Tyrosine kinase inhibitors for radioiodine refractory differentiated thyroid cancer: A systematic review and meta-analysis.

BACKGROUND: The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs) in radioiodine refractory differentiated thyroid cancer (RAIR-DTC). However, the available evidence cannot determine the optimal choice of TKI in RAIR-DTC. METHODS: This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT) of RAIR-DTC patients treated with the TKI system. Outcomes, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were reported. RESULTS: Seven studies involving 1310 patients with RAIR-DTC was conducted to compare the PFS and OS of various TKI monotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR] 0.19, 95% credible interval [CrI] 0.14-0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18-0.97) and anlotinib (HR 0.36, 95% CrI 0.18-0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR-DTC, although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR-DTC patients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment. CONCLUSIONS: The results of this meta-analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine-refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR-DTC. This study is beneficial for formulating patients' treatment plans and guides clinicians' decision-making.

Cancer-associated fibroblasts mediate resistance to anti-EGFR therapies in cancer.

Over the last decade, epidermal growth factor receptor (EGFR)-targeted therapies have transformed the treatment landscape for patients with advanced solid tumors. Despite these advances, resistance to anti-EGFR therapies is still a significant clinical challenge. While cell-autonomous mechanisms of resistance are well-documented, they do not fully elucidate the complexity of drug resistance. Cancer-associated fibroblasts (CAFs), key mediators within the tumor microenvironment (TME), have emerged as pivotal players in cancer progression and chemoresistance. Recent evidence implicates CAFs in resistance to anti-EGFR therapies, suggesting they may undermine treatment efficacy. This review synthesizes current data, highlighting the critical role of CAFs in resistance pathogenesis and summarizing recent therapeutic strategies targeting CAFs. We underscore the challenges and advocate for the exploration of CAFs as a potential dual-targeted approach.

Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection.

The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.

Associations and attributable burdens in late-life exposure to PM2.5 and its major components and depressive symptoms in middle-aged and older adults: A nationwide cohort study.

BACKGROUND: Depression in late life has been associated with reduced quality of life and increased mortality. Whether the chronic fine particular matter (PM2.5) and its components exposure are contributed to the older depression symptoms remains unclear. METHOD: Middle-aged and older adults (>45 years) were selected from the China Health and Retirement Longitudinal Study during the four waves of interviews. The concentrations of PM2.5 and its major constituents were calculated using near real-time data at a spatial resolution of 10 km during the study period. The depressive symptom was evaluated by the Depression Center for Epidemiologic Studies Depression (CES-D)-10 score. The fix-effect model was applied to evaluate the association between PM2.5 and its major constituents with depressive symptoms. Three three-step methods were used to explore the modification role of sleep duration against the depressive symptoms caused by PM2.5 exposure. RESULTS: In our study, a total of 52,683 observations of 16,681 middle-aged and older adults were assessed. Each interquartile range (IQR) level of PM2.5 concentration exposure was longitudinally associated with a 2.6 % (95 % confidence interval [CI]: 1.3 %, 4.0 %) increase in the depression CES-D-10 score. Regarding the major components of PM2.5, OM, NO3-, and NH4+ showed the leading toxicity effects, which could increase the depression CES-D-10 score by 2.2 % (95 %CI: 1.0 %, 3.4 %), 2.2 % (0.6 %, 3.9 %), and 2.0 % (95 %CI: 0.6 %, 3.4 %) correspondingly. Besides, males were more susceptible to the worse depressive symptoms caused by PM2.5 and its major components exposure than female subpopulations. Shortened sleep duration might be the mediator of PM2.5-associated depressive symptoms. CONCLUSION: Our results suggest that long-term exposure to PM2.5 and its major components were associated with an increased risk for depressive symptoms in middle-aged and older adults. Reducing the leading components of PM2.5 may cost-effectively alleviate the disease burden of depression and promote healthy longevity in heavy pollutant countries.

BMI trajectories in late middle age, genetic risk, and the incident diabetes in older adults: evidence from a 26-year longitudinal study.

This study investigated the association between BMI trajectories in late middle age and incident diabetes in later years. A total of 11,441 participants aged 50-60 years from the Health and Retirement Study with at least two self-reported BMI records were included. Individual BMI trajectories representing average BMI changes per year were generated using multilevel modeling. Adjusted risk ratios (ARRs) and 95% confidence intervals (95% CIs) were calculated. Associations between BMI trajectories and diabetes risk in participants with different genetic risks were estimated for 5720 participants of European ancestry. BMI trajectories were significantly associated with diabetes risk in older age (slowly increasing vs. stable: ARR 1.31, 95% CI 1.12-1.54; rapidly increasing vs. stable: ARR 1.5, 95% CI 1.25-1.79). This association was strongest for normal-initial-BMI participants (slowly increasing: ARR 1.34, 95% CI 0.96-1.88; rapidly increasing: ARR 2.06, 95% CI 1.37-3.11). Participants with a higher genetic liability to diabetes and a rapidly increasing BMI trajectory had the highest risk for diabetes (ARR 2.15, 95% CI 1.67-2.76). These findings confirmed that BMI is the leading risk factor for diabetes and that although the normal BMI group has the lowest incidence rate for diabetes, people with normal BMI are most sensitive to changes in BMI.

Association between nut consumption and cancer risk: a meta-analysis.

This study aims to conduct a meta-analysis and dose-response analysis of the relationship between nut intake and cancer risk and mortality. Electronic databases were searched. A meta-analysis was conducted to calculate the pooled effect sizes (ESs) with the corresponding 95% CIs, and a dose-response analysis was performed. A random-effects model was used in the statistical analysis. Two independent reviewers completed the full-text screening, data extraction, and quality assessment. We included 17 articles in the present meta-analysis. Total nuts intake was revealed to be significantly associated with reduced cancer risk (ES: 0.9; 95% CI: 0.86-0.95; P < 0.001) and cancer mortality (ES: 0.88; 95% CI: 0.85-0.92, P < 0.001), especially lung cancer risk (ES: 0.86; 95% CI: 0.81-0.91, P < 0.001) and gastric cancer risk (ES: 0.79; 95% CI: 0.68-0.91, P = 0.001). Moreover, a 10 g/d increment of tree nuts consumption was associated with a 20% cancer mortality reduction (ES: 0.80; 95% CI: 0.71-0.89; P < 0.0001). Nuts intake is significantly associated with the reduction of cancer risk and mortality. Especially, nuts intake is significantly associated with reduced lung cancer risk and gastric cancer risk. Noticeably, a 10 g/d increase in tree nuts intake is related to a 20% reduction in overall cancer mortality.

Depression Trajectories, Genetic Risk, and Cognitive Performance in Older Adults: Multilevel Model with a 10-Year Longitudinal Cohort.

INTRODUCTION: Cognitive performance in older ages is strongly affected by individuals' genetic predispositions. We investigated whether depression trajectories were associated with subsequent cognitive performance independent of participants' genetic predispositions. METHODS: Participants from the Health and Retirement Study with European ancestry and aged over 50 were included in the analysis. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale, and the 6-year trajectories were fitted using latent class linear mixed models. Linear multilevel regression was applied to model the associations between depression trajectory and subsequent cognitive performance. Stratified analyses were performed to investigate these associations in participants with different genetic predispositions of cognitive performance and APOE ε4 allelic status. RESULTS: A total of 5,942 eligible participants were included in the study. Four depression trajectories were identified. Compared with the nondepression trajectory, all other depression trajectories were associated with worse cognitive performance (ß [95% CI]: mild-depression trajectory: -0.20 [-0.56, -0.06], p = 0.007; worsening-depression trajectory: -0.29 [-0.47, -0.12], p = 0.001; persistent-depression trajectory: -0.32 [-0.53, -0.13], p = 0.001). Although these associations were independent of participants' inherent genetic risk, the participants with a low polygenetic score for cognitive performance were more likely to have an enhanced association between depression trajectories and cognitive decline. Similar relationships were also found in APOE ε4 noncarriers. CONCLUSION: Among older participants with European ancestry, even a mild-depression trajectory was associated with worse cognitive performance. Early intervention in participants with any degree of depression might benefit regarding preventing cognitive performance decline.

Association between BMI trajectories in late-middle age and subsequent dementia risk in older age: a 26-year population-based cohort study.

BACKGROUND: The association between body mass index (BMI) and dementia risk differs depending on follow-up time and age at BMI measurement. The relationship between BMI trajectories in late-middle age (50-65 years old) and the risk of dementia in older age (> 65 years old) has not been revealed. METHODS: In the present study, participants from the Health and Retirement Study were included. BMI trajectories were constructed by combining BMI trend and variation information. The association between BMI trajectories at the age of 50-65 years and dementia risk after the age of 65 years was investigated. Participants with European ancestry and information on polygenic scores for cognitive performance were pooled to examine whether genetic predisposition could modify the association. RESULTS: A total of 10,847 participants were included in the main analyses. A declining BMI trend and high variation in late-middle age were associated with the highest subsequent dementia risk in older age compared with an ascending BMI trend and low variation (RR = 1.76, 95% CI = 1.45-2.13). Specifically, in stratified analyses on BMI trajectories and dementia risk based on each individual's mean BMI, the strongest association between a declining BMI trend with high variation and elevated dementia risk was observed in normal BMI group (RR = 2.66, 95% CI = 1.72-4.1). Similar associations were found when participants were stratified by their genetic performance for cognition function without interaction. CONCLUSIONS: A declining BMI trend and high variation in late-middle age were associated with a higher risk of dementia. Early monitoring of these individuals is needed to prevent dementia in older individuals.

Association between fish oil supplementation and cancer risk according to fatty fish consumption: A large prospective population-based cohort study using UK Biobank.

Whether regular fish oil supplementation is associated with cancer risk is controversial. We aimed to evaluate the association of fish oil supplementation on cancer risk according to fatty fish consumption patterns. From the UK Biobank cohort, 470 804 participants with fish oil supplementation data were included. A total of 147 316 individuals with fish oil supplementation were in the exposed group; the other 323 488 were in the unexposed group. No association was found between self-report regular fish oil supplementation and overall cancer risk (hazard ratio [HR] = 0.97, 95% confidence intervals [CIs] = 0.95-1). Stratified by fatty fish consumption level, we found the association between fish oil supplementation and lower cancer risk in participants who consumed fatty fish less than two times per week, with association noted for both overall cancer (HR = 0.96, 95% CI = 0.94-0.99) and some specific cancers (colon cancer: HR = 0.84, 95% CI = 0.75-0.94; hepatobiliary cancer: HR = 0.74, 95% CI = 0.58-0.96; lung cancer: HR = 0.87, 95% CI = 0.78-0.98). On the contrary, a higher risk of breast cancer was observed (HR = 1.16, 95% CI = 1.01-1.32) in participants who consumed fatty fish at least two times per week. In conclusion, our findings underscore the need to refine recommendations for nutritional supplements according to inherent diet habits.

Survival outcomes following treatment delays among patients with early-stage female cancers: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians. METHODS: We analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients. RESULTS: A total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC (adjustedHazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01-1.23, p = 0.044) and stage I infiltrating breast cancer (adjustedHR = 1.23, 95% CI 1.11-1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC (adjustedHR = 1.04, 95% CI 1.01-1.06, p = 0.010) and in those with stage I breast cancer (adjustedHR = 1.03, 95% CI 1.00-1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I (adjustedHR = 1.31, 95% CI 1.02-1.68, p = 0.032). CONCLUSION: After adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

Pulmonary granulomatous inflammation after ceritinib treatment in advanced ALK-rearranged pulmonary adenocarcinoma.

Ceritinib is a new anaplastic lymphoma kinase (ALK) inhibitor that has shown greater potency in patients with advanced ALK-rearranged non-small cell lung cancer, including those who had disease progression in crizotinib treatment. Here we reported, after several months of ceritinib treatment, two patients with advanced ALK-rearranged pulmonary adenocarcinoma exhibited a spectrum of respiratory symptoms like cough and dyspnea, with significantly higher inflammatory indicators. Chest computed tomography (CT) showed multiple bilateral and peripheral lesions in lungs. The prior considerations taken into account were disease progression or infection. However, biopsies of the pulmonary nodules revealed features of granulomatous inflammation without definite cancer cells. We documented for the first time that ceritinib might be associated with pulmonary granulomatous inflammation, and clinicians should be alert to the possibility that the rare adverse event emerged during ceritinib treatment.

Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis.

PURPOSE: Brain radiotherapy combined with concomitant and six cycles of adjuvant temozolomide (TMZ) is the standard treatment for newly diagnosed high-grade gliomas (HGGs). However, the optimal number of cycles of TMZ is still controversial. We conducted this retrospective cohort study to evaluate whether prolonging adjuvant TMZ beyond six cycles resulted in better survival outcomes. METHODS: Patients with high-grade gliomas treated with standard brain radiotherapy combined with TMZ were retrospectively analysed. The duration of adjuvant TMZ ranged from 6 to 12 cycles. Those with 6 cycles of adjuvant TMZ were defined as the standard STUPP group, and those with 7-12 cycles were called the extended STUPP group. Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazards model was adopted to estimate the Hazard ratio (HR) associated with PFS and OS. RESULTS: From September 2011 to May 2021, 372 patients were eligible (143 in the standard group, 229 in the extended group). Patients who received extended STUPP had better PFS and OS compared with standard STUPP. The median PFS for the standard STUPP group was 12 months and for the extended STUPP group 22 months (log-rank P < 0.001). The median OS for the standard STUPP group and extended STUPP group were 12 months and 36 months, respectively (log-rank P < 0.001). In the subgroup analysis, the two treatments did not differ in IDH-mutated patients, while patients with IDH wild-type had a significantly better response to extended treatment than to standard treatment (PFS: log-rank P = 0.004; OS log-rank P = 0.001). Patients with MGMT promoter methylation treated with extended STUPP obtained longer PFS and OS than those treated with standard STUPP (PFS: log-rank P = 0.015; OS log-rank P = 0.010). Adverse events including leukopenia (P < 0.001), thrombocytopenia (P = 0.090), fatigue (P < 0.001) and nausea/vomiting (P = 0.004) were more frequent in the extended group. CONCLUSION: Extended TMZ treatment was superior to standard 6-cycle TMZ for both PFS and OS. The incidence of toxicities in extended group was higher but tolerable.

Lactate dehydrogenase as promising marker for prognosis of brain metastasis.

BACKGROUND: Lactate dehydrogenase (LDH) is a biomarker for cancer. However, the relationship between serum LDH levels and the survival of patients with brain metastasis has been fully revealed. We aimed to evaluate the serum LDH levels and assess its prognostic value in patients with BM. METHODS: The serum LDH levels were collected from 2507 patients with BM. Patients were categorized into four groups according to the quartile of serum LDH levels. The association between serum LDH levels and overall survival (OS) was evaluated using Cox regression models and Kaplan-Meier curves. Three predictive models were used to evaluate patients. RESULTS: The Kaplan-Meier curve for survival by the serum LDH group demonstrates clear separation between four groups (P < 0.001). The participants in the lower group had longer OS than those in the higher group. After adjusting in multivariate Cox regression models remained significant for patients in the Q4 compared with patients in the Q1 (Q4:Q1 OR 1.58, 95% CI 1.38-1.80). Furthermore, the GPA-LDH model generates a pooled area under the curve of 0.630 (95% CI 0.600, 0.660). CONCLUSIONS: Serum LDH levels and OS in patients with brain metastasis is an inverse association. Moreover, Serum LDH levels can improve the prognosis of the GPA model.

Effectiveness of eHealth interventions for cancer-related pain, fatigue, and sleep disorders in cancer survivors: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To systematically evaluate the effects of Electronic health (eHealth) interventions on fatigue, pain, and sleep disorders in cancer survivors. DESIGN: A systematic review and meta-analysis was conducted. METHODS: Relevant studies were searched from five databases (MEDLINE, Embase, the Cochrane Central Register of Controlled trials, CINAHL, and PsycINFO). The comprehensive literature search was done in December 2020. Only randomized controlled trials (RCTs) that examined the effects of eHealth interventions among cancer survivors were included. FINDINGS: Twenty-five RCTs were included. The meta-analysis showed that eHealth interventions had a positive impact on pain interference (SMD = -0.37, 95% CI: -0.54 to -0.20, p = 0.0001) and sleep disorders (SMD = -0.43, 95% CI: -0.77 to -0.08, p = 0.02) but not on pain severity or fatigue in cancer survivors. The sensitivity and subgroup analyses indicated that the pooled results were robust and reliable. CONCLUSION: eHealth interventions are effective in improving pain interference and sleep disorders in cancer survivors. Additional high-quality RCTs are needed to test the effectiveness of eHealth interventions on fatigue, pain, and sleep disorders in cancer survivors. CLINICAL RELEVANCE: This systematic review and meta-analysis provides evidence to offer effective and sustainable eHealth care for symptom management among cancer survivors.

Treatment plan comparison of volumetric-modulated arc therapy to intensity-modulated radiotherapy in lung stereotactic body radiotherapy using either 6- or 10-MV photon energies.

PURPOSE: The aim of this study was to dosimetrically compare volumetric-modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) techniques using either 6- or 10-MV photon beam energies in lung stereotactic body radiation therapy (SBRT) plans. METHODS: Thirty patients with primary or metastatic lung tumors eligible for SBRT were randomly selected. VMAT and IMRT treatment plans using either 6- or 10-MV photon energies were generated through automatic SBRT planning software in the RayStation treatment planning system. RESULTS: For planning target volume, there was no difference in D95% for all plans, whereas D2% and D50% were significantly increased by 5.22%-5.98% and 2.47%-2.59%, respectively, using VMAT6/10-MV plans compared to IMRT6/10-MV plans. When comparing the Dmax of organs at risk (OARs), VMAT6/10-MV was 18.32%-47.95% lower than IMRT6/10-MV for almost all OARs. VMAT6/10-MV obviously decreased Dmean , V5Gy , V10Gy , and V20Gy of whole lung by 9.68%-20.92% than IMRT6/10-MV . Similar results were found when comparing VMAT6-MV with IMRT10-MV or VMAT10-MV with IMRT6-MV . The differences in the D2% , heterogeneity index, and conformity index between 6- and 10-MV plans are not statistically significant. Plans using 6-MV performed 4.68%-8.91% lower levels of Dmax of spinal cord, esophagus, great vessels, and trachea and proximal bronchial tree than those using 10-MV plans. Similarly, Dmean , V5Gy , V10Gy , and V20Gy of whole lung were also reduced by 2.79%-5.25% using 6-MV. For dose fall-off analysis, the D2cm and R50% of VMAT6/10-MV were lower than those of IMRT6/10-MV . Dose fall-off curve based on 10 rings was steeper for VMAT plans than IMRT plans regardless of the energy used. CONCLUSIONS: For lung SBRT plans, VMAT-based plans significantly reduced OARs dose and steepened dose fall-off curves compared to IMRT-based plans. A 6-MV energy level was a better choice than 10-MV for lung SBRT. In addition, the dose differences between different techniques were more obvious than those between different energy levels.

Interleukin-7-loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma.

BACKGROUND: T cell with chimeric antigen receptors (CAR-T) has presented remarkable efficacy for blood cancer as an emerging immunotherapy. However, for solid tumors, the therapeutic efficacy is much impaired due to the lack of infiltration and persistence of CAR-T in tumor tissue. Thus, we constructed an interleukin-7-loaded oncolytic adenovirus and combined the use of oncolytic virus and CAR-T to improve the therapeutic outcome. METHODS: We constructed an interleukin-7-loaded oncolytic adenovirus (oAD-IL7) and a B7H3-targeted CAR-T and explored the efficacy of the single use of oAD-IL7, B7H3-CAR-T, or the combined therapy for glioblastoma in vitro and in vivo. The improved CAR-T anti-tumor efficacy was evaluated according to the proliferation, survival, persistence, exhaustion of T cells, and tumor regression. RESULTS: Constructed oAD-IL7 and B7H3-CAR-T presented moderate cytotoxicity during in vitro study, but failed to induce a thorough and persistent anti-tumor therapeutic efficacy in vivo. The combination of oAD-IL7 and B7H3-CAR-T in vitro resulted in enhanced T cell proliferation and reduced T cell apoptosis. The joint efficacy was further confirmed using tumor-bearing xenograft mice. During in vivo study, the mice treated with both oAD-IL7 and B7H3-CAR-T showed prolonged survival and reduced tumor burden. According to the ex vivo study, oAD-IL7 improved the proliferation and persistence of tumor-infiltrating B7H3-CAR-T, but failed to reverse the exhaustion. CONCLUSIONS: Our results indicated that oAD-IL7 is a promising auxiliary therapy to improve the therapeutic efficacy of B7H3-CAR-T in glioblastoma by providing the activating signals for tumor-infiltrating T cells. Our results also lay the basis for the future clinical trials for the combination of IL7-loaded oncolytic adenovirus and CAR-T therapy for glioblastoma.

Clinicopathological and prognostic significance of speckle-type POZ protein in cancers: a systematic review and meta-analysis.

BACKGROUND: Controversial findings have been reported in the impact of speckle-type POZ protein (SPOP) on clinicopathological features and prognosis in diverse cancers. We conducted this meta-analysis to confirm whether SPOP was an effective biomarker to predict clinical stage, cancer differentiation and survival. METHODS: We searched studies published before June 2021 through Medline, Embase, the Cochrane library register of controlled trials and Wanfang databases. The corrections of SPOP expression with expression disparity, tumor differentiation, clinical stage and survival were analyzed. RESULTS: Our meta-analysis found that higher expression of SPOP was significantly associated with earlier clinical stage, well differentiation and better overall survival. Subgroup analysis showed that the SPOP expression of adjacent tissue was significantly higher than that in cancer tissues of prostate and liver. However, renal cancer presented improved expression of SPOP in cancer tissue. CONCLUSIONS: SPOP has the potential function to act as a novel and effective biomarker for cancer diagnosis and prognostic stratification.

Observation versus radiotherapy with or without temozolomide in postoperative WHO grade II high-risk low-grade glioma: a retrospective cohort study.

The optimal adjuvant treatment of high-risk low-grade glioma (LGG) is controversial. We performed this retrospective cohort study to compare three treatments including observation, radiotherapy (RT) alone, and radiotherapy combined with concomitant and adjuvant temozolomide (TMZ) chemotherapy (STUPP regimen) in patients with high-risk LGG. Patients with high-risk (age > 40 or undergoing subtotal resection or biopsy) LGG treated with observation or radiotherapy alone or STUPP regimen after operation were retrospectively analyzed. Survival rates were evaluated by the Kaplan-Meier method; the log-rank test was applied to compare differences between groups. A total of 250 patients met the inclusion criteria. Median follow-up for living people was 70 months. Overall, patients who received radiotherapy with or without temozolomide had better progression-free survival (PFS) and overall survival (OS) when compared with observation (median PFS: observation, 59 months; RT, 82 months; STUPP, not reached; median OS: observation, 96 months; RT, not reached; STUPP, not reached), whereas STUPP regimen did not further prolong PFS or OS than RT alone (PFS, P = 0.203; OS, P = 0.146). In oligodendroglioma (IDH mutant and 1p/19q codeleted) subtype, only STUPP regimen brought longer PFS when compared with observation (P = 0.008). The incidence of grade 3 or 4 neutropenia (P < 0.001) and nausea or vomiting (P = 0.004) was higher in the STUPP group than the figure for the RT alone group. PFS and OS were similarly improved in patients with high-risk LGG receiving RT alone or STUPP regimen. However, only STUPP regimen was able to bring better PFS for oligodendroglioma (IDH mutant and 1p/19q codeleted) subgroup. Longer follow-up time is needed to determine an association with treatment effect in different histological and molecular subgroups.

Induction chemotherapy followed by intensity-modulated radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma: A retrospective analysis.

OBJECTIVES: The optimal treatment strategy of combining systemic chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC) is controversial. This study aimed to compare the efficacy and toxicities of induction chemotherapy followed by intensity-modulated radiotherapy (IC-RT) versus concurrent chemoradiotherapy (CCRT) in NPC. METHODS: Of 448 stage II-IVb NPC patients treated with IC-RT or CCRT were retrospectively analysed. The primary outcome was overall survival, which was analysed by using Kaplan-Meier curves and log-rank (Mantel-Cox) test. RESULTS: The median follow-up was 66 months (interquartile range, 46-84 months). There was no statistically significant difference in the estimated 5-year overall survival (OS), progression-free survival (PFS), distance metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) between IC-RT group and CCRT group (OS: 89.5% vs 91.7%, P = .568; PFS: 85.2% vs 87.5%, P = .615; DMFS: 90.9% vs 91.7%, P = .847; LRFS: 92.0% vs 96.9%, P = .104). In the multivariate analysis, the treatment group (IC-RT vs CCRT) was not an independent prognostic factor for OS, PFS, DMFS and LRFS. Less advanced tumour stage and lymph node stage were predictive of higher OS. EBV-DNA level was an independent prognostic factor that was only significantly associated with LRFS. CONCLUSIONS: IC-RT achieves similar survival outcomes and treatment-related toxicities as CCRT in OS, PFS, DMFS and LRFS for patients with NPC. We need multicentre randomised controlled trials to reconfirm our data.

Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma.

Sorafenib provides survival benefits in patients with advanced renal cell carcinoma (RCC), but its use is hampered by acquired drug resistance. It is important to fully clarify the molecular mechanisms of sorafenib resistance, which can help to avoid, delay or reverse drug resistance. Extracellular vesicles (EVs) can mediate intercellular communication by delivering effector molecules between cells. Here, we studied whether EVs are involved in sorafenib resistance of RCC and its possible molecular mechanisms. Using differential centrifugation, EVs were isolated from established sorafenib-resistant RCC cells (786-0 and ACHN), and EVs derived from sorafenib-resistant cells were uptaken by sensitive parental RCC cells and thus promoted drug resistance. Elevated exogenous miR-31-5p within EVs effectively downregulated MutL homolog 1 (MLH1) expression and thus promoted sorafenib resistance in vitro. Mice experiments also confirmed that miR-31-5p could mediate drug sensitivity in vivo. In addition, low expression of MLH1 was observed in sorafenib-resistant RCC cells and upregulation of MLH1 expression restored the sensitivity of resistant cell lines to sorafenib. Finally, miR-31-5p level in circulating EVs of RCC patients with progressive disease (PD) during sorafenib therapy was higher when compared to that in the pretherapy status. In conclusion, EVs shuttled miR-31-5p can transfer resistance information from sorafenib-resistant cells to sensitive cells by directly targeting MLH1, and thus magnify the drug resistance information to the whole tumor. Furthermore, miR-31-5p and MLH1 could be promising predictive biomarkers and therapeutic targets to prevent sorafenib resistance.