cellular thermal shift assay (CETSA), and immunofluorescence experiments, collectively explained this finding. Our results suggest that the binding of Ga(III) to tubulin led to significant changes in the morphology and distribution of microtubules in cells. The blocked microtubule formation or microtubule depolymerization as a result of the binding of Ga(III) to tubulin may be an important molecular mechanism by which Ga(III) exerts its cytotoxic effects in T24 cells to inhibit tumor cell growth.

Melanoma is one of the most aggressive forms of skin cancer. Accurate and early diagnosis of melanoma is crucial for improving patient outcomes. This study develops two TYR-activatable molecular probes, Mn-TyrEDTA and Al-18F-TyrEDTA, for the selective detection of melanoma in vivo. In vitro studies reveal that Mn-TyrEDTA exhibits TYR activity-dependent relaxivity enhancement, undergoing TYR-mediated oxidative polymerization, resulting in the formation of paramagnetic oligomers. UV-vis analysis supports this mechanism, showing time- and TYR concentration-dependent increases in broad band absorbance in the UV-vis region, specifically around 475 nm, due to the formation of o-quinone intermediates and melanin-like oligomers. HPLC analysis further confirmed the presence of polar oligomeric products in Mn-TyrEDTA solutions incubated with TYR/O2. MRI studies demonstrate Mn-TyrEDTA's selective retention and signal enhancement in TYR-expressing melanoma tissues. Furthermore, PET imaging with Al-18F-TyrEDTA conducted using a dual-xenograft mouse model reveals significantly higher uptake and retention of Al-18F-TyrEDTA in TYR-expressing melanoma compared to TYR-negative tumors. This selective retention could be attributed to a TYR-mediated proximity labeling mechanism, where highly reactive quinones form covalent bonds with nearby tumor proteins. In summary, our findings establish Mn-TyrEDTA and Al-18F-TyrEDTA as promising TYR-activatable imaging probes, offering a novel strategy for the early diagnosis and prognosis of melanoma.

Colon cancer, a prevalent malignancy, is subject to intricate immune modulation, which substantially affects both treatment efficacy and prognostic outcomes. Furthermore, colon cancer is highly heterogeneous, and our comprehensive understanding of its immune microenvironment has not yet been fully realized. There is still ample opportunity for in-depth investigation into the composition and interactions of immune cells within colon cancer, as well as their implications for disease prognosis. In this study, we employed single-cell data from colon cancer to distinguish immune cells from non-immune cells through cluster analysis. Furthermore, we conducted an in-depth analysis of myeloid and T cells, which were categorized into 20 distinct cell subpopulations. Functional enrichment analysis revealed T cells' active involvement in the Fatty Acid Metabolism and Adipogenesis pathways, while immune checkpoint-associated genes (ICGs) were notably upregulated in CD8+ T cells. Subsequent analysis involved calculating gene scores to characterize cell subpopulations, which, when combined with patient survival time analysis, revealed a significant association between the gene characterization score (referred to as "imm-score") and the survival of colon cancer patients. Specifically, the presence of CD8+-ANXA1hi-T cells was linked to shortened overall survival in the high imm-score subgroup. Subsequently, combined with genomic analysis, patients in the high imm-score subgroup exhibited elevated tumor mutation burden (TMB) and heightened activity in both the epithelial-mesenchymal transition (EMT) and Notch signaling pathway. Finally, according to our new algorithm, scores calculated predicted the effectiveness of immunotherapy for patients. The results revealed that patients with lower scores could achieve better therapeutic outcomes with immunotherapy. This study offers an extensive analysis of the interplay between T cells and myeloid cells within colon cancer tissues, exploring their impact on the survival and prognosis of colon cancer patients. Additionally, it unveils the potential significance of the imm-score in colon cancer, potentially indicating a poor prognosis and providing novel insights into the immune-regulatory mechanisms underlying the disease.

Uterine corpus endometrial carcinoma (UCEC), a prevalent malignancy in the female reproductive system, has witnessed a 30% increase in recent year. Recognizing the significance of early treatment in reducing patient mortality, the identification of potential biomarkers for UCEC plays a crucial role in early diagnosis. This study was to identify key genes associated with UCEC utilizing the Gene Expression Omnibus database, followed by validating their prognostic value across multiple databases. Analysis of four UCEC databases (GSE17025, GSE36389, GSE63678, GSE115810) yielded 72 co-expressed genes. KEGG and GO enrichment analyses revealed their involvement in physiological processes such as transcriptional misregulation in cancer. Constructing a protein-protein interaction network for these 72 genes, the top 10 genes with significant interactions were identified. Survival regression analysis highlighted NR3C1 as the gene with a substantial impact on UCEC prognostic outcomes. Differential expression analysis indicated lower expression of NR3C1 in UCEC compared to normal endometrial tissue. Cox regression analysis, performed on clinical datasets of UCEC patients, identified clinical stage III, clinical stage IV, age, and NR3C1 as independent prognostic factors influencing UCEC outcomes. The LinkedOmics online database revealed the top 50 positively and negatively correlated genes with NR3C1 in UCEC. Subsequent investigations into the relationship between NR3C1 and tumor-infiltrating immune cells were conducted using R software. Gene set enrichment analysis provided insights into NR3C1-related genes, showing enrichment in processes such as Ribosome, Oxidative phosphorylation in UCEC. Collectively, these comprehensive analyses suggest that NR3C1 may serve as a potential biomarker indicating the prognosis of UCEC.

With the rise of immunotherapy, the treatment approach for non-small cell lung cancer (NSCLC) has undergone revolutionary changes. However, the prognosis for NSCLC patients has not been significantly improved due to the development of acquired drug resistance. Therefore, there is an urgent need to develop new and more effective drugs for treating NSCLC or improving tumor treatment resistance. Traditional Chinese medicine (TCM) has been gradually incorporated into the combined treatment of NSCLC. Its active components (also known as natural products) exhibit novel structures, multi-target effects, diverse pathways, minimal toxicity, and varied biological activities, which play a therapeutic role in various diseases. Thus, natural products hold great potential for future clinical applications.

Screening main traditional plants widely used in NSCLC and their derived natural products, as well as exploring the mechanisms by which these natural products act on NSCLC-particularly focusing on their applications-can provide valuable insights for the development of therapeutic drugs targeting NSCLC.

A comprehensive, computerized literature search was conducted in PubMed, Embase, Web of Science, Cochrane Library, CNKI Scholar, the American Chemical Abstracts, and Wanfang Database up to June 2024, using the following keywords: "traditional Chinese medicine", "herbal medicine", "medicinal plants", and "herbal", paired with terms such as "non-small cell lung cancer", "therapy", "natural products", and "active ingredient".

Summarizing current research findings, we discovered eleven medicinal plants containing a total of fourteen natural products. Natural products have a significant impact on tumor progression in NSCLC, including apotosis, autophagy, pyrotosis, cell-cycle arrest and metasis. Moreover, natural products can modulate the activities of various immune cells and reshape the immune microenvironment. Combined with conventional cancer treatments, natural products demonstrate promising therapeutic effects and effectively reverse drug resistance. Furthermore,the use of nano-drug delivery systems to address limitations associated with natural products.

This review summarizes eleven medicinal plants containing a total of fourteen natural products that can enhance NSCLC treatment and indicates their action mechanisms. Furthermore, we also discuss limitations of natural products and explore the use of nano-drug delivery systems to address limitations associated with natural products.

In the course of tumor treatment, radiation therapy (RT) not only kills cancer cells, but also induces complex biological effects in non-malignant cells around cancer cells. These biological effects such as angiogenesis, changes in stromal composition and immune cell infiltration remodel the tumor microenvironment (TME). As one of the major components of the TME, Cancer‑associated fibroblasts (CAFs) are not only involved in tumorigenesis, progression, recurrence, and metastasis but also regulate the tumor-associated immune microenvironment. CAFs and tumor cells or immune cells have complex intercellular communication in the context of tumor radiation.

Different cellular precursors, spatial location differences, absence of specific markers, and advances in single-cell sequencing technology have gradually made the abundant heterogeneity of CAFs well known. Due to unique radioresistance properties, CAFs can survive under high doses of ionizing radiation. However, radiation can induce phenotypic and functional changes in CAFs and further act on tumor cells and immune cells to promote or inhibit tumor progression. To date, the effect of RT on CAFs and the effect of irradiated CAFs on tumor progression and TME are still not well defined.

In this review, we review the origin, phenotypic, and functional heterogeneity of CAFs and describe the effects of RT on CAFs, focusing on the mutual crosstalk between CAFs and tumor or immune cells after radiation. We also discuss emerging strategies for targeted CAFs therapy.

The field of cardio-oncology has expanded over the past 2 decades to address the ever-increasing issues related to cardiovascular disease in patients with cancer and survivors. There is increasing recognition that nearly all cancer treatments pose some short- or long-term risk for development of cardiovascular disease and that pediatric patients with cancer may be especially vulnerable to cardiovascular disease because of young age at treatment and expected long life span afterward. Anthracycline chemotherapy and chest-directed radiotherapy are the most well-studied cardiotoxic therapies, and dose reduction, use of cardioprotection for anthracyclines, and modern radiotherapy approaches have contributed to improved cardiovascular outcomes for survivors. Newer treatments such as small-molecule inhibitors, antibody-based cytotoxic therapy, and immunotherapy have expanded options for previously difficult-to-treat cancers but have also revealed new cardiotoxic profiles. Application of effective surveillance strategies in patients with cancer and survivors has been a focus of practitioners and researchers, whereas the prevention and treatment of extant cardiovascular disease is still developing. Incorporation of new strategies in an equitable manner and appropriate transition from pediatric to adult care will greatly influence long-term health-related outcomes in the growing population of childhood cancer survivors at risk for cardiovascular disease.

Advances in medical care have made cancer rehabilitation an essential component of comprehensive cancer treatment. However, bibliometric analyses in this field remain limited. This study maps the global research landscape of cancer rehabilitation over the past decade.

Relevant publications on cancer rehabilitation from 2013 to 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted using VOSviewer, CiteSpace, and the R package "Bibliometrics."

A total of 6743 publications from 98 countries demonstrated sustained growth, peaking in 2022. The USA (1581 publications) and China (974) led in research output, while the Netherlands recorded the highest citation impact (32.75 citations per paper). Key institutions included the University of Texas MD Anderson Cancer Center (148 publications) and Memorial Sloan Kettering Cancer Center (40.58 citations per paper). Supportive Care in Cancer ranked as the most influential journal. Research efforts primarily focused on exercise interventions (n = 404), quality of life (n = 688), and breast cancer rehabilitation (n = 440). Recent trends highlighted telemedicine, digital health, and breast cancer-related lymphedema.

This analysis highlights the dominance of high-income countries in cancer rehabilitation research and identifies exercise, quality of life, and breast cancer as enduring focal points. Emerging priorities include technology-driven interventions and lymphedema management. However, critical gaps remain, such as the underrepresentation of low-resource regions, limited focus on pediatric populations, and insufficient integration of advanced technologies (e.g., AI, wearables). Future efforts should emphasize equitable resource distribution, evidence-based pediatric rehabilitation models, and scalable technology-driven solutions to address global disparities and improve survivorship care.

This review aims to summarize the evolution of surgical techniques for periacetabular metastatic cancer, assess their strengths and limitations, and clarify the corresponding indications. We conducted a comprehensive literature review on periacetabular metastatic cancer, summarizing surgical techniques involving both open and minimally invasive approaches. Additionally, we evaluated the indications for different minimally invasive techniques and proposed potential combinations of these techniques. Our review underscores the benefits of minimally invasive surgery, including reduced surgical trauma, improved patient mobility, lower complication rates, and expedited recovery times, facilitating earlier initiation of systemic cancer therapies. These techniques show substantial potential for broader application in the future. Despite the historical reliance on open surgery as the standard treatment, minimally invasive approaches are emerging as a promising alternative, particularly for managing osteolytic metastases around the acetabulum. This review provides insights into the optimal integration of these techniques, aiming to support evidence-based clinical decision-making and improve patient outcomes.

Prostate cancer (PCa) is the most prevalent cancer and the third deadliest in Europe among men. PCa has several well-established risk factors; however, the influence of lifestyle factors remains under investigation, which may hinder efforts to encourage healthier behavior adoption. Thus, this systematic review explored the general population's perceptions, knowledge, and attitudes regarding PCa-related risk factors.

Eighteen qualitative studies were included after searching PubMed, Scopus, Web of Science, and EMBASE scientific databases between January 2013 and February 2023. Five major themes emerged from the 18 included studies: PCa knowledge, risk factors, lifestyle pattern changes, motivation/barriers to changing habits, and lifestyle advice support. Participants identified age, family history, genetics, and race/ethnicity as risk factors for PCa, but no consensus has been reached regarding lifestyle. However, most of the participants were willing to adopt healthier habits. Support from healthcare professionals (HPs), family, and friends, the desire for more time with loved ones, and fear of PCa consequences were cited as motivators for habit changes. However, poor economic conditions, work schedules, age, and PCa limitations hamper lifestyle changes. Effective interventions require personalized support and credible information from healthcare providers. Collaboration between family, friends, and HPs is crucial for promoting healthier behaviors and enhancing PCa management. This systematic review highlights the need for further research and innovative approaches to empower individuals towards healthier lifestyles, which could help prevent PCa or, at the very least, promote better treatment outcomes.

There is limited information regarding how a history of cancer and related treatment with radiation therapy (RT) impacts outcomes after total knee arthroplasty (TKA). Therefore, our study assessed the risk of developing medical and surgical complications following TKA in patients with cancer as well as those with a history of prior RT.

Within a national federated research network, we conducted a retrospective cohort study, querying for patients who underwent a primary TKA from 2002 to 2022. Amongst these patients, we identified three pairs of cohorts: (1) those with and without a history of RT, (2) those with and without a cancer history, and (3) those with a history of cancer who were treated with and without RT. Following propensity-score matching for comorbidities, surgical and medical complications within the 30-day, 90-day, and 1-year postoperative periods were assessed.

RT was associated with an increased risk of multiple medical complications. When controlling for cancer, patients receiving RT had lower odds of medical complications, and there was no association with these medical complications. Cancer patients had an increased risk of multiple medical complications including venous thromboembolism at all time-intervals. PJI risk was increased at 1-year among cancer patients that received RT compared to those that did not (OR: 1.5, 95% CI: 1.1-2.0).

While RT may not increase the risk of medical complications, a history of cancer was associated with adverse outcomes following TKA. Our findings serve to help educate this patient population and encourage collaboration with patients' oncologists during the pre-operative optimization process.

The number of people living longer after a cancer diagnosis is increasing. Guidelines for cancer survivorship recommend a healthy diet and maintaining a healthy weight post-treatment. While cancer survivors often express the need for professional support for nutrition management, few report seeing a dietitian. This study aimed to explore primary care dietitians' experiences, practices, and perspectives in providing nutritional care to cancer survivors in Australia.

This qualitative study used in-depth, semi-structured interviews with primary care dietitians working in private practice and community care. Interviews were recorded and transcribed. A qualitative descriptive methodological approach integrated with a working analytical framework was utilized for coding and data analysis.

Twenty-four dietitians working in primary care participated. Four themes and 13 sub-themes were identified: (1) diversity in dietetic practice and cancer-related care interactions; (2) accessing referral pathways and funding sources in a complex healthcare system; (3) the application of nutrition education, and upskilling in cancer care; (4) client barriers and dietitians' challenges and factors influencing confidence in cancer care.

Dietitians in this study highlighted the need for clear referral pathways to primary care particularly as a continuation of cancer-related care following the acute setting. There is a need for tailored support for dietitians supporting people diagnosed with cancer in the primary care setting, including opportunities to upskill in cancer care.

The primary purpose was to assess the feasibility and acceptability of a group health coaching (GHC) program with cancer patients and survivors; secondarily, to determine the preliminary effects of GHC on several behavioral lifestyle factors.

GHC was provided to people diagnosed with cancer via videoconference by trained health coaches across six GHC sessions over a 3-month period. Qualitative and quantitative data were collected. Data on recruitment, attrition, attendance, fidelity, retention, safety, and barriers and facilitators to implementation were assessed. Participant-reported outcomes collected via surveys included physical activity, eating habits, perceived stress, anxiety, depression, sleep, and quality of life, followed by post-program focus groups and in-depth interviews. Survey results were analyzed using repeated measures multilevel modeling. Qualitative data was analyzed using inductive thematic analysis.

Overall, 26 participants with a variety of cancer types attended an average of 74% of coaching sessions. The intervention was feasible to implement and found acceptable by participants and health coaches. Over the course of the intervention, there was a moderate increase in total weekly physical activity minutes (baseline = 365.25, follow-up = 510.30, p = 0.032, d = 0.50), and a small increase in weekly moderate-vigorous physical activity frequency (baseline = 4.07 bouts, follow-up = 5.44 bouts, p = 0.045, d = 0.39). Additionally, a moderate increase was found in functional well-being (baseline = 16.30, follow-up = 18.93, p < 0.001, d = 0.50). CONCLUSIONS AND IMPLICATIONS: GHC may be a feasible and acceptable way to promote behavior change for physical activity in cancer patients and survivors, reducing cancer burden and enhancing functional well-being.

We evaluated healthcare providers' current knowledge, practices, and perspectives on a novel clinical decision tool (beta-version) to facilitate individualized exercise prescriptions and discussions in clinical settings.

We recruited healthcare providers who had treated or provided care to breast cancer survivors aged ≥ 35-years in the past 12 months. The participants were presented with a tool to provide individualized exercise recommendations considering women's individual, clinical, and contextual characteristics. Validated and reliable pre-existing instruments were used to survey providers' current knowledge, practices regarding exercise discussions, and perspectives on the beta-version (paper-draft) of the novel tool.

The sample consisted of complete survey responses from 177 healthcare providers including breast oncologists (27.7%), primary care physicians (10.7%), exercise specialists (19.8%), occupational/physical therapists (18.1%), advanced care providers, nurses, navigators, and social workers (23.7%). Median years of experience was 8-years (range: 5-13). Overall, 62.1% (n = 110) reported that they were knowledgeable about counseling survivors based on exercise guidelines. Among breast oncologists and primary care physicians (n = 68), only 39.7% reported that they were knowledgeable about identifying patients for exercise referals. The majority agreed that they would find the tool offering individualized information useful (n = 148, 83.6%), and would use it regularly to inform practice (82.5%). 'Exercise Readiness', 'Exercise Resources at Home', and 'Quality-of-Life' were the highest rated items for inclusion in the tool for exercise prescriptions. Provider perspectives were incorporated into the beta-version of the tool.

A clinical decision tool considering individual, clinical, and contextual characteristics may support exercise prescriptions and discussions in clinical settings.

An evidence-based tool for exercise prescriptions may increase healthcare provider confidence to discuss, educate, encourage, and provide exercise referrals for breast cancer survivors.

The rising prevalence of skin lesions places a heavy burden on global health resources and necessitates an early and precise diagnosis for successful treatment. The diagnostic potential of recent multi-modal skin lesion detection algorithms is limited because they ignore dynamic interactions and information sharing across modalities at various feature scales. To address this, we propose a deep learning framework, Multi-Modal Skin-Imaging-based Information-Switching Network (MDSIS-Net), for end-to-end skin lesion recognition. MDSIS-Net extracts intra-modality features using transfer learning in a multi-scale fully shared convolutional neural network and introduces an innovative information-switching module. A cross-attention mechanism dynamically calibrates and integrates features across modalities to improve inter-modality associations and feature representation in this module. MDSIS-Net is tested on clinical disfiguring dermatosis data and the public Derm7pt melanoma dataset. A Visually Intelligent System for Image Analysis (VISIA) captures five modalities: spots, red marks, ultraviolet (UV) spots, porphyrins, and brown spots for disfiguring dermatosis. The model performs better than existing approaches with an mAP of 0.967, accuracy of 0.960, precision of 0.935, recall of 0.960, and f1-score of 0.947. Using clinical and dermoscopic pictures from the Derm7pt dataset, MDSIS-Net outperforms current benchmarks for melanoma, with an mAP of 0.877, accuracy of 0.907, precision of 0.911, recall of 0.815, and f1-score of 0.851. The model's interpretability is proven by Grad-CAM heatmaps correlating with clinical diagnostic focus areas. In conclusion, our deep multi-modal information-switching model enhances skin lesion identification by capturing relationship features and fine-grained details across multi-modal images, improving both accuracy and interpretability. This work advances clinical decision making and lays a foundation for future developments in skin lesion diagnosis and treatment.

Prostate cancer (PCa) is a highly prevalent malignancy among men, with significant regional variations in incidence and poor survival rates in advanced stages. Ribosome biogenesis (RB) is pivotal for cancer cell proliferation, yet the specific role of the ribosomal biogenesis factor (RBIS) gene in PCa remains underexplored. This study aims to elucidate the biological and clinical relevance of RBIS in PCa progression.

We analyzed RNA-sequencing data from the TCGA database and three GEO datasets to compare RBIS expression in normal versus tumor tissues. The relationship between RBIS expression and clinicopathological features, including tumor stage, Gleason score, and progression-free survival (PFS), was assessed. Co-expression and functional enrichment analyses identified key biological processes involving RBIS, while genetic alterations, immune infiltration, and drug sensitivity were also evaluated.

RBIS expression was significantly higher in PCa tissues and correlated with advanced tumor stage, higher Gleason scores, and poorer PFS. Multivariate analysis confirmed RBIS as an independent prognostic marker. Functional analysis implicated RBIS in energy metabolism and protein synthesis. Moreover, RBIS expression was associated with immune cell infiltration and drug sensitivity, highlighting its potential as a therapeutic target.

RBIS represents a promising biomarker for PCa diagnosis, prognosis, and therapy. Further research is required to validate these findings and advance RBIS's clinical application, offering novel insights into PCa management.

To explore the association of wearable device-measured moderate-to-vigorous intensity physical activity (MVPA) with cardiovascular disease (CVD) risk in long-term cancer survivors.

This retrospective analysis involved a prospective cohort of 6109 cancer survivors without CVD from the UK Biobank accelerometry subsample. The MVPA volume is categorised into four groups based on guideline recommendations (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week). Cox proportional hazard models are used to investigate the association of MVPA with incident CVD.

Over a median follow-up of 7.88 years, there were 539 incident CVD events (361 incident coronary artery disease (CAD) events, 155 incident heart failure (HF) events, and 109 incident stroke events). Adjusted CVD incidence rates (95% CIs) across MVPA groups (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week) were 15.30 (12.90, 18.10), 13.50 (11.00, 16.40), 12.00 (10.20, 14.10) and 9.86 (8.35, 11.60) per 1000 person-years, respectively. Adjusted HRs (95% CI) for CVD, CAD, HF and stroke in the highest MVPA group (≥300 min/week) compared with those in the lowest MVPA group (0-75 min/week) were 0.63 (0.49, 0.80), 0.68 (0.51, 0.91), 0.66 (0.42,1.06) and 0.72 (0.42, 1.23), respectively. For obesity-related cancers, the beneficial effect on CVD was observed when exceeding 300 MVPA min/week (HR 0.54 (0.37-0.81)) compared with the lowest MVPA group.

Findings from the UK Biobank study suggest that longer MVPA durations are associated with reduced CVD risk in cancer survivors, underscoring the potential for physical activity to serve as a key component in cardio-oncology care.

Ovarian clear cell carcinomas (OCCCs) are a rare histological subtype of epithelial ovarian cancer characterized by resistance to platinum-based therapy. CDK8/19, a component of the regulatory CDK module associated with Mediator complex, has been implicated in transcriptional reprogramming and drug resistance in various solid tumors. Our study aimed to investigate the therapeutic potential of CDK8/19 kinase inhibition using selective inhibitors SNX631 and SNX631-6 in OCCC treatment, both as monotherapy and in combination with standard chemotherapeutics.

CDK8 and Ki67 levels were evaluated via immunohistochemistry in benign, primary, and metastatic ovarian cancer tissues. The efficacy of SNX631 alone and in combination with cisplatin or paclitaxel was assessed in OCCC cell lines (ES-2, TOV-21-G, RMG-1). In vivo evaluation utilized xenograft models with subcutaneous and intraperitoneal delivery of the OCCC ES2 cells and oral delivery of SNX631-6, with the monitoring of tumor growth, metastatic spread, and survival.

CDK8 protein levels were elevated in OC tissues, particularly in OCCC primary and metastatic lesions compared to benign tissue. While CDK8/19 inhibition showed limited effects on in vitro cell proliferation, SNX631-6 demonstrated significant antitumor and anti-metastatic activity in vivo. Notably, SNX631-6 enhanced the efficacy of cisplatin, substantially inhibiting tumor growth and extending overall survival.

Therapeutically achievable doses of CDK8/19 inhibitors may provide clinical benefit for OCCC patients by inhibiting tumor growth and reversing platinum resistance, potentially addressing a critical treatment challenge in this rare ovarian cancer subtype.