Relapsed/Refractory (R/R) diffuse large B-cell lymphoma (DLBCL) represents a subgroup with a high incidence and dismal prognosis. Currently, there is a lack of robust models for predicting R/R DLBCL. Therefore, we conducted a retrospective study to identify key determinants to be incorporated into a novel nomogram to enhance the identification of DLBCL patients at elevated risk of refractoriness/recurrence.

We included 293 newly-diagnosed DLBCL patients from Harbin Medical University Cancer Hospital, collected from 2008-2017. Patients were randomly divided into a training cohort (n = 206) and a validation cohort (n = 87) at a 7:3 ratio. The training cohort underwent univariable analysis to select variables for a binary logistic regression model. These variables were also prioritized using a random forest algorithm. The developed nomogram was evaluated with the receiver-operator characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) for its clinical utility.

Univariable analysis pinpointed several factors significantly associated with refractoriness/recurrence, including pathological subtype, lactate dehydrogenase (LDH), International Prognostic Index (IPI), treatment, absolute lymphocyte count (ALC), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI). Binary logistic regression highlighted pathological subtype, LDH, treatment, and ALC as key predictors, which were incorporated into the nomogram. The nomogram showed excellent calibration and accuracy in both cohorts, and comparative DCA and ROC analysis demonstrated its superior net benefit and area under the curve (AUC) compared to traditional indexes like IPI, R-IPI, and NCCN-IPI.

This nomogram serves as a valuable tool for predicting the likelihood of refractoriness or recurrence in DLBCL patients.

Recent studies on head and neck squamous cell carcinoma (HNSCC) tumorigenesis have revealed several dysregulated molecular pathways. The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in HNSCC, making it an attractive target for therapies. PHT-427 is a dual inhibitor of PI3K and the mammalian target of AKT/PDK1. This study evaluates the anticancer efficacy of the inhibitor PHT-427 loaded into polymeric nanoparticles (NP) based on α-TOS (NP-427) administered by intratumoral injection into a hypopharyngeal squamous cell carcinoma (FaDu cells) heterotopic xenograft mouse model. The nanocarrier system, based on block copolymers of N-vinylpyrrolidone (VP) and a methacrylic derivative of α-TOS (MTOS), was synthesized, and PHT-427 was loaded into the delivery system. First, we evaluated the effect of NP-427 on tumor growth by measuring tumor volume, mouse weight, survival, and the development of tumor ulceration and necrosis. In addition, we measured PI3KCA/AKT/PDK1 gene expression, PI3KCA/AKT/PDK1 protein levels, Epidermal Growth Factor Receptor (EGFR), and angiogenesis in the tumor tissue. PHT-427 encapsulation increased drug efficacy and safety, as demonstrated by decreased tumor volume, reduced PI3K/AKT/PDK1 pathway expression, and improved antitumor activity and necrosis induction in the mouse xenograft model. EGFR and angiogenesis marker (Factor VIII) expression were significantly lower in the NP-427 group compared to other experimental groups. Administration of encapsulated PHT-427 at the tumor sites proves promising for HNSCC therapy.

Depressive symptoms are prevalent among parents of children with cancer, significantly impacting their well-being. Problem-solving skills, strongly linked to depressive symptoms, offer a promising avenue for intervention. This study aimed to identify latent profiles of parental problem-solving skills and evaluate differences in depressive symptoms across these profiles.

A cross-sectional survey was conducted with 318 parents of children with cancer in mainland China. Self-reported data on demographics, problem-solving skills, and depressive symptoms were collected. Latent profile analysis was used to classify parental problem-solving skills into distinct profiles, and multiple logistic regression identified predictors of profile membership.

Three profiles of problem-solving skills were identified: (1) problem-oriented and constructive (n ​= ​94, 29.6%), (2) impulsivity-oriented and irrational (n ​= ​76, 23.9%), and (3) emotion-oriented and avoidant (n ​= ​148, 46.5%). Parents with higher education, greater income, and urban residency were more likely to belong to the problem-oriented group. Fathers predominated in the impulsivity-oriented group, while mothers were more represented in the emotion-oriented group. Significant differences in depressive symptoms were observed across profiles, with the problem-oriented group reporting the lowest levels.

This study highlights the heterogeneity of problem-solving skills among parents of children with cancer and underscores the need for tailored interventions. Addressing specific characteristics of each profile can improve parental well-being and provide targeted support for this vulnerable population.

ChiCTR2300071828.

Advances in artificial intelligence offer the promise of automated analysis of optical coherence tomography (OCT) scans to detect ocular complications from anticancer drug therapy. To explore how such AI outputs are interpreted in clinical settings, we conducted a survey-based interview study with 27 clinicians -comprising 10 ophthalmic specialists, 10 ophthalmic practitioners, and 7 oncologists. Participants were first introduced to core AI concepts and realistic clinical scenarios, then asked to assess AI-generated OCT analyses using standardized Likert-scale questions, allowing us to gauge their understanding, trust, and readiness to integrate AI into practice.

We developed a questionnaire through literature review and consultations with ophthalmologists, computer scientists, and AI researchers. A single investigator interviewed 27 clinicians across three specialties and transcribed their responses. Data were summarized as medians (ranges) and compared with Mann-Whitney U tests (α = 0.05).

We noted important differences in the impact of various explainability methods on trust, depending on the clinical or AI scenario nature and the staff expertise. Explanations of AI outputs increased trust in the AI algorithm when outputs simply reflected ground truth expert opinion. When clinical scenarios were complex with incorrect AI outcomes, a mixed response to explainability led to correctly reduced trust in experienced clinicians but mixed feedback amongst less experienced clinicians. All clinicians had a general consensus on lack of current knowledge in interacting with AI and desire more training.

Clinicians' trust in AI algorithms are affected by explainability methods and factors, including AI's performance, personal judgments and clinical experience. The development of clinical AI systems should consider the above and these responses ideally be factored into real-world assessments. Use of this study's findings could help improve the real world validity of medical AI systems by enhancing the human-computer interactions, with preferred explainability techniques tailored to specific situations.

The tumor suppressor protein p53 plays a crucial role in the pathogenesis of breast cancer; however, its function is often compromised due to MDM2 overexpression or mutations in the p53 gene, which occurs in approximately 30-35 % of breast cancer cases. Piperine, a natural bioactive compound, has shown potential in inhibiting breast cancer cell growth by upregulating p53 expression. However, its clinical application is hindered by poor bioavailability, potential toxicity, and the risk of undesirable drug interactions. In the present study, a novel derivative of Piperine, YL-1-9, was synthesized and evaluated for its anticancer activity against breast cancer. YL-1-9, a bicyclic amide derivative of Piperine, was evaluated for antitumor effects both in vitro and in vivo using MTT assays and the chick embryo chorioallantoic membrane (CAM) model. Further investigations into its effects on breast cancer cell clonogenicity, adhesion, invasion, and migration were conducted through colony formation assays, EdU assays, cell adhesion and invasion studies, and wound healing experiments. Western blot analysis was performed to elucidate the effects of YL-1-9 on the cell cycle and apoptosis, which were further validated using YO-PRO-1 and propidium iodide dual staining. YL-1-9 significantly inhibited breast cancer cell proliferation, adhesion, invasion, and migration, while inducing cell cycle arrest and promoting apoptosis. Mechanistically, YL-1-9 downregulated critical proteins in the CDK4/6-cyclin D-Rb-E2F pathway and the Caspase 3/Bax/Bcl-2 apoptosis signaling pathway. These findings position YL-1-9 as a promising candidate for breast cancer therapy; however, further clinical studies are necessary to fully assess its therapeutic potential.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited diagnostic biomarkers. Carbohydrate antigen 19-9 (CA19-9) is a widely used clinical biomarker and is generally considered to correlate with PDAC malignancy. However, the relationship between CA19-9 expression levels and tumor aggressiveness remains underexplored. In this study, we report a biphasic relationship between CA19-9 expression levels and PDAC malignancy, where both negative (<5 U/mL) and high (>37 U/mL) CA19-9 levels are associated with increased tumor aggressiveness. We defined CA19-9 negative PDAC as tumors that lack CA19-9 expression intracellulary, on the cell membrane, and in secreted form. In PDAC cell lines and patient-derived organoids, CA19-9 negativity, confirmed by immunofluorescence, flow cytometry and ELISA, correlated with more aggressive behaviors. In PDAC patients, tumors from those with serum CA19-9 levels below 5 U/mL exhibited stronger metabolically activity, more immunosuppressive tumor microenvironment, and worse survival than CA19-9 positive tumors, with over 90 % showing absent CA19-9 expression by immunohistochemistry (IHC). Glycoproteomics profiling identified CD44 as a highly expressed biomarker in CA19-9 negative PDAC. Elevated CD44 expression effectively distinguished CA19-9 negative PDAC from both CA19-9 positive PDAC and CA19-9 negative benign pancreatic diseases, suggesting its potential as a diagnostic tool. Furthermore, we developed a radionuclide-labeled CD44 antibody 89Zr-1M2E3, which specifically recognized CA19-9 negative PDAC tumors in preclinical models using PET-CT imaging. These findings highlight CD44 as a promising biomarker and therapeutic target for diagnosing and treating CA19-9 negative PDAC.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide, characterized by a dismal prognosis and elusive therapeutic targets. Dysregulated cholesterol metabolism is a critical hallmark of cancer cells, facilitating tumor progression. Here, we used whole genome sequencing data from several ESCC cohorts to identify the important role of squalene epoxidase (SQLE) in promoting ESCC tumorigenesis and metastasis. Specifically, our findings highlight the significance of 2,3-oxidosqualene, an intermediate metabolite of cholesterol biosynthesis, synthesized by SQLE and metabolized by lanosterol synthase (LSS), as a key regulator of ESCC progression. Mechanistically, the interaction between 2,3-oxidosqualene and vinculin enhances the nuclear accumulation of Yes-associated protein 1 (YAP), thereby increasing YAP/TEAD-dependent gene expression and accelerating both tumor growth and metastasis. In a 4-nitroquinoline 1-oxide (4-NQO)-induced ESCC mouse model, overexpression of Sqle resulted in accelerated tumorigenesis compared to wild-type controls, highlighting the pivotal role of SQLE in vivo. Furthermore, elevated SQLE expression in ESCC patients correlates with a poorer prognoses, suggesting potential therapeutic avenues for treatment. In conclusion, our study elucidates the oncogenic function of 2,3-oxidosqualene as a naturally occurring metabolite and proposes modulation of its levels as a promising therapeutic strategy for ESCC.

Dysphagia is one of the most serious adverse events in the treatment of head and neck cancer. This cross-sectional study aimed to assess pharyngeal residue, and penetration/aspiration in oropharyngeal cancer patients (OPC) after radiotherapy using flexible endoscopic evaluation of swallowing (FEES).

A total of 35 OPC patients who had received radio-(chemo) therapy (R(C)T), including 8 patients with primary R(C)T), were included and examined by FEES to determine the swallowing status and were asked to indicate their swallowing ability on a visual scale to reflect the problem perceived by the patient. During FEES the patients were given three standardized bolus consistencies and four test pills. Penetration, aspiration, and residue were evaluated and classified.

Relevant dysphagia was present in 23/35 (66%) patients. Almost half of all patients (15/35) showed aspiration (53% (8/15) silent). Residue occurred in 91% but without correlation to aspiration. A significant association between dysphagia and impaired pill swallowing was found (P = .003) occurring in 20 of 35 patients. Even in patients with small tumors and without prior surgery severe dysphagia was found.

Severe dysphagia is frequent after R(C)T affecting more than half of the patients with OPC. The frequent impaired pill swallowing ability should be considered Therefore, regular dysphagia diagnostics in the follow-up setting are advisable to initiate appropriate treatment and raise patients' quality of life, prevent aspiration pneumonia, and improve overall outcomes after tumor therapy.

Phototherapy is a treatment method that uses the characteristics of different bands of light to treat diseases. Tumor immunotherapy, on the other hand, treats tumors by regulating the body's immune system. The combination of phototherapy and immunotherapy can significantly enhance the treatment of melanoma. In this study, we prepared and characterized INEs, a novel ethosome composed of the photosensitizer IR251 and the Indoleamine-2, 3-dioxygenase (IDO) inhibitor NLG919. INEs demonstrated excellent phototherapeutic properties, strong phototoxicity, and a notable ability to inhibit IDO. Under 808 nm laser irradiation, INEs effectively induced immunogenic cell death (ICD) in melanoma cells. In vivo experiments demonstrated that INEs injection into primary tumors triggered ICD, promoted maturation of DC cells, and activated naive T cells, leading to the production of effector T cells (specifically CD4+ and CD8+ T cells) that targeted and killed tumor cells. Both primary and distant tumors were treated simultaneously with favorable biosafety. In conclusion, INEs represent a promising strategy for melanoma treatment by a combination of phototherapy and immunotherapy with high safety. This study provides new insights and a theoretical basis for the clinical treatment of melanoma.

Liver homeostasis is coordinated by crosstalk between resident and infiltrating inflammatory cells. Liver disease creates a dynamic inflammatory microenvironment characterized by aberrant metabolism and continuous hepatic regeneration, making it an important risk factor for hepatocellular carcinoma (HCC) as well as liver failure. Recent studies have revealed a critical heterogeneous population of myeloid-derived suppressor cells (MDSCs), which influence liver disease progression and malignancy by dynamically regulating the immune microenvironment. MDSCs play an important role in preventing excessive immune responses in the liver. However, MDSCs are also associated with the promotion of liver injury and liver cancer progression. The plasticity of MDSCs in liver disease is a unique challenge for therapeutic intervention strategies and requires a deeper understanding of the underlying mechanisms. Here, we review the role of MDSCs in the establishment and progression of liver disease and highlight the evidence for MDSCs as a priority target for current and future therapeutic strategies. We explore the fate of MDSCs from hepatitis to liver cancer, providing recent insights into potential targets for clinical intervention.

Mori Folium, the leaf of Morus alba L., is a traditional Chinese medicine (TCM) known for its diverse pharmacological activities, including anti-inflammatory and immunomodulatory effects. While the Morus alba itself has been reported to contain various bioactive compounds with anticancer properties, the anticancer activity of Mori Folium and its underlying mechanisms remain insufficiently understood.

This study aimed to investigate the effects of Mori Folium ethanol extracts (MFEE) on gastric cancer (GC) and to elucidate its underlying mechanisms.

To investigate the anti-GC properties of MFEE, CCK-8, colony formation, EdU, flow cytometry, and soft agar, scratch, and transwell assays were employed. Western blot was employed to analyze the expression of ferroptotic proteins, while ferroptotic cellular events were also assessed, including iron accumulation, GSH levels, reactive oxygen species (ROS) production, mitochondrial changes, and lipid peroxidation. The chemical profile of MFEE was characterized using a UPLC-ESI-MS/MS system. Additionally, network pharmacology analysis was performed to investigate the potential anti-GC mechanisms of MFEE. Finally, the in vivo anti-cancer effects of MFEE were evaluated using a subcutaneous mouse model, with hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining to assess histopathological and molecular changes.

This study demonstrated that MFEE suppresses GC cell proliferation, blocks the G1-S cell cycle transition, and inhibits migration and invasion by promoting Fe²⁺ accumulation, increasing MDA levels and ROS, depleting GSH, and downregulating the expression of xCT and GPX4, thereby inducing ferroptosis. Chemical analysis identified 1596 phytochemicals, including 35 bioactive compounds. The induction of ferroptosis by MFEE was associated with the inhibition of the PI3K/AKT signaling pathway, modulating the AKT/GSK3β/NRF2 axis. Activation of AKT by SC79 was found to mitigate MF-induced ferroptosis. Notably, MFEE enhanced the chemosensitivity of GC cells to cisplatin, potentially through ferroptosis induction.

This study revealed that MFEE induces ferroptosis in GC cells by modulating the PI3K/AKT signaling pathway, enhancing chemosensitivity to cisplatin, and providing a potential therapeutic strategy for GC.

To explore the role of GFPT2 in the sensitivity of STK11/KRAS lung cancer cells to cisplatin chemotherapy, and its underlying mechanism.

A549 and H460 cells were used to analyze the effect of GFPT2 on cisplatin chemotherapy sensitivity, as both carry KRAS mutations and H460 has LKB1 inactivation mutations, meeting the requirements of a KRAS/LKB1 co mutant tumor model. The levels of UDP-GlcNAc, OGT, OGA, and O-GlcNAc in the HBP pathway were also determined. To verify the potential role of HBP, we added OGT inhibitors. In vivo, we constructed a nude mouse model bearing A549 tumor to further validate the results of in vitro cell experiments.

GFPT2 silencing can significantly inhibit cell proliferation, invasion, and migration, promote cell apoptosis, and enhance the effect of cisplatin (p < 0.05). After OSMI-1 processing, GFPT2 enhances O-GlcNAc modification levels via the OGT-mediated HBP, thereby decreasing the sensitivity of STK11/KRAS mutant cells to cisplatin chemotherapy. In addition, GFPT2 silencing enhances the chemotherapy sensitivity of cisplatin and inhibits tumor growth, while overexpression of GFPT2 weakens this effect (p < 0.05). The above results provide new targets and combination therapy options for the clinical treatment of KRAS/LKB1 mutant lung cancer.

Our study found that inhibiting GFPT2 can enhance the chemotherapy sensitivity of cisplatin to STK11/KRAS/LKB1 mutant NSCLCs cells through the OGT mediated HBP pathway, filling a key gap in the chemotherapy resistance mechanism of KRAS/LKB1 mutant lung cancer.

Follistatin-like 3 (FSTL3) is a glycoprotein known to promote tumor growth, invasion, and angiogenesis in various cancers. However, its role in Colorectal Cancer (CRC), particularly concerning the hypoxia-inducible factor 1α (HIF1α) signaling pathway, remains unclear. The HIF1α pathway is critical in CRC progression, enabling tumor cells to adapt to hypoxia through angiogenesis, Epithelial-Mesenchymal Transition (EMT), and metabolic reprogramming. Analysis of The Cancer Genome Atlas (TCGA) and GSE39582 datasets revealed that FSTL3 is significantly upregulated in CRC tissues and correlates with poor Overall Survival (OS), Progression-Free Survival (PFS), and aggressive features such as venous, lymphatic, and perineural invasion. In vitro experiments demonstrated that FSTL3 overexpression in HCT15 and HCT116 cells promoted proliferation, migration, and cell cycle progression, whereas knockdown in LOVO and Caco2 cells suppressed these processes and induced apoptosis. Transcriptome sequencing and western blot analysis indicated that FSTL3 activated the HIF1α pathway by upregulating HIF1α, ANGPT2, and HK3, which are key regulators of angiogenesis and glycolysis. Importantly, treatment with the HIF1α inhibitor KC7F2 reversed the oncogenic effects of FSTL3 overexpression both in vitro and in vivo. In xenograft and tail vein metastasis models, KC7F2 suppressed tumor growth, reduced pulmonary metastasis, and restored lung tissue integrity, further downregulating FSTL3 and HIF1α expression. These findings suggest that FSTL3 promotes CRC progression via the HIF1α pathway and highlight its potential as a prognostic biomarker and therapeutic target for CRC treatment.

Colorectal cancer (CRC) ranks third for morbidity and second for mortality among all digestive malignant tumors worldwide, but its pathogenesis remains not entirely clear. Bioinformatic analyses were performed to find out important biomarkers for CRC. For validation, reverse transcription-quantitative PCR, western blotting, and immunohistochemistry were performed. Then, cell transfection, gain- and loss-of-function assays, immunofluorescence, cell line RNA-sequencing and analyses, and in vivo tumorigenesis assay were also performed to further explore the mechanism. We prioritized phosphoserine aminotransferase 1 (PSAT1) as an important biomarker in CRC. PSAT1 expression was gradually up-regulated as the CRC disease progresses and may relate to poor prognosis. PSAT1 promoted the malignant behaviors of CRC cells. Although PSAT1 is an enzyme essential to serine biosynthesis, an exogenous supplement of serine did not completely rescue the malignant behaviors in PSAT1-knockdown CRC cells. Interestingly, PSAT1 inhibited the Hippo tumor-suppressor pathway by promoting the nucleus-localization of YAP/TAZ and increasing the expression of ID1 in CRC cells. Furthermore, AMOT, a vascular-related molecule that molecularly interacts with YAP/TAZ, was up-regulated upon PSAT1 knockdown in CRC cells. Knocking down AMOT partially rescued the inhibition of proliferation and the reduced nuclear localization of YAP/TAZ caused by PSAT1 knockdown in CRC cells. Moreover, PSAT1 was closely related to vascular-related pathways, in which AMOT might act as a mediator. Finally, PSAT1 promoted CRC proliferation by negatively regulating AMOT in vivo. PSAT1 could enhance the progression of colorectal cancer by regulating Hippo-YAP/TAZ-ID1 axis via AMOT, which is independent of the metabolic function of PSAT1.

Overall survival (OS) among patients with limited-disease small-cell lung cancer (LD-SCLC) receiving chemoradiotherapy can be significantly influenced by subsequent treatments. Thus, the present study aimed to examine the interplay between progression-free survival (PFS), post-progression survival (PPS) and OS in patients with LD-SCLC undergoing chemoradiotherapy. This study retrospectively analyzed 84 patients with relapsed LD-SCLC who received chemoradiotherapy between April 2007 and June 2021. The correlations between PFS and OS as well as PPS and OS post-chemoradiotherapy were analyzed at the individual patient level. Spearman's rank correlation and linear regression analyses revealed a robust correlation between PPS and OS (r=0.76; P<0.05; R2=0.85). PFS was moderately correlated with OS (r=0.57; P<0.05; R2=0.25). Furthermore, the presence of liver metastases upon relapse and the administration of platinum re-challenge chemotherapy were significantly associated with PPS (P<0.05). The analysis of relationships between OS and PFS as well as OS and PPS in this patient cohort revealed that OS was more strongly correlated with PPS than PFS. These findings suggest that factors such as liver metastases at relapse and the administration of platinum re-challenge chemotherapy may influence PPS.

Radiotherapy (RT) is a gold standard cancer treatment worldwide. However, RT has limitations and many side effects. Nanoparticles (NPs) have exclusive properties that allow them to be used in cancer therapy. Consequently, the combination of NP and RT opens up a new frontier in cancer treatment. Among NPs, gold nanoparticles (GNPs) are the most extensively studied and are considered ideal radiosensitizers for radiotherapy due to their unique physicochemical properties and high X‑ray absorption. This review analyzes the various roles of NPs as radiosensitizers in radiotherapy of glioblastoma (GBS), prostate cancer, and breast cancer and summarizes recent advances. Furthermore, the underlying mechanisms of NP radiosensitization, including physical, chemical, and biological mechanisms, are discussed, which may provide new directions for next-generation GNP optimization and clinical transformation.

This review aims to investigate the issue of treatment nonadherence and to present the available strategies to improve adherence to oral treatments in breast cancer. A literature search was conducted to contextualise the issue of nonadherence, investigate the reasons behind nonadherence, and demonstrate strategies to address treatment nonadherence in breast cancer. Findings indicate that adherence rates decrease while discontinuation rates increase with increasing lengths of breast cancer treatment course. Lack of adherence is proven to be detrimental to treatment outcomes. Patients struggle to adhere to treatment due to inadequate relationships with healthcare providers, lack of information, psychological distress, and side effects. Healthcare providers should evaluate patient's experience to provide the necessary support. Following this assessment, healthcare providers may recommend interventions addressing patient knowledge, psychological distress or side effects. Treatment adherence remains an issue for oral therapeutics in breast cancer. After patient assessment, healthcare providers can offer personalised strategies to improve treatment adherence. The most crucial interventions address patient knowledge, psychological distress, and side effects.

Osteosarcoma predominantly affects adolescents and young adults and is characterized as a malignant bone tumor. In recent decades, substantial advancements have been achieved in both diagnosing and treating osteosarcoma. Resulting in enhanced survival rates. Despite these advancements, the intricate relationship between ferroptosis and cuproptosis genes in osteosarcoma remains inadequately understood. Leveraging TARGET and GEO datasets, we conducted Cox regression analysis to select prognostic genes from a cohort of 71 candidates. Subsequently, a novel prognostic model was engineered using the LASSO algorithm. Kaplan-Meier analysis demonstrated that patients stratified as low risk had a substantially better prognosis compared with their high-risk counterparts. The model's validity was corroborated by the area under the receiver operating characteristic (ROC) curve. Additionally, we ascertained independent prognostic indicators, including clinical presentation, metastatic status, and risk scores, and crafted a clinical scoring system via nomograms. The tumor immune microenvironment was appraised through ESTIMATE, CIBERSORT, and single-sample gene set enrichment analysis. Gene expression within the model was authenticated through PCR validation. The prognostic model, refined by Cox regression and the LASSO algorithm, comprised two risk genes. Kaplan-Meier curves confirmed a significantly improved prognosis for the low-risk group in contrast to those identified as high-risk. For the training set, the ROC area under the curve (AUC) values stood at 0.636, 0.695, and 0.729 for the 1-, 3-, and 5-year checkpoints, respectively. Although validation set AUCs were 0.738, 0.668, and 0.596, respectively. Immune microenvironmental analysis indicated potential immune deficiencies in high-risk patients. Additionally, sensitivity to three small molecule drugs was investigated in the high-risk cohort, informing potential immunotherapeutic strategies for osteosarcoma. PCR analysis showed increased mRNA levels of the genes FDX1 and SQLE in osteosarcoma tissues. This study elucidates the interaction of ferroptosis and cuproptosis genes in osteosarcoma and paves the way for more targeted immunotherapy.

There is a lack of research on how menopausal hormone therapy (MHT) affects the prognosis of postmenopausal thyroid cancer (TC) survivors. This study aimed to evaluate the association between MHT and the risk of death in postmenopausal TC survivors.

This retrospective cohort study used the data of women with the diagnostic code for TC from the Korean National Health Insurance Database between 2007 and 2021. The postmenopausal women with TC who received radical treatment such as surgery or/and radioactive iodine therapy were divided into two groups - MHT group and non-MHT group - according to whether or not they received MHT after TC treatment. The risk of death in TC survivors was analysed according to the type and duration of the MHT regimen.

Among postmenopausal TC survivors, the risk of death did not differ between the women with MHT duration > 5 years and the non-MHT group, with a hazard ratio (HR) of 0.964 [95 % confidence interval (CI) 0.697-1.334] (p = 0.826). However, MHT duration < 5 years was associated with increased risk of death, with the MHT group having an HR of 1.744 (95 % CI 1.105-2.753) (p = 0.017) compared with the non-MHT group. A trend was observed towards increased risk of death in women with MHT duration ≤ 6 months, with an HR of 1.703 (95 % CI 0.98-2.962) (p = 0.059). The risk of death did not differ between women with MHT duration > 6 months and women in the non-MHT group (HR 1.205, 95 % CI 0.79-1.839) (p = 0.064). In analyses by MHT regimen, no increase in the risk of death was observed for any MHT regimen for any duration.

The risk of death in postmenopausal TC survivors who used MHT for > 5 years did not differ from that of their counterparts who did not use MHT. However, postmenopausal TC survivors who used MHT for < 5 years, particularly those who used MHT for < 6 months, had a higher risk of death than their counterparts who did not use MHT.

To evaluate the role of 17β-oestradiol (E2) in the sex-dependent progression of colorectal cancer (CRC), the present study focused on E2 signalling mediated via the nuclear receptors [oestrogen receptor (ESR)1 and ESR2] and the membrane G protein-coupled oestrogen receptor 1 (Gper1) in males and females diagnosed with CRC. This study also investigated Gper1 signalling in the CRC cell lines DLD1 and LoVo, which differ in the p53 pathway. In cancer tissue, Gper1 becomes by far the most abundant E2 receptor due to an increase in Gper1 and a decrease in ESR2 expression. These changes are more prominent in males than in females. More pronounced differences in Gper1 expression between cancer and adjacent tissues were observed in males in lower stages compared with those in higher stages of disease and females. High expression of Gper1 was associated with worse survival in males without nodal involvement but not in females. The expression of E2 receptors in the CRC cell lines DLD1 and LoVo resembles that of human cancer tissue. Silencing of Gper1 (siGper1) caused an increase in the rate of metabolism in LoVo cells with wild-type tp53. In DLD1 cells with the mutated form of tp53, siGper1 did not exert this effect. High levels of Gper1 were associated with worse survival and could contribute to sex-dependent changes in the CRC prognosis. Tumour suppressor effects of Gper1 were, at least to some extent, dependent on signalling downstream of p53, which was more frequently deficient in males than in females. Overall, this suggests that up-regulation of Gper1 (or administration of a Gper1 agonist) would be more beneficial for patients with wild-type tp53.

Prostate cancer (PCa) remains a significant public health challenge in the United States, disproportionately affecting African American (AA) men, who face higher incidence rates, more aggressive disease, and elevated mortality compared to Caucasian American (CA) men. This review explores the multifactorial underpinnings of these disparities, integrating genomic, socioeconomic, environmental, and systemic contributors. Genomic analyses reveal that AA men harbor distinct molecular alterations, including higher frequencies of FOXA1, BRAF, and CHD1 mutations, as well as DNA damage repair defects, highlighting the critical need for population-specific precision medicine. Immune-oncologic pathways and stromal interactions within the tumor microenvironment further underscore biological differences driving aggressive disease phenotypes. Concurrently, adverse social determinants-including limited access to care, lower PSA screening rates, delayed treatment, medical mistrust, and underrepresentation in clinical trials-contribute to poorer outcomes. Despite these challenges, evidence from equal-access healthcare systems indicates that when provided equitable treatment, AA men can achieve outcomes comparable to or better than their CA counterparts. This review emphasizes actionable strategies to reduce disparities, including increasing AA representation in clinical trials, enhancing culturally competent patient-provider communication, improving access to early detection and high-quality care, and expanding community-based outreach initiatives. A holistic, interdisciplinary approach is essential to dismantle systemic barriers and achieve health equity in prostate cancer outcomes.

Survivors of head and neck cancer have complex nutritional and supportive care needs. These needs result from the tumour's proximity to organs essential for normal eating function and the intensive treatment targeting those organs. Despite the crucial role of nutrition and supportive care in head and neck cancer, research and funding are lacking compared with other cancer types. This Review was compiled and written by a team of multidisciplinary medical professionals. Topics include poor access to medical nutrition therapy (MNT), MNT reimbursement policies, long-term survivorship care needs, percutaneous endoscopic gastrostomy tube placement, nutrition literacy, psychological services, speech-language pathology care, and concomitant physical activity. The goal of this work is to define current issues in research and practice, advocate for the expansion of head and neck cancer funding opportunities, and raise awareness of head and neck cancer supportive care needs and challenges. This work provides a roadmap for health-care professionals, researchers, policy makers, and funding agencies to prioritise nutrition in head and neck cancer care, with the overarching goal of improving treatment outcomes and quality of life.

The low response rate of current immune checkpoint inhibitors in cancer has necessitated the development of new immune targets. Survival and public databases analyses were performed to determine the clinical significance of immunoglobulin-like transcript 3 (ILT3). The impact of ILT3 and apolipoprotein E (APOE) on tumor-associated macrophage (TAM) recruitment and polarization were evaluated by transwell assay, flow cytometry (FCM), and real-time PCR, while their impact on T cell survival and cytotoxicity was detected by CFSE, apoptotic assay, FCM and ELISA. These pro-tumoural activity of (an ortholog of ILT3 in mouse) were verified in vivo models. Survival and public databases analyses revealed that high ILT3 expression was significantly associated with worse prognosis in lung adenocarcinoma (LUAD), but not in squamous cell carcinoma. The same association was observed with its ligand, APOE. In vitro assays demonstrated that tumor-derived ILT3/APOE promoted recruitment and M2-like polarization of TAMs in LUAD and directly inhibited T cell proliferation and cytotoxicity. In vivo knockdown of gp49b enhanced anti-tumor immunity and suppressed tumor progression by counteracting TAM- and dysfunctional T cell-induced tumor microenvironment immunosuppression. Furthermore, combined inhibition of gp49b and programmed cell death ligand 1 (PD-L1) showed the most drastic tumor regression in C57BL/6 mice models. Tumor-derived ILT3 overexpression suppresses anti-tumor immunity by recruiting M2-like TAMs and impairing T cell activities, while ILT3 inhibition counteracts this immunosuppression and enhances the efficacy of PD-L1 blockade in LUAD. Thus, ILT3 could be a promising novel immunotherapeutic target for combined immunotherapy.

Non-coding RNAs (ncRNAs) are frequently dysregulated in various cancers and have been implicated in the etiology and progression of cancer. Ovarian cancer, the most fatal gynecological cancer, has a poor prognosis and a high patient fatality rate due to metastases. In this study, we classified patients with ovarian cancer into three groups based on their ncRNA expression levels. Notably, an ncRNA transcribed by RNA polymerase III, RNA component of mitochondrial RNA processing endoribonuclease (RMRP), is highly expressed in a group with a poor prognosis. Functional assays using SKOV3 and HeyA8 human ovarian cancer cell lines revealed that while RMRP modulation had no significant effect on cell viability, it markedly enhanced cell invasion. Knockdown and ectopic expression experiments demonstrated that RMRP promotes the secretion of matrix metalloproteinase (MMP)-2 and -9, thereby facilitating ovarian cancer cell invasiveness. Transcriptomic analysis further revealed a positive correlation between RMRP expression and genes involved in cellular localization, including RAB31, a member of the Ras-related protein family. Notably, RAB31 knockdown abrogated the pro-invasive effects of RMRP, identifying it as a key downstream effector in SKOV3 and HeyA8 cells. In addition, MechRNA analysis identified RAB31 as a putative RMRP-interacting transcript. These findings establish RMRP as a critical regulator of RAB31-dependent MMP secretion and ovarian cancer cell invasion. Moreover, our results suggest that RMRP could serve as a promising prognostic biomarker for ovarian cancer.

This study aimed to explore the risk of stroke death (SD) in cancer patients, estimate rates, and identify risk factors associated with SD.

In this retrospective study, we used the 17 National Cancer Institute Surveillance, Epidemiology, and End Results registries (2000-2020). A total of 5,922,533 patients diagnosed with their first primary cancer were included. The primary outcome was the standardized mortality ratio (SMR) of SD in cancer patients. Secondary outcomes included SD incidence rates and risk factors. Rates were calculated per 100,000 persons with the annual percentage change (APC).

Among included patients, 56,686 (2.0 %) died due to stroke. Compared to the general population, younger patients (≤39 years) (SMR: 2.31) and patients receiving no treatment (SMR: 1.36) had the highest risk. Cancer types with the fastest-declining SD rates were in the male genital (APC: -13.9 %) and breast (APC: -11.8 %). Older age (hazard ratio [HR]: 1.11, p < 0.001), male sex (HR: 1.06, p < 0.001), and non-white race (HR: 1.13, p < 0.001) were associated with increased risk of SD. Cancers of the nervous system (HR: 3.42, p < 0.001), respiratory (HR: 1.38, p < 0.001), and head and neck (HR: 1.37, p < 0.001) had higher risk of SD vs. breast cancer. Patients with primary chemotherapy (HR: 0.69, p < 0.001) and radiotherapy (HR: 0.69, p < 0.001) demonstrated less risk vs. those without treatment.

SD has declined over the years for both sexes and all cancer types. Older age, non-white race, and certain cancers (nervous system, respiratory system, and head and neck) pose significant risks for SD.

Among cancer patients, those in advanced stages generally face higher mortality rates, highlighting the importance of early diagnosis in improving cure rates and survival outcomes. Compared to normal cells, tumor cells exhibit a lower polarity in their microenvironment, providing a promising avenue for early cancer detection. It is feasible to distinguish tumor cells from normal cells by leveraging the fluorescence response of probes to polarity. In this study, we designed a fluorescence probe, PCC, with high sensitivity to polarity for early cancer diagnosis. The probe demonstrated a remarkable fluorescence intensity increase of 100-fold in a low-polarity solvent (1,4-dioxane) compared to a high-polarity solvent (water). Additionally, PCC exhibited excellent tumor-targeting ability, large Stokes shift, strong anti-interference capability, and high photostability. When applied to tumor cells (HeLa and CT26、SGC-7901) and normal cells (RAW 264.7、HUVEC、L-02), the probe produced a fluorescence intensity difference exceeding fourfold. These findings indicate that PCC, as a polarity-sensitive fluorescence probe, holds significant promise for early cancer diagnosis.

This review evaluates the long-term outcomes and adverse events associated with chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

We conducted the search in relevant databases up to June 2024. We included clinical trials on CAR T-cell therapy for patients with r/r B-ALL. Meta-analyses were conducted using Comprehensive Meta-Analysis V3 and Review Manager 5.4.

Out of 2659 identified studies, 10 were included in this review. The pooled analysis demonstrated a high minimal residual disease-negative complete remission, with an overall event rate (ER) of 70% (95% CI: 61%-78%, I2 =8 8.35%). Anti-CD19 CAR T-cell therapy showed the highest efficacy with an ER of 74.75% (95% CI: 61%-80%, I2 = 89.84%). Combination therapies targeting CD19 and CD22 had an ER of 69% (95% CI: 53%-83%, I2 = 82.56%). Significant adverse effects included cytokine release syndrome with a mean incidence of 81.8% (95% CI: 76.7%-86.9%), neurotoxicity at 33.2% (95% CI: 28.1%-38.3%), and hematologic toxicities at 71.9% (95% CI: 66.4%-77.4%).

CAR T-cell therapy is a groundbreaking advancement in treating r/r B-ALL, offering high rates of durable remissions.

This study's objective was to develop predictive models for bladder cancer (BLCA) using tumor infiltrated immune cell (TIIC)-related genes. Multiple RNA expression data and scRNA-seq were downloaded from the TCGA and GEO databases. A tissue specificity index was calculated and a computational framework developed to identify TIIC signature scores based on three algorithms. Univariate Cox analysis was performed, and the TIIC-related model was generated by 20 machine learning algorithms. A significant correlation between TIIC signature score and survival status, tumor stage, and TNM staging system was found. Patients in the high-score BLCA group had more favorable survival outcomes and enhanced response to PD-L1 immunotherapy as compared to those in the low-score group. This TIIC model showed better performance in prognosing BLCA. Diverse frequencies of mutations were observed in human chromosomes across groups categorized by TIIC score. No statistically significant correlation was observed between noncancerous bladder conditions and BLCA when examining the single nucleotide polymorphisms (SNPs) associated with the genes in the prognostic model. However, a statistically significant association was found at the SNP sites of rs3763840. There was no significant association between bladder stones and BLCA, but there was a significant association on the SNP sites of rs3763840. A novel TIIC signature score was constructed for the prognosis and immunotherapy for BLCA, which offers direction for predicting overall survival of patients with BLCA.

The effectiveness of local treatment in lymph node metastasis from uterine cancer has been proven; the standard treatment is surgical intervention. Although radiotherapy, including particle radiotherapy (PRT), is an alternative local treatment, its application is often contraindicated owing to its proximity to the gastrointestinal tract. Combination treatment with spacer placement surgery followed by PRT is a potential solution to this problem. This study aimed to evaluate the outcomes of this combination treatment of lymph node metastases from uterine cancer.

Between December 2007 and March 2023, ten consecutive patients who underwent combination treatment comprising spacer placement surgery and subsequent PRT were assessed for treatment outcomes.

The median survival time was 53.5 months; the 3- and 5-year overall survival rates were 76.2% and 38.1%, respectively. The 3- and 5-year local control rates in all patients were both 88.9%. The median volume irradiated at 95% of the treatment planning dose (V95%) of the gross tumor volume, clinical target volume, and planning target volume were 100.0%, 99.8%, and 92.2%, respectively. The median dose intensity covering 95% of the target volume (D95%) of the gross tumor volume/planned dose, clinical target volume/planned dose, and planning target volume/planned dose were 98.9%, 99.0%, and 87.2%, respectively.

Spacer placement surgery contributed to the optimized PRT dose distribution and might have contributed to favorable local control and survival rates. This innovative combination treatment might have a significant effect on the treatment of lymph node metastases from uterine cancers.

Familial multiple myeloma (MM) is a relatively rare entity. Data on epidemiology, underlying germline genetic predisposition, and clinical features of familial MM continue to expand, especially in recent years. The risk of MM has been reported to be increased by 2 to 4 times among first-degree relatives of MM patients along with monoclonal gammopathy of undetermined significance (MGUS), other hematological malignancies, and several solid tumors by multiple groups. The association between MM risk and having a first-degree relative with a history of MM is stronger among African Americans/Blacks (OR = 5.52, 95% CI: 1.87-16.28) than European Americans/Whites (OR = 1.26, 95% CI: 0.75-2.10). Although data on clinical features and prognosis of familial cases are limited, preliminary data suggest a better prognosis among familial cases. Sequencing studies in familial cases have discovered rare disease-causing variants among which CDKN2A, USP45, MYH14, EPOR, HERC1, KLHL18, and KLHDC3 are shared by independent groups. Some of these candidate genes possess functions related to myelomagenesis such as B-cell development, immunoglobulin gene regulation, immune pathways, DNA damage/repair, ubiquitination, and cell adhesion mechanisms. Our group has recently completed an analysis among our Turkish MM families to confirm the findings of the International Consortium. The odds ratio (OR) for single nucleotide polymorphism rs28199 in nonfamilial MM cases compared to healthy control was 1.18, with an OR of 2.86 in familial MM cases compared to nonfamilial cases. Despite the accumulation of data, most questions remain to be answered. Future studies may elucidate underlying biological mechanisms, and develop polygenic risk scores, leading advancements in prognostic evaluation and clinical management.

Radical resection remains the only curative option for intrahepatic cholangiocarcinoma (iCCA).1-3 Patients with multifocal tumors, vascular invasion, or lymph node metastasis are considered to have locally advanced disease.4 Neoadjuvant chemotherapy with gemcitabine and cisplatin as first line or with capecitabine and irinotecan as second line have shown oncological benefit.5-8 More recently, Durvalumab has also showed benefit in addition to chemotherapy.9 For tumours with major vascular invasion, stereotactic body radiation therapy (SBRT) is a safe treatment option where upfront surgery may not provide the desired oncological outcomes.10-13 We present a video where combination of modalities was used to achieve downstaging followed by surgery.

A 64-year-old male patient was diagnosed with locally advanced iCCA involving left lobe with left portal vein thrombosis, left hepatic vein (LHV) encasement, and middle hepatic vein (MHV) abutment. Cancer antigen (CA) 19-9 was 1890 U/mL. After three cycles of gemcitabine and cisplatin, response computed tomography (CT) scan showed disease progression, and second-line chemotherapy with immunotherapy (capecitabine, irinotecan, durvalumab) was started with stereotactic body radiation therapy. Response CT showed significant size reduction. CA 19-9 dropped to 17 U/mL. Patient was planned for left hepatectomy with portal vein resection (PVR) and segment 8 venous reconstruction.

1. Kocherization, inter-aortocaval nodal sampling, and peri-portal dissection. 2. Parenchymal transection with left hepatic duct division, PVR with primary repair 3. Isolation of segment 8 vein, division distal to MHV-LHV confluence, specimen retrieval. 4. Reconstruction of segment 8 vein to MHV-LHV confluence using polytetrafluoroethylene graft (PTFE). Final histopathology report revealed complete pathological response. Patient was planned for two more cycles of same chemotherapy followed by observation.

Resection with periportal lymphadenectomy and negative margins remains the only curative option for iCCA. Multimodality options can be utilized to downstage tumor, and complex liver resection with vascular reconstruction can achieve excellent oncological outcomes.

The challenges that remain in the treatment of solid tumors with chimeric antigen receptor (CAR)-T cells include limited solid tumor-specific targets and poor CAR-T cell expansion and function due to limited availability of solid tumor antigens outside the tumor microenvironment. Prostate cancer is the second most common cancer among men worldwide. Current CAR-T therapies for prostate cancer lack specific targets, posing safety risks. To overcome these problems, we identified prostatic acid phosphatase (PAP, also known as ACPP or ACP3) as a feasible CAR-T target for prostate cancer and developed CoupledCAR, a novel approach for expanding tumor-targeting CAR-T cells without tumor antigens.

We analyzed the expression of PAP from The Cancer Genome Atlas database and validated its expression in normal and cancer tissues through immunohistochemistry staining. To generate anti-PAP specific antibodies, we screened the human single-chain antibody library using transmembrane PAP-His antigen and selected antibodies based on their binding ability and specificity. We constructed PAP-targeted CAR and evaluated their antitumor efficacy both in vitro and in vivo. We validated the function of PAP CoupledCAR in both in vitro and in vivo experiments, and further analyzed its mechanism using single-cell RNA sequencing (scRNA-Seq).

PAP was specifically expressed in prostate epithelial and prostate cancer cells, with no expression in other tissues. Seven single-chain variable fragments were screened from the human single-chain antibody library, with S5D1 showing the highest binding ability for the PAP. PAP CAR-T cells demonstrated strong antitumor efficacy both in vitro and in vivo. Furthermore, the CoupledCAR system significantly expanded PAP CAR-T cells, promoting memory-like status, reducing exhaustion, and enhancing their antitumor efficacy. The scRNA-Seq demonstrated that the expansion of PAP CAR-T cells in the CoupledCAR system is mediated by costimulatory signals and cytokine signals, rather than T-cell receptor signals.

Our study is the first to demonstrate that PAP is a specific target for CAR-T therapy in prostate cancer, both in vitro and in vivo. We developed the CoupledCAR platform technology for solid tumor CAR-T cell therapy, enabling the expansion of tumor-targeting CAR-T cells without requiring tumor antigens and thereby enhancing their functionality against solid tumors.

Lung squamous cell carcinoma (LUSC) is an extremely metastatic cancer with limited available treatment and poor outcomes. Connexin43 (Cx43) is frequently overactivated and positively correlated with tumorigenesis in many cancers, including breast cancer and lung adenocarcinoma, but its role in LUSC remains elusive. In this study, we demonstrated that Cx43 was highly expressed in LUSC tissues as compared to matching normal lung tissues (n = 103) and negatively related to prognosis. Through the 3D spheroid cell invasion assay, zCDX (zebrafish cell line-derived xenograft), and orthotopic lung cancer xenograft model, we further revealed that Cx43 promotes LUSC invasion and migration via forming GJIC. Knockdown of Cx43 reduced the Ca2+ transmission and ERK phosphorylation, whereas the addition of Ca2+ enhanced ERK phosphorylation and promoted LUSC invasion and migration. Furthermore, verapamil (40 μM and 80 μM), a calcium channel inhibitor, significantly inhibited ERK phosphorylation as well as the invasion and migration of LUSC cells. Mechanistically, Cx43 promoted the invasion and metastasis of LUSC via activating the Ca2+/ERK signaling pathway by gap junctional intracellular communication (GJIC). Our findings provide a novel mechanism insight for LUSC invasion and migration and a proof of concept for a new therapeutic strategy to tackle this disease.

Small intestine tumors, though rare, have shown a concerning increase in incidence and mortality in recent years. This study aimed to investigate the historical trends in histological composition and causes of death among patients with small intestine tumors using the SEER database. A total of 18,234 patients diagnosed with primary small intestine cancer from 1992 to 2018 were included in this study. Demographic details, tumor characteristics, treatment modalities, and outcomes were collected. Cause-specific mortality was analyzed using Fine and Gray regression, with non-small intestine-specific deaths considered as competing risks. Small intestine-specific deaths were the leading cause of mortality, with adenocarcinoma and carcinoid tumors being the most common histological types. Heart disease emerged as a significant cause of death following diagnosis, surpassing small intestine-specific deaths after 5-6 years. The study revealed variations in mortality causes across histological subtypes and identified risk factors for small intestine-specific mortality, including age, tumor site, grade, and treatment modalities. The findings highlight the substantial impact of heart disease on the long-term survival of patients with small intestine tumors. This underscores the potential benefits of adopting comprehensive management strategies that integrate oncological and cardiological care to improve survival rates and quality of life. A multidisciplinary approach in oncocardiology may help address the complex needs of these patients and optimize clinical outcomes.