BMC Cancer[JOURNAL]
Sun
200 papers
Comparative efficacy of postoperative adjuvant chemoradiotherapy versus no chemoradiotherapy in the treatment of pancreatic adenocarcinoma.
Ren B, Guo Q, Ma J … +7 more , Zhu W, Wang Y, Feng Z, Shen Y, Zhu Y, Xie L, Peng Q
BMC Cancer · 2026 Jun · PMID 42380817 · Full text
BACKGROUND: The benefit of adjuvant chemoradiotherapy (CRT) for pancreatic adenocarcinoma (PAAD) is debated. This study aimed to elucidate the impact of adjuvant CRT on survival outcomes. METHODS: We searched major medic...
BACKGROUND: The benefit of adjuvant chemoradiotherapy (CRT) for pancreatic adenocarcinoma (PAAD) is debated. This study aimed to elucidate the impact of adjuvant CRT on survival outcomes. METHODS: We searched major medical databases for clinical and retrospective studies comparing postoperative CRT vs. no CRT in PAAD. Data were synthesized using RevMan 5.4 and Stata 17.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall survival (OS), local recurrence, and distant metastasis. RESULTS: Our analysis included 19 studies involving 4,581 patients. Adjuvant CRT was associated with a significant improvement in 2-year OS compared to no CRT (OR = 0.63, 95% CI: 0.53-0.76, P < 0.001). This benefit was consistent in subgroup analyses compared to chemotherapy alone (OR = 0.54, P = 0.0003) and the observation group (OR = 0.61, P < 0.001). The 5-year OS analysis showed a non-significant trend favoring CRT (OR = 0.66, 95% CI: 0.43-1.02, P = 0.06). In subgroup analyses, CRT was associated with a significant survival benefit compared with observation alone (OR = 0.67, 95% CI: 0.47-0.97, P = 0.03), but not compared with chemotherapy alone (OR = 0.57, 95% CI: 0.06-5.46, P = 0.62). Notably, patients with high-risk features, including lymph node-positive (2-year OS: OR = 0.47, P < 0.001; 5-year OS: OR = 0.53, P < 0.001) and margin-positive disease (2-year OS: OR = 0.45, P < 0.001), derived substantial survival benefits from CRT. Furthermore, CRT was significantly associated with reduced local recurrence rates (OR = 0.27, P = 0.008) but did not affect the incidence of distant metastasis (OR = 1.11, P = 0.72). CONCLUSIONS: This study shows that adjuvant CRT significantly improves 2-year OS and local tumor control in resected PAAD, especially for patients with lymph node metastasis. However, its effect on long-term (5-year) survival is limited, and it was not associated with distant metastasis. These findings support the selective use of adjuvant CRT for local control in high-risk patient subgroups, such as those with positive lymph nodes or positive surgical margins. Further research is needed to prospectively validate these findings and identify patients most likely to benefit.
Artificial intelligence for cervical cancer screening and diagnosis using Pap smear images: a systematic review.
Esmailzadeh A, Rashki Kemmak A, Rasoulian A … +2 more , Alizadeh Tabatabaei FS, Mazaheri Habibi MR
BMC Cancer · 2026 Jun · PMID 42380812 · Full text
BACKGROUND: Cervical cancer continues to be the second most prevalent type of cancer in women globally, especially in the less developed areas. Among several screening methods Pap test, more popularly known as the Papani...
BACKGROUND: Cervical cancer continues to be the second most prevalent type of cancer in women globally, especially in the less developed areas. Among several screening methods Pap test, more popularly known as the Papanicolaou test or Pap smear, is one of the most efficient ones for the early detection of this type of cancer. AI has recently made possible the large-scale screening of the whole process. This whole thing has been done in order to increase the early detection rates, which is the long-term aim of reducing the number of cases and deaths that are due to cervical cancer. OBJECTIVE: This systematic review aimed to investigate the role of artificial intelligence in the diagnosis of cervical cancer based on Pap smear results. METHODS: A comprehensive search was conducted in PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar from database inception to January 2025, with the final search update performed on January 30, 2025. The search strategy was designed using relevant keywords and their synonyms related to "artificial intelligence," "diagnosis," and "cervical cancer."This review included only the English-language studies that had investigated the application of AI in the diagnosis of cervical cancer using Pap test data. The titles and abstracts were initially reviewed by two independent reviewers, and subsequently, full-text assessment was carried out. Data extraction followed the use of standardized forms that collected information on study title, country, number of participants, study purposes, AI technique, error rate, accuracy, and performance outcomes. RESULTS: The initial search identified 844 studies, of which 22 met the inclusion criteria and were included in the final analysis. Most studies reported that AI-based algorithms improved the accuracy and efficiency of cervical cancer detection using Pap smear images. Deep learning and machine learning approaches demonstrated high diagnostic performance, with several studies reporting accuracy rates above 90%. CONCLUSION: AI-based approaches show considerable potential for improving the accuracy and timeliness of cervical cancer diagnosis using Pap smear analysis. However, further high-quality studies are required to validate these tools and support their integration into clinical practice.
Priority setting for the implementation of effective interventions for cancer prevention through collaboration among patients, the public and researchers in Japan.
Yamaguchi M, Nishihara M, Kaji Y … +8 more , Yamashita M, Odawara M, Saito J, Mimura A, Yamaki C, Inoue M, Nakayama T, Shimazu T
BMC Cancer · 2026 Jun · PMID 42380796 · Full text
BACKGROUND: Despite the availability of effective interventions for cancer prevention, Japan faces substantial evidence-practice gaps, such as in the low utilization of smoking cessation treatments, HPV vaccination, and...
BACKGROUND: Despite the availability of effective interventions for cancer prevention, Japan faces substantial evidence-practice gaps, such as in the low utilization of smoking cessation treatments, HPV vaccination, and cancer screening. Implementation research plays a critical role in bridging this gap by promoting the uptake of effective interventions in real-world settings. Globally, however, prioritization of the implementation of these various interventions remains unclear. To address this need, we conducted a structured priority-setting exercise using the CHNRI method and incorporating perspectives from diverse stakeholders, including citizens. METHODS: We conducted a four-phase research prioritization process using the CHNRI method to identify which effective interventions for cancer prevention should be prioritized for implementation in Japan. The process included listing effective interventions for cancer prevention, surveying stakeholders, conducting a web-based survey among researchers, and calculating priority scores. RESULTS: Among 215 invited researchers, 92 (42.8%) and 67 (31.2%) researchers responded to the first and second surveys, respectively. In both surveys, physicians accounted for the largest proportion of respondents. Across both surveys, HPV vaccination for females, cervical cancer screening, fecal occult blood testing (FOBT), mammography, and tobacco control policies were identified as top priorities. CONCLUSIONS: Priorities for implementing effective interventions for cancer prevention were set through collaboration with researchers and citizens, providing a foundation for future research and progress.
Association between comorbidities and major adverse cardiovascular events in patients undergoing immune checkpoint blockade.
Daetwyler E, Jauch A, Aeschlimann N … +4 more , Rommers N, Kasenda B, Zippelius A, Kuster GM
BMC Cancer · 2026 Jun · PMID 42374316 · Full text
BACKGROUND: Cancer patients have an increased risk for cardiovascular diseases (CVDs). Conflicting information exists regarding whether cancer treatment with immune checkpoint inhibitors (ICIs) itself increases the risk...
BACKGROUND: Cancer patients have an increased risk for cardiovascular diseases (CVDs). Conflicting information exists regarding whether cancer treatment with immune checkpoint inhibitors (ICIs) itself increases the risk for CVDs. We therefore assessed the incidence of major adverse cardiovascular events (MACE) in cancer patients treated with versus without ICIs. METHODS: One hundred fifty-eight and 163 cancer patients, treated with and without ICIs respectively, were compared. The primary endpoint was the incidence of MACE, defined as acute coronary syndrome, ischemic stroke, transient ischemic attack, new or worsening coronary artery disease or peripheral arterial occlusive disease, or cardiovascular death. We used Cox proportional hazard models and competing risk models (death), adjusted for age, sex and comorbidities (Charlson Comorbidity index, CCI) to investigate the cause-specific association between ICI-treatment and MACE. RESULTS: Over a median follow-up of 30.6 months, 37 MACE occurred. The overall incidence of MACE was 14.0% in patients with and 9.3% in patients without ICI-treatment. In the multivariate analysis CCI was significantly associated with MACE (HR 1.19, 95% CI [1.03, 1.37]), whereas no association was found for ICI-treatment (HR 1.12, 95% CI [0.56, 2.22]). Competing risk analysis showed no treatment associations. CCI was associated with non-cardiovascular mortality. CONCLUSIONS: We did not observe statistical evidence of an association between ICI treatment and MACE. There is evidence that a higher comorbidity burden is associated with MACE. Comorbidities are clearly associated with non-cardiovascular mortality in cancer patients. Further prospective studies are required to investigate whether treating comorbidities and optimizing cardiovascular risk factors result in improved outcomes among cancer patients.
Pre-operative proton versus photon-based chemoradiotherapy as an addition to best systemic therapy in the management of oesophageal cancer: protocol for the UK multi-centre randomised phase 2 PROTIEUS study.
Radhakrishna G, Jones CM, Bleaney CW … +21 more , Blackshaw J, Blencowe N, Brand D, Clarke CS, Gwynne S, Hava N, King A, Lewis GJ, Lopes A, Mak KM, Miles E, Mukherjee S, Nicholas O, Rashid M, Owczarczyk K, Shiu KK, Smyth E, Tattum J, Underwood T, Veiga C, Hawkins MA
BMC Cancer · 2026 Jun · PMID 42374301 · Full text
BACKGROUND: Oesophageal cancer is a major cause of morbidity and mortality. Around 40% of patients present with locally advanced disease. Outcomes are poor, with 5-year survival of around 50% for locally advanced oesopha...
BACKGROUND: Oesophageal cancer is a major cause of morbidity and mortality. Around 40% of patients present with locally advanced disease. Outcomes are poor, with 5-year survival of around 50% for locally advanced oesophageal adenocarcinoma (OAC) and 60% for oesophageal squamous cell carcinoma (OSCC). Over a fifth of recurrences are locoregional. These may be reduced by the addition of chemoradiotherapy (CRT) to best pre-operative systemic anti-cancer therapy (SACT). However, photon-based CRT is associated with a higher frequency of complications than chemotherapy alone. This study will explore whether, in patients with locally advanced OAC and OSCC managed with hypofractionated CRT following best pre-operative systemic therapy, the use of proton beam therapy (PBT) reduces post-operative complications when compared with photon-based treatment. METHODS/DESIGN: PROTIEUS is an investigator-initiated randomised multi-centre phase 2 trial aiming to recruit 170 patients with locally advanced OAC (n = 130) or OSCC (n = 40) from the UK National Health Service. Patients with locally advanced cT ≥ 2, N0-2 non-metastatic disease are eligible for inclusion and will be randomised 1:1 to receive 40.05 Gy (RBE) in 15 fractions over three weeks using either PBT or intensity modulated/rotational arc photon radiotherapy. All patients will receive three one-week cycles of concurrent intravenous carboplatin/paclitaxel. CRT will be delivered following best pre-operative SACT. The primary endpoint is the rate of severe post-operative complications within 90 days post-surgery (grade 3 or higher Clavien-Dindo classification and CTCAE v5.0). Secondary endpoints relate to efficacy (pathological complete response and clear resection margin rate, disease-free and overall survival), tolerability (completion of planned CRT regime, time to and completion of adjuvant therapy), morbidity (long-term quality of life measures) and health economics (cost-effectiveness analyses using EQ-5D-5 L and resource use assessments). DISCUSSION: There is a need to improve local control in OAC and OSCC. Given only modest gains with perioperative immune checkpoint inhibition and a disease landscape in which there are few targets for precision or personalised therapies, there are limited options to achieve further gains across the disease population using SACT. This study will therefore determine which of PBT or photon-based pre-operative CRT is the most tolerable and least toxic for integration into existing systemic treatment paradigms. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN50098578.
The prognostic significance of pretreatment systemic immune-inflammation index and prognostic nutritional index in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
Yang X, Fu P, Liu H
BMC Cancer · 2026 Jun · PMID 42374297 · Full text
BACKGROUND: Systemic immune-inflammation index (SII) and Prognostic nutritional index (PNI) are emerging inflammation-related indicators that have previously been linked to prognosis of cancer patients, but the results h...
BACKGROUND: Systemic immune-inflammation index (SII) and Prognostic nutritional index (PNI) are emerging inflammation-related indicators that have previously been linked to prognosis of cancer patients, but the results have been inconsistent. This meta-analysis aims to review and report the latest data regarding the prognostic value of the SII and PNI in cancer patients treated with immune checkpoint inhibitors (ICIs). METHODS: We searched the relevant literature in PubMed, Cochrane Library, and Embase databases from inception to February 15, 2026. Meta-analyses were performed for overall survival (OS) and progression-free survival (PFS) to assess the prognostic role of SII and PNI in cancer patients treated with ICIs. The pooled OS and PFS were estimated using hazard ratios (HR) with 95% confidence intervals (95% CI) by the random-effects model. Subgroup analysis was also conducted to investigate the correlation between indicators and study features. RESULTS: A total of 27 studies comprising 4000 patients treated with ICIs were included in this meta-analysis. In terms of the results based on multivariate analysis, the pooled results revealed that high SII level was an unfavorable predictor for OS (HR = 2.42, 95% CI = 1.88-3.10) and PFS (HR = 1.99, 95% CI = 1.36-2.90). In addition, lower level of PNI was correlated with worse OS (HR = 2.28, 95% CI = 1.68-3.08), as well as PFS (HR = 1.84, 95% CI = 1.56-2.17). Furthermore, subgroup analysis was conducted, and we found similar conclusions. CONCLUSION: Our findings support SII and PNI as promising biomarkers for adequately studied cancer types, but extending them to all malignancies requires prospective validation in less-studied cancers.
Cutaneous and mucosal melanoma among the Palestinian population: a retrospective clinicopathological study with comparative regional context.
Salhi I, Bannoura S, Abedaljawwad O … +1 more , Salah Z
BMC Cancer · 2026 Jun · PMID 42374290 · Full text
BACKGROUND: Cutaneous and mucosal melanoma are biologically and clinically distinct malignancies whose epidemiology varies markedly across populations and skin phototypes. In Arab and other Eastern Mediterranean populati...
BACKGROUND: Cutaneous and mucosal melanoma are biologically and clinically distinct malignancies whose epidemiology varies markedly across populations and skin phototypes. In Arab and other Eastern Mediterranean populations, melanoma is comparatively uncommon but is frequently diagnosed at an advanced stage and shows a relatively high proportion of acral and mucosal subtypes. Data describing melanoma in the Palestinian population are scarce. We characterised the clinicopathological profile of cutaneous and mucosal melanoma diagnosed at a large Palestinian diagnostic pathology service and placed the findings in a comparative regional context. METHODS: We performed a retrospective review of all histopathologically confirmed cases of cutaneous and mucosal melanoma reported at Medicare Diagnostic Laboratories, West Bank, Palestine, between May 2008 and May 2026. Demographic variables (age, sex), anatomical site, melanoma subtype, depth of invasion (Clark level), and, where recorded, Breslow thickness and American Joint Committee on Cancer (AJCC) stage were abstracted from pathology records. Diagnoses were confirmed on haematoxylin-eosin sections supported by immunohistochemistry (S100, SOX10, HMB-45, Melan-A). Repeat specimens were consolidated to the patient level, and findings were compared with published series from neighbouring countries. RESULTS: Fifty-seven patients with primary melanoma were identified, comprising 47 cutaneous (82.5%) and 10 mucosal (17.5%) tumours. The mean age at diagnosis was 59.5 +/- 17.0 years (range 10-87), and there was a slight female predominance (30 women, 52.6%; male-to-female ratio 0.90:1). Acral sites (sole, heel, plantar, and subungual regions) accounted for 15 of 47 cutaneous melanomas (31.9%), the most common single location, followed by the head and neck (14, 29.8%). Among mucosal tumours, the anorectum was the predominant site (6 of 10, 60%). A histological subtype was explicitly recorded in only 19 of 57 cases; within this limited subset the nodular pattern predominated (18 of 19), although the large proportion of cases without a stated subtype precludes firm conclusions about the true distribution of melanoma subtypes in this cohort. The Clark level was documented in 27 patients, of whom 26 (96.3%) had level IV-V (deep) invasion. A further 17 patients presented with metastatic melanoma deposits without a primary tumour in the archive. Melanoma in this Palestinian cohort was characterised by a slight female predominance, a high proportion of acral (31.9% of cutaneous) and mucosal (17.5% of all primary) tumours, a predominantly nodular phenotype among the subset of cases with a recorded subtype, and deep invasion at diagnosis. This profile mirrors patterns reported in neighbouring Arab and Eastern Mediterranean populations and contrasts with more lightly pigmented (Fitzpatrick I-II) Western populations. The findings underline the need for improved melanoma awareness, routine examination of acral and mucosal sites, and strengthened cancer registration in Palestine.
Urologic malignancy in renal transplant recipients: Analysis of OPTN/UNOS data from 2000 to 2022.
Hao X, Ye C, Lai W … +17 more , Xu J, Wu Y, Sun Y, Pang H, Lv C, Lv K, Yang G, Wang J, Gao Y, Lu Y, Huang S, Luo Z, Dong J, Zhao M, Zhang X, Chen H, Yuan Q
BMC Cancer · 2026 Jun · PMID 42374287 · Full text
PURPOSE: The increasing incidence of urologic malignancy after renal transplantation (RT) has become a leading cause of recipient mortality. However, no recent analyses have been performed to identify the risk factors fo...
PURPOSE: The increasing incidence of urologic malignancy after renal transplantation (RT) has become a leading cause of recipient mortality. However, no recent analyses have been performed to identify the risk factors for post-transplant urologic malignancy (PTUM) and to evaluate the effect of PTUM on RT outcomes. MATERIALS AND METHODS: This retrospective, population-based cohort study was based on Organ Procurement and Transplantation Network data. RESULTS: A total of 268,606 recipients underwent RT from January 2000 to December 2019 and met the inclusion criteria. Of these, 2,079 (0.77%), 1,983 (1.20% of male recipients), and 846 (0.32%) patients were diagnosed with renal cancer (RCa), prostate cancer (PCa), and bladder cancer (BCa), respectively, after RT. Urologic malignancy was a major cause of patient death after RT (RCa: 41.5%, PCa: 23.5%, BCa: 50.4%). The 5-year survival rates of the four groups ranking from best to worst were as follows: [95% confidence interval, lower value-upper value], PCa, 93.3% [92.2%-94.4%]; cancer-free, 87.2% [87.0%-87.3%]; RCa, 87.2% [85.8%-88.7%]; BCa, 81.0% [78.4%-83.7%] (P < 0.001 for all, except cancer-free vs. RCa, P = 1.00). CONCLUSIONS: The effects of PTUM on RT outcomes differ depending on the type of malignancy. Thus, a personalized approach to screening may be an appropriate strategy to address the multitude of complex issues that RT recipients encounter.
Timing and clinical burden of febrile neutropenia and treatment discontinuation during neoadjuvant chemotherapy.
Nakada K, Takada K, Gose A … +10 more , Nishimoto M, Nishikawa M, Kochi A, Watanabe C, Tauchi Y, Ogisawa K, Kinoshita H, Shibutani M, Morisaki T, Kashiwagi S
BMC Cancer · 2026 Jun · PMID 42374286 · Full text
BACKGROUND: Febrile neutropenia (FN) remains a major complication of neoadjuvant chemotherapy (NAC) and is a frequent cause of treatment disruption. However, FN is a heterogeneous clinical entity, and the impact of its t...
BACKGROUND: Febrile neutropenia (FN) remains a major complication of neoadjuvant chemotherapy (NAC) and is a frequent cause of treatment disruption. However, FN is a heterogeneous clinical entity, and the impact of its timing and clinical severity on treatment continuity has not been fully elucidated. This study aimed to characterize the timing and clinical burden of FN and to clarify their associations with treatment discontinuation during NAC. METHODS: We retrospectively analyzed 137 consecutive patients with HER2-positive breast cancer who received NAC. FN timing was assessed by chemotherapy cycle and days from NAC initiation, with early FN defined a priori as FN occurring at cycle ≤ 2. FN severity was evaluated based on the requirement for hospitalization. Treatment discontinuation was defined as premature discontinuation of NAC due to chemotherapy-related adverse events; dose reductions or treatment delays without permanent discontinuation were not included in this endpoint. Logistic regression analyses were performed to identify factors associated with treatment discontinuation. RESULTS: FN occurred in 18 patients (13.1%). The median time to FN onset was 46 days (interquartile range, 19-112), with half of FN events occurring by cycle 2. Although FN events were evenly distributed across chemotherapy cycles, cumulative incidence analysis revealed early clustering on a time-based scale. Hospitalization was required in 50.0% of patients with FN. Treatment discontinuation occurred in 8.4% of patients without FN, 11.1% of patients with non-hospitalized FN, and 44.4% of patients with hospitalized FN. Exploratory multivariable analyses demonstrated that hospitalized FN was associated with treatment discontinuation after adjustment for age and host-related factors (odds ratio, 11.20-13.33 across models), whereas low body mass index and reduced renal function were not independent predictors. CONCLUSIONS: The impact of FN on treatment continuity during NAC appears to be determined by both its timing and clinical severity. FN requiring hospitalization, particularly when occurring early during NAC, was associated with an increased likelihood of treatment discontinuation. These findings underscore the importance of early identification and prevention of severe FN to optimize treatment delivery during neoadjuvant chemotherapy, while recognizing the statistical uncertainty inherent to the limited number of events.
Reproductive factors and lung cancer risk in never-smoking women: a prospective cohort study.
Nie Y, Liang D, Jin Y … +9 more , Gao M, Li J, Wang S, Wu S, Shi J, Liu Y, Su X, Cui S, He Y
BMC Cancer · 2026 Jun · PMID 42374272 · Full text
BACKGROUND: The association between endogenous estrogen and lung cancer in never-smoking women remains unclear. This study investigated the associations of various reproductive factors, as proxies for cumulative estrogen...
BACKGROUND: The association between endogenous estrogen and lung cancer in never-smoking women remains unclear. This study investigated the associations of various reproductive factors, as proxies for cumulative estrogen exposure, with lung cancer risk among never-smoking women from a lung cancer screening cohort. METHODS: Associations between reproductive factors and lung cancer risk were evaluated using multivariable logistic regression and restricted cubic splines. Mediation analysis assessed the mediating role of body mass index (BMI). Subgroup analyses were stratified by baseline characteristics. Robustness was verified through propensity score matching and inverse probability of treatment weighting. RESULTS: The study included 155,103 never-smoking women, identifying 657 incident lung cancer cases. Early menarche (< 13 years: OR, 1.41; 95% CI, 1.06-1.87), a shorter reproductive span (≤ 32 years: OR, 1.25; 95% CI, 1.02-1.54), and parity (≥ 1) (OR, 2.02; 95% CI, 1.16-3.52) were associated with increased risk. Later age at first birth (≥ 30 years) (OR, 0.63; 95% CI, 0.41-0.98) and a history of benign breast disease (OR, 0.64; 95% CI, 0.47-0.87) were inversely associated with lung cancer risk, with age at first birth showing a non-linear dose-response relationship. Mediation analyses suggested a potential role of BMI in these associations. Stratified analyses revealed significant effect modification by age, BMI, and clinical history. CONCLUSION: Reproductive factors are associated with lung cancer risk among never-smoking women. Integrating reproductive histories into routine lung cancer screening programs will facilitate more precise risk stratification.
Nano-silymarin combined with methylene blue photodynamic therapy versus monotherapies of head and neck squamous cell carcinoma: in-vitro study.
Hefzi D, Koopaie M, Hakimiha N … +1 more , Younespour S
BMC Cancer · 2026 Jun · PMID 42374269 · Full text
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges due to its aggressiveness and the morbidity of conventional treatments. Photodynamic therapy (PDT) offers a localized...
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges due to its aggressiveness and the morbidity of conventional treatments. Photodynamic therapy (PDT) offers a localized approach, but its efficacy can be limited. This study investigated the potential of nano-silymarin, a bioactive flavonolignan complex with known anticancer properties, in combination with methylene blue-mediated PDT (MB-PDT) in HNSCC cells. METHODS: The cytotoxic, apoptotic, and anti-migratory effects of various treatments were assessed in HN5 cells. Groups included controls, individual agents (nano-silymarin, MB, laser), dual therapies, and the triple combination (nano-silymarin + MB + laser). Cell viability was measured using the MTT assay, apoptosis by flow cytometry, and migration by the scratch assay. Results were analyzed using one-way ANOVA with Tukey's post hoc test. Synergy was quantified using the Bliss independence, Loewe additivity, and zero interaction potency models. RESULTS: The triple combination (nano-silymarin + MB-PDT) demonstrated the most potent effect, synergistically reducing cell viability to 40.63% (compared with 69.65% for nano-silymarin and 77.32% for MB-PDT). It induced the highest level of total apoptosis (42.93%) and nearly completely inhibited cell migration (97.2% wound openness at 72 h). This anti-migratory effect was significantly greater than the sum of the effects of the individual monotherapies, indicating a synergistic blockade of cellular invasion. Synergy analysis confirmed a strong synergistic interaction, with a Combination index of 0.682. CONCLUSION: Nano-silymarin significantly potentiates the anticancer efficacy of MB-PDT against HNSCC cells through strong synergistic interactions, thereby enhancing cytotoxicity, apoptosis, and migration inhibition. These findings support further development of nano-silymarin in combinatorial PDT regimens for HNSCC.
Targeted genomic DNA sequencing (506-gene panel) and whole-exome sequencing analysis of EBV-positive inflammatory follicular dendritic cell sarcoma.
You Z, Chen S, Chen X … +2 more , Chen X, Wang C
BMC Cancer · 2026 Jun · PMID 42374265 · Full text
INTRODUCTION: Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS), recently reclassified in the 5th edition of the WHO classification of lymphoid neoplasms, is a rare mesenchymal and d...
INTRODUCTION: Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS), recently reclassified in the 5th edition of the WHO classification of lymphoid neoplasms, is a rare mesenchymal and dendritic cell tumor distinct from conventional follicular dendritic cell sarcoma (FDCS) in cellular origin and clinicopathological features. To address this, we present the largest sequencing cohort of EBV+ IFDCS to date, combining targeted next-generation sequencing (NGS) of 12 cases and whole-exome sequencing (WES) of 3 cases. This study aims to elucidate the molecular characteristics of EBV+ IFDCS to better understand its pathogenesis and identify potential therapeutic targets. MATERIALS AND METHODS: 12 EBV+ IFDCS cases were analyzed using next-generation sequencing (NGS) with a 506-gene panel, and whole-exome sequencing (WES) was performed on 3 cases. The analysis focused on identifying copy number variations (CNVs), gene fusions, and pathogenic mutations. KEGG pathway analysis was conducted to explore enriched oncogenic pathways. RESULTS: CNV analysis via WES identified focal chromosomal deletions in 2 of 3 cases: 7p and 14q deletions in Case 1, and 17p deletion plus deep deletions in NPRL2 (chromosome 3) and STK11 (chromosome 19) in Case 6. While pathogenic/drug-sensitive SNVs varied across the 12 patients (Fig. 2). Only Patient 3 (48-year-old female, splenic classical subtype EBV+ IFDCS) was TMB-H (11.2 mutations/Mb, ≥ 10 mutations/Mb as threshold), harboring NQO1 p.P187S (VAF = 32.6%) and a germline PKHD1 Class 3 VUS. This case had no unique somatic mutations vs. low-TMB cases, with histological features (fascicular spindle cells, moderate lymphoplasmacytic infiltration) consistent with the classical subtype (Fig. 1A). KEGG pathway analysis revealed enrichment in PI3K-AKT, cell cycle, Notch, and EBV infection pathways. WES of Patients 1, 6, 10 showed TMB-L (1.8-3.5 mutations/Mb); Patient 3's TMB-H (11.2 mutations/Mb, ≥ 10 mutations/Mb as solid tumor threshold) was validated via targeted NGS (723× coverage). WES of TMB-L cases revealed predominant missense mutations/SNVs (C > T transitions: 50% of SNPs, Fig. 5C), with 3-9 somatic mutations per case and no shared mutations-highlighting potential potential high tumor heterogeneity, further supported by Patient 3's unique TMB-H phenotype. CONCLUSION: This study reveals the unique molecular landscape of EBV+ IFDCS, characterized by frequent NQO1 mutations and activation of key oncogenic pathways. These findings provide critical insights into the tumor's pathogenesis and suggest potential molecular targets for future therapeutic strategies.
Assessing the prognostic value of SIL1 in pan-cancer cohorts and its practical application as a biomarker in glioma practice.
Liu P, Peng Y, Sun Y … +3 more , Hu S, Lv D, Yan Y
BMC Cancer · 2026 Jun · PMID 42374254 · Full text
BACKGROUND: Gliomas are aggressive brain tumors associated with a poor prognosis. Although SIL1, an endoplasmic reticulum chaperone factor, is known to maintain protein homeostasis, its specific role in glioma pathogenes...
BACKGROUND: Gliomas are aggressive brain tumors associated with a poor prognosis. Although SIL1, an endoplasmic reticulum chaperone factor, is known to maintain protein homeostasis, its specific role in glioma pathogenesis remains poorly understood. This study aimed to investigate the clinical significance and biological functions of SIL1 in glioma. METHODS: We performed a pan-cancer multi-omics analysis using TCGA and GTEx datasets to evaluate SIL1 expression, its prognostic value, and its associations with genomic instability, tumor stemness, and immune infiltration. Gene set enrichment analysis (GSEA) was utilized to identify potentially involved signaling pathways. For in vitro functional validation, human glioma cell lines (U251 and A172) were subjected to siRNA-mediated knockdown and lentiviral rescue assays to assess cellular proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) dynamics. RESULTS: SIL1 was significantly upregulated in gliomas and correlated with poor patient survival. High SIL1 expression was associated with increased tumor heterogeneity (based on MATH scores), DNA methylation-derived stemness indices, and an immunosuppressive microenvironment characterized by the enrichment of M2 macrophages, regulatory T cells (Tregs), and immune checkpoint molecules. In vitro, SIL1 knockdown suppressed glioma cell proliferation and invasion, promoted mitochondrial apoptosis, and mitigated the EMT phenotype, potentially by impairing SNAIL nuclear translocation. Notably, these phenotypic changes were effectively rescued following lentiviral overexpression of SIL1. CONCLUSION: Our findings suggest that SIL1 is a potential prognostic biomarker in glioma. Its elevated expression correlates with increased malignancy, stemness features, EMT, and an immunosuppressive microenvironment, indicating that SIL1 may serve as a promising therapeutic target for glioma intervention.
Single-cell transcriptomics reveals MAFB-driven macrophage reprogramming and immune divergence in recurrent glioblastoma.
He Y, Yu J, Huang M … +4 more , Lu P, Liu B, Zhang C, Zhang C
BMC Cancer · 2026 Jun · PMID 42374253 · Full text
BACKGROUND: Glioblastoma (GBM) is the most aggressive and most common type of primary brain tumor, with poor prognosis despite standard therapies. The mechanisms driving recurrence remain poorly understood. Tumor-associa...
BACKGROUND: Glioblastoma (GBM) is the most aggressive and most common type of primary brain tumor, with poor prognosis despite standard therapies. The mechanisms driving recurrence remain poorly understood. Tumor-associated macrophages (TAM) dominate the GBM microenvironment and promote tumor growth, angiogenesis, and immune suppression, yet their activation states and transcriptional programs are not well defined. RESULTS: By integrating large-scale single-cell transcriptomic datasets, we delineate profound immune microenvironmental divergence in recurrent GBM, characterized by the emergence of a distinct CXCL3⁺ tumor-associated macrophage (TAM) population. These CXCL3⁺ TAMs exhibit a robust pro-inflammatory cytokine program, intensified interactions with malignant and immunosuppressive immune cells, and a strong association with poor patient survival. Regulatory network analysis identifies MAFB as the central transcriptional regulator of this TAM state. MAFB is selectively enriched in macrophages, markedly upregulated in recurrent tumors, and strongly correlated with pro-inflammatory gene signatures. Immunohistochemistry and multiplex immunofluorescence further demonstrate an expanded population of MAFB⁺ mesenchymal-like TAMs in recurrent GBM. Depletion of MAFB in patient-derived GBM cells suppresses intracranial tumor growth and prolongs survival in vivo. CONCLUSIONS: Our study highlights profound immune remodeling in primary and recurrent GBM. We further define a MAFB-driven CXCL3⁺ macrophage program that shapes the immune landscape of recurrent GBM and underscore this axis as a promising target for microenvironmental reprogramming.
Integrated multi-omics analysis reveals folate metabolism-related genes as prognostic markers and therapeutic targets in clear cell renal cell carcinoma.
Lin J, Li S, Zhou Y … +10 more , Han Z, Chen W, Zheng H, Liu S, Dai J, Cheng W, Fu C, Deng W, Xi H, Zeng J
BMC Cancer · 2026 Jun · PMID 42374231 · Full text
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with high metastatic potential and therapeutic resistance, yet the role of folate metabolism in its pathogenesis and immune evasion remains uncle...
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with high metastatic potential and therapeutic resistance, yet the role of folate metabolism in its pathogenesis and immune evasion remains unclear. This study aims to develop and validate a folate metabolism-related gene (FMRG) scoring system to stratify patients by prognostic risk and immune phenotypes, and to explore the functional role of key FMRGs in ccRCC progression. METHODS: Using transcriptomic and clinical data from The Cancer Genome Atlas (TCGA), we developed a folate metabolism-related gene (FMRG) scoring system via integrative machine learning and validated it in an external cohort. We analyzed associations of the FMRG score with clinicopathological features, biological pathways, immune infiltration, therapeutic responsiveness, and drug sensitivity. Single-cell RNA sequencing and spatial transcriptomics mapped candidate gene expression, and in vitro experiments validated the functional role of NGF. RESULTS: A ten-gene prognostic model based on the FMRG score stratified ccRCC patients into groups with distinct clinical outcomes, immune profiles, and therapeutic responses. NGF was upregulated in ccRCC, with heterogeneous spatial expression. Functional assays showed that NGF enhances proliferation, migration, and invasion. CONCLUSIONS: This folate metabolism-based scoring framework facilitates prognostic stratification, tumor microenvironment characterization, and prediction of immunotherapy response in ccRCC. NGF is identified as a functional mediator of tumor progression, offering potential therapeutic targets and insights into metabolic-immune crosstalk.
Potential evaluation of SULT1A3 as an early diagnostic marker for nasopharyngeal carcinoma: a study based on serum proteomics screening and ELISA validation.
Lin Z, Song W, Liang W … +3 more , Liu J, Gan R, Wang Y
BMC Cancer · 2026 Jun · PMID 42365246 · Full text
BACKGROUND: Nasopharyngeal carcinoma (NPC) represents a highly prevalent and aggressive malignancy endemic to Southeast Asia. Early and accurate diagnosis is critical to improving survival outcomes; however, the absence...
BACKGROUND: Nasopharyngeal carcinoma (NPC) represents a highly prevalent and aggressive malignancy endemic to Southeast Asia. Early and accurate diagnosis is critical to improving survival outcomes; however, the absence of robust, stage-specific biomarkers remains a key obstacle to clinical implementation of early screening strategies. METHODS: We performed untargeted serum proteomic profiling using mass spectrometry in 15 treatment-naïve early-stage NPC patients and 15 VCA-IgA-positive healthy controls. Bioinformatics analyses were conducted to identify differentially expressed proteins (DEPs). Machine learning (random forest combined with recursive feature elimination) was employed to prioritize candidate biomarkers, which were subsequently verified using enzyme-linked immunosorbent assay (ELISA) in independent sample cohorts. RESULTS: In total, 1,428 serum proteins were identified, among which 1,410 were reliably quantified. We observed 31 upregulated and 189 downregulated proteins in NPC patients relative to controls. Spearman correlation analysis revealed significant associations: LTA4H (leukotriene A4 hydrolase) levels correlated with serum cell infiltration (r = 0.383, p = 0.032) and CD8 + T-cell abundance (r = 0.408, p = 0.021); both SULT1A3 (sulfotransferase family 1 A member 3) and FGL1 (fibrinogen-like protein 1) levels were positively associated with M1 macrophage infiltration (r = 0.510, p = 0.003 and r = 0.430, p = 0.015, respectively). In a preliminary validation cohort (n = 80), ELISA yielded AUC values of 0.631 (95% CI: 0.515-0.736, p = 0.04) for LTA4H, 0.787 (95% CI: 0.681-0.871, p < 0.001) for SULT1A3, and 0.688 (95% CI: 0.575-0.787, p = 0.002) for FGL1. In large-scale independent validation, SULT1A3 achieved an AUC of 0.826 (95% CI: 0.766-0.876; sensitivity = 78.89%, specificity = 75.47%) in cohort 1 (n = 196) and 0.796 (95% CI: 0.723-0.857; sensitivity = 76.67%, specificity = 76.67%) in cohort 2 (n = 150). CONCLUSIONS: Through an integrated workflow combining proteomic screening, machine learning prioritization, and multi-stage ELISA validation, we identified SULT1A3 as a candidate serum-based biomarker for early detection of NPC. Preliminary findings suggest that SULT1A3 may have potential utility in clinical screening, though further validation in independent, multi‑center cohorts is required.
Am80 (tamibarotene) and ATRA induce highly similar molecular responses and myeloid differentiation in non-APL AML, enhanced by LSD1/GCN5 inhibition and increased RARA expression.
Ghazvini Zadegan F, Stanko C, Fiedler F … +15 more , Ölsner L, Özcan SG, Schütt J, Schnöder TM, Sbirkov Y, Szymanski L, Stengel S, Dittrich P, Müller JP, Heidel FH, Hochhaus A, Scholl S, Schnetzke U, Brioli A, Schenk T
BMC Cancer · 2026 Jun · PMID 42365243 · Full text
BACKGROUND: Acute myeloid leukemia (AML) remains a challenging disease with a poor prognosis, necessitating more personalized therapeutic strategies. Retinoic acid receptor (RAR) activation is crucial for myeloid differe...
BACKGROUND: Acute myeloid leukemia (AML) remains a challenging disease with a poor prognosis, necessitating more personalized therapeutic strategies. Retinoic acid receptor (RAR) activation is crucial for myeloid differentiation, but non-APL AML cells resist differentiation induced by the pan-RAR agonist all-trans retinoic acid (ATRA). Am80 (tamibarotene), a specific RARA agonist, has been reported to partially overcome this resistance in AML with high RARA expression. However, its effects on myeloid differentiation, especially in comparison to ATRA, remain understudied. METHODS: In this study we compared the effects of Am80 and ATRA in non-APL AML samples, focusing on subsets with high RARA and/or RARG expression, using molecular and phenotypic differentiation assessments. RESULTS: In contrast to previous findings, Am80 showed no advantage over ATRA in inducing differentiation in AML cell lines or primary samples, regardless of RARA and RARG expression levels. Cotreatment with inhibitors of the epigenetic modifiers LSD1 and GCN5, which facilitates retinoid-induced myeloid differentiation, enhanced the effects of both Am80 and ATRA to the same extent, with more pronounced responses observed in RARA-high samples. Gene expression analysis revealed identical molecular responses to Am80 and ATRA. CONCLUSIONS: The study provides evidence that ATRA can be substituted by the more stable Am80 in retinoid-based AML therapies. It also identifies elevated RARA expression as a potential marker for sensitivity to combination therapy with retinoids and epigenetic inhibitors in AML.
Study protocol: targeted delivery of interleukin-12 in combination with hepatic artery infusion pump therapy for patients with adrenocortical carcinoma liver metastases.
Friedman LR, Smith EC, Sarvestani AL … +18 more , Eade AV, Ho J, Pu T, Larrain C, Hannah CE, Magee T, Smith KM, Satterwhite AA, Xiao S, Burke JF, Sinha S, Desai PP, Remmert K, Cavnar MJ, Gulley JL, Schlom J, Del Rivero J, Hernandez JM
BMC Cancer · 2026 Jun · PMID 42365236 · Full text
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy often detected at an advanced stage with limited effective treatment options beyond first-line chemotherapy. The liver is a common site of metas...
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy often detected at an advanced stage with limited effective treatment options beyond first-line chemotherapy. The liver is a common site of metastasis, and patients frequently present with substantial hepatic disease burden that precludes complete resection. Locoregional therapies, including hepatic artery infusion pump (HAIP) delivery of floxuridine, have not been thoroughly evaluated for treatment of ACC liver metastasis, likely due to its rare incidence and highly aggressive nature. PDS01ADC (previously referred to as NHS-IL12) is a novel antibody-drug conjugate designed to deliver the immunomodulatory cytokine interleukin-12 to areas of tumor necrosis and modulate the tumor microenvironment to support immune surveillance and cytotoxic tumor responses. Combination of PDS01ADC with HAIP therapy (HAIP-delivered floxuridine plus systemic chemotherapy) was recently found to be feasible for clinical evaluation by an interim analysis in patients with colorectal liver metastases. Patients who received PDS01ADC with HAIP therapy had extended overall survival compared to patients who received HAIP therapy alone in a nonrandomized prior sequential study. We discuss herein the rationale and initiation of a new clinical trial arm to evaluate HAIP therapy with PDS01ADC for patients with ACC liver metastasis who have failed standard of care therapy. METHODS: Patients with unresectable ACC liver metastasis and either resectable or no progressive extrahepatic disease will receive combination therapy including HAIP floxuridine and subcutaneous injection of PDS01ADC administered concurrently with systemic gemcitabine and oxaliplatin in 28-day cycles. The primary outcome measured is overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. Secondary outcomes measured in this study include intrahepatic and extrahepatic progression-free survival, overall survival, and safety of PDS01ADC combination therapy with HAIP-delivered floxuridine. DISCUSSION: For select patients with ACC liver metastasis, HAIP therapy with PDS01ADC may improve disease control and thereby prolong survival. TRIAL REGISTRATION: Study ID NCT05286814 version 2026-05-04; https://clinicaltrials.gov/study/NCT05286814.
Doxorubicin-loaded chitosan/gold nanoparticles enhance anticancer effects and reduce CLMAT3 and ZNRD1-AS1 expression in colorectal cancer cells.
Alizadeh F, Rajabi A, Goharmomayez S … +2 more , Fathi M, Safaralizadeh R
BMC Cancer · 2026 Jun · PMID 42365229 · Full text
BACKGROUND: Globally, colorectal cancer (CRC) stands as the second most lethal malignancy. Chemotherapeutic drugs have shown some limitations, including systemic toxicity and non-specificity. Nanocarriers such as chitosa...
BACKGROUND: Globally, colorectal cancer (CRC) stands as the second most lethal malignancy. Chemotherapeutic drugs have shown some limitations, including systemic toxicity and non-specificity. Nanocarriers such as chitosan/gold nanoparticles (CS/Au NPs) facilitate drug localization at tumor sites, thereby reducing off-target adverse effects. METHODS: Doxorubicin-loaded CS/Au NPs were synthesized, and their physicochemical properties were analyzed using Fourier transform infrared (FT-IR) spectroscopy and dynamic light scattering (DLS). HCT116 cells were treated with both free doxorubicin and CS/Au-DOX NPs. In vitro cytotoxic effects were evaluated using the MTT assay. Additionally, apoptosis induction, cell cycle arrest, and cellular uptake assay were examined by flow cytometry. The scratch assay used to evaluate the effect of CS/Au-DOX NPs on the cell migration potential of HCT116, and the expression levels of CLMAT3 and ZNRD1-AS1 were determined by qRT-PCR. RESULTS: CS/Au-DOX NPs exhibited high encapsulation efficiency (78%) with favorable nanoscale properties, and were markedly more potent than free doxorubicin against HCT116 cells (IC 0.5 vs. 3 µM). Flow cytometry revealed significant apoptosis induction, G2/M arrest, and enhanced cellular uptake in HCT116 following treatment with CS/Au-DOX NPs. These NPs also reduced the migration potential of CRC cells. In CRC tissues, CLMAT3 and ZNRD1-AS1 were upregulated, with CLMAT3 overexpression associated with lymph node metastasis, while both lncRNAs showed limited diagnostic value. Notably, CS/Au-DOX NPs downregulated CLMAT3 and ZNRD1-AS1 expression in HCT116 cells. CONCLUSION: CS/Au-DOX NPs substantially enhanced the anticancer efficacy of DOX in the HCT116 cell line. Furthermore, CLMAT3 and ZNRD1-AS1 exhibited only limited utility as diagnostic biomarkers in CRC, suggesting that their clinical applicability in early detection may be restricted.
A phase II study of cabozantinib in metastatic or unresectable refractory gastrointestinal stromal tumour(GIST): a single-centre study from India.
Ventrapragada N, Rastogi S, Singh K … +5 more , Singh A, Shamim SA, Gamanagatti S, Yadav R, Dash NR
BMC Cancer · 2026 Jun · PMID 42363143 · Full text
BACKGROUND: Beyond third-line therapy, options for metastatic/advanced GIST are limited, especially in low- and middle-income countries (LMICs) where access to fourth-line ripretinib is often restricted. Cabozantinib, a...
BACKGROUND: Beyond third-line therapy, options for metastatic/advanced GIST are limited, especially in low- and middle-income countries (LMICs) where access to fourth-line ripretinib is often restricted. Cabozantinib, a multi-kinase inhibitor targeting KIT and related resistance pathways, could serve as a pragmatic alternative. This Phase II study evaluated the efficacy and safety of cabozantinib in patients with metastatic/advanced GIST who had progressed after ≥ 3 prior Tyrosine Kinase Inhibitors (TKIs). METHODS: This is a single-arm phase II trial that enrolled patients with advanced GIST who had progressed on ≥ 3 TKIs with ECOG PS 0-2. Cabozantinib was given orally at 60 mg daily (40 mg if < 40 kg and/or ECOG PS 2). The primary endpoint was 3-month Progression Free Rate (PFR) by RECIST v1.1. Overall Response Rate (ORR) was assessed by RECIST v1.1 and Choi Criteria. Quality of Life (QoL) was done by EORTC-QLQ-C30. Using Ahern's single-stage phase II design, the trial tested whether cabozantinib could achieve a 3-month PFR of at least 25% in the fourth-line setting versus a null PFR of 5% or less. With a one-sided alpha of 0.05 and 90% power, the required sample size for this single-arm study was 25 patients. RESULTS: Sixteen patients were enrolled. The cohort had a median age of 54.3 years, and most patients were male (75%). Median prior lines were 3 (range 3-5), and 44% had ECOG PS 2. Primary sites were stomach (50%) and small intestine (25%). Liver was the predominant side of metastases (81.3%). Primary mutations included KIT exon 11 (56%), exon 9 (25%), and SDH-deficient GIST (12.5%); the most common secondary mutation pattern was exon 11 + 17 (43%). The 3-month PFR was 62.5% by RECIST v1.1, with median PFS of 4.0 months. ORR was 6.2% by RECIST and 18.8% by Choi criteria. Common grade 3 adverse events were hand-foot skin reaction (18.8%), hypertension (18.8%), and diarrhoea (12.5%). Treatment interruptions and dose reductions occurred in 80% and 73.3%, respectively. Overall, QoL and Global Health Status remained stable. CONCLUSION: Cabozantinib demonstrated clinically meaningful activity with manageable toxicity in refractory metastatic/advanced GIST after ≥ 3 TKIs, supporting its role as a potential option in LMIC contexts where ripretinib access is limited. Larger, comparative phase III trials are warranted to confirm efficacy and better define optimal patient selection and dosing strategies. TRIAL REGISTRATION: Trial Registration Number-CTRI/2024/06/068636. Our trial was registered with Clinical Trials Registry - India (CTRI) on 10/06/2024.
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