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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with extremely poor patient survival rates. A key reason for the poor prognosis is the lack of effective diagnostic tools to detect the disease at curable, premetastatic stages. Tumor surgical resection is PDAC's first‐line treatment, however distinguishing between cancerous and healthy tissue with current imaging tools remains a challenge. In this work, we report a DOTA‐based fluorescent probe targeting plectin‐1 for imaging PDAC with high specificity. To enable heterogeneous functionalization of the DOTA‐core with multiple targeting peptide units and the fluorophore, a novel, fully clickable synthetic route that proceeds in one pot was developed. Extensive validation of the probe set the stage for PDAC detection in mice and human tissue. Altogether, these findings may pave the way for improved clinical understanding and early detection of PDAC progression as well as more accurate resection criteria. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with extremely poor patient survival rates. A key reason for the poor prognosis is the lack of effective diagnostic tools to detect the disease at curable, premetastatic stages. Tumor surgical resection is PDAC's first‐line treatment, however distinguishing between cancerous and healthy tissue with current imaging tools remains a challenge. In this work, we report a DOTA‐based fluorescent probe targeting plectin‐1 for imaging PDAC with high specificity. To enable heterogeneous functionalization of the DOTA‐core with multiple targeting peptide units and the fluorophore, a novel, fully clickable synthetic route that proceeds in one pot was developed. Extensive validation of the probe set the stage for PDAC detection in mice and human tissue. Altogether, these findings may pave the way for improved clinical understanding and early detection of PDAC progression as well as more accurate resection criteria. [ABSTRACT FROM AUTHOR]

Purpose: The extent of tumor regression varies widely among locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). The purpose of this retrospectively study is to assess prognostic factors in LARC patients with NCRT, and further to analyze survival outcomes in patients with different tumor regression grades (TRGs). Methods: This study includes LARC patients who underwent NCRT and TME at our institution. We retrospectively analyzed the clinicopathological characteristics and survival of all patients, and performed subgroup analysis for patients with different TRGs. Survival differences were compared using the Kaplan-Meier method and the log rank test. Additionally, a multiple Cox proportional hazard model was used to identify independent prognostic factors. Results: The study included 393 patients, with 21.1%, 26.5%, 45.5%, and 6.9% achieving TRG 0, TRG 1, TRG 2, and TRG 3, respectively. The overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 89.4% and 70.7%, respectively. Patients who achieved TRG 0–3 had different 5-year OS rates (96.9%, 91.1%, 85.2%, and 68.8%, P = 0.001) and 5-year DFS rates (80.8%, 72.4%, 67.0%, 55.8%, P = 0.031), respectively. Multivariate analyses showed that the neoadjuvant rectal (NAR) score was an independent prognostic indicator for both overall survival (OS) (HR = 4.040, 95% CI = 1.792–9.111, P = 0.001) and disease-free survival (DFS) (HR = 1.971, 95% CI = 1.478–2.628, P ˂ 0.001). In the subgroup analyses, the NAR score was found to be associated with DFS in patients with TRG 1 and TRG 2. After conducting multivariate analysis, it was found that ypT stage was a significant predictor of DFS for TRG 1 patients (HR = 4.384, 95% CI = 1.721–11.168, P = 0.002). On the other hand, ypN stage was identified as the dominant prognostic indicator of DFS for TRG 2 patients (HR = 2.795, 95% CI = 1.535–5.091, P = 0.001). However, none of these characteristics was found to be correlated with survival in patients with TRG 0 or TRG 3. Conclusion: NAR score, in particular, appears to be the most powerful prognostic factor. It is important to consider various prognostic predictors for patients with different TRGs. [ABSTRACT FROM AUTHOR]

Background: The treatment of oral squamous cell carcinoma (OSCC) remains challenging and survival rates have not been improved significantly over the past decades. Integrins have been recognized driving the cancer progression and high expression levels cause poor outcomes in patients afflicted with OSCC. Integrin αvβ6 and its subunit integrin beta 6 (ITGB6) were discovered to enhance the invasiveness by providing beneficial effects on downstream pathways promoting the cancer progression. The objective of this study was to establish a CRISPR/Cas9-mediated knock out of ITGB6 in the human OSCC cell line HN and investigate the effects on the migration and proliferation ability. Methods: ITGB6 knock out was performed using the CRISPR/Cas9-system, RNPs, and lipofection. Monoclonal cell clones were achieved by limiting dilution and knock out verification was carried out by sanger sequencing and FACS on protein level. The effects of the knock out on the proliferation and migration ability were evaluated by using MTT and scratch assays. In addition, in silico TCGA analysis was utilized regarding the effects of ITGB6 on overall survival and perineural invasion. Results: In silico analysis revealed a significant impact of ITGB6 mRNA expression levels on the overall survival of patients afflicted with OSCC. Additionally, a significantly higher rate of perineural invasion was discovered. CRISPR/Cas9-mediated knock out of ITGB6 was performed in the OSCC cell line HN, resulting in the generation of a monoclonal knock out clone. The knock out clone exhibited a significantly reduced migration and proliferation ability when compared to the wildtype. Conclusions: ITGB6 is a relevant factor in the progression of OSCC and can be used for the development of novel treatment strategies. The present study is the first to establish a monoclonal CRISPR/Cas9-mediated ITGB6 knockout cell clone derived from an OSCC cell line. It suggests that ITGB6 has a significant impact on the proliferative and migratory capacity in vitro. [ABSTRACT FROM AUTHOR]

Background: Inherited variations in DNA double-strand break (DSB) repair pathway are known to influence ovarian cancer occurrence, progression and treatment response. Despite its significance, survival-associated genetic variants within the DSB pathway remain underexplored. Methods: In the present study, we performed a two-phase analysis of 19,290 single-nucleotide polymorphisms (SNPs) in 199 genes in the DSB repair pathway from a genome-wide association study (GWAS) dataset and explored their associations with overall survival (OS) in 1039 Han Chinese epithelial ovarian carcinoma (EOC) patients. After utilizing multivariate Cox regression analysis with bayesian false-discovery probability for multiple test correction, significant genetic variations were identified and subsequently underwent functional prediction and validation. Results: We discovered a significant association between poor overall survival and the functional variant GEN1 rs56070363 C > T (CT + TT vs. TT, adjusted hazard ratio (HR) = 2.50, P < 0.001). And the impact of GEN1 rs56070363 C > T on survival was attributed to its reduced binding affinity to hsa-miR-1287-5p and the resultant upregulation of GEN1 mRNA expression. Overexpression of GEN1 aggregated EOC cell proliferation, invasion and migration presumably by influencing the expression of immune inhibitory factors, thereby elevating the proportion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and then constructing an immunosuppressive tumor microenvironment. Conclusions: In conclusion, GEN1 rs56070363 variant could serve as a potential predictive biomarker and chemotherapeutic target for improving the survival of EOC patients. Highlights: Inherited variations in DSB repair pathway are known to influence ovarian cancer occurrence, progression and treatment response. In the present study, we performed a two-phase analysis of 19,290 SNPs in 199 genes in the DSB repair pathway among 1,039 ovarian cancer patients. Ultimately, we identified that the poor overall survival was significantly associated with functional variant GEN1 rs56070363 C > T. Further investigations revealed the mechanism underlying this association: the C > T transition resulted in decreased binding affinity to hsa-miR-1287-5p and subsequent upregulation of GEN1 mRNA expression. Overexpression of GEN1 aggregated EOC cell proliferation, invasion and migration presumably by influencing the expression immune inhibitory factors, thereby elevating the proportion of PMN-MDSCs and then constructing an immunosuppressive tumor microenvironment. Our findings thus provide novel molecular targets and a theoretical basis for individualized treatment approaches in ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: As gastric cancer patients aged ≥ 85 years have a short life expectancy and often die from other diseases such as pneumonia, indications for surgery are controversial. In this study, we retrospectively analyzed the prognostic factors of elderly patients with gastric cancer who are candidates for curative gastrectomy. Methods: Among 114 patients aged ≥ 85 years with gastric cancer at our hospital between 2010 and 2019, prognostic factors were examined using the Cox proportional hazards model in 76 patients excluding those with cStage IVB or endoscopic submucosal dissection. We also analyzed the factors of pneumonia death. Results: cStage was I/IIA/IIB/III/IVA in 37/6/14/14/5 patients, respectively. Treatment included distal gastrectomy in 28 patients, total gastrectomy in 6, local resection in 9, others in 3, and no surgery in 30. In univariate analyses of overall survival, Eastern Cooperative Oncology Group Performance Status, physiological score of Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), Onodera's prognostic nutritional index, cStage, and treatment were prognostic factors. In a multivariate analysis, POSSUM physiological score, cStage, treatment method {no surgery vs. distal gastrectomy: hazard ratio (HR) 5.78, 95% confidence interval (CI) 2.33–14.3}, (total gastrectomy vs. distal gastrectomy: HR 4.26, 95% CI 1.22–14.9) were independent prognostic factors. In univariate analyses of pneumonia-specific survival, treatment (total gastrectomy vs. distal gastrectomy: HR 6.98, 95% CI 1.18–41.3) was the only prognostic factor. Conclusions: The prognosis of distal gastrectomy was better than that of non-surgery even in patients aged ≥ 85 years. However, total gastrectomy was considered to be avoidable due to the high rate of postoperative pneumonia death. [ABSTRACT FROM AUTHOR]

Diffuse large B‐cell Lymphoma (DLBCL) is an aggressive subtype of non‐Hodgkin lymphoma (NHL). The disease generally occurs in older patients. Although at a lower prevalence, the disease also occurs in the adolescent and young adult group (AYA). There is paucity of data in the literature on racial and ethnic disparities in the incidence and survival outcomes of DLBCL in the AYA group. The objective of our study is to demonstrate the disparities in these outcomes. Utilizing SEER, we obtained data on patient demographics, incidence, and survival from 2000 to 2020. We observed statistically significant reduced incidence of DLBCL in all racial groups, except the non‐Hispanic Asian and Pacific Islander group (NHAPI). The non‐Hispanic Black group (NHB) had one of the lowest survival despite showing the largest decrease in incidence in DLBCL. The differences in the survival could be secondary to socioeconomic factors, however other reasons need to be explored. The increased incidence among the NHAPI group mirrors that of large population‐based studies in East Asian countries, however, underlying reasons have not been elucidated. [ABSTRACT FROM AUTHOR]

Objective: Using the preoperative pan-immune-inflammation value (PIV) and the monocyte to high-density lipoprotein ratio (MHR) to reflect inflammation, immunity, and cholesterol metabolism, we aim to develop and visualize a novel nomogram model for predicting the survival outcomes in patients with colorectal cancer (CRC). Methods: A total of 172 patients with CRC who underwent radical resection were retrospectively analyzed. Survival analysis was conducted after patients were grouped according to the optimal cut-off values of PIV and MHR. Univariate and multivariate analyses were performed using Cox proportional hazards regression to screen the independent prognostic factors. Based on these factors, a nomogram was constructed and validated. Results: The PIV was significantly associated with tumor location (P < 0.001), tumor maximum diameter (P = 0.008), and T stage (P = 0.019). The MHR was closely related to gender (P = 0.016), tumor maximum diameter (P = 0.002), and T stage (P = 0.038). Multivariate analysis results showed that PIV (Hazard Ratio (HR) = 2.476, 95% Confidence Interval (CI) = 1.410–4.348, P = 0.002), MHR (HR = 3.803, 95%CI = 1.609–8.989, P = 0.002), CEA (HR = 1.977, 95%CI = 1.121–3.485, P = 0.019), and TNM stage (HR = 1.759, 95%CI = 1.010–3.063, P = 0.046) were independent prognostic indicators for overall survival (OS). A nomogram incorporating these variables was developed, demonstrating robust predictive accuracy for OS. The area under the curve (AUC) values of the predictive model for 1-, 2-, and 3- year are 0.791,0.768,0.811, respectively. The calibration curves for the probability of survival at 1-, 2-, and 3- year presented a high degree of credibility. Furthermore, Decision curve analysis (DCA) for the probability of survival at 1-, 2-, and 3- year demonstrate the significant clinical utility in predicting survival outcomes. Conclusion: Preoperative PIV and MHR are independent risk factors for CRC prognosis. The novel developed nomogram demonstrates a robust predictive ability, offering substantial utility in facilitating the clinical decision-making process. [ABSTRACT FROM AUTHOR]

Summary: In this multicentre, real‐world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) in T‐lymphoblastic lymphoma (T‐LBL). A total of 130 Ann Arbor stage III or IV T‐LBL patients (>16 years) treated with allo‐HSCT across five transplant centres were enrolled. The 2‐year cumulative incidence of disease progression, the probabilities of progression‐free survival (PFS), overall survival (OS) and non‐relapse mortality (NRM) after allo‐HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo‐HSCT in non‐remission (NR) had a poorer PFS compared with those receiving allo‐HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo‐HSCT, measurable residual disease (MRD) positivity before allo‐HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo‐HSCT in NR were associated with disease progression. Thus, our real‐world data suggested that allo‐HSCT appeared to be an effective therapy for adult T‐LBL patients with Ann Arbor stage III or IV disease. [ABSTRACT FROM AUTHOR]

Summary: Although progression‐free survival (PFS) is a commonly used surrogate end‐point for clinical trials of follicular lymphoma (FL), no analyses have evaluated the strength of surrogacy for PFS with overall survival (OS). A systematic review was performed and 20 studies (total participants, 10 724) met final inclusion criteria. PFS was weakly associated with OS (correlation coefficient; 0.383, p < 0.001). The coefficient of determination was 0.15 (95% CI: 0.002–0.35) suggesting 15% of OS variance could be explained by changes in PFS. This challenges the role for PFS as a surrogate end‐point for clinical trials and drug approvals. [ABSTRACT FROM AUTHOR]

Summary: Targeted therapy development for acute myeloid leukaemia (AML) requires an understanding of specific expression profiles. We collected flow cytometry data on 901 AML patients and recorded aberrant CD7 expression on leukaemic blasts. 263 (29.2%) had blasts positive for CD7. CD7+ AML was more likely to be adverse risk (64.6% vs. 55.6%, p = 0.0074) and less likely to be favourable risk (15.2% vs. 24.1%, p = 0.0074) by European LeukemiaNet 2022 criteria. Overall survival was inferior (11.9 [95% CI, 9.7–15.9] vs. 19.0 months [95% CI, 16.1–23.0], p = 0.0174). At relapse, 30.4% lost and 19.0% gained CD7, suggesting moderate instability over time. [ABSTRACT FROM AUTHOR]

Summary: The bendamustine–rituximab (BR) schedule is an efficient first‐line therapy in Waldenström macroglobulinaemia (WM). A previous analysis of 69 patients who received this treatment confirmed a high response rate and good progression‐free (PFS) and overall survival (OS). With a median follow‐up of 76.1 months (95% confidence interval [CI] 69.9–80.6), 5‐year outcome is still excellent at 66.63% (95% CI 56.09–79.17) for PFS and 80.01% (95% CI 70.82–90.41) for OS. The rate of secondary cancers is 17.66% (IQR 7.99–27.64) at 66 months. Relapsed patients who received ibrutinib as second‐line clearly benefited from this schedule. This confirms current recommendations suggesting BR long‐term efficacy as first‐line option in WM. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. Methods: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. Results: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). Conclusions: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic marker in several types of malignant tumors. Prognostic value of HALP score remains unclear for MDS. To determine the prognostic value of baseline HALP score in MDS. We retrospectively analyzed data from 130 newly diagnosed MDS patients evaluated and classified under HALP score. By the receiver operating characteristic (ROC) analysis, the optimal cut-off value of HALP was > 67.5 in predicting mortality. Patients were divided into two groups: with low and high HALP scores, and the characteristics were compared between both groups. Patients' median age was 68 (19–84) years, and 79 (60.8%) were male. Higher HALP score was detected in MDS patients with intermediate-risk under IPSS score, and at high and very high risks under IPSS-R score, and those receiving azacitidine (AZA) treatment. The survival rates of those with a HALP score > 67.5 were significantly lower than those with low HALP score at 17.77 ± 3.98 (median ± SE) (p < 0.001). The 3-, 5- and 10-years survival rates of individuals with HALP scores > 67.5 were found as 25, 18, and 11%, respectively. Median overall survival (OS) was also determined as 33.10 (95% CI 16.34–49.88) months by the Kaplan–Meier method. HALP score has shown an ability to be a useful prognostic biomarker in various cancers, including MDS. The meaningful cut-off value of HALP is disease-specific and largely study-specific. High HALP score is associated with unfavorable clinicopathological characteristics. Also, it may be useful in predicting OS and mortality of MDS. [ABSTRACT FROM AUTHOR]

Background: Penpulimab, a new‐generation antiprogrammed cell death‐1 immunoglobulin G1 monoclonal antibody, was engineered to optimize receptor occupancy and eliminate fragment crystallizable γ‐mediated effector function. In this multicenter, phase 1b/2, multicohort study, the objective was to investigate the efficacy, safety, and immunogenicity of penpulimab in advanced solid tumors. Methods: Patients who had unresectable, advanced solid tumors were enrolled from six centers and received 200 mg penpulimab on day 1 every 2 weeks for up to 24 months. The primary end point was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors, version criteria 1.1. Results: Between September 2, 2019, and January 1, 2020, 65 patients were enrolled and received penpulimab. At the time of data cutoff (May 11, 2022), the median follow‐up was 12.6 months (range, 1.1–28.6 months). The ORR was 12.3 (95% confidence interval [CI], 5.5%–22.8%), with three (4.6%) complete responses and five (7.7%) partial responses. Twelve patients (18.5%) achieved stable disease, resulting in a disease control rate of 30.8% (95% CI, 19.9%–43.4%). The median duration of response was not reached (95% CI, 6.70 months to not estimable). In all cohorts, the median progression‐free survival was 1.74 months (95% CI, 1.41–2.69 months), and the median overall survival was 16.59 months (95% CI, 7.82–22.18 months). Grade 3 or greater treatment‐related adverse events and immune‐related adverse events occurred in 9.2% and 27.7% of patients, respectively. Positive antidrug antibody responses to penpulimab were observed in one patient (1.8%). Conclusions: Penpulimab showed promising antitumor activity with an acceptable safety profile, offering a potential new treatment approach for solid tumors. These findings supported the evaluation of penpulimab's durable activity and safety, as monotherapy or in combination therapy, in specific malignancies. Penpulimab, as a novel antiprogrammed cell death‐1 immunoglobulin G1 monoclonal antibody, was engineered to eliminate fragment crystallizable γ receptor binding and fragment crystallizable‐mediated effector functions. Penpulimab showed durable clinical benefits and a favorable safety profile without unexpected safety concerns in solid tumors. [ABSTRACT FROM AUTHOR]

Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P <.001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). Methods: Retrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis. Results: Twelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89–30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61–7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67–43.33 months) for Group 3 (n = 4), and 19 months (range 7.89–30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004). Conclusion: Surgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with operable non-small-cell lung carcinoma (NSCLC). By constructing the nomogram model, it can provide a reference for clinical work. Methods: A total of 899 patients with non-small cell lung cancer who underwent surgery in our hospital between January 2017 and June 2021 were retrospectively included. ALI was calculated by body mass index (BMI) × serum albumin/neutrophil to lymphocyte ratio (NLR). The optimal truncation value of ALI was obtained using the receiver operating characteristic (ROC) curve and divided into two groups. Survival analysis was represented by the Kaplan-Meier curve. The predictors of Overall survival (OS) were evaluated by the Cox proportional risk model using single factor and stepwise regression multifactor analysis. Based on the results of multi-factor Cox proportional risk regression analysis, a nomogram model was established using the R survival package. The bootstrap method (repeated sampling 1 000 times) was used for internal verification of the nomogram model. The concordance index (C-index) was used to represent the prediction performance of the nomogram model, and the calibration graph method was used to visually represent its prediction conformity. The application value of the model was evaluated by decision curve analysis (DCA). Results: The optimal cut-off value of ALI was 70.06, and the low ALI group (ALI < 70.06) showed a poor survival prognosis. In multivariate analyses, tumor location, pathological stage, neuroaggression, and ALI were independently associated with operable NSCLC-specific survival. The C index of OS predicted by the nomogram model was 0.928 (95% CI: 0.904–0.952). The bootstrap self-sampling method (B = 1000) was used for internal validation of the prediction model, and the calibration curve showed good agreement between the prediction and observation results of 1-year, 2-year, and 3-year OS. The ROC curves for 1-year, 2-year, and 3-year survival were plotted according to independent factors, and the AUC was 0.952 (95% CI: 0.925–0.979), 0.951 (95% CI: 0.916–0.985), and 0.939 (95% CI: 0.913–0.965), respectively. DCA shows that this model has good clinical application value. Conclusion: ALI can be used as a reliable indicator to evaluate the prognosis of patients with operable NSCLC, and through the construction of a nomogram model, it can facilitate better individualized treatment and prognosis assessment. [ABSTRACT FROM AUTHOR]

AbstractObjective: To evaluate the overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) receiving either ibrutinib monotherapy as a first-line (1L) treatment or chemotherapy/chemoimmunotherapy-based (CT/CIT) regimens in 1L followed by ibrutinib in the second line (1L CT/CIT-2L ibrutinib) after disease progression by emulating a randomized trial comparing both treatment sequences.Methods: Patient-level data from the RESONATE-2 trial (NCT01722487) and real-world PHEDRA databases were analyzed. Three scenarios were considered using the following data sources: (1) RESONATE-2, (2) combined RESONATE-2/PHEDRA, (3) combined RESONATE-2/PHEDRA for 1L ibrutinib and PHEDRA for 1L CT/CIT-2L ibrutinib. Propensity score-based weights and inverse probability of censoring weighting were used to adjust for baseline (Scenarios 2 and 3) and time-dependent confounding (all scenarios), and to address potential biases. A weighted Cox proportional hazards model was used to estimate the OS hazard ratio (HR) and 95% confidence interval (CI) for 1L ibrutinib versus 1L CT/CIT-2L ibrutinib.Results: Results from Scenario 1 showed a significantly lower risk of death with 1L ibrutinib compared with 1L chlorambucil followed by 2L ibrutinib (HR 0.35 [95% CI 0.20–0.62]). Results from Scenarios 2 and 3 demonstrated a reduced risk of death with 1L ibrutinib compared with 1L CT/CIT-2L ibrutinib (HR 0.35 [0.21–0.61] and 0.64 [0.39–1.04], respectively).Conclusion: The analyses consistently showed a reduced risk of death when ibrutinib was used as a 1L treatment in CLL compared to delaying its use until 2L after CT/CIT regimens, which suggests that initiating ibrutinib in 1L is advantageous for improving survival outcomes. [ABSTRACT FROM AUTHOR]

To evaluate the prognostic value of biomarkers from peripheral blood obtained as routine laboratory assessment for overall survival in a cohort of stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiochemotherapy at a high-volume cancer center. Seven blood biomarkers from 160 patients treated with definitive radiochemotherapy for stage III NSCLC were analyzed throughout the course treatment. Parameters were preselected using univariable and multivariable proportional hazards analysis and were assessed for internal validity using leave-one-out cross validation. Cross validated classifiers including biomarkers in addition to important clinical parameters were compared with classifiers containing the clinical parameters alone. An increased C-reactive protein (CRP) value in the final week of radiotherapy was found as a prognostic factor for overall survival, both as a continuous (HR 1.099 (1.038–1.164), p < 0.0012) as well as categorical variable splitting data at the median value of 1.2 mg/dl (HR 2.214 (1.388–3.531), p < 0.0008). In the multivariable analysis, the CRP value-maintained significance with an HR of 1.105 (1.040–1.173) and p-value of 0.0012. The cross validated classifier using CRP at the end of radiotherapy in addition to clinical parameters separated equally sized high and low risk groups more distinctly than a classifier containing the clinical parameters alone (HR = 2.786 (95% CI 1.686–4.605) vs. HR = 2.287 (95% CI 1.407–3.718)). Thus, the CRP value at the end of radiation therapy has successfully passed the crucial cross-validation test. The presented data on CRP levels suggests that inflammatory markers may become increasingly important during definitive radiochemotherapy, particularly with the growing utilization of immunotherapy as a consolidation therapy for stage III NSCLC. [ABSTRACT FROM AUTHOR]

Background: The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood. Methods: This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the "limma" package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration. Results: Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment. Conclusions: The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value. [ABSTRACT FROM AUTHOR]

Summary: Background: With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas. Methods: Data from adult patients with brainstem glioma at Hokkaido University Hospital between 2006 and 2022 were retrospectively analyzed. Patient characteristics, treatment methods, genetic features, and prognosis were evaluated. Results: Of 12 patients with brainstem glioma with proven histopathology, 4 were identified with IDH mutation. All patients underwent local radiotherapy with 54 Gray in 27 fractions combined with chemotherapy with temozolomide. Three patients had IDH1 R132H mutation and one had IDH2 R172G mutation. The median progression-free survival and overall survival were 68.4 months and 85.2 months, respectively, longer than that for IDH-wildtype gliomas (5.6 months and 12.0 months, respectively). At the time of initial onset, contrast-enhanced lesions were observed in two of the four cases in magnetic resonance imaging. Conclusion: As some adult brainstem gliomas have IDH mutations, and a clearly different prognosis from those with IDH-wildtype, biopsies are proactively considered to confirm the genotype. [ABSTRACT FROM AUTHOR]

Background: Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables. Methods: This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001–2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools. Results: Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival. Conclusions: We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management. [ABSTRACT FROM AUTHOR]

AbstractSince 1980’s, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patientsfrom a clinical trial with a matched population from the Swedish AML Registrytreated withan increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successfulpropensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio:0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, andremission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group. [ABSTRACT FROM AUTHOR]

Background: A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to patients with HNSCCs related to tobacco and alcohol abuse. In the microenvironment of solid tumors, including HNSCCs, oxygen levels are often reduced, and a hypoxic state is induced. This can lead to a poor treatment response and a worse patient prognosis. One of the hypoxia-responsive genes is aspartate-β-hydroxylase (ASPH), whose activity promotes the growth, invasiveness, and metastasis of many types of solid tumors. Methods: In our study, HNSCC samples were analyzed for the expression of ASPH and selected endogenous hypoxia markers by real-time PCR and/or multiplex fluorescence immunohistochemistry. Results: Except for the EPAS1 gene, which had higher mRNA expression in the HPV-negative group of HNSCC (p < 0.05), we found no other differences in the expression of the tested genes that were related to HPV status. On the contrary, a statistically significantly higher number of cells producing ASPH (p < 0.0001), HIF1A (p < 0.0001), GLUT1 (p < 0.0001), and MMP13 (p < 0.05) proteins were detected in the HPV-positive tumor group than in the HPV-negative sample group. All the evaluated markers, except for MMP9/13, were more abundant in the tumor parenchyma than in the tumor stroma. The Cox proportional hazard models showed that increased numbers of cells with GLUT1 and HIF1A protein expression were positive prognostic markers for overall and disease-specific survival in patients independent of HPV tumor status. Conclusion: The study examined HNSCC samples and found that elevated ASPH and hypoxia marker proteins, typically associated with poor prognosis, may actually indicate active HPV infection, the strongest prognostic factor in HNSCC patients. In cases where HPV status is uncertain, increased expression of HIF1A and GLUT1 can serve as positive prognostic factors. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive prostate cancer (mHSPC). Methods: We conducted a systematic search through the databases of PubMed®, Web of Science®, and Cochrane library® in April 2023 based on the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement. A pooled meta-analysis was performed to assess the prognostic differences between LT + HT and HT alone according to randomized and non-randomized controlled studies (RCTs and NRCTs, respectively). Results: The search identified three RCTs and eight NRCTs. In RCTs, LT did not show prognostic benefits regarding biochemical-failure free rate nor overall survival (OS), although in patients with low tumor burdens, the LT + HT group showed better OS (HR: 0.68, 95% CI: 0.54–0.86). In the NRCTs, the LT+HT group showed superior progression-free survival (hazard ratio (HR): 0.42, 95% confidence interval (CI): 0.21–0.87), cancer-specific survival (HR: 0.39, 95% CI: 0.20–0.76), and OS (HR: 0.63, 95% CI: 0.57–0.69) to the HT alone group. In addition, better OS was observed in the LT +HT group regardless of the type of treatment modality for LT; radical prostatectomy (HR: 0.52, 95% CI: 0.39–0.69), radiotherapy (HR: 0.63, 95% CI: 0.56–0.71) in NRCTs. Conclusions: LT to the primary lesion in metastatic hormone-sensitive prostate cancer may provide prognostic benefits and especially in patients with low tumor burden. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a prevalent malignancy with a pressing need for improved therapeutic response and prognosis prediction. This study delves into a novel predictive model related to ferroptosis, a regulated cell death mechanism disrupting metabolic processes. Results: Single-cell sequencing data analysis identified subpopulations of HCC cells exhibiting activated ferroptosis and distinct gene expression patterns compared to normal tissues. Utilizing the LASSO-Cox algorithm, we constructed a model with 10 single-cell biomarkers associated with ferroptosis, namely STMN1, S100A10, FABP5, CAPG, RGCC, ENO1, ANXA5, UTRN, CXCR3, and ITM2A. Comprehensive analyses using these biomarkers revealed variations in immune infiltration, tumor mutation burden, drug sensitivity, and biological functional profiles between risk groups. Specific associations were established between particular immune cell subtypes and certain gene expression patterns. Treatment response analyses indicated potential benefits from anti-tumor immune therapy for the low-risk group and chemotherapy advantages for the high-risk group. Conclusions: The integration of this single-cell level model with clinicopathological features enabled accurate overall survival prediction and effective risk stratification in HCC patients. Our findings illuminate the potential of ferroptosis-related genes in tailoring therapy and prognosis prediction for HCC, offering novel insights into the intricate interplay among ferroptosis, immune response, and HCC progression. [ABSTRACT FROM AUTHOR]

AbstractIndolent cancers are characterized by long overall survival (OS) times. Therefore, powering a clinical trial to provide definitive assessment of the effects of an experimental intervention on OS in a reasonable timeframe is generally infeasible. Instead, the primary outcome in many pivotal trials is an intermediate clinical response such as progression-free survival. In several recently reported pivotal trials of interventions for indolent cancers that yielded promising results on an intermediate outcome, however, more mature data or post-approval trials showed concerning OS trends. These problematic results have prompted a keen interest in quantitative approaches for monitoring OS that can support regulatory decision-making related to the risk of an unacceptably large detrimental effect on OS. The US Food and Drug Administration, the American Association for Cancer Research, and the American Statistical Association recently organized a one-day multi-stakeholder workshop entitled ‘Overall Survival in Oncology Clinical Trials’. In this paper, we propose OS monitoring guidelines tailored for the setting of indolent cancers. Our pragmatic approach is modeled, in part, on the monitoring guidelines the FDA has used in cardiovascular safety trials conducted in Type 2 Diabetes Mellitus. We illustrate proposals through application to several examples informed by actual case studies. [ABSTRACT FROM AUTHOR]

PURPOSE: The choice of threshold and reliability of high tumor mutational burden (TMB) to predict outcomes and guide treatment choice for patients with metastatic melanoma receiving first-line immune checkpoint inhibitor (ICI) therapy in the real world is not well known. METHODS: Using a deidentified nationwide (US-based) melanoma clinicogenomic database, we identified a real-world cohort of patients with metastatic melanoma (N = 497) who received first-line monotherapy anti–PD-1 (n = 240) or dual anti–PD-1 and anti–CTLA-4 ICI (n = 257) and had a tissue-based comprehensive genomic profiling test TMB score. RESULTS: TMB-high (TMB-H; ≥10 mutations per megabase [muts/Mb], n = 352, 71%) was independently predictive of superior real-world progression-free survival and overall survival versus TMB-low (<10 mut/Mb, n = 145, 29%) in both mono ICI (hazard ratio [HR], 0.45 [95% CI, 0.32 to 0.63]; P <.001; HR, 0.61 [95% CI, 0.41 to 0.90]; P =.01, respectively) and dual ICI (HR, 0.67 [95% CI, 0.49 to 0.90]; P =.009; HR, 0.61 [95% CI, 0.42 to 0.88]; P =.007, respectively) patients. Dual ICI offered no significant advantage in BRAF wt patients and unexpectedly demonstrated greatest benefit in the TMB 10-19 mut/Mb group, identifying a TMB-very high (≥20 mut/Mb, n = 247, 50%) BRAF mut patient subgroup for whom mono ICI may be preferable. CONCLUSION: TMB-H predicts superior outcomes on ICI while coassessment of BRAF status and TMB may inform first-line regimen choice. Melanoma TMB predicts real-world ICI outcome but BRAF coassessment may better inform regimen choice. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common malignancy with poor survival and requires long-term follow-up. Hence, we collected information on patients with Primary Hepatocellular Carcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a deep learning with a multilayer neural network (the NMTLR model) for predicting the survival rate of patients with Primary Hepatocellular Carcinoma. HCC patients pathologically diagnosed between January 2011 and December 2015 in the SEER (Surveillance, Epidemiology, and End Results) database of the National Cancer Institute of the United States were selected as study subjects. We utilized two deep learning-based algorithms (DeepSurv and Neural Multi-Task Logistic Regression [NMTLR]) and a machine learning-based algorithm (Random Survival Forest [RSF]) for model training. A multivariable Cox Proportional Hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into a training set and a test set in a 7:3 ratio. The training dataset underwent hyperparameter tuning through 1000 iterations of random search and fivefold cross-validation. Model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-year, 3-year, and 5-year survival rates was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Area Under the Curve (AUC). The primary outcomes were the 1-year, 3-year, and 5-year overall survival rates. Models were developed using DeepSurv, NMTLR, RSF, and Cox Proportional Hazards regression. Model differentiation was evaluated using the C-index, calibration with concordance plots, and risk stratification capability with the log-rank test. The study included 2197 HCC patients, randomly divided into a training cohort (70%, n = 1537) and a testing cohort (30%, n = 660). Clinical characteristics between the two cohorts showed no significant statistical difference (p > 0.05). The deep learning models outperformed both RSF and CoxPH models, with C-indices of 0.735 (NMTLR) and 0.731 (DeepSurv) in the test dataset. The NMTLR model demonstrated enhanced accuracy and well-calibrated survival estimates, achieving an Area Under the Curve (AUC) of 0.824 for 1-year survival predictions, 0.813 for 3-year, and 0.803 for 5-year survival rates. This model's superior calibration and discriminative ability enhance its utility for clinical prognostication in Primary Hepatocellular Carcinoma. We deployed the NMTLR model as a web application for clinical practice. The NMTLR model have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with primary liver cancer. [ABSTRACT FROM AUTHOR]

Sorting nexin 16 (SNX16), a pivotal sorting nexin, emerges in tumor progression complexity, fueling research interest. However, SNX16's biological impact and molecular underpinnings in hepatocellular carcinoma (HCC) remain elusive. This study probes SNX16's function, clinical relevance via mRNA, and protein expression in HCC. Overexpression/knockdown assays of SNX16 were employed to elucidate impacts on HCC cell invasion, proliferation, and EMT. Additionally, the study delved into SNX16's regulation of the EGFR-AKT signaling cascade mechanism. SNX16 overexpression in HCC correlates with poor patient survival; enhancing proliferation, migration, invasion, and tumorigenicity, while SNX16 knockdown suppresses these processes. SNX16 downregulation curbs phospho-EGFR, dampening AKT signaling. EGFR suppression counters SNX16-overexpression-induced HCC proliferation, motility, and invasiveness. Our findings delineate SNX16's regulatory role in HCC, implicating it as a prospective therapeutic target. [ABSTRACT FROM AUTHOR]

Disulfidptosis represents a novel cell death mechanism triggered by disulfide stress, with potential implications for advancements in cancer treatments. Although emerging evidence highlights the critical regulatory roles of long non-coding RNAs (lncRNAs) in the pathobiology of lung adenocarcinoma (LUAD), research into lncRNAs specifically associated with disulfidptosis in LUAD, termed disulfidptosis-related lncRNAs (DRLs), remains insufficiently explored. Using The Cancer Genome Atlas (TCGA)-LUAD dataset, we implemented ten machine learning techniques, resulting in 101 distinct model configurations. To assess the predictive accuracy of our model, we employed both the concordance index (C-index) and receiver operating characteristic (ROC) curve analyses. For a deeper understanding of the underlying biological pathways, we referred to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) for functional enrichment analysis. Moreover, we explored differences in the tumor microenvironment between high-risk and low-risk patient cohorts. Additionally, we thoroughly assessed the prognostic value of the DRLs signatures in predicting treatment outcomes. The Kaplan–Meier (KM) survival analysis demonstrated a significant difference in overall survival (OS) between the high-risk and low-risk cohorts (p < 0.001). The prognostic model showed robust performance, with an area under the ROC curve exceeding 0.75 at one year and maintaining a value above 0.72 in the two and three-year follow-ups. Further research identified variations in tumor mutational burden (TMB) and differential responses to immunotherapies and chemotherapies. Our validation, using three GEO datasets (GSE31210, GSE30219, and GSE50081), revealed that the C-index exceeded 0.67 for GSE31210 and GSE30219. Significant differences in disease-free survival (DFS) and OS were observed across all validation cohorts among different risk groups. The prognostic model offers potential as a molecular biomarker for LUAD prognosis. [ABSTRACT FROM AUTHOR]

Background: Despite transarterial chemoembolization (TACE) was recommended as first line therapy for intermediate hepatocellular carcinoma (HCC), the efficacy of transarterial embolization (TAE) has not been widely recognized. This work was to determine whether TAE was as effective and safe as TACE for unresectable HCC. Methods: We performed a systematic search of electronic databases and other sources for randomized controlled studies (RCTs) comparing TAE with TACE for unresectable HCC. Results were expressed as Hazard Ratio (HR) for survival and Odds Ratio (OR) for dichotomous outcomes using RevMan 5.4.1. Results: We included 6 trials with 683 patients. The risk of bias of included RCTs was from unclear to high risk. There were no significant differences between TACE and TAE for progression-free survival (HR 0.83, 95% CI 0.45–1.55; p = 0.57), overall survival (HR 1.10, 95% CI 0.90–1.35; p = 0.36), and objective response rate (OR 1.17, 95% CI 0.80–1.71; p = 0.42) without obvious publication bias. Sensitivity analyses confirmed the robustness of the results. TAE group reported similar or less adverse effects than TACE group in all the studies. Conclusions: Our study demonstrated that TAE was as effective as TACE. Since TAE was simpler, cheaper and had less adverse effects than TACE, TAE should be a better choice in most cases where TACE was indicated for unresectable HCC. [ABSTRACT FROM AUTHOR]

Background: Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain controversial. The aim of this meta-analysis was to evaluate the comparative effect of ADCs and other anti-HER2 therapy on progression-free survival (PFS) and overall survival (OS) for treatment of HER2-positive locally advanced or metastatic BC. Methods: Relevant randomized controlled trials (RCTs) were retrieved from five databases. The risk of bias was assessed with the Cochrane Collaboration's tool for RCTs by RevMan5.4 software. The hazard ratio (HR) and 95% confidence intervals (CIs) were extracted to evaluate the benefit of ADCs on PFS and OS in HER2-positive advanced BC by meta-analysis. Results: Meta-analysis of six RCTs with 3870 patients revealed that ADCs significantly improved PFS (HR: 0.63, 95% CI: 0.49–0.80, P = 0.0002) and OS (HR: 0.79, 95% CI: 0.72–0.86, P < 0.0001) of patients with HER2-positive locally advanced or metastatic BC. Subgroup analysis showed that PFS and OS were obviously prolonged for patients who previously received HER2-targeted therapy. Sensitivity analysis and publication bias suggested that the results were stable and reliable. Conclusion: Statistically significant benefits for PFS and OS were observed with ADCs in HER2-positive locally advanced or metastatic BC, especially for those who received prior anti-HER2 treatment. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development of chemoresistance. Despite the emergence of PARP inhibitors, which have revolutionized the therapeutic management of some of these ovarian cancers, the 5-year overall survival rate remains around 45%. Therefore, it is crucial to develop new therapeutic strategies, to identify predictive biomarkers and to predict the response to treatments. In this context, functional assays based on patient-derived tumor models could constitute helpful and relevant tools for identifying efficient therapies or to guide clinical decision making. Method: The OVAREX study is a single-center non-interventional study which aims at investigating the feasibility of establishing in vivo and ex vivo models and testing ex vivo models to predict clinical response of ovarian cancer patients. Patient-Derived Xenografts (PDX) will be established from tumor fragments engrafted subcutaneously into immunocompromised mice. Explants will be generated by slicing tumor tissues and Ascites-Derived Spheroids (ADS) will be isolated following filtration of ascites. Patient-derived tumor organoids (PDTO) will be established after dissociation of tumor tissues or ADS, cell embedding into extracellular matrix and culture in specific medium. Molecular and histological characterizations will be performed to compare tumor of origin and paired models. Response of ex vivo tumor-derived models to conventional chemotherapy and PARP inhibitors will be assessed and compared to results of companion diagnostic test and/or to the patient's response to evaluate their predictive value. Discussion: This clinical study aims at generating PDX and ex vivo models (PDTO, ADS, and explants) from tumors or ascites of ovarian cancer patients who will undergo surgical procedure or paracentesis. We aim at demonstrating the predictive value of ex vivo models for their potential use in routine clinical practice as part of precision medicine, as well as establishing a collection of relevant ovarian cancer models that will be useful for the evaluation of future innovative therapies. Trial registration: The clinical trial has been validated by local research ethic committee on January 25th 2019 and registered at ClinicalTrials.gov with the identifier NCT03831230 on January 28th 2019, last amendment v4 accepted on July 18, 2023. [ABSTRACT FROM AUTHOR]

Background: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. Methods: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. Results: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P <.0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P <.001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P =.001), shorter 6-min walk distance (P =.001), and reduced cardiac performance (cardiac index, P =.016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P =.0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27–5.33; P <.0087). Comparisons of ML–derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62–0.79) for PAH. Conclusions: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification. [ABSTRACT FROM AUTHOR]

The adaptability of glioblastoma (GBM) cells, encouraged by complex interactions with the tumour microenvironment (TME), currently renders GBM an incurable cancer. Despite intensive research, with many clinical trials, GBM patients rely on standard treatments including surgery followed by radiation and chemotherapy, which have been observed to induce a more aggressive phenotype in recurrent tumours. This failure to improve treatments is undoubtedly a result of insufficient models which fail to incorporate components of the human brain TME. Research has increasingly uncovered mechanisms of tumour-TME interactions that correlate to worsened patient prognoses, including tumour-associated astrocyte mitochondrial transfer, neuronal circuit remodelling and immunosuppression. This tumour hijacked TME is highly implicated in driving therapy resistance, with further alterations within the TME and tumour resulting from therapy exposure inducing increased tumour growth and invasion. Recent developments improving organoid models, including aspects of the TME, are paving an exciting future for the research and drug development for GBM, with the hopes of improving patient survival growing closer. This review focuses on GBMs interactions with the TME and their effect on tumour pathology and treatment efficiency, with a look at challenges GBM models face in sufficiently recapitulating this complex and highly adaptive cancer. [ABSTRACT FROM AUTHOR]

Introduction: Glioblastoma, as the most common and lethal primary malignant brain tumor, has estimated mean survival of 15 months. GBM is reported more in men. Malignant glioma is the cause of 2.5% of cancer deaths. The standard therapy for patients with newly diagnosed GBM includes tumor resection surgeries, followed by radiotherapy and chemotherapy. The prognosis of glioma is a major challenge, and the outcome of GBM has remained almost unchanged for past years. The present study aimed to determine patient survival. Methods: Patients with glioblastoma tumors who visited Al-Zahra and Kashani hospitals from 2013 to 2021 were included in this study. All patients were classified with morphological codes according to the International Classification of Diseases for Oncology. The patients' information was recorded in the checklist, and then, the patients were followed up by phone. The data were measured regarding age, gender, exposure to chemicals, body mass index (BMI), and survival from the patient's surgery to death. Several questions were asked from the families of deceased patients and survivors based on the KPS Status Scale. Finally, the sample was analyzed with SPSS version 26. Result: The patient's mean age was 51.93 years, and the male–female ratio was 1:1.7. The patients' mean overall survival was 29 months and a total of 9 patients survived. There was a significant difference between the age groups in terms of 1-year survival so that more deaths were observed in the age group of more than 50 years. The mean tumor size was 5.2 ± 2.1 cm. The survival analysis indicated that the temporal lobe was more than the other in 2-year survival. The most common symptom of patients before surgery was headache (31.8%) followed by motor dysfunction. The 1-year, 2-year, 5-year, and overall survival of the patients was 4.5%, 18.38%, 37.13%, and 33.68%, respectively. Conclusions: The results of the present study indicated that the patients' survival improved over time with the advancement of adjuvant therapies. Therefore, if patients care get better for the first year after surgery, their survival will improve from the second year after the operation. [ABSTRACT FROM AUTHOR]

Objective: Primary tracheal tumors are very rare and their management is not definitely established. Due to its rarity, providing patient care in terms of optimal management poses a considerable challenge. The purpose of this study was to investigate treatment outcomes in patients with these rare tumors. Methods: We carried out a retrospective analysis of 89 patients with primary tracheal tumors treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, over sixteen years. The study assessed patient demographics, tumor characteristics and treatment. Different treatment options were compared in terms of overall survival, disease-free survival, and progression-free survival. Results: A total of 89 patients were included in the study. In the group presented, 45 patients underwent primary radical treatment and 44 were qualified for palliative treatment. Surgical resection was performed in 13 patients out of radically treated patients. The 5 year OS rates in the group of patients who underwent radical treatment and in the group of patients who underwent palliative treatment were 45.9% and 2.3%, respectively. In the group of patients who underwent radical surgical treatment, the 5 year OS was 76.9% compared to 35.8% in the group of patients who underwent nonsurgical treatment. Conclusion: A multidisciplinary team should decide treatment options, including in-depth consideration of surgical treatment options. [ABSTRACT FROM AUTHOR]

Neuroendocrine carcinoma (NEC) is a rare yet potentially perilous neoplasm. The objective of this study was to develop prognostic models for the survival of NEC patients in the genitourinary system and subsequently validate these models. A total of 7125 neuroendocrine neoplasm (NEN) patients were extracted. Comparison of survival in patients with different types of NEN before and after propensity score-matching (PSM). A total of 3057 patients with NEC, whose information was complete, were extracted. The NEC influencing factors were chosen through the utilization of the least absolute shrinkage and selection operator regression model (LASSO) and the Fine & Gary model (FGM). Furthermore, nomograms were built. To validate the accuracy of the prediction, the efficiency was verified using bootstrap self-sampling techniques and receiver operating characteristic curves. LASSO and FGM were utilized to construct three models. Confirmation of validation was achieved by conducting analyses of the area under the curve and decision curve. Moreover, the FGS (DSS analysis using FGM) model produced higher net benefits. To maximize the advantages for patients, the FGS model disregarded the influence of additional occurrences. Patients are expected to experience advantages in terms of treatment options and survival assessment through the utilization of these models. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101–0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169–8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071–0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28–80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies. [ABSTRACT FROM AUTHOR]

Breast Cancer is the most common cancer among women globally. Despite significant improvements in overall survival, many tumours are refractory to therapy and so novel approaches are required to improve patient outcomes. We have evaluated patient-derived explants (PDEs) as a novel preclinical platform for breast cancer (BC) and implemented cutting-edge digital pathology and multi-immunofluorescent approaches for investigating biomarker changes in both tumour and stromal areas at endpoint. Short-term culture of intact fragments of BCs as PDEs retained an intact immune microenvironment, and tumour architecture was augmented by the inclusion of autologous serum in the culture media. Cell death/proliferation responses to FET chemotherapy in BC-PDEs correlated significantly with BC patient progression-free survival (p = 0.012 and p = 0.0041, respectively) and cell death responses to the HER2 antibody therapy trastuzumab correlated significantly with HER2 status (p = 0.018). These studies show that the PDE platform combined with digital pathology is a robust preclinical approach for informing clinical responses to chemotherapy and antibody-directed therapies in breast cancer. Furthermore, since BC-PDEs retain an intact tumour architecture over the short-term, they facilitate the preclinical testing of anti-cancer agents targeting the tumour microenvironment. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. Methods: We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. Results: Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. Conclusion: The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy. [ABSTRACT FROM AUTHOR]

Ferroptosis, a type of iron-dependent non-apoptotic cell death, plays a vital role in both tumor proliferation and resistance to chemotherapy. Here, our study demonstrates that MAX's Next Tango (MNT), by involving itself in the spermidine/spermine N1-acetyltransferase 1 (SAT1)-related ferroptosis pathway, promotes the proliferation of lung adenocarcinoma (LUAD) cells and diminishes their sensitivity to chemotherapy. Initially, an RNA-sequence screen of LUAD cells treated with ferroptosis inducers (FINs) reveals a significant increase in MNT expression, suggesting a potential link between MNT and ferroptosis. Overexpression of MNT in LUAD cells hinders changes associated with ferroptosis. Moreover, the upregulation of MNT promotes cell proliferation and suppresses chemotherapy sensitivity, while the knockdown of MNT has the opposite effect. Through the intersection of ChIP-Seq and ferroptosis-associated gene sets, and validation by qPCR and western blot, SAT1 is identified as a potential target of MNT. Subsequently, we demonstrate that MNT binds to the promoter sequence of SAT1 and suppresses its transcription by ChIP-qPCR and dual luciferase assays. Restoration of SAT1 levels antagonizes the efficacy of MNT to inhibit ferroptosis and chemosensitivity and promote cell growth in vitro as well as in vivo. In the clinical context, MNT expression is elevated in LUAD and is inversely connected with SAT1 expression. High MNT expression is also associated with poor patient survival. Our research reveals that MNT inhibits ferroptosis, and impairing chemotherapy effectiveness of LUAD. The transcription factor MNT binds to the SAT1 promoter region and represses its transcription, leading to ferroptosis and chemotherapy resistance in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Type I interferon (IFN) is a potent antitumoral drug, with an important history in the treatment of hematologic malignancies. However, its pleiotropic nature leads to severe dose-limiting toxicities that blunt its therapeutic potential. To achieve selective targeting of specific immune or tumor cells, AcTakines (Activity-on-Target Cytokines), i.e., immunocytokines utilizing attenuated cytokines, and clinically optimized A-Kines™ were developed. In syngeneic murine models, the CD20-targeted murine IFNα2-based AcTaferons (AFNs) have demonstrated clear antitumoral effects, with excellent tolerability. The current study explores the antitumoral potential of the humanized huCD20-Fc-AFN in 5 different humanized patient derived xenograft (PDX) models of huCD20+ aggressive B non-Hodgkin lymphomas (B-NHLs). The huCD20-Fc-AFN consists of a huCD20-specific single-domain antibody (VHH) linked through a heterodimeric 'knob-in-hole' human IgG1 Fc molecule to an attenuated huIFNα2 sequence. An in vitro targeting efficacy of up to 1.000-fold could be obtained, without detectable in vivo toxicities, except for selective (on-target) and reversible B cell depletion. Treatment with huCD20-Fc-AFN significantly increased the median overall survival (mOS) in both non-humanized (mOS 31 to 45 days; HR = 0.26; p = 0.001), and humanized NSG/NOG mice (mOS 34 to 80 days; HR = 0.37; p < 0.0001). In humanized mice, there was a trend for increased survival when compared to equimolar rituximab (mOS 49 to 80 days; HR = 0.73; p = 0.09). The antitumoral effects of huCD20-Fc-AFN were partly due to direct effects of type I IFN on the tumor cells, but additional effects via the human immune system are essential to obtain long-term remissions. To conclude, huCD20-Fc-AFN could provide a novel therapeutic strategy for huCD20-expressing aggressive B-NHLs. Key points: The A-Kine™-principle allows for up to 1.000-fold targeting efficacy, enabling reduced toxicities of IFNα2-based therapies. huCD20-Fc-AFN demonstrates significant antitumoral efficacy in 5 humanized PDX models of aggressive huCD20+ B-NHLs. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES The prognosis of patients diagnosed with melanoma is highly dependent on staging, early detection, and early intervention. In this systematic review, the authors aimed to investigate the impact of surgical delay (time between diagnostic biopsy and definitive surgical excision) on melanoma-specific outcomes. MATERIAL AND METHODS A systematic review was conducted from Embase (1974-present), MEDLINE (1946-present), Cochrane Central Register of Controlled Trials (2005-present), Scopus, and Web of Science. A total of 977 studies were included for review after removal of duplicates. A total of 10 studies were included for final analysis. RESULTS In total, 70% (7/10) of the studies found that longer wait times between initial biopsy and surgical intervention are correlated with lower overall survival. Among the 9 studies that reported overall survival as a percentage, the median and SD overall survival was 82% 6 5.87. CONCLUSION There is evidence that prolonged surgical delay in patients diagnosed with Stage I cutaneous melanoma is associated with worsened overall mortality, whereas the effect of surgical delay on overall mortality in Stages II and III melanomas is uncertain. Future prospective studies and randomized clinical trials are needed to better define the appropriate surgical wait times between biopsy and surgical treatment. [ABSTRACT FROM AUTHOR]

We assessed the real-world effectiveness of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors as first-line treatments in postmenopausal patients with HR+/HER2− advanced breast cancer, focusing on younger (<45 years) and older (>78 years) populations not considered in clinical trials. We analyzed nationwide claims data from the Health Insurance Review and Assessment Service between November 2016 and February 2021. In this retrospective cohort study, patients using CDK4/6 inhibitors and aromatase inhibitors were selected and grouped by age as follows: 45–78 years (trial-enrolled), <45 years (younger), and >78 years (older). We estimated the median real-world progression-free survival (rwPFS) and overall survival (OS) using the Kaplan-Meier method. We conducted Cox regression analysis using a sub-distribution hazard model to evaluate risk factors (age, history of prior systemic treatment, presence of metastasis, comorbidity index, and type of provider) and estimated hazard ratios (HR). Among the 2,830 patients who received CDK4/6 inhibitors as first-line therapy, we identified 358 (12.65%) younger and 148 (5.23%) older underrepresented patients. The younger patient group (50.84%) had the highest rate of prior systemic therapy, followed by the trial-enrolled (25.39%) and older patient groups (8.11%). The median rwPFS was shorter in the older group (19.30 months) than those in the younger and the trial-enrolled age groups (30.33 and 34.53 months, respectively; p =.002). The HR of older age for death was 1.59 (95% confidence interval (CI) = 1.24–2.03). For rwPFS, the HR of prior systemic therapy was 1.19 (95% CI = 1.04–1.37). The younger age group, which was underrepresented in the trial, did not show a significant difference in risk compared with the enrolled age group. However, the older age group, which was also underrepresented in the trial, faces a risk of mortality but not progression. Patients who fall outside the specified age groups for the clinical trial can still expect the same level of effectiveness in terms of progression. [ABSTRACT FROM AUTHOR]

Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related factor secreted by the liver that is aberrantly expressed and functionally abnormal in human malignancies. However, the role of FGL1 in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analysed FGL1 expression in HNSCC and its impact on patient survival using the TCGA database. The role of FGL1 in HNSCC cells was investigated by Cell Counting Kit-8, colony formation, and Transwell assays. In addition, we conducted in vivo experiments to assess the effect of FGL1knockdown on tumour growth. We found that FGL1 was highly expressed in HNSCC and correlated with a poor prognosis. Downregulation of FGL1 expression inhibited the proliferation and invasion of HNSCC cells. Furthermore, mechanistic analysis revealed that FGL1 induced an epithelial-mesenchymal transition (EMT) phenotype and, thus, the malignant progression of HNSCC cells. Finally, xenograft models showed that FGL1 knockdown significantly inhibited EMT in HNSCC in vivo. Our study revealed that FGL1, an oncogene, promotes the malignant progression of HNSCC, providing new perspective on and potential therapeutic target for the treatment of HNSCC. [ABSTRACT FROM AUTHOR]

Sirtuin 1 (SIRT1) participates in the initiation and evolution of hepatocellular carcinoma (HCC). However, the specific mechanism of SIRT1 in HCC remains unclear. The mRNA expression of miR-29a in HCC were identified by qRT-PCR. miR-29a mimic and inhibitor were employed. The alteration of biological behavior was evaluated by Cell Counting Kit-8 (CCK8), clone formation, transwell and wound-healing assay. SIRT1 was verified to be a target gene which directly regulated by miR-29a. Luciferase reporter assay and co-IP were employed to evaluate the direct binding of miR-29a and SIRT1. Animal model was used to evaluate its function on tumor growth and metastasis in vivo. The relationship between miR-29a/SIRT1 and prognosis of HCC patients was analyzed. SIRT1 overexpression accompanied by low expression of miR-29a were detected in HCC which was negatively correlated, and associated with overall survival, vascular invasion and TNM stage. Up-regulation of miR-29a suppressed cell growth and motility. Deprivation of miR-29a expression led to opposite effect. The direct binding of miR-29a to SIRT1 was confirmed by luciferase reporter assay and co-IP. miR-29a repressed SIRT1, DKK2 and β-catenin, but their expression was obviously elevated by miR-29a inhibitor. Animal model suggested miR-29a could reduce the expression of SIRT1, thereby inhibiting HCC growth and metastasis by inactivating Wnt/β-catenin pathway. Low expression of miR-29a and high expression of SIRT1 predicted shorter survival time in HCC patients. miR-29a had the function of tumor suppressor which directly inhibited oncogenic SIRT1. The loss of miR-29a led to up-regulation of SIRT1, aggravate malignant transformation and poor prognosis of HCC. [ABSTRACT FROM AUTHOR]