Scopoletin (6-methoxy-7-hydroxycoumarin) belongs to the family of coumarins with numerous pharmacological benefits. The present study deals with examining the efficacy of Nanoencapsulated polymeric Scopoletin (NEP-Sc) in murine colon cancer model. Male Balb/c mice were supplemented with NEP-Sc (2.5 and 5 mg/kg b.w.) and 5-fluorouracil (25 mg/kg b.w.) for 10 days consecutively post-induction of colon cancer. Colon polyps and morphology were assessed using a macroscopical inspection, and their score establishes the ameliorative effect of NEP-Sc. Body weight, diarrhoea score, and spleen weight were also measured. The antioxidant status of the mucosal levels of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (LPO) and nitric oxide (NO) were evaluated. The β-catenin and Ki-67 levels were analyzed through immunohistochemistry analysis to assess the inflammatory response. ELISA-based analysis was used to measure IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, and VEGF levels. All the aforementioned parameters were mitigated in AOM/DSS-triggered colon cancer in mice treated with NEP-Sc. Nanoencapsulated polymeric Scopoletin offered protection against AOM/DSS-induced colon cancer in mice. To sum up, our research findings suggest that NEP-Sc may act as a promising candidate for treating colon-associated cancer.

p16/Ki-67 dual stain is a biomarker-based test that can identify oncogenic transformation in cervical cells with higher sensitivity than cervical cytology, using the same samples taken for human papillomavirus (HPV) testing and liquid-based cytology. Dual stain is approved by the US Food and Drug Administration (FDA) for triage of women with positive results by primary HPV testing or by HPV/cytology co-testing and has recently been incorporated into management guidelines. In this review, we summarize the data showing the utility of dual stain in detecting precancers, reducing the number of unnecessary colposcopies, and reassuring women who test negative. We also discuss the implications of dual stain for future treatment practice and health economics.

This study explores the role of circ_0000467 in colorectal cancer (CRC) progression and its potential as a therapeutic target. Circ_0000467 expression was analyzed using public datasets and clinical samples from 103 CRC patients. Functional assays evaluated its influence on CRC cell proliferation, migration, and stem-like properties. Molecular interactions with miR-520g and TCF4 were examined, and in vivo experiments assessed tumor growth. Circ_0000467 was significantly overexpressed in CRC and associated with poor prognosis. Its upregulation enhanced tumor growth, invasion, epithelial-mesenchymal transition, and stem-like characteristics by increasing key markers (CD44, EpCAM, SOX2, and Nanog). Mechanistically, circ_0000467 acted as a molecular sponge for miR-520g, leading to increased TCF4 expression and activation of the Wnt/β-catenin pathway. Silencing TCF4 or overexpressing miR-520g reversed these effects. Circ_0000467 promotes CRC progression by regulating the TCF4/Wnt/β-catenin pathway through miR-520g, highlighting its potential as a biomarker and therapeutic target for CRC.

Liquid-based thin layer cytology (TCT) and HR-HPV detection are the most important screening methods for cervical cancer. These two methods have limited sensitivity and specificity, so some cervical lesions are still missed or misdiagnosed. This paper mainly discusses the value of P16 protein detection in cervical cancer screening. In particular, it is effective and practical in high-grade squamous epithelial and above cervical lesions (CINII+). In this retrospective study, the diagnostic specificity and positive predictive value (PPV) of P16 protein detection for cervical CINII+ lesions were significantly higher than that of TCT and HR-HPV detection, and the accuracy was the highest. P16 protein detection can also reduce the rate of missed diagnoses in HR-HPV-negative patients and reduce unnecessary colposcopic biopsies. Our data highlight the feasibility and significance of P16 protein detection in cervical disease screening.

Psoriasis is a chronic immune-mediated skin disease characterized by the infiltration of multiple inflammatory cells and abnormal differentiation of keratinocytes in the skin. The treatment of psoriasis is primarily based on immunosuppressive drugs; however, their long-term use can lead to various adverse effects. Euphorbia humifusa Willd. (EuH) is used in traditional Chinese medicine for its anti-inflammatory properties and effects on skin diseases such as psoriasis.

This study aimed to evaluate the anti-psoriasis effects of EuH extract, and explore its underlying mechanisms.

The main components of EuH extract were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technology. Then, we administered EuH extract to imiquimod-induced psoriasis mice for 6 consecutive days, and evaluated the effects according to the psoriasis area and severity index (PASI), spleen index, histological analysis, immunohistochemical and immunofluorescence staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and flow cytometry analysis. The potential mechanism was revealed using RNA sequencing (RNA-seq) and validated by target prediction, ELISA, qRT-PCR and Western blot (WB) analysis.

The UPLC-QTOF-MS/MS analysis showed that phenolics were the essential components in the water extracts of EuH, including flavonoids, phenolic acids, and gallotannins. Treatment with EuH alleviated psoriatic symptoms including skin condition, high PASI scores (erythema, scaling, and thickness), and spleen index values in imiquimod-induced mice. EuH treatment also inhibited keratinocyte hyperproliferation, reduced epidermal thickness, reduced inflammatory cell infiltration into skin lesions, decreased the mRNA levels of inflammatory factors, and restored T and Treg cellular balance in the spleen. RNA-seq, ELISA, qRT-PCR and WB analyses indicated that EuH extract reduced the inflammatory response and keratinocyte hyperproliferation by inhibiting the IL-17 signaling pathway.

Our findings suggest that EuH extract suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting the IL-17 signaling pathway, supporting EuH as a potential treatment for psoriasis.

To investigate the correlation between the maximum standardized uptake value (SUVmax) of positron emission tomography (PET)/computed tomography (CT) scanning imaging with the clinicopathologic parameters of aggressive non-Hodgkin's lymphoma (NHL) and its diagnostic value.

A total of 128 patients with NHL were retrospectively selected. PET/CT examination was performed to calculate SUVmax, and clinicopathological data were collected. Pearson correlation test was used to analyze the correlation between them, and the relevant indicators were detected according to the pathological results. ROC curve was used to analyze the diagnostic value.

The level of PET/CT SUVmax was positively correlated with the levels of β2-microglobulin (β2-MG), lactate dehydrogenase (LDH), Ki-67, tumor size and bone marrow infiltration (P<0.05). The PET/CT SUVmax and serum β2-MG, LDH and Ki-67 levels in the aggressive group were significantly higher than those in the indolent group (P<0.05). The AUC of the combined detection of PET/CT SUVmax, β2-MG, LDH and Ki-67 in the diagnosis of aggressive NHL was 0.920, and the combined detection had a high diagnostic value.

PET/CT SUVmax was correlated with a variety of clinicopathological parameters. Combined detection of PET/CT SUVmax has high diagnostic value in aggressive NHL.

Transarterial radioembolization (TARE) is a primary palliative treatment for advanced liver cancer. Nonetheless, its therapeutic efficacy is frequently hindered by resistance to tumor cell apoptosis induced by inter-radiotherapy. Induction of multiple cell death modalities provides a potential solution to this challenge. Ferroptosis, a distinct form of cell death from apoptosis, is dependent on the intracellular Fe2+-mediated Fenton reaction for the production of hydroxyl radicals (·OH) and is gaining recognition as a promising approach for cancer treatment. In this study, we synthesized a therapeutic radionuclide iodine-131 (131I)-based TARE agent by combining 131I-labeled iron-based MIL-88B(Fe) nanoparticles (NPs) (abbreviated as 131I-MIL-88B(Fe)) with Lipiodol to achieve a combined apoptosis-ferroptosis tumor therapy. Specifically, a mixture of Lipiodol and 131I-MIL-88B(Fe) NPs was injected into the liver tumors through the hepatic artery. Lipiodol blocks the arterial blood supply of the tumor, causing tumor tissue necrosis, whereas 131I inter-radiotherapy damages deoxyribonucleic acid (DNA) through direct action or indirectly via the production of ·OH through H2O radiolysis, leading to tumor cell apoptosis. Importantly, hydrated electrons (eaq-), a byproduct of H2O radiolysis, promoted the conversion of Fe3+ to Fe2+ in MIL-88B(Fe) NPs, enhancing the efficacy of the Fenton reaction and triggering ferroptosis. In vitro experiments demonstrated that compared to 131I alone, 131I-MIL-88B(Fe) NPs significantly enhanced ferroptosis-mediated tumor cell death due to 131I-induced Fe2+ production, which increased catalytic activity in the Fenton reaction. In a rat model bearing orthotopic N1S1 liver tumors, TARE with Lipiodol and 131I-MIL-88B(Fe) NPs induced tumor cell necrosis, apoptosis, and ferroptosis, resulting in improved therapeutic outcomes. This study leverages eaq- to facilitate Fe3+/Fe2+ conversion for efficient ferroptosis, turning waste into a valuable resource. This demonstrated the innovative integration of multiple treatment strategies to augment the efficacy of TARE in liver cancer therapy.

To explore whether a CT-based AI framework, leveraging multi-scale features, can offer a non-invasive approach to accurately predict pathological grade and Ki67 index in clear cell renal cell carcinoma (ccRCC).

In this multicenter retrospective study, a total of 1073 pathologically confirmed ccRCC patients from seven cohorts were split into internal cohorts (training and validation sets) and an external test set. The AI framework comprised an image processor, a 3D-kidney and tumor segmentation model by 3D-UNet, a multi-scale features extractor built upon unsupervised learning, and a multi-task classifier utilizing XGBoost. A quantitative model interpretation technique, known as SHapley Additive exPlanations (SHAP), was employed to explore the contribution of multi-scale features.

The 3D-UNet model showed excellent performance in segmenting both the kidney and tumor regions, with Dice coefficients exceeding 0.92. The proposed multi-scale features model exhibited strong predictive capability for pathological grading and Ki67 index, with AUROC values of 0.84 and 0.87, respectively, in the internal validation set, and 0.82 and 0.82, respectively, in the external test set. The SHAP results demonstrated that features from radiomics, the 3D Auto-Encoder, and dimensionality reduction all made significant contributions to both prediction tasks.

The proposed AI framework, leveraging multi-scale features, accurately predicts the pathological grade and Ki67 index of ccRCC.

The CT-based AI framework leveraging multi-scale features offers a promising avenue for accurately predicting the pathological grade and Ki67 index of ccRCC preoperatively, indicating a direction for non-invasive assessment.

Non-invasively determining pathological grade and Ki67 index in ccRCC could guide treatment decisions. The AI framework integrates segmentation, classification, and model interpretation, enabling fully automated analysis. The AI framework enables non-invasive preoperative detection of high-risk tumors, assisting clinical decision-making.

Hepatocellular carcinoma (HCC) is recognized as the prime and lethal form of liver cancer caused by the hepatitis B virus (HBV) and hepatitis C virus (HCV) globally. Lactate is an end product of glycolysis that influences epigenetic expression through histone lactylation. While MKI67 and RACGAP1 play crucial roles in HBV- and HCV-related HCC. However, the role of lactylation-related genes (LRGs) effects in this context remains unclear. This study innovatively explored the role of LRGs in HBV/HCV-associated HCC, identifying novel biomarkers for diagnosis and prognosis.

The present study used various online databases for analysis, and the findings were validated via immunohistochemical (IHC) analysis of HCC patient samples (n=60).

We identified six signature LRGs (ALB, G6PD, HMGA1, MKI67, RACGAP1, and RFC4) possess prognostic potential, correlation with immune infiltration, and lactylation-related pathways, providing novel insights into tumor microenvironment (TME) of HCC. Moreover, MKI67 and RACGAP1 were significantly associated with HBV- and HCV-related HCC. IHC confirmed these findings, with high expression of MKI67 and RACGAP1 was significantly linked with HBV/HCV-associated HCC compared to non-viral HCC. The expression is also significantly associated with key clinical variables.

Our results suggest that MKI67 and RACGAP1 could serve as promising biomarkers for detecting and predicting HCC caused by HBV/HCV via lactylation, opening a new direction for immune-targeted therapies.

Phloretin (Ph), an apple polyphenol, has been shown to possess anti-tumor effects. This study aimed to investigate the anti-tumor effects of the combination of Ph and radiotherapy on lung cancer.

The proliferative rate of Lewis lung carcinoma (LLC) cells treated with Ph was evaluated using the MTT assay. The radiosensitization effect of Ph was assessed using the clone formation assay. Additionally, the anti-tumor and radiosensitization effects of Ph were explored in LLC xenografts in mice.

Ph inhibited the proliferation of LLC cells in a time- and dose-dependent manner (p < 0.05). Moreover, the combination of Ph with radiotherapy significantly inhibited LLC cell colony formation (p < 0.05). In vivo studies demonstrated that the combination of Ph with radiotherapy significantly inhibited tumor growth, achieving a tumor inhibition rate of 74.44% compared to the control group (p < 0.01). This combination also prolonged the median survival times of mice by 31 days compared to the control group (p < 0.01), reduced tumor glucose uptake, promoted tumor cell apoptosis, and suppressed tumor cell proliferation.

This study suggests that the combination of Ph with radiotherapy exhibits promising activity against lung cancer, potentially through mechanisms including inhibition of glucose transport and promotion of apoptosis. These findings may provide a new therapeutic strategy for improving lung cancer treatment.

Analyzing characteristics of ocular surface squamous cell neoplasia (OSSN) at first diagnosis and potential risk factors for aggressive growth behaviour.

Retrospective.

Including patients with first diagnosis of OSSN at a tertiary center from 2013 until 2022. Cases were analyzed regarding demographics, clinical findings, and histopathological findings, including Ki-67 expression.

A total of 153 patients with first diagnosis of histopathological confirmed OSSN were included. Mean age was 72 years (36-98), with a slight male predominance (66%; n = 101). Most patients had invasive squamous cell carcinoma (SCC; 45.8%, 70), followed by carcinoma in situ (CIS; 37.9%, 58) and epithelial dysplasia (ED; 16.3%, 25). Duration of symptoms varied significantly: ED 6 months (0-36), CIS 1.5 (0-48), SCC 3 (0-36) (p = 0.048). 44.3% (51/115) of cases were previously misdiagnosed, and, therefore, inadequately treated. Orbital involvement was observed in 8.5% (13), intraocular in 1.3% (2), metastasis in 2.7% (4) at initial diagnosis. Ki-67 labeling index (LI) varied significantly across subtypes: ED 35% (2-87%), CIS 45% (11-85%), SCC 50% (18-93%) (p = 0.007) and was higher with involvement of the caruncle, lower fornix, lower eyelid margin, or tarsus (p = 0.023). Patients with globe or orbit invasion had significantly longer median symptom duration (6 months (0-48) vs 2 (0-48); p = 0.01). Patients with metastasis exhibited significantly higher Ki-67 LI (p = 0.027).

Our study found extended time intervals from first symptoms to first correct diagnosis correlate with higher risk for advanced SCC. Further, elevated Ki-67 LI correlated with more invasive tumor entities, such as SCC and CIS, and indicate an increased risk of metastasis.

The purpose of this research is to evaluate the predictive capabilities of a radiomics model for the Ki67 index and its correlation with prognosis in advanced gastric tubular adenocarcinoma patients.

Clinical data from 213 patients were analyzed, categorizing patients into high and low Ki67 index groups. The radiomic features of 192 patients were selected by lasso method and the model was constructed, which was validated using the TCIA dataset. Univariate and multivariate Cox regression analyses were used to further analyze clinical features associated with the prognosis of gastric cancer, radiomic models are also used to assess patient outcomes.

The radiomics model demonstrated moderate accuracy, with AUC values of 0.634, 0.666, and 0.602 for the training, validation 1, and validation 2 sets, respectively. Additionally, a significant correlation was found between the Ki67 index and radiomics scores, a higher Ki67 index was associated with improved outcomes. Kaplan-Meier analysis showed distinct survival differences between patients with high and low radiomics scores, indicating that higher scores predict better prognosis.

The radiomics model accurately predicts the Ki67 index and correlates with prognosis in advanced gastric tubular adenocarcinoma, offering valuable insights for clinical decision-making and personalized treatment strategies.

The Ki-67 marker reflects tumor proliferation and correlates with meningioma prognosis. Here we aim to evaluate the performance of MRI-derived radiomics for Ki-67 index prediction in meningiomas.

After a comprehensive search in Web of Science, PubMed, Embase, and Scopus, data extraction and risk of bias assessment was performed. Pooled sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) were computed. The summary receiver operating characteristic (sROC) curve was generated and area under the curve (AUC) was calculated. Separate meta-analyses were conducted for radiomics models and combined models. Heterogeneity was evaluated using the I2 statistic, and subgroup analysis was performed to identify potential sources of heterogeneity. Sensitivity analysis was carried out to detect possible outliers.

Seven studies were included, with six studies analyzed for radiomics model and four for combined model. For radiomics model, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 67 %, 82 %, 8.61, 3.54, 0.43, and 0.79, respectively. For combined model, pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 78 %, 78 %, 12.19, 3.47, 0.30, and 0.79, respectively. Sensitivity analysis identified no outliers. In radiomics model, potential sources of heterogeneity included mean age and the application of N4ITK bias correction. For combined model, heterogeneity was influenced by mean age, application of N4ITK bias correction, and the use of external validation.

Radiomics shows promising ability to predict the Ki-67 index status in meningioma patients, potentially enhancing clinical decision-making and management strategies.

Esophageal cancer is highly prevalent in China, predominantly represented by squamous cell carcinoma. This retrospective study sought to evaluate the diagnostic efficacy of four staining protocols in identifying early stage esophageal squamous cell carcinoma (ESCC).

A consecutive series of ninety biopsy samples of esophageal mucosa, collected retrospectively from March 2016 to December 2019, were obtained at Beijing Chao-Yang Hospital, a tertiary care facility in Beijing, China. These samples were categorized into four groups: non-neoplastic squamous lesions (Non-NSL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and early stage ESCC. Baseline, molecular analyses (p53 by immunohistochemistry and Ki-67 by immunohistochemistry), and staining analyses (hematoxylin & eosin (HE) and periodic acid-Schiff (PAS) were conducted across the categories. The staining protocols included HE, HE + p53 + Ki-67, HE + p53 + Ki-67 + PAS, and HE + p53/PAS + Ki-67/PAS.

Patients with HGD and ESCC were significantly older and had larger lesions. Elevated p53 and Ki-67 mutation rates were observed in HGD and ESCC, while increased PAS positivity was noted in RE and LGD. The p53, Ki-67, and PAS staining results showed mostly no correlation among the four groups. Abnormal Ki-67 basal layer distribution pattern correlated with histological grades, with higher proportions in HGD and ESCC. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS demonstrated complete consistency with the reference standard, with weighted κ values of 1. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS protocols exhibited 100% accuracy, sensitivity, and specificity for diagnosing ESCC or ESCC combined with HGD, outperforming the other protocols.

Incorporating specific staining protocols, particularly HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS, enhances the diagnostic accuracy for early stage ESCC, showing promise in advancing the pathology diagnostic pathway.

The brachial plexus is usually involved by tumours of adjacent areas like the lungs, breast, and cervical spine. Primary tumour of the brachial plexus are rare. It constitutes less than 5% of upper extremity tumours. Still rare are malignant tumours. Once malignancy is diagnosed there should be no delay in surgery considering the aggressive nature. Here, we discuss the diagnostic dilemma in a case of a malignant peripheral nerve sheath tumour and its surgical approach. Surgical excision was challenging because of the complex anatomy, retroclavicular/infraclavicular extension and proximity tumour to adjacent vital structures.

Costunolide (COS), a sesquiterpene lactone extracted from the roots of Saussurea costus, is known to possess anticancer properties in various cancers, including colon, oral, and lung cancers, but its mechanism of action in skin carcinogenesis has not yet been explored. Present study investigates the chemopreventive mechanism of COS on skin inflammation and carcinogenesis both in vitro and in vivo.

The cytotoxicity of COS was examined on a normal murine epidermal cell line, JB6, by treating with COS using the WST-8 assay. Subsequently, the effect of COS on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cellular transformation was assessed through a soft-agar assay. Furtherly, cell cycle and apoptosis analysis and the expression of related proteins were determined via flow cytometry and Western blotting, respectively. The effects of COS on tumor promotion induced by DMBA/TPA treatment and the underlying molecular mechanisms in mouse skin carcinogenesis were identified through H&E staining and immunohistochemical analysis.

COS significantly inhibited colony growth and number in TPA-induced JB6 cells transformation, arrested the cell cycle at the G2/M phase, increased p21 expression, and decreased cyclin B expression. In addition, COS induced cell apoptosis and increased the related markers expression including cleaved caspase-3 and - 7. COS suppressed the expression of phosphorylated AKT and its downstream signaling proteins and effectively reduced the translocation of phosphorylated NF-κB from the cytosol to the nucleus. Moreover, COS reduced papilloma formation in mouse skin and inhibited hyperplasia and phosphorylated AKT expression in tissues.

These results demonstrate that COS inhibits TPA-induced cellular transformation and skin carcinogenesis both in vitro and in vivo through the AKT signaling pathway. Our findings suggest the potential of COS as a chemopreventive agent for skin carcinogenesis, highlighting its significance for further investigation in cancer prevention and therapy.

Incorporating fluorine-containing groups into the chemical skeleton is expected to enhance bioactivity and bioavailability. Directly introducing fluorine groups into the parthenolide skeleton remains challenging and limited. In this research, a series of novel fluorine-containing parthenolide derivatives were synthesized through late-stage diversification strategy. And the most promising derivate 1 exhibited good antiproliferative activity against NCI-H820 (IC50: 2.66 μM), Huh-7 (IC50: 2.36 μM), and PANC-1(IC50: 2.16 μM). The preliminary mechanism study indicated compound 1strongly inhibited the colony formation number of NCI-H820, Huh-7 and PANC-1 cells and inhibited lung cancer metastasis with a dose-dependent manner through inhibiting STAT3 signaling pathway. Compound 16, a prodrug of compound 1, showed a significant improvement in aqueous solubility and oral bioavailability compared with parthenolide. Moreover, compound 16 significantly suppressed tumor growth in lung patient-derived tumor xenograft model without obvious toxicity. Based on the above results, we propose that compound 16 may be a promising lead compound for treatment of lung cancer.

To analyze the correlation between vasoactive intestinal peptide (VIP) protein expression in neuroblastoma (NB) tumors and NB clinical features and prognosis.

Clinical data were collected from 91 patients with NB aged < 18 years who underwent tumor resection at the Shengjing Hospital of China Medical University between January 2015 and December 2021. VIP expression levels in tumor tissues were evaluated by immunohistochemistry, and the correlation between VIP expression intensity and NB clinical characteristics and prognosis was analyzed.

VIP expression was detected in 25/91 patients with NB (27.5%). VIP expression intensity was significantly increased in children with diarrhea and hypokalemia (P < 0.001, and P < 0.001, respectively), and was significantly associated with histopathological classification, prognosis, bone marrow metastasis, and tumor stage (P = 0.003, P = 0.036, P = 0.018, and P = 0.027, respectively). VIP expression intensity was positively correlated with synaptophysin expression (rs = 0.342, P = 0.001), and negatively correlated with expression of chromogranin A and proliferating cell nuclear antigen (Ki67) (rs = -0.265, P = 0.011; rs = -0.317, P = 0.002, respectively). There were no significant differences in VIP expression levels according to sex, age, tumor site, or levels of neuron specific enolase, 24-h urine vanillylmandelic acid, and lactate dehydrogenase.

VIP is one of the main causes of refractory diarrhea in patients with NB, and may be a potential biomarker of good prognosis.

Retrospectively registered.

Non‑small cell lung cancer (NSCLC) is a malignant tumor of significant clinical relevance. Curcumin has been investigated for its potential anticancer properties, as it has been reported to act through multiple cancer‑related targets and pathways. The present study aimed to explore the effects of curcumin in NSCLC using both in vitro and in vivo models. NSCLC cell lines (specifically, A549 and NCI‑H1299 cells), and a mouse tumor model established through the subcutaneous injection of A549 cells, were utilized to evaluate the effects of curcumin intervention. The effects of treatment with curcumin on NOD‑like receptor pyrin domain‑containing 3 (NLRP3) ubiquitination, cell pyroptosis and pyroptosis‑associated factors were also evaluated. In addition, Smad ubiquitination regulatory factor 2 (Smurf2) was analyzed via a series of knockdown and overexpression experiments, both in vitro and in vivo, aimed at investigating its association with curcumin and NLRP3. The results obtained from these experiments showed that curcumin inhibited NSCLC cell growth, promoted pyroptosis and reduced the level of NLRP3 ubiquitination. NLRP3 knockdown reversed the curcumin‑induced increase in pyroptosis‑associated factors both in vitro and in vivo. Additionally, Smurf2 interacted with NLRP3 and alterations in Smurf2 expression levels influenced NLRP3 ubiquitination and cell pyroptosis. Moreover, molecular docking analysis demonstrated that curcumin could bind directly to Smurf2, which subsequently led to an inhibition of Smurf2 activity. Knockdown of Smurf2 enhanced curcumin's ability to stabilize NLRP3 and to promote pyroptosis, whereas Smurf2 overexpression negated these effects. In the in vivo animal model, curcumin treatment led to reduced tumor volumes and weights, in addition to a decreased expression level of Ki67 and increased expression levels of NLRP3 and pyroptosis‑associated factors. Similarly, these effects were enhanced or reversed by Smurf2 knockdown or overexpression, respectively. In conclusion, the findings of the present study showed that curcumin inhibited Smurf2 activity, thereby promoting NLRP3‑dependent pyroptosis in NSCLC cells. In addition, these findings have provided mechanistic insights into the role of curcumin in NSCLC, opening an avenue for its potential therapeutic application.

The relationships between Ki-67/MKI67 expression, lymph node metastasis (LNM), vascular invasion (VI), and perineural invasion (PI) in esophageal squamous cell cancer (ESCC) remain unclear. This retrospective cohort study was performed to evaluate the prognostic value of Ki-67 expression and its association with LNM in patients with resected ESCC.

The analysis included 168 patients with ESCC with available Ki-67 protein expression data. The patients were divided into Ki-67 high-expression group (Ki-67 High, 93 cases) and Ki-67 low-expression (Ki-67 Low, 75 cases) groups. Associations between Ki-67 expression and ESCC pathological features was assessed using chi-square test. Overall survival (OS) was compared between the two groups using Kaplan-Meier survival analysis and Cox proportional hazards model.

Median follow-up duration was 33.5 months (range 3.0-60.0 months). High Ki-67 expression was significantly associated with poor OS in patients with ESCC compared to that of the low-expression in both univariate (hazard ratios (HR) = 3.42, 95% CI [2.22-5.27], P < 0.001) and multivariate analyses (HR = 1.98, 95% CI [1.33-2.94], P < 0.001). Furthermore, high Ki-67 expression was significantly associated with an increased risk of LNM (χ 2 = 11.219, P = 0.011), VI (χ 2 = 6.359, P = 0.012), and PI (χ 2 = 8.877, P = 0.003).

High Ki-67 protein expression is associated with poor prognosis in ESCC. Increased Ki-67 expression significantly increases the risk of LNM, VI, and PI in ESCC, and thus may serve as an indication for adjuvant therapy in ESCC management.

nuclear-associated antigen Ki67 (Ki67) emerges as a clinically practical biomarker for proliferation assessment among many cancer types. However, the definite prognostic value of Ki67 against a specific cancer type has remained vague. This study aims to perform a comprehensive pan-cancer analysis of the prognosis value of Ki67 across various cancer types.

This study explored the expression, prognostic value, and tumor-infiltrating immune of MKI67 in the TCGA database by pan-cancer, and then performed immunohistochemical, correlation analysis and prognostic analysis using 10028 patients of the top 10 cancer patients in China we collected. The correlation between MKI67 expression and survival outcome, clinical features, MSI, TMB, and tumor-infiltrating immune cells by TCGA database, xCell, and TIMER algorithms.

MKI67 expression was significantly upregulated across varied cancer types verified by datasets. We found MKI67 expression was significantly associated with poor prognosis in LUADLUSC, LIHC, and BRCA patients, but good prognosis in COADREAD and READ patients via Kaplan-Meier survival analysis using 10028 patients collected. These results of our validation were generally consistent with TCGA database except BRCA, COADREAD and READ. Meanwhile, upregulation of MKI67 elevates the degree of immune infiltration of several immune cell subtypes, such as functional T cells, CD4+ T cells, and CD8+ T cells, as well as, MKI67 was related to Cell cycle, Oocyte meiosis, p53 and other pathways.

Our comprehensive analysis may supply useful guidance on MKI67 applicability across various cancer types. These observed results contribute to the promise of MKI67 in a realistic clinical setting and improve the outcomes of cancer patients.

Over the years, numerous ligand-based organotin(IV) Schiff base compounds have shown remarkable cytotoxicity and anticancer activities, but their clinical use is restricted by systemic toxicity, prompting the search for targeted therapies. Targeted delivery can be enhanced by exploiting the inherent characteristics of cancer cells such as glutamine addiction, which is essential to support cellular biosynthesis and cell growth to sustain aberrant proliferation. Our previous study revealed glutamine-conjugated organotin(IV) compounds have strong DNA/protein affinities, favorable in silico ADME profiles, and significant antiproliferative activity. In this study, these compounds demonstrated significant cytotoxicity against human colon carcinoma and adenocarcinoma cell lines via the induction of cell cycle arrest and apoptosis. In DMH/DSS-induced experimental colon carcinogenesis, these compounds reduced tumor burden and volume and inhibited cell proliferation and induced apoptosis, with minimal toxicity. Tissue distribution studies revealed selective accumulation in the colon. These findings support their potential as chemotherapeutic candidates for colon cancer.

Lung cancer remains a leading cause of cancer-related mortality worldwide. Our study investigates the involvement of the PD-L1/MALAT1/miR-200a-3p axis in lung tumor progression using a murine model of lung carcinogenesis. Lung tumors were induced in rats, which were divided into groups and sacrificed at different stages of tumor development. A histopathological examination was performed to assess tumor progression. Immunohistochemistry was applied to evaluate the expression of Ki-67 and programmed death-ligand 1 (PD-L1). The level of carcinoembryonic antigen (CEA) and expression analysis of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-200a-3p, and zinc finger E-box binding homeobox 1 (ZEB1) were evaluated for each stage of induction. Immunohistochemical analysis demonstrated a progressive upregulation of the proliferative marker Ki-67 and the immune checkpoint protein PD-L1 during the induction process, indicative of enhanced tumor proliferation and immune evasion. Additionally, CEA levels revealed a progressive increase across induction stages, with a significant increase in advanced tumor stages, highlighting its clinical relevance as a biomarker for lung cancer progression. Expression analysis revealed dynamic upregulation of MALAT1 and downregulation of miR-200a during lung tumor induction, which correlated with advanced tumor stages and elevated PD-L1 expression, suggesting that the negative correlation between MALAT1 and miR-200a is involved in the development of lung tumors. ZEB1 expression exhibited a notable increase in the advanced stages of induction, consistent with its association with aggressive lung cancer. Our findings underscore the interplay between molecular pathways involved in lung tumor development and the potential diagnostic and therapeutic implications of the PD-L1/MALAT1/miR-200a-3p axis.

Uterine corpus endometrial carcinoma (UCEC) is one of the most frequent female genital malignant tumors. Targeting DNA damage and cell apoptosis are regarded as effective ways for UCEC therapy. Celastrol is a natural anti-cancer product from the Celastraceae plant family, while its role in UCEC has not been investigated.

UCEC cell lines Ishikawa and HEC-1-A were applied and treated with different concentrations of Celastrol. The appropriate and nontoxic concentrations were used for the subsequent experiments. Functional experiments analyzed the cell viability, cell cycle distribution, DNA damage, apoptosis and the expression of related proteins. We determined tumor growth in xenograft nude mice. Bioinformatic analysis, protein coimmunoprecipitation (Co-IP), luciferase assay, cell experiments were performed to reveal the relationship of Celastrol/KAT2B/RBPJ/MCM4 in UCEC.

Treatment of Celastrol inhibited cell viability in a dose-dependent manner, and caused cell cycle arrest, accompanied by the downregulation of CDK2 and cyclin E expression and the upregulation of p21. Celastrol treatment resulted DNA damage and apoptosis in cultured cells, as demonstrated by increased number of TUNEL-positive cells, activity of caspase-3 and expression of cleaved-caspase-9, cleaved PARP1 and γ-H2AX. In xenograft nude mice, Celastrol also repressed tumor growth. Furthermore, lysine acetyltransferase KAT2B was a putative target of Celastrol, and its expression was upregulated by Celastrol in vitro and in vivo. Overexpression of KAT2B in UCEC inhibited cell proliferation and increased DNA damage and apoptosis. KAT2B knockdown overcame the anti-proliferative and pro-apoptotic roles of Celastrol. Moreover, Co-IP demonstrated that KAT2B bound to RBPJ, a transcriptional repressor, and increased the acetylation of RBPJ. RBPJ could bind to the MCM4 promoter to suppress the luciferase activity. Further functional analysis revealed that the functions of KAT2B in UCEC cell proliferation, DNA damage and apoptosis were mediated by MCM4, and Celastrol enhanced RBPJ acetylation and reduced MCM4 expression.

These results underscore that Celastrol is a promising anti-cancer agent in UCEC with preferential anti-proliferative, pro-apoptotic and DNA damage effects through the KAT2B/RBPJ/MCM4 axis, and KAT2B is a promising therapeutic target for UCEC.

Metabolic reprogramming is a hallmark of cancer. The"Warburg effect", also known as aerobic glycolysis, is an essential part of metabolic reprogramming and a central contributor to cancer progression. Moreover, hypoxia is one of the significant features of pancreatic ductal adenocarcinoma (PDAC). Under hypoxic conditions, the "Warburg effect" occurs to meet the nutrient and energy demands of rapid genome replication, remodeling the tumor microenvironment (TME) and influencing tumor immunity. α-Enolase (ENO1) is a multifunctional protein, acting as a glycolytic enzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid. ENO1 was found to be overexpressed in multiple types of cancers. Here, we investigated the role of ENO1 in modulating the PDAC microenvironment. Using bioinformatic analyses, we demonstrated that ENO1 was highly expressed in PDAC patients, which was related to a poor prognosis. In vitro, Eno1 knockdown resulted in reduced PDAC cell proliferation and colony formation, along with enhanced apoptosis in PDAC cells. In vivo, tumorigenesis was suppressed in mouse PDAC models by Eno1 knockdown. Flow cytometry analysis revealed that high expression of Eno1 altered the tumor immune microenvironment (TIME), particularly the impaired tumor infiltration and function of CD8+ T cells. Mechanistic studies revealed that ENO1 upregulated PD-L1 to prevent CD8+ T cells infiltration through the hypoxia-inducible factor (HIF)-1α signaling pathway, leading to PDAC progression. In conclusion, our findings indicate that ENO1 might serve as a potential biomarker for PDAC and a novel onco-immunotherapeutic target via its role in altering the TIME.

There is an urgent necessity to devise efficient tactics to tackle the inevitable development of resistance to osimertinib, which is a third-generation epidermal growth factor receptor (EGFR) inhibitor used in treating EGFR-mutant nonsmall cell lung cancer (NSCLC). This study demonstrates that combining itraconazole with osimertinib synergistically reduces the proliferation and migration, enhances the apoptosis of osimertinib-resistant cells, and effectively inhibits the growth of osimertinib-resistant tumors. Mechanistically, itraconazole combined with osimertinib promotes the proteasomal degradation of sonic hedgehog (SHH), resulting in inactivation of the SHH/Dual-specificity phosphatase 13B (DUSP13B)/p-STAT3 and Hedgehog pathways, suppressing Myc proto-oncogene protein (c-Myc). Additionally, DUSP13B interacts with signal transducer and activator of transcription 3 (STAT3) and modulates its phosphorylation. Interestingly, it is observed that SHH overexpression partially rescues the synergistic effects of this combination treatment strategy through the SHH/DUSP13B/p-STAT3 signaling axis. Moreover, it is found that SHH, (GLI1), p-STAT3, and DUSP13B play significant predictive roles in osimertinib resistance. In lung adenocarcinoma, p-STAT3 is positively correlated with SHH but negatively correlated with DUSP13B. Together, these results highlight the crucial role of itraconazole in reversing the acquired resistance to osimertinib and provide a scientific rationale for the therapeutic strategy of combining osimertinib with itraconazole.

Although antiretroviral therapy (ART) effectively inhibits viral replication, it does not fully mitigate the immunosenescence instigated by HIV infection. Cellular metabolism regulates cellular differentiation, survival, and senescence. Serine hydroxymethyltransferase 2 (SHMT2) is the first key enzyme for the entry of serine into the mitochondria from the de novo synthesis pathway that orchestrates its conversion glutathione (GSH), a key molecule in neutralising ROS and ensuring the stability of the immune system. It remains incompletely understood whether SHMT2 is involved in the senescence of CD8+ T cells, crucial for immune vigilance against HIV.

HIV-infected individuals receiving antiretroviral therapy were enrolled in our study. SHMT2-siRNA was electroporated into T cells to disrupt the gene expression of SHMT2, followed by the quantification of mRNA levels of crucial serine metabolism enzymes using real-time PCR. Immunophenotyping, proliferation, cellular and mitochondrial function, and senescence-associated signalling pathways were examined using flow cytometry in CD8+ T cell subsets.

Our findings revealed that CD8+ T cells in HIV-infected subjects are inclined towards senescence, and we identified that SHMT2, a key enzyme in serine metabolism, plays a role in CD8+ T cell senescence. SHMT2 can regulate glutathione (GSH) synthesis and protect mitochondrial function, thus effectively controlling intracellular reactive oxygen species (ROS) levels. Moreover, SHMT2 significantly contributes to averting immunosenescence and sustaining CD8+ T cell competence by modulating downstream DNA damage and phosphorylation cascades in pathways intricately linked to cellular senescence. Additionally, our study identified glycine can ameliorate CD8+ T cell senescence in HIV-infected individuals.

Decreased SHMT2 levels in HIV-infected CD8+ T cells affect ROS levels by altering mitochondrial function and GSH content. Increased ROS levels activate senescence-related signalling pathways in the nucleus. However, glycine supplementation counteracts these effects and moderates senescence.

This study was supported by grants from the National Key R&D Program of China (2021YFC2301900-2021YFC2301901), National Natural Science Foundation of China (82372240), and Department of Science and Technology of Liaoning Province Project for the High-Quality Scientific and Technological Development of China Medical University (2022JH2/20200074).

Breast cancer is the most common malignant tumor in the world, and its metastasis is the main cause of death in breast cancer patients. However, the differences between primary breast cancer tissue and lymphatic node, bone, and brain metastases at the single-cell level are not fully understood. We analyzed the microenvironment heterogeneity in samples of primary breast cancer (n = 4), breast cancer lymphatic node metastasis (n = 4), breast cancer brain metastasis (n = 3), and breast cancer bone metastasis (n = 2) using single-cell sequencing data from the GEO database. The malignant epithelial cells were characterized by InferCNV algorithm. The cell-cell communication was analyzed using CellChat package. The biological function of cell subpopulations was analyzed using gene set variation analysis. The expression of STMN1 was analyzed using immunohistochemical staining. The proportion of pCAFs in breast cancer was explored using multispectral immunohistochemical staining. We identified seven cell clusters in primary and metastatic breast cancer (Lymphatic node, brain, and bone metastases) by analyzing single-cell transcriptomic profiles. T-NK and B cells dominated breast cancer with lymphatic node metastasis, whereas fibroblasts were prevalent in brain metastases and primary breast cancer. We identified five T cells (T memory, CD8 + T cells, regulatory T cells, natural killer cells, CD4 + T cells), three B cells (naïve B cells, memory B cells, plasma B cells), and five cancer-associated fibroblasts (CAFs) subpopulations (Smooth muscle cells (SMC), pericyte, antigen-presenting CAFs (apCAFs), proliferative CAFs (pCAFs), and matrix CAFs (mCAFs)). Notably. pCAFs dominated breast cancer with lymphatic node, bone, and brain metastasis. Furthermore, we identified four malignant epithelial cell subpopulations: G0, G1, G2, and G3. The G2 cell population exhibited strong invasion ability, it can differentiate into G3 with strong proliferative ability and proliferation-related G1 cell population after metastasis. Cell-cell communication demonstrated an interaction between pCAFs and metastasis-associated malignant epithelial cells. Finally, we discovered that in advanced breast cancer, the proportion of pCAF increased and was associated with a poor prognosis of breast cancer. This study elucidated the potential cellular origins and drivers of breast cancer metastases to lymphatic nodes, brain, and bone, utilizing single-cell transcriptomic profiles. Furthermore, it demonstrated that increased pCAFs were associated with advanced breast cancer and a poor prognosis.

Background: The aim of this study was to evaluate biomarkers and biological characteristics of tumor biopsies from patients with head and neck cancer (HNC) to assess the risk of early death. Furthermore, we analyzed whether any combination of markers could be used for the prognostication of death within six months after cancer diagnosis. Materials and Methods: Patients diagnosed with HNC, receiving curative treatment decision at a multidisciplinary tumor board meeting, and who died within six months of diagnosis were included in this study. Nine patients who died within six months from diagnosis were identified and matched according to the tumor site and stage to seventeen patients who survived for at least two years. Results: The expression of markers was compared between the early-death patients and survivors. There was significantly higher Ki-67 expression in patients who died within six months than in those surviving for two years, with a mean difference of 21% (p = 0.038). A significant difference in cytoplasmic survivin expression was noted where early-death patients had increased expression compared to the survivors (p = 0.021). Furthermore, the intensity of survivin staining differed between the groups (p = 0.006). Conclusions: The results of this pilot study indicate that Ki67 and survivin could be potential prognostic biomarkers for early death in patients with HNC and possibly included in a panel of prognostic markers of value for treatment decision making.

The aim of this study was to verify the safety and efficacy of endoscopic resection (ER) for gastric gastrointestinal stromal tumors (GISTs).

Among a consecutive series of resections for gastric GISTs performed in a single center, the outcomes of patients who had ER were compared to standard surgical resection (SR).

In the cohort, 329 consecutive primary localized gastric GISTs patients (n, ER/SR = 251/78) were enrolled. Patients receiving ER were revealed to have preferable post-treatment outcomes, prolonged overall survival (OS) and disease-free survival (DFS). Tumor diameter, the only independent risk factor for a complicated post-operative course, was utilized for propensity score matching (PSM). In the PSM cohort, patients receiving ER and SR with similar tumor size (4.0 [2.7-4.5] cm) shared similar aggressiveness in terms of stomach layers of tumor origination and invasion, and modified National Institutes of Health (mNIH) risk criteria. Shorter operative time, fewer economic costs, and shorter post-operative stay were still observed in the ER group (ER vs. SR: 80 [49-120] vs. 120 [98-160] minutes, p < 0.001; 44 [38-51] vs. 60 [49-84] thousand Renminbi [kRMB], p < 0.001; 7.0 [6.0-8.0] vs. 8.5 [6.0-12] days, p = 0.018, respectively). No significant difference in OS and DFS was demonstrated in the PSM cohort.

ER is safe and effective, thus a feasible treatment option for indicated gastric GISTs patients with the advantage of faster recovery and lower economic costs.

Ovarian cancer is difficult to detect in its early stages, and it has a high potential for invasion and metastasis, along with a high rate of recurrence. These factors contribute to the poor prognosis and reduced survival times for patients with this disease. The effectiveness of conventional chemoradiotherapy remains limited. Nano-particles, as a novel drug delivery system, have significant potential for improving therapeutic efficacy and overcoming these challenges.

According to the high expression level of matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, MMP-2 responsive nano-particles (PVGLIG-MTX-D/T-NMs) containing docetaxel and triptolide were prepared by the thin-film dispersion method. The synergistic effect between docetaxel and triptolide was systematically investigated, the ratio of the two drugs was optimized, and the physicochemical properties of the nano-particles and their ability to inhibit ovarian cancer cell growth and metastasis were evaluated in vitro and in vivo.

PVGLIG-MTX-D/T-NMs enhanced the targeting, stability, and bioavailability of the drug, while reducing the dose and toxicity. In addition, by regulating the expression levels of E-Cadherin, N-Cadherin, matrix metalloproteinases (MMPs), hypoxia-inducible factor 1-alpha (HIF-1α), and vascular endothelial growth factor (VEGF), it exhibited an inhibitory effect on epithelial-mesenchymal transformation (EMT) and tumor cell angiogenesis, and effectively inhibited the invasion and metastasis of ovarian cancer cells.

PVGLIG-MTX-D/T-NMs achieved passive targeting of tumor sites by enhancing permeability and retention (EPR) effects. Subsequently, the uptake of the drug by tumor cells was enhanced by MMP-2 responsiveness and the modification of methotrexate targeting ligands. By regulating the expression levels of invasion- and metastasis-related proteins in tumor tissues, the nano-particles affected the EMT process, inhibited tumor angiogenesis, and suppressed the malignant potential of invasion and metastasis in ovarian cancer. These findings provided a new direction for further exploration of tumor-targeted therapy.

Primary mediastinal liposarcomas (PLMs) are extremely rare. Patients typically present with symptoms caused by tumor size, as the mass can compress surrounding tissues and organs. Here, we report a case of a large primary mediastinal liposarcoma that was successfully resected thoracoscopically. By reviewing the available literature on mediastinal liposarcomas and sharing perioperative insights, we aim to provide guidance on the diagnosis and surgical management of large mediastinal liposarcomas.

A 38-year-old male presented to our hospital with complaints of dysphagia after meals. Chest computed tomography (CT) revealed a large space-occupying lesion in the posterior upper mediastinum, and gastroscopy identified esophageal compression without evidence of new growth. The patient underwent thoracoscopic resection, resulting in significant improvement of his dysphagia postoperatively. He experienced no postoperative complications and was discharged one week following surgery.

The incidence of PLM is very low. Due to the proximity of vital structures such as the vena cava, esophagus, trachea, and subclavian artery, surgical resection presents elevated risks and complexity. While minimally invasive thoracoscopic techniques offer both safety and efficacy, careful preservation of surrounding organs is essential during the procedure.

RING finger protein 112 (RNF112) exerts a key role in human tumors. However, its biological function in colorectal cancer (CRC) has not been discussed. We aimed to explore the function and molecular mechanism of RNF112 in CRC.

In this study, RNF112 expression was notably decreased in CRC tissues and cells. Clinical analysis revealed a significant association between low RNF112 expression and tumor size, N classification and TNM stage. In vitro experiments demonstrated that overexpression of RNF112 repressed cell viability, promoted cell cycle arrest and apoptosis, while knocking down RNF112 had the opposite function. The tumor formation results in nude mice supported that RNF112 overexpression exerted anti-tumor effects by inhibiting cell growth and promoting cell apoptosis. Mechanistically, Krüppel-like factor 4 (KLF4) acted as an upstream regulator of RNF112 by mediating its transcription. Furthermore, we explored the downstream mechanism of RNF112 and discovered that it promoted ubiquitination and degradation of oncoprotein N-alpha-acetyltransferase 40 (NAA40) through ubiquitin ligase activity. In addition, overexpression of NAA40 eliminated the effect of RNF112 overexpression on CRC tumorigenesis.

In summary, our findings confirm that RNF112, whose transcription is regulated by KLF4, inhibits CRC growth through promoting ubiquitin-dependent degradation of NAA40. We have unraveled the mechanism of KLF4-RNF112-NAA40 axis in CRC, which shed light on the therapeutic strategies for this disease.

Cancer immunotherapy has transformed metastatic cancer treatment, yet challenges persist regarding therapeutic efficacy. RECQL4, a RecQ-like helicase, plays a central role in DNA replication and repair as part of the DNA damage response, a pathway implicated in enhancing efficacy of immune checkpoint inhibitor (ICI) therapies. However, its role in patient response to ICI remains unclear.

We analysed whole exome and bulk RNA sequencing data from a pan-cancer cohort of 25 775 patients and cutaneous melanoma cohorts (untreated: n = 471, anti-progressive disease [PD]-1 treated: n = 212). RECQL4 copy number variations and expression levels were assessed for patient outcomes. We performed gene set enrichment analysis to identify RECQL4-dependent signalling pathways and explored the association between RECQL4 levels and immunoscores. We evaluated the interplay of ICI response and RECQL4 expression in melanoma cohorts of 95 responders and 85 non-responders prior to and after ICI-targeted therapy and tested the prognostic power of RECQL4. Finally, we generated genetically engineered RECQL4 variants and conducted comprehensive multi-omic profiling, employing techniques such as liquid chromatography with tandem mass spectrometry, to elucidate mechanistic insights.

We identified RECQL4 as a critical negative regulator of poor prognosis and response to ICI therapy, but also demonstrated its suitability as an independent biomarker in melanoma. High tumour purity and limited signatures of tumour immunogenicity associated with response to anti-PD-1 correlated with high RECQL4 activity. We found alterations in the secretion profile of immune regulatory factors and immune-related pathways robustly suppressed in tumours with high RECQL4 levels, underscoring its crucial role in fostering immune evasion. Mechanistically, we identified RECQL4-mediated regulation of major histocompatibility complex class II molecule expression and uncovered class II major histocompatibility complex transactivator as a mediator bridging this regulation.

Our findings unraveled the pivotal role of RECQL4 in immune modulation and its potential as both a predictive biomarker and therapeutic target for optimising immunotherapeutic strategies across various cancer types.

High RECQL4 expression limits survival and can act as an independent prognostic factor in melanoma patients. RECQL4 has the potential to act as a negative feedback mediator of immune checkpoint-targeted therapy by limiting signatures associated with therapeutic efficacy. RECQL4 favours an immune-evasive phenotype by downregulating major histocompatibility complex class II molecules.

Curcumin has been reported to have anti-hepatocellular carcinoma (HCC) effects, but the underlying mechanism is not well known.

To investigate whether membrane-associated RING-CH 1 (MARCH1) is involved in the curcumin-induced growth suppression in HCC and its underlying molecular mechanism. A few recent patents for curcumin for cancer are also reviewed in this article.

The effect of curcumin on growth inhibition of HCC cells was analyzed through in vitro and in vivo experiments, and the expression levels of MARCH1, Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 signaling molecules were measured in HCC cells and the xenograft tumors in nude mice. Cell transfection with MARCH1 siRNAs or expression plasmid was used to explore the role of MARCH1 in the curcumin-induced growth inhibition of HCC cells.

Curcumin inhibited cell proliferation, promoted apoptosis, and arrested the cell cycle at the G2/M phase in HCC cells with the decrease of Bcl-2, VEGF, cyclin B1, and cyclin D1 expression as well as JAK2 and STAT3 phosphorylation, resulting in the growth suppression of HCC cells. MARCH1 is highly expressed in HCC cells, and its expression was downregulated after curcumin treatment in a dose-dependent manner. The knockdown of MARCH1 by siRNA decreased the phosphorylation levels of JAK2 and STAT3 and inhibited the growth of HCC cells. In contrast, opposite results were observed when HCC cells overexpressed MARCH1. A xenograft tumor model in nude mice also showed that curcumin downregulated MARCH1 expression and decelerated the growth of transplanted HCC with the downregulation of JAK2/STAT3 signaling and functional molecules. The ADC value of MRI analysis showed that curcumin slowed down the progression of HCC.

Our results demonstrated that curcumin may inhibit the activation of JAK2/STAT3 signaling pathway by downregulating MARCH1 expression, resulting in the growth suppression of HCC. MARCH1 may be a novel target of curcumin in HCC treatment.

The Ki-67 labeling index is essential for predicting the prognosis of breast cancer and for diagnosing neuroendocrine and gastrointestinal stromal tumors. However, current manual counting and digital image analysis (DIA)-based methods are limited in terms of accurate estimation. This study aimed to assess and compare the capabilities of different DIA systems for Ki-67 counting using the conventional manual counting method. A total of 239 tissue microarray cores from patients with stomach cancer were immunohistochemically stained for Ki-67 and digitally scanned. For the analysis, we employed three different annotation methods: whole TMA core, box selection of the epithelium, and hand-free selection of the epithelium. We used DIA system of 3DHistech, Roche, aetherAI, and manual counting by the pathologists. The annotation methods showed different Ki-67 positivity but were lower than the pathologist manual counting. The results demonstrate that the Roche system is the preferred method for analyzing the entire TMA, whereas aetherAI outperforms the box selection method. Furthermore, 3DHistech is the most accurate method for hands-free selection of the epithelium. The manual counting results showed good agreement among pathologists, with an average intraclass correlation coefficient of 0.93. These results emphasize the importance of carefully selecting annotation methods to determine Ki-67 positivity. To determine the most suitable method for individual laboratories, multiple approaches should be assessed before implementing a DIA system in routine practice.