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.

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.

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.

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.

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.

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.

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.

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.

To enhance immunotherapy efficacy in pancreatic cancer, it is crucial to characterize its immune landscape and identify key factors driving immune alterations. To achieve this, we quantitatively analyzed the immune microenvironment using multiplex immunohistochemistry, assessing the spatial relationships between immune and tumor cells to correlate with patient survival rates and oncological factors. Additionally, through Whole Exome Sequencing analysis based on public data, we explored genetic mutations that could drive these compositions. Finally, we validated T cell (Tc) migration mechanisms using patient-derived tumor organoids with induced KRAS mutation subtypes. Through this approach, we obtained the following meaningful results. First, immune cells in pancreatic cancer are denser in stromal regions than near tumor cells, with higher Tc distribution linked to increased patient survival rates. Second, the distance between tumor and Tc was within 100 μm, with higher Tc density found within 15-30 μm of the tumor cells. Third, while increasing CAF levels correspond to higher Tc density, higher ECM density tends to decrease Tc presence. Fourth, compared to KRAS G12D, KRAS G12V mutation increases various immune cells, notably Tc, which is closely linked to a dramatic rise in vascular cells. Finally, Tc migration was enhanced in tumor organoids with the G12V mutation, attributed to a reduction in the secretion of immunosuppressive cytokines. Our results indicate that KRAS mutation subtypes influence immune cell composition and function in the pancreatic cancer microenvironment, leading to varied immunotherapy responses. This underscores the need for personalized immune therapeutics and research models specific to KRAS mutations.

Micro-photodynamic therapy (MWPDT) combines photo-dynamic (PDT) and microwave-dynamic (MWDT) therapies with sensitizers, offers new avenues for cancer treatment. Despite the fact that novel sensitizers for MWPDT have been successfully synthesized, only a few are being employed effectively. The low tumor-targeting specificity, inability to transport sensitizer's deeper intratumorally, and deteriorating tumor microenvironment all restrict their anti-tumor efficacy. The current work was done aiming at microwave assisted drug delivery of titanium dioxide / rose Bengal conjugated chitosan nanoparticles (TiO2/RB@CSNP) for micro- photo-dynamic skin cancer (SKCA) treatment in vitro and in vivo as activated cancer treatment up-to-date modality.

The study was conducted in vitro on human SKCA cells (A-375) and the study protocol application groups in vivo on Swiss albino mice treated with 7,12-dimethylbenz[a]anthracene (DMBA)/croton oil only and were not received any treatment for inducing SKCA, and only after SKCA induction the study treatment protocol began, treatment was daily with TiO2/RB@CSNP as MWPDT sensitizer with or without exposure to laser (IRL) or microwave (MW) or a combination of them for 3 min for two weeks.

Revealed that CSNP can be employed as effective TiO2/RB delivery system that directly targets SKCA cells. Additionally TiO2/RB@CSNP is a promising MWPS for and when combined with MWPDT can be very effective in treatment of SKCA-A-375 in vitro (cell viability decreased in a dose-dependent basis, the cell cycle progression in G0/G1 was slowed down, and cell death was induced as evidenced by an increase in the population of Pre-G cells, an increase in early and late apoptosis and necrosis, and an increase in autophagic cell death) and DMBA/croton oil SKCA-induce mice in vivo (induced antiproliferative genes (caspase 3,9, p53, Bax, TNFalpha), suppressed antiapoptotic and antiangiogenic genes (Bcl2,VEGF respectively) effectively reducing the tumors growth and leading to cancer cell death as well as decreased oxidative stress (MDA), and ameliorated enzymatic and non-enzymatic antioxidants (SOD, GR, GPx, GST, CAT, GSH, TAC) as well as renal (urea, creatinine) and hepatic (ALT, AST) functions. This process could be attributed to MWPDT; microwave and/or photo-chemical TiO2/RB activation mechanism and antioxidant potential of non activated TiO2/RB as well.

The results indicate that TiO2/RB@CSNP has great promise as an innovative, effective delivery system for selective localized treatment of skin cancer that is activated by MWPDT.

Aberrant expression of SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 2 (SPOCK2) plays a role in the development and progression of several human cancers. However, the importance of its expression and function in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to elucidate the role of SPOCK2 in the growth of LUAD and propose a novel therapeutic insight for LUAD through SPOCK2. SPOCK2 protein expression was significantly reduced in LUAD tissues and cells by Immunohistochemical assay and Western blot. CCK-8, colony formation, and Transwell assays were used to demonstrate that SPOCK2 overexpression inhibited both proliferation and migration of LUAD cells in vitro. This inhibition of tumor growth was further confirmed by a LUAD xenograft mouse model in vivo. To explore downstream target signal of SPOCK2 in LUAD, RNA transcriptome sequencing was performed and enrichment analysis showed an association between SPOCK2 expression and the MAPK pathway. Furthermore, HEK293T cells were modified with SPOCK2, and extracellular vesicles (EVs) containing SPOCK2 (SPOCK2-EVs) were collected through ultra-high-speed centrifugation. Interestingly, co-culture with SPOCK2-EVs significantly increased SPOCK2 levels within LUAD cells. Furthermore, SPOCK2-EVs effectively inhibited LUAD growth in vitro and in vivo studies. Because directly injecting SPOCK2-EVs into tumors presents challenges for internal organs, we investigated the efficacy of nebulized SPOCK2-EVs for LUAD treatment. Consistent with our findings from intratumoral injection, nebulized inhalation of SPOCK2-EVs resulted in significant inhibition of LUAD growth. These results strongly suggest that SPOCK2 released by HEK293T-EVs can effectively inhibit LUAD tumor growth and hold promise for future clinical translation in cancer therapy.

Breast cancer is a fatal malignancy facing human health, with most patients experiencing recurrence and resistance to chemotherapy. The immunosuppressive tumor microenvironment (TME) greatly limits the actual outcome of immunotherapy. This study aimed to develop a modality of theranostics nanoparticles for breast cancer based on a near-infrared light-triggered nanoparticle for the targeted delivery of ginsenoside Rg3 and immune adjuvants imiquimod (R837) for effective breast cancer immunotherapy. Folate-receptor (FA) targeting IR780-R837/ginsenoside Rg3-perfluorohexane (PFH) @ polyethylene glycol (PEG)-poly (lactide-co-glycolic acid) (PLGA) nanoparticles (FA-NPs) can be activated by near-infrared laser irradiation in tumors, which leads to rapid release of ginsenoside Rg3 and R837 in the regions with high expression of folate receptors and glucose transporter 1 (GLUT1). Meanwhile, the nanoparticles can be used as dual-mode contrast agents for photoacoustic and ultrasound imaging. This strategy provides a strong immune memory effect, which can prevent tumor recurrence after eliminating the initial tumor.

The primary aim of the study was to analyze novel long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) to assess their roles as potential oncogenes and tumor suppressors and to develop a survival prediction model based on their expression levels. Data from The Cancer Genome Atlas, GSE135631, and GSE214846, were utilized to evaluate changes in lncRNA expression in HCC and their associations with patient prognosis. A risk model was created based on lncRNA expression to predict patient mortality. The co-expression network was employed to identify associated pathways, and the results were subsequently validated using the RT-qPCR method. The findings indicated that 14 lncRNAs were down-regulated in HCC, and their increased expression was associated with a favorable prognosis. Additionally, eight lncRNAs were overexpressed and correlated with poorer patient outcomes. The multivariate Cox regression analysis demonstrated that overexpression of AKR1B10P1, RP11-465B22.3, WASH8P, and the downregulation of NPM1P25 could independently predict patient survival, irrespective of clinical variables. The risk score model based on these lncRNAs effectively stratified patients by their mortality risk. Furthermore, the co-expression network analysis revealed that the identified lncRNAs might be involved in various pathways, including fatty acid metabolism, mTOR signaling, glycolysis, angiogenesis, Wnt-β-catenin pathway, and DNA repair. RT-qPCR results validated the significant increase in the expression level of WASH8P in cancer specimens compared to normal tissues. Our results unveiled that changes in the expression levels of AKR1B10P1, RP11-465B22.3, WASH8P, and NPM1P25 were significantly and independently associated with prognosis. Moreover, the patient mortality risk model constructed using these four lncRNAs exhibited a robust capacity to accurately predict patients' survival rates.

Lung cancer remains a significant global health challenge, demanding innovative treatment strategies. Immune checkpoint blockade has revolutionized cancer care, leading to improved survival across advanced malignancies and has now become a standard therapy for earlier stage, resectable lung cancer. This review article consolidates the current landscape and future prospects of neoadjuvant and perioperative immunotherapy in lung cancer. The authors outline key findings from clinical trials in resectable lung cancer, including early efficacy, safety profiles, and emerging impact on disease recurrence, and overall survival. Additionally, this review elucidates the challenges encountered, including patient selection criteria, optimal treatment schedules, immune-related adverse events, and impact on surgery. This comprehensive analysis amalgamates current evidence with future directions, providing a roadmap for clinicians, researchers, and stakeholders to navigate the dynamic realm of immunotherapy for surgically resectable lung cancer.

While CD49d (α4 integrin) is an established prognostic marker in chronic lymphocytic leukaemia (CLL) and is associated with aggressive disease, its impact on T-cell biology remains poorly understood. Compared to healthy donors, CLL patients exhibited significantly elevated CD49d expression in both CD4+ and CD8+ T cells (p < 0.001) as detected by flow cytometry, which was also confirmed by the single-cell RNA sequencing (scRNA-seq) (p < 0.001). Differentially expressed genes in CD49d+ T (both CD8+ and CD4+ T cells) versus CD49d- T cells identified in CLL patients were enriched in cellular senescence pathways, while this phenomenon is absent in healthy individuals. Functional validation demonstrated that CD49d+ T cells displayed elevated senescence-associated markers (e.g. interferon-gamma, granzyme B) and a shift towards memory phenotypes, correlating with immunosuppressive signatures. This discovery suggests that targeting CD49d-dependent senescence pathways may reverse T-cell dysfunction in CLL immunotherapy.

Obstructions can occur during any stage of colorectal cancer and correspond with poor prognosis. Obstructive colorectal cancer (OCRC) is harder and exhibits increased tumor budding and proliferation of myofibroblasts compared with nonobstructive colorectal cancer, suggesting that the occurrence of obstruction may be related to extracellular matrix (ECM) remodeling. In this study, we found that colorectal cancer and OCRC samples differed substantially in ECM composition, specifically in collagen (newly formed and mature) and proteoglycans (including glycosaminoglycan, hyaluronic acid, and chondroitin sulfate). OCRC also exhibited considerable changes in ECM biomechanics and collagen arrangement. Interestingly, OCRC samples presented a notable increase in matrix cancer-associated fibroblasts (mCAF). The abundance of mCAFs correlated with the accumulation of palmitic acid (PA), and high concentrations of PA increased the secretion of ECM-related proteins by mCAFs. Additionally, PA did not directly affect normal fibroblasts but rather activated the NF-κB pathway in tumor cells to stimulate secretion of CSF1, TGFβ1, and CXCL8, which promoted the activation of normal fibroblasts into mCAFs and exacerbated ECM stiffening. Drug screening with a natural compound library identified vanillylacetone as a potential inhibitor of PA-induced cytokine secretion and ECM stiffening. These findings highlight intratumoral PA accumulation as a key mechanism driving ECM alterations and OCRC progression and suggest that targeting this axis may be useful for treating patients with colorectal cancer with risk of obstruction. Significance: Palmitic acid accumulation activates the NF-κB pathway in colorectal cancer cells to promote cytokine secretion that facilitates the generation of matrix cancer-associated fibroblasts, driving extracellular matrix remodeling and development of obstructions.

The purpose of the current study was to compare the diagnostic performances of radiolabeled FAPI and 18F-FDG PET/CT for the detection of lymph node (LN) metastasis in head and neck cancer (HNC) patients.

The PubMed, Cochrane database, and EMBASE database, from the earliest available date of indexing through December 31, 2024, were searched for studies comparing diagnostic performances of radiolabeled FAPI and 18F-FDG PET/CT for the detection of metastatic LN in HNC patients. We estimated pooled sensitivities and specificities across studies.

Across 8 studies (14 results), the pooled sensitivity of FAPI PET/CT was 0.89 and the pooled specificity was 0.93. The pooled sensitivity of 18F-FDG PET/CT was 0.91 and the pooled specificity was 0.50. On patient-based analysis, the estimated sensitivity and specificity of FAPI were 0.96 and 0.96, and those of 18F-FDG were 0.95 and 0.34, respectively. On lesion-based analysis, the estimated sensitivity and specificity of FAPI were 0.84 and 0.94, and those of 18F-FDG were 0.86 and 0.78, respectively. On neck side-based analysis, the estimated sensitivity and specificity of FAPI were 0.88 and 0.79, and those of 18F-FDG were 0.91 and 0.29, respectively.

Radiolabeled FAPI showed a good diagnostic performance for the detection of metastatic LN in HNC patients. Also, 18F-FDG PET/CT revealed low specificity for LN staging in HNC patients. Future large multicenter research with more patients would be necessary to provide a more comprehensive overview of the usefulness of radiolabeled FAPI for LN staging in HNC patients.

The tumor microenvironment (TME) plays a crucial role in cancer development and spreading being considered as "the dark side of the tumor". Within this term tumor cells, immune components, supporting cells, extracellular matrix and a myriad of bioactive molecules that synergistically promote tumor development and therapeutic resistance, are included. Recent findings revealed the profound impacts of TME on cancer development, serving as physical support, critical mediator and biodynamic matrix in cancer evolution, immune modulation, and treatment outcomes. TME targeting strategies built on vasculature, immune checkpoints, and immuno-cell therapies, have paved the way for revolutionary clinical interventions. On this basis, the relevance of pre-clinical and clinical investigations has rapidly become fundamental for implementing novel therapeutical strategies breaking cell-cell and cell -mediators' interactions between TME components and tumor cells. This review summarizes the key players in the breast and pancreatic TME, elucidating the intricate interactions among cancer cells and their essential role for cancer progression and therapeutic resistance. Different tumors such breast and pancreatic cancer have both different and similar stroma features, that might affect therapeutic strategies. Therefore, this review aims to comprehensively evaluate recent findings for refining breast and pancreatic cancer therapies and improve patient prognoses by exploiting the TME's complexity in the next future.

Ovarian cancer ranks as the fifth most common cause of cancer-related deaths in women worldwide. Macrophages M2 is believed to support tumor growth by suppressing immune responses and promoting angiogenesis.

A macrophage M2-related signature (MRS) was developed by applying machine learning methods that included 10 algorithms and utilized data from the TCGA, GSE14764 and GSE140082 datasets. The predictive capacity of the MRS for immunotherapy response was evaluated through various methods, including immunophenoscore, TIDE score, TMB score, immune escape score, as well as two immunotherapy cohorts (IMvigor210 and GSE91061).

The optimal MRS, developed using the lasso algorithm, served as an independent prognostic factor and demonstrated stable performance in predicting overall survival rates in ovarian cancer. In the TCGA dataset, the AUC values for the 1-, 3-, and 5-year ROC curves were 0.874, 0.808, and 0.813, respectively. The C-index of our MRS was superior to that of clinical stage, tumor grade, and several other established prognostic signatures. Ovarian cancer patients with low risk score exhibited higher ESTIMATE score, increased levels of immune cells, elevated PDI&CTLA4 immunophenoscore, higher TMB score, reduced TIDE score, and lower immune escape score. Additionally, the survival prediction nomogram displayed significant potential for clinical application in estimating the 1-, 3-, and 5-year overall survival rates of ovarian cancer patients.

Our study developed a novel MRS for ovarian cancer, which could act as an indicator for predicting the prognosis and immunotherapy response in ovarian cancer.

Mechanisms underlying sex differences in the development and prognosis of many diseases remain largely elusive. Here, we systematically investigated sex differences in the genetic regulation of plasma proteome (>5800 protein targets) across two cohorts (30,307 females; 26,058 males). Plasma levels of two-thirds of protein targets differ significantly by sex. In contrast, genetic effects on protein targets are remarkably similar across sexes, with only 103 sex-differential protein quantitative loci (sd-pQTLs; for 2.9% and 0.3% of protein targets from antibody- and aptamer-based platforms, respectively). A third of those show evidence of sexual discordance, i.e., effects observed in one sex only (n = 30) or opposite effect directions (n = 1 for CDH15). Phenome-wide analyses of 365 outcomes in UK Biobank did not provide evidence that the identified sd-pQTLs accounted for sex-differential disease risk. Our results demonstrate similarities in the genetic regulation of protein levels by sex with important implications for genetically-guided drug target discovery and validation.

Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in the treatment of colorectal cancer (CRC). However, most evidence has come from clinical trials with strict eligibility criteria. Understanding real-world effectiveness and safety of ICIs in CRC is important to guide routine clinical practice across diverse populations.

A systematic review following PRISMA guidelines was conducted to identify observational studies evaluating ICI-based regimens compared to conventional or combination therapies in patients with CRC. Three databases (MEDLINE, Embase, and Scopus) were searched from inception through March 15, 2025. Eligible studies reported at least one efficacy outcome (e.g., progression-free survival [PFS], overall survival [OS], etc.) and/or safety outcome (e.g., adverse events) among real-world populations with CRC treated with ICIs. Study quality was assessed using the Newcastle-Ottawa Scale, and a narrative synthesis was performed to summarize the key findings. Eleven real-world studies met the inclusion criteria, encompassing data from 2,049 patients. In MSI-H/dMMR metastatic CRC, real-world findings aligned with the survival benefits observed in clinical trials, demonstrating improved PFS and OS compared to conventional therapies. For MSS/pMMR metastatic CRC, combining ICIs with other agents (e.g., tyrosine kinase inhibitors or chemotherapy) showed improvements but yielded conflicting results. Overall, the safety profiles were comparable to conventional therapies, with treatment-related adverse events occurring at similar rates. Real-world evidence supports the efficacy of ICI monotherapy in MSI-H/dMMR metastatic CRC and suggests potential benefits of ICI-based combination therapies in MSS/pMMR metastatic CRC. However, most of the data are derived from small, single-center cohorts, which limit their generalizability. Further multi-center studies are needed, especially to assess the efficacy of ICI-based combination therapies in the broader CRC population.

Analyze cancer incidence and mortality in the U.S. 1999-2021, focusing on variations by sex, race, cancer type, and state. The study aims to identify disparities in cancer rates and highlight regions and populations most affected, to inform public health policies and interventions.

Age-adjusted rates were analyzed by race, cancer type, sex, and state. Bayesian statistical techniques were employed for accurate trend estimation, and cancer hotspots were identified using the Getis-Ord Gi* statistic. Joinpoint regression was used to estimate the Average Annual Percent Change (AAPC) in cancer rates. The analysis was conducted using R.

The overall trend was noted reduction in aggregate cancer rate (AAPC =-0.007) and mortality (AAPC =-0.004). Regional and racial disparities are still prevalent with outcomes showing that Kentucky, West Virginia, and Mississippi have the highest prevalence of both. Cancer incidence was reduced most significantly among Black or African American individuals (AAPC=-0.008) and mortality in (AAPC=-0.021) but their rates are still higher. Hotspot analyses identified high cancer incidence and mortality clusters, particularly in the Midwestern and Southern regions of the United States.

The implications arising from these results suggest that focused public health campaigns need to be directed toward cancer, smoking, and access to care services for effective health promotion. These findings therefore call for innovative public health measures to reduce the burden of cancer and disparity in the future. More sophisticated studies of the social, environmental, and genetic causes of these trends are required to improve the efficacy of cancer control.

Non-small cell lung cancer (NSCLC) patients receiving third-generation EGFR TKIs with thoracic radiotherapy (TRT) significantly prolong survival and also increase the incidence of radiation pneumonitis (RP). The aim of our study was to investigate the incidence and risk factors of RP in NSCLC patients receiving third-generation EGFR TKIs and TRT.

We retrospectively evaluated NSCLC patients who received both third-generation EGFR TKIs and TRT at the General Hospital of Ningxia Medical University from January 2023 to September 2024. RP was diagnosed by clinical symptoms on computed tomography (CT) scans and graded according to the Common Terminology Criteria for Adverse Events 5.0. Risk factors for RP were determined by univariate and multivariate logistic regression analysis.

Of the 42 patients included, 26 (61.9%) developed RP and 14 (33.3%) developed grade ≥ 2 RP. Grade ≥ 2 RP all occurred within 6 months of receiving TRT, and the median time from TRT to RP was 3.69 months (2-10 months). GTV ≥ 39 ml and total lung V20 ≥ 14.95% were found to be independent risk factors for RP development.

The strategy of combining a third-generation TKI with TRT significantly increases the incidence of RP, and the risk of RP in these patients can be reduced by adjusting lung radiation dosimetry parameters. In NSCLC patients taking triple-generation TKIs with primary tumour progression, the timing and dose of TRT addition must be strictly controlled to optimise the therapeutic strategy and reduce the incidence of RP.

Not applicable.

Kidney-sparing endoscopic surgery is considered the preferred approach for the treatment of low-risk upper tract urothelial cancer (UTUC), yet its impact on subsequent radical nephroureterectomy's (RNU) surgical complexity remains uncertain. This study aims to evaluate the effect of prior endoscopic procedures on peri-operative outcomes of UTUC patients undergoing RNU.

A retrospective analysis of 176 consecutive UTUC patients who underwent RNU from July 2008 to July 2023 at a single tertiary center. Demographic, clinical, and pathological data were recorded. The cohort was stratified based on the intention of endoscopic intervention: patients who did not undergo ureteroscopy and those who underwent a single diagnostic ureteroscopy only (non-mURS group) were compared to those who underwent multiple endoscopic treatments with laser ablation as part of a kidney-sparing strategy before RNU referral (mURS group). Statistical analyses addressed the correlations between ureteroscopy frequency and surgical complexity. Multivariate regression analysis was conducted to assess surgical complexity.

Among 176 patients who underwent RNU, 63 (35.7%) were included in the mURS group, and 113 (64.3%) in the non-mURS group. The mURS patients had longer RNU duration (306 ± 114 vs. 269 ± 114 min, p = 0.005), greater blood loss (hemoglobin decrease of 3.5 ± 1.1 vs. 1.02 ± 0.49 g/dL, p < 0.001), increased peri-ureteral adhesions (88.9% vs. 25.7%, p < 0.001), higher postoperative opioid use (87% vs. 53%, p < 0.001), and higher prevalence of fibrosis in pathology reports (88.9% vs. 30.9%, p < 0.001). No significant differences were found in post-operative complications.

Pre-RNU endoscopic treatment for UTUC is associated with increased surgical complexity of RNU without adversely affecting postoperative complication rates.

GLP-1 receptor agonists are a revolutionary treatment for obesity and investigations into other uses of these agents are ongoing. Epidemiologic data suggest that prostate cancer risk may decrease following GLP-1 receptor agonist initiation. To better define the potential role of GLP-1 receptor agonist use among men with prostate cancer, we will define changes that occur in men with prostate cancer following lifestyle intervention; illuminate the current relationship between these interventions and prostate cancer risk; and explore the potential mechanism of action on tumor biology, providing rationale for evaluating its effects on prostate cancer in a planned clinical trial.

The currently available clinical anticancer approaches pertaining to the treatment of prostate cancer are summarized here. After providing an overview of the main features of this highly impactful global disease, the currently available clinical treatments are briefly reviewed. Then, alternative and innovative nano-based therapeutic options that have been proposed or are currently being explored to significantly improve prostate cancer management (i.e. anti-prostate cancer polymeric nanoparticles loaded with drugs to promote their release and biological activity, including non-targeted and functionalized PLGA-PEG NPs and AuNPs), are introduced. Furthermore, the problem of gathering insights into the mechanistic aspects related to the fate of the nanoformulation in complex matrices, such as blood plasma, is addressed.

Metabolic abnormalities in gastric juice usually directly reflect pathological changes of the gastric mucosa. Accurate in-situ gastric metabolic dynamics acquisition is crucial for understanding the occurrence and development of gastric diseases but is challenging. Here, an integrated magnetoplasmonic system (MPS) for long-term spatiotemporal metabolic information profiling and ulcer assessment in vivo is presented. Porous calcium alginate-silver plasmonic hydrogel shell and FeCo@Graphene magnetic core were fabricated into the durable magnetoplasmonic system via a coaxial electrospinning technique. MPS pumped gastric juice through enriching, filtering and magnetic actuation, which had synergistic effect on improving efficient capture of free-metabolites with promotion of 9.76 times. Multiplexed metabolites vibration fingerprint profiles were concurrently determined both in harsh simulated gastric fluid (SGF) and isolated stomach models. We also successfully achieved acquisition of in-situ metabolites changes within rat stomach. Marginal histograms, derived from time-resolved surface-enhanced Raman spectroscopy (SERS) investigations of free small molecules adenine, tyrosine, and phenylalanine, suggested a positive correlation in metabolite levels across different stages. Moreover, ulcers revelation was accomplished with high precision through leveraging spectral dimensionality reduction and random forest classification of SERS profiles. Metabolites correlation analysis indicated that Raman signal appearing at 1602 cm-1 and 2112 cm-1 corresponding to phenylalanine and amine exhibited strong positive correlations following ulcer onset. This research represents the first endeavor to profile in-situ metabolic information within stomach and explore their correlations during the genesis of disease, demonstrating its potential in facilitating clinical diagnosis.

Rates of triple negative breast cancer (TNBC) are higher in Black women than in non-Hispanic White women. Breastfeeding duration and younger age at first birth are known risk factors for TNBC and vary by race. To quantify the contribution of these risk factors to disparities in TNBC, we calculated the population-attributable fraction (PAF). A PubMed search was performed to identify relevant studies and pooled odds ratios for breastfeeding for < 6 months and age at first birth < 25 years were calculated. PAF was calculated using the Levin formula. PAF of breastfeeding for < 6 months was 12% (95% confidence interval (CI) 5-20%) among White women and 15% (95%CI 3-26%) among Black women. We estimate that up to 15% of annual new TNBC in Black women and 12% in White women might be avoided by supporting breastfeeding. Policies supporting breastfeeding could hence reduce TNBC incidence and lessen racial disparities.