This study aimed to assess the clinical outcomes and prognostic factors of patients with synchronous head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC) who underwent simultaneous concurrent chemoradiotherapy (CCRT) and esophagectomy.

Sorafenib, a ferroptosis agonist, is a first-line treatment for advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is limited due to drug resistance, resulting in modest improvements in patient survival. Hence, the present study has been designed to identify critical molecular targets associated with sorafenib resistance and investigate the potential inhibitors in overcoming this therapeutic challenge.

Acquired resistance is unavoidable in lung adenocarcinoma (LUAD) treated with osimertinib, however, the underlying mechanisms remain largely unknown. Here, we report that the long non-coding RNA (lncRNA) APCDD1L-AS1 is upregulated in osimertinib-resistant LUAD tissues and cells and is associated with short survival of osimertinib-resistant LUAD patients. Our data showed that APCDD1L-AS1 upregulation is an independent risk factor for overall survival in patients with osimertinib-resistant LUAD. APCDD1L-AS1 knockdown enhanced osimertinib sensitivity both in vitro and in vivo, whereas APCDD1L-AS1 overexpression promoted osimertinib resistance. Mechanistically, APCDD1L-AS1 accelerates the tricarboxylic acid (TCA) cycle by forming complexes and maintaining the stability of dihydrolipoamide S-succinyltransferase (DLST), which inhibits the ubiquitination and degradation of DLST. Moreover, we demonstrate that hypoxia-inducible factor (HIF)-1α transcriptionally activates APCDD1L-AS1 by binding to the APCDD1L-AS1 promoter region under hypoxic conditions. Overall, our data confirm that APCDD1L-AS1 is upregulated by hypoxia-induced HIF-1α, which drives the TCA cycle by stabilising DLST to further promote osimertinib resistance in LUAD. Our findings provide new insights into the role of HIF-1α/APCDD1L-AS1/DLST axis-related reprogramming of hypoxia and the TCA balance in conferring osimertinib resistance in LUAD and confirm the therapeutic potential for targeting the APCDD1L-AS1.

To evaluate the clinical efficacy of evidence-based Enhanced Recovery After Surgery (ERAS) nursing protocols in patients undergoing robotic-assisted partial nephrectomy using the Da Vinci system.

To explore the clinical data and CT findings associated with outcomes prognosis of patients with sarcomatoid non-small cell lung cancer (s-NSCLC).

The incidence of local recurrence remains noteworthy among lung cancer patients treated with stereotactic body radiation therapy (SBRT). The aim of the study is to identify the risk factors and develop a nomogram for local control (LC) prediction.

Effective management of patients undergoing treatment with lutetium-177 labeled DOTA-ibandronic acid (177Lu-DOTA-IBA) necessitates the identification of radiological response biomarkers that can mitigate disease progression and facilitate patient stratification for subsequent treatment decisions. This study aims to evaluate the metabolic tumor volume (MTV) as a quantitative measure of radiological response in bone metastases using gallium-68 labeled DOTA-ibandronic acid (68Ga-DOTA-IBA) PET/CT.

The number of people with HIV (PWH) in Africa is rising due to population growth and antiretroviral therapy (ART) availability, with diffuse large B-cell lymphoma (DLBCL) a major cause of mortality. HIV and ART alter DLBCL tumor biology, but few studies of DLBCL include PWH or African patients, limiting translation of emerging treatment strategies. Here, we performed whole exome sequencing of 48 tumors (40 HIV-positive [HIV+]) with paired germline of DLBCL patients from Malawi and South Africa. HIV + DLBCL tumors had distinct mutations depending on ART exposure, and there were several recurrent deleterious variants, with ANKRD11 mutations being prognostic. One tumor from each cohort had high tumor mutational burden and microsatellite-instability with PMS2 and ARID1A mutation. These findings suggest shared genomic characteristics among HIV + DLBCL in Africa, offering opportunities for tailored biomarkers and therapeutic targets for this underserved population.

Immunotherapy has made a breakthrough in triple negative breast cancer (TNBC). The aim of this study is to investigate the specific role and regulatory mechanism of 3-oxoacid CoA-transferase 1 (OXCT1) in influencing TNBC growth and immune escape induced by aerobic glycolysis. OXCT1-induced enhancement of TNBC cell proliferation and PD-L1 expression is reversed by 2-DG. After interference with OXCT1 in TNBC patient-derived organoids (PDOs), tumor cell proliferation and lactic acid secretion are attenuated, and T-cell killing is enhanced. OXCT1 correlates with phosphoglycerate kinase 1 (PGK1) protein expression in clinical TNBC samples. In vitro overexpression of OXCT1 has no significant effect on PGK1 mRNA expression, but increases the succinylation level of PGK1 K146 and its protein stability, while decreasing its ubiquitination. The H4K20me1 level in the OXCT1 promoter region is increased in TNBC tissues, and in vitro lysine methyltransferase 5 A (KMT5A) overexpression increases the H4K20me1 level in the OXCT1 promoter region to promote OXCT1 expression. In conclusion, OXCT1 interference reverses the KMT5A-induced enhancement of TNBC cell viability, proliferation, and PD-L1 expression. KMT5A promotes OXCT1 expression through histone methylation, and OXCT1 increases PGK1 protein stability through succinylation modification, thereby promoting aerobic glycolysis and immune escape in TNBC.

Breast cancer remains a leading cause of cancer-related mortality in women worldwide. Hypericin (HYP) is a natural photosensitizer and hypericin-mediated photodynamic therapy (HYP-PDT) has shown promise in cancer treatment. PARP inhibitors like Olaparib are effective in BRCA1-mutant breast cancers but have limited efficacy in BRCA1 wild-type breast cancer. This study investigated the synergistic antitumor effects of HYP-PDT combined with Olaparib in BRCA1 wild-type breast cancer cells. MCF-7 cell line, a well-characterized and commonly utilized model for BRCA1 wild-type breast cancer was employed in this study. We evaluated the cellular responses to varying concentrations of HYP and Olaparib followed by PDT, through assessments of reactive oxygen species (ROS) production, DNA damage signaling pathways, apoptosis, cell cycle distribution, and migration capabilities. Results demonstrated that both HYP-PDT and Olaparib individually inhibited cell proliferation in a dose-dependent manner, with their combination synergistically enhancing antitumor efficacy. HYP-PDT induced intracellular ROS generation and DNA damage, which were further amplified by Olaparib. The combination treatment modulated the ATM/p53/RAD51 signaling pathway, leading to apoptosis and G2/M phase cell cycle arrest through the regulation of mitochondrial apoptosis-associated proteins and cell cycle checkpoint proteins. Furthermore, the combination treatment inhibited epithelial-to-mesenchymal transition (EMT), thereby reducing MCF-7 cell migratory capability. These findings highlight the potential of combining HYP-PDT with Olaparib as a promising strategy to overcome the limitations of monotherapies and provide a novel approach for treating BRCA1 wild-type breast cancer.

Colorectal cancer (CRC) poses a formidable challenge to global health, necessitating the quest for novel biomarkers to improve therapeutic strategies. This study explores ABCE1 (ATP-binding cassette subfamily E member 1) as a potential biomarker for CRC and delves into its intricate molecular mechanisms. Through integrated bioinformatic analyses, this study underscores the significant oncogenic role of ABCE1 in CRC, opening new avenues for promising therapeutic interventions. Deletion of ABCE1 reduced cell growth, abrogated aerobic glycolysis, and promoted apoptosis in HT-29 and HCT-116 cells. Further validation through experimentation with irinotecan revealed compelling outcomes, including diminished cell growth, induces G1 phase cell cycle arrest, and promotes apoptosis in HCT-116 and HT-29 colorectal cancer cells. ABCE1 KO with irinotecan combined treatment significantly increased the inhibition of cell proliferation and aerobic glycolysis in CRC cells, accentuating the multifaceted role of ABCE1 in CRC progression. Moreover, this work also demonstrated the complex relationship between ABCE1 and the p53 signalling pathway, which was confirmed in experimental assays. These assays also revealed that deletion of ABCE1 with irinotecan might regulate G1 phase cell cycle arrest, inhibit metabolic regulation, and activate the p53 pathway to induce apoptosis in HCT-116 cells. Molecular docking analyses further supported these findings, revealing the strong binding affinity of irinotecan for targets of the p53 signalling cascade. Collectively, these comprehensive insights support the potential therapeutic efficacy of targeting ABCE1 in CRC treatment strategies. Overall, the findings from this study underscore the importance of ABCE1 as a potential biomarker in CRC and illuminate its complex molecular mechanisms. The demonstrated effectiveness of ABCE1 inhibition, particularly through irinotecan, coupled with its interplay with crucial signalling pathways such as p53, highlights its potential as a promising therapeutic option for colorectal cancer treatment.

The tumor microenvironment (TME) is a crucial mediator of tumor progression and treatment response. Here, we compare the immune microenvironments of HBV and non-HBV hepatocellular carcinoma (HCC) and investigate the reason for the persistence of HBV infection in the liver. We combine the Viral-Track method with scRNA sequencing and profile the transcriptomes of 70,056 cells from HBV and non-HBV-HCC patients. In addition to hepatocytes and macrophages, HBV transcripts were also detected in T and B cells using the Viral-Track method, confirming the lymphotropic nature of HBV in scRNA-sequencing data for the first time, to the best of our knowledge. HBV-HCC tumors have reduced levels of NK cells, macrophages, DCs, and increased malignant hepatocytes compared with those in non-HBV HCC. Notably, we report the enrichment of metallothioneins (MTs), particularly MT1G, in HBV-related HCC TAMs, which is associated with a worse prognosis. HBV-tumor-infiltrated CD8⁺ T cells exhibit a dysfunctional cytotoxic phenotype, characterized by upregulated MDK and CTLA4 expression and reduced IFN-γ production, unlike the non-HBV-HCC. Additionally, HBV-HCC exhibits immunosuppressive ligand-receptor interactions, whereas non-HBV-HCC exhibits antitumor ligand-receptor interactions. Our deeper understanding of the HBV-HCC ecosystem using Viral-Track integrated scRNA sequencing provides insights into immune evasion mechanisms and HBV lymphotropism associated with viral persistence.

The results from DESTINY-Breast 04 and the subsequent introduction of trastuzumab-deruxtecan as a potential treatement for HER2-low breast cancer necessitated the reevaluation of HER2 scoring. The discordance in HER2 scoring reported in previous studies led us to initiate a regional ring study and to assess our data. This ring study involved 61 breast pathology experts from four countries across the Balkans region. The research comprised 20 samples, including biopsies and surgical specimens, sourced from the archives of one institution. We amassed a total of 1220 scores. The findings indicate a significant degree of interobserver agreement among pathologists in scoring individual categories (scores 0, 1+, 2+, and 3+), with even higher agreement observed when scores 1 + and 2 + were combined into a single, HER2-low category. The findings of this study indicate that adequate education, awareness regarding the therapeutic significance of the HER2-low category, and expertise in breast pathology facilitate the accurate identification of HER2-low breast cancers. These findings will promote ongoing training in breast pathology within the region and will provide a reference for subsequent research efforts.

Anemia is known to correlate with tumor progression, which can result in narrowing of the airways. Although therapeutic bronchoscopy effectively manages central airway stenosis, restenosis frequently occurs. This study aimed to examine the relationship between hemoglobin levels and the risk of malignant central airway (MCA) restenosis in patients with lung squamous cell carcinoma (LUSC) undergoing interventional bronchoscopy. Data were collected from 196 LUSC patients with MCA stenosis who underwent therapeutic bronchoscopy between April 2014 and November 2023 at a tertiary hospital. Rates of MCA restenosis at 30 and 60 days post-therapeutic bronchoscopy were assessed. Piecewise linear regression, Cox regression analyses, and survival analysis were used to evaluate the impact of hemoglobin levels on restenosis risk, adjusting for potential confounders. The 30-day and 60-day rates of MCA restenosis were 27.0% and 56.1%, respectively. Hemoglobin levels, categorized into four groups, showed a significant trend of increased restenosis risk with decreasing levels (P for trend < 0.01), particularly pronounced in patients with hemoglobin levels < 120 g/L. Compared to those with hemoglobin ≥ 120 g/L, adjusted hazard ratios (aHRs) for restenosis were elevated at both 30-day (aHR 2.21, 95% CI 1.17-4.16) and 60-day (aHR 1.85, 95% CI 1.20-2.86). Interaction analysis indicated higher restenosis risk trends among patients ≤ 60 years old and those who received stent implantation. Anemia is linked to a heightened risk of MCA restenosis in patients with LUSC after interventional bronchoscopy, especially noticeable among younger patients. Moreover, stent implantation did not mitigate the risk of MCA restenosis within 2 months.

Insulin resistance (IR) has been shown to be correlated with increased cancer risk. Nevertheless, few studies have explored the relationship between IR and small cell lung cancer (SCLC). The triglyceride glucose (TyG) index, TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for IR (METS-IR) are recognized as reliable indicators for evaluating IR. In our investigation, 235 patients with pathologically confirmed SCLC were enrolled, along with 235 healthy individuals matched for age and sex as controls. Univariate binary logistic regression analyses revealed a significant association between elevated levels of all IR surrogates and the risk of SCLC. This finding persisted even after adjusting for other established high-risk factors. Concurrently, a progressive increase in the incidence of SCLC was observed across the tertiles of the TyG index, TyG-BMI, TG/HDL-C, and METS-IR. Furthermore, this article is the first to conclude that the four IR surrogates did not significantly differ across different stages of SCLC, implying that IR might exert a greater influence on the onset than on the progression of SCLC. Among these factors, TG/HDL-C has emerged as the most effective predictor of SCLC. Consequently, lifestyle modifications and pharmacological interventions should be actively pursued in individuals with IR to mitigate their risk of developing SCLC. Our findings also offer a promising avenue for the identification of novel therapeutic targets.

Clear cell renal cell carcinoma (ccRCC) is characterized by the accumulation of high quantities of lipids in cytoplasmic lipid droplets. Owing to the tissue heterogeneity of ccRCC, adjacent biopsies from a tumor can diverge substantially in molecular characteristics. To elucidate metabolic alterations leading to extensive lipidomic changes in grade 2 human nephrectomies, we applied a dual lipidome-transcriptome analytical procedure that allows performing correlational studies of the two datasets. Linked to the mean 100 fold increase of esterified cholesterol (ChE) in ccRCC we found multiple significant correlations between ChE and the main membrane lipids that might be mediated by an increased capacity for lipid hydrolysis linked to lysosomes and the endoplasmic reticulum.Our results suggest that the accumulation of ChE from extracellular sources might be a determinant metabolic flux in low-grade ccRCC. ChE mobilization by non-canonical hydrolytic systems might confer increased metabolic flexibility to obtain free cholesterol and fatty acids. Based on correlations between lipidome and lipometabolic transcriptome, this study provides new perspectives for evaluating pharmacological lipid management as a future therapeutic approach for low-grade ccRCC treatment.

Prostate cancer (PCa), a common urinary malignancy, is the leading cause of mortality and morbidity among men worldwide. Curcuma amada extract has demonstrated antitumor properties in preclinical models of various cancers, however, its mechanisms against prostate cancer remain unclear. The current study aims to investigate the underlying mechanism of C. amada rhizome extract (CARE) in treating PCa through network pharmacology, bioinformatics analysis and in-vitro experiments. UHPLC-QTOF-HRMS/MS detected 16 phytoconstituents in C. amada, with 15 constituents passing drug-likeness criteria. Public databases identified 1,311 CARE and 473 PCa related targets, with 59 overlapping targets. PPI analysis revealed P53, CTNNB1, EGFR, AKT1, ESR1, HIF1A, CCND1, PIK3CA, and BCL2 as hub targets. Further,4-hydroxycinnamic acid, 13-hydroxylabda-8(17),14-dien-18-oic acid, labda-8(17),12-diene-15,16-dial, zederone, zedoarondiol, zerumin A and caffeic acid were identified as core compounds with high degree values. GO and KEGG analysis identified targets primarily associated with apoptosis and PI3K-AKT signalling pathway. Molecular docking confirmed good binding potential of core compounds with key hub targets, while molecular dynamics (MD) simulation validated the stability of these interactions with minimal fluctuations throughout the simulation. Additionally, mRNA expression levels, immune infiltration and genetic alteration of the hub targets were analyzed. CARE significantly inhibited the proliferation of PC-3 cells, induced apoptosis, and caused G2/M phase arrest. In addition, qRT-PCR analysis revealed that CARE was able to suppress mRNA expression of genes involved in the PI3K-AKT signalling pathway. Thus, the study highlights the underlying mechanism of CARE as a promising treatment option for prostate cancer.

Neoadjuvant therapy (NAT) has become increasingly common in pancreatic ductal adenocarcinoma (PDAC). Still, PDAC remains one of the deadliest cancers and clinically useful biomarkers are needed. Matrix metalloproteinase 8 (MMP-8) has previously been identified as a potential biomarker for PDAC patients undergoing up-front surgery. We investigated the prognostic significance of MMP-8 in PDAC patients treated with NAT and evaluated the association of MMP-8 expression to treatment response. We studied MMP-8 expression using immunohistochemistry in a tissue microarray with samples from 115 NAT and 144 up-front surgery patients. We examined NAT response from resection specimens by estimating the amount of residual tumour cells. We analysed the association of MMP-8 immunoexpression with survival and treatment response. High MMP-8 immunoexpression associated with better survival among patients with strong NAT response (HR 0.22, CI95% 0.05-0.86, p = 0.030). This association was not observed among patients with poor NAT response nor in the overall NAT group. Furthermore, MMP-8 expression did not differ significantly between the NAT and up-front surgery groups. In conclusion, the MMP-8 tissue expression after NAT is a protective biomarker in PDAC patients with strong NAT response but fails to associate with favourable prognosis in patients with poor NAT response.

NADPH oxidase 4 (NOX4) is a key regulator of intracellular reactive oxygen species (ROS) and plays a critical role in tumorigenesis and cancer progression. It contributes to cancer cell transformation, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). To elucidate the molecular mechanisms underlying NOX4-mediated tumorigenesis, we performed a comprehensive pan-cancer bioinformatics analysis, integrating data from The Cancer Genome Atlas (TCGA), and validated our findings with in vitro experiments. We systematically analyzed NOX4 expression patterns across various cancer types and explored the correlations between NOX4 expression and patient survival, immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). In vitro assays, including Wound healing, Transwell, and CCK-8 assays, were conducted to validate the biological functions of NOX4 in breast cancer cells. Pan-cancer analysis revealed that NOX4 is significantly upregulated in various cancers, including breast cancer. Elevated NOX4 expression is associated with poor patient prognosis, immune cell infiltration, TMB, and MSI. Functional experiments confirmed that downregulation of NOX4 can inhibit the proliferation and metastasis of breast cancer cells. Our pan-cancer analysis provides valuable insights into the role of NOX4 in tumorigenesis. These results highlight NOX4 as a promising biomarker for prognosis and a potential therapeutic target for anti-tumor treatments across multiple cancer types.

The novel protein acylation modifications have played a vital role in protein post-translational modifications. However, the functions and effects of the protein acylation modifications in lung adenocarcinoma are still uncertain. Currently, there is still a lack of global identification of acylation modifications in lung adenocarcinoma cells. Therefore, in this study, we detected 10 currently known acylation modifications in lung adenocarcinoma cells by Western blot. We found that the abundance of lysine lactylation (Kla), crotonylation (Kcr) and succinylation (Ksu) is likely higher. Subsequently, we identified the above three modifications together with phosphorylation by global mass spectrometry-based proteomics in lung adenocarcinoma cells. As a result, we got 3110 Kla sites in 1220 lactylated proteins, 16,653 Kcr sites in 4137 crotonylated proteins, 4475 Ksu sites in 1221 succinylated proteins, and 15,254 phosphorylation sites in 4139 phosphorylated proteins. Recent studies have highlighted the role of lactylation modifications in tumor cell resistance to radiation and chemotherapy by affecting homologous recombination. Our subsequent investigations have shown that key factors in the nonhomologous end joining (NHEJ) pathway, such as Ku70 and Ku80, undergo lactylation modifications. Inhibition of lactylation impairs the efficiency of nonhomologous end joining. In conclusion, our results provide a proteome-wide database to study Kla, Kcr and Ksu and phosphorylation in lung adenocarcinoma, and new insights into the role of acylation modification in lung adenocarcinoma.