TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism.

Blockade of the T cell immunoreceptor with the immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) can enhance innate and adaptive tumor immunity and radiotherapy (RT) can enhance anti-tumor immunity. However, our data suggest that TIGIT-mediated immune suppression may be an impediment to such goals. Herein, we report on the synergistic effects of RT combined with anti-TIGIT therapy and the mechanism of their interaction. Treatment efficacy was assessed by measuring primary and secondary tumor growth, survival, and immune memory capacity. The function of CD103 + dendritic cells (DCs) under the combined treatment was assessed in wild-type and BATF3-deficient (BATF3-/-) mice. FMS-like tyrosine kinase 3 ligand (Flt3L) was used to confirm the role of CD103 + DCs in RT combined with anti-TIGIT therapy. TIGIT was upregulated in immune cells following RT in both esophageal squamous cell carcinoma patients and mouse models. Administration of the anti-TIGIT antibody enhanced the efficacy of RT through a CD8 + T cell-dependent mechanism. It was observed that RT and the anti-TIGIT antibody synergistically enhanced the accumulation of tumor-infiltrating DCs, which activated CD8 + T cells. The efficacy of the combination therapy was negated in the BATF3-/- mouse model. CD103 + DCs were required to promote the anti-tumor effects of combination therapy. Additionally, Flt3L therapy enhanced tumor response to RT combined with TIGIT blockade. Our study demonstrated TIGIT blockade can synergistically enhance anti-tumor T cell responses to RT via CD8 + T cells (dependent on CD103 + DCs), suggesting the clinical potential of targeting the TIGIT pathway and expanding CD103 + DCs in RT.

Research on structural strengthening technology for regenerative denitration catalysts.

The cost of replacing failed selective catalytic reduction (SCR) catalysts and their disposal as hazardous solid waste is high. If failed catalysts are recovered and regenerated into new SCR denitration catalysts, the cost of flue gas denitration can be effectively reduced. However, regenerated SCR catalysts have relatively low structural strength and activity and cannot yet form an effective replacement. In this study, aluminum dihydrogen phosphate, aluminum nitrate, and aluminum sulfate were used as structural strengthening agents in the regeneration of SCR catalysts, and over-impregnation, drumming-assisted impregnation, and ultrasonic-assisted preparation techniques were compared. The corresponding regenerated SCR catalysts were then prepared and analyzed for compressive strength, wear strength, H2-TPR, NH3-TPD, and in situ IR. Factors influencing the structural strength, physical properties, and catalytic activity of the regenerated catalysts were investigated. The best results were obtained as follows: compressive strength of 4.57 MPa, wear rate of 0.088% kg-1, and denitration of 58% after 10 min of drumming-assisted impregnation in an aluminum sulfate solution with a concentration of 16%. Based on this, a synergistic method for catalyst activity and structural strengthening was explored to support the design of better SCR catalysts for regeneration.

Prophylactic cranial irradiation (PCI) versus active surveillance in patients with limited-stage small cell lung cancer: a retrospective, multicentre study.

BACKGROUND: The recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) is primarily based on evidence from the pre-magnetic resonance imaging (MRI) era. However, as MRI accuracy improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC has become uncertain. This study aims to compare the contemporary survival outcomes of patients with LS-SCLC treated with PCI versus active surveillance. METHODS: We conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved a good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary medical centres between June 2009 and June 2019. Of these patients, 440 received PCI, while 628 received surveillance without PCI. Propensity score matching with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were overall survival (OS) and the incidence of brain metastasis (BM). RESULTS: In total, 648 patients were matched. The baseline characteristics were generally well balanced. At a median follow-up of 64.5 months (range 2-190), patients who underwent PCI had a significantly lower risk for BM than those who underwent surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5-33.8%) in the PCI cohort and 38.5% (32.6-44.5%) in the surveillance cohort (Gray's p = 0.002). However, the lower incidence of BM in the PCI cohort did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6-44.0 months) in the PCI cohort versus 32 months (26.4-37.6 months) in the surveillance cohort (HR 0.90, 95% CI 0.74-1.10, p = 0.29). Multivariable analysis showed that disease stage, chemoradiotherapy sequence, and response to chemoradiotherapy were independent prognostic factors for BM or OS. CONCLUSIONS: Overall, PCI reduces the risk for BM but does not substantially prolong OS compared with active surveillance. A phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results.

Efficacy and safety of immune checkpoint inhibitors plus anlotinib in small cell lung cancer with brain metastases: a retrospective, multicentre study.

BACKGROUND: Previous studies showed that both immune checkpoint inhibitors (ICIs) and anlotinib have central nervous system (CNS) efficacy. This study aimed to evaluate the efficacy and safety of ICIs combined with anlotinib in small cell lung cancer (SCLC) patients with brain metastases (BMs). METHODS: We retrospectively reviewed SCLC patients with CNS metastases confirmed by brain magnetic resonance imaging (MRI). Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and Response assessment in neuro-oncology brain metastases (RANO-BM) were used to evaluate treatment response to ICIs plus anlotinib. Kaplan-Meier analysis and Cox regression analysis were performed to determine patient's prognosis. RESULTS: Sixty-six patients with baseline BMs were included. For patients with measurable intracranial lesions, the intracranial objective response rate (ORR) was 29.2% based on RECIST 1.1 criteria and was 27.1% based on RANO-BM criteria. The median intracranial progression-free survival (PFS) was 9.0 months (95% confidence interval [CI], 6.5-11.5 months). The median overall survival (OS) was 13.4 months (95% CI, 10.7-20.5 months). Multivariate Cox regression analysis showed that high disease burden (hazard ratio [HR] = 4.83, P < 0.001), multiple BMs (HR = 2.71, P = 0.036), and more than or equal to 3 prior lines of therapy (HR = 2.56, P = 0.023) were independent negative predictors of OS. The overall incidence of treatment-related adverse events (TRAEs) was 75.8%, and grade 3-4 TRAEs were reported in 19.7% of patients. CONCLUSIONS: Our results suggested that ICIs plus anlotinib had potent CNS efficacy with tolerable toxicity and could be a promising treatment option for SCLC patients with BMs.

Magnetic resonance spectroscopy associations with clinicopathologic features of estrogen-dependent endometrial cancer.

BACKGROUND: We studied the magnetic resonance spectroscopy (MRS) associations with clinicopathologic features of estrogen-dependent endometrial cancer (type I EC). METHODS: Totally 45 patients with type I EC who underwent preoperative multi-voxel MRS at 3.0 T were enrolled. The mean ratio of the Cho peak integral to the unsuppressed water peak integral (Cho/water) of the tumor was calculated. The Cho/water and apparent diffusion coefficient (ADC) of type I EC with and without local invasion, as well as with different levels of Ki-67 staining index (SI) (≤ 40% and > 40%), were compared. Correlation test was used to examine the relationship of Cho/water, as well as mean ADC, with Ki-67 SI, tumor stage, and tumor grade. RESULTS: The mean Cho/water of EC with Ki-67 SI ≤ 40% (2.28 ± 0.93) × 10-3 was lower than that with Ki-67 SI > 40% (4.08 ± 1.00) × 10-3 (P < 0.001). The mean Cho/water of EC with deep and superficial myometrial invasion was (3.41 ± 1.26) × 10-3 and (2.43 ± 1.11) × 10-3, respectively (P = 0.011). There was no significant difference in Cho/water between type I EC with and without cervical invasioin ([2.68 ± 1.00] × 10-3 and [2.77 ± 1.28] × 10-3, P = 0.866). The mean Cho/water of type I EC with and without lymph node metastasis was (4.02 ± 1.90) × 10-3 and (2.60 ± 1.06) × 10-3, respectively (P = 0.014). The Cho/water was positively correlated with the Ki-67 SI (r = 0.701, P < 0.001). There were no significant differences in ADC among groups (all P > 0.05). CONCLUSION: MRS is helpful for preoperative assessment of clinicopathological features of type I EC.

Assessment of postpartum haemorrhage for placenta accreta: Is measurement of myometrium thickness and dark intraplacental bands using MRI helpful?

BACKGROUND: This study aimed to investigate the predictive values of magnetic resonance imaging (MRI) myometrial thickness grading and dark intraplacental band (DIB) volumetry for blood loss in patients with placenta accreta spectrum (PAS). METHODS: Images and clinical data were acquired from patients who underwent placenta MRI examinations and were diagnosed with PAS from March 2015 to January 2021. Two radiologists jointly diagnosed, processed, and analysed the MR images of each patient. The analysis included MRI-based determination of placental attachment, as well as myometrial thickness grading and DIB volumetry. The patients included in the study were divided into three groups according to the estimated blood loss volume: in the general blood loss (GBL) group, the estimated blood loss volume was < 1000 ml; in the massive blood loss (MBL) group, the estimated blood loss volume was ≥ 1000 ml and < 2000 ml; and in the extremely massive blood loss (ex-MBL) group, the estimated blood loss volume was ≥ 2000 ml. The categorical, normally distributed, and non-normally distributed data were respectively analysed by the Chi-square, single-factor analysis of variance, and Kruskal-Wallis tests, respectively. The verification of correlation was completed by Spearman correlation analysis. The evaluation capabilities of indicators were assessed using receiver operating characteristic curves. RESULTS: Among 75 patients, 25 were included in the GBL group, 26 in the MBL group, and 24 in the ex-MBL group. A significant negative correlation was observed between the grade of myometrial thickness and the estimated blood loss (P < 0.001, ρ = - 0.604). There was a significant positive correlation between the volume of the DIB and the estimated blood loss (P < 0.001, ρ = 0.653). The areas under the receiver operating characteristic curve of the two MRI features for predicting blood loss ≥ 2000 ml were 0.776 and 0.897, respectively. CONCLUSIONS: The grading and volumetric MRI features, myometrial thickness, and volume of DIB, can be used as good prediction indicators of the risk of postpartum haemorrhage in patients with PAS.

The prognostic value of TCF1+CD8+T in primary small cell carcinoma of the esophagus.

TCF1+CD8+T cells are reported to exhibit stem-like properties with the ability to self-renew and differentiate into terminal effector T cells (TCF1-CD8+T cells) to enhance antitumor response. Previous studies indicated that TCF1+CD8+ tumor-infiltrating lymphocytes (TILs) are related to response to immunotherapy. However, their role in predicting prognosis for patients with primary small cell carcinoma of the esophagus (PSCCE) remains unclear. In this study, the expression of TCF1+CD8+T was analyzed by multiplex fluorescence immunohistochemistry in tumor tissues of 79 patients with PSCCE. High infiltration of TCF1+CD8+T cells had longer overall survival (OS) than low infiltration (P = .009, hazard ratio [HR] = 0.506). High TCF1+CD8/CD8 ratio (>21%) showed superior OS compared with low ratio (≤21%) (P < .001, HR = 0.394). In the validation set (n = 20), the prognostic value of TCF1+CD8+T cells on OS was also verified. TCF1+CD8+T cells are strong prognostic predictors.

Study on the correlation between preoperative inflammatory indexes and adhesional perinephric fat before laparoscopic partial nephrectomy.

OBJECTIVE: This study was aimed to evaluate the effect of preoperative composite inflammatory index on adhesional perinephric fat (APF), providing a help for preoperative risk assessment of laparoscopic partial nephrectomy (LPN) in patients with renal cell carcinoma. MATERIALS AND METHODS: A retrospective study was conducted on 231 patients with renal cell carcinoma, who underwent laparoscopic partial nephrectomy. They were divided into two groups according to whether there was APF during operation. Relevant clinical data, laboratory parameters and imaging examination were obtained before operation to calculate the composite inflammatory index and MAP score. The composite inflammatory index was divided into high value group and low value group by ROC curve method. The related predictive factors of APF were analyzed by logistic regression method. RESULTS: The APF was found in 105 patients (45.5%). In multivariate analysis, systemic immune inflammation index (SII) (high/low), MAP score, tumor size and perirenal fat thickness were independent predictors of APF. The operation time of patients with APF was longer, and the difference of blood loss was not statistically significant. CONCLUSION: SII is an independent predictor of APF before laparoscopic partial nephrectomy. Trial registration ChiCTR, ChiCTR2100045944. Registered 30 April 2021-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=125703 .

Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki-67, HIF-1α and VEGF.

Prostate cancer (PCa) is the second most common cancer in men. The Gleason score (GS) and biomarkers play important roles in the diagnosis and treatment of patients with PCa. The purpose of this study was to investigate the relationship between the apparent diffusion coefficient (ADC) and the molecular markers Ki-67, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in PCa. Thirty-nine patients with 39 lesions, who had been diagnosed with PCa, were enrolled in this study. All patients underwent diffusion-weighted magnetic resonance imaging (DW-MRI) (b = 800 s/mm2 ). The expression of Ki-67, HIF-1α and VEGF was assessed by immunohistochemistry. Statistical analysis was applied to analyze the association between ADC and prostate-specific antigen (PSA), GS and the expression of Ki-67, HIF-1α and VEGF. The group differences in ADC among different grades of Ki-67, HIF-1α and VEGF were also analyzed. The mean ± standard deviation of ADC was (0.76 ± 0.27) × 10-3  mm2 /s. ADC correlated negatively with PSA and GS (p < 0.05). The Ki-67 staining index (SI), HIF-1α expression and VEGF expression in PCa were correlated inversely with ADC, controlling for age (r = -0.332, p < 0.05; r = -0.662, p < 0.0005; and r = -0.714, p < 0.0005, respectively). ADC showed a significant difference among different grades of Ki-67 (F = 9.164, p = 0.005), HIF-1α (F = 40.333, p < 0.0005) and VEGF (F = 22.048, p < 0.0005). In conclusion, ADC was correlated with PSA, GS, and Ki-67, HIF-1α and VEGF expression in patients with PCa. ADC may be used to evaluate tumor proliferation, hypoxia and angiogenesis in PCa.

Differentiation of pancreatobiliary-type from intestinal-type periampullary carcinomas using 3.0T MRI.

PURPOSE: To differentiate pancreatobiliary-type from intestinal-type periampullary carcinomas using combined magnetic resonance cholangiopancreatography (MRCP), contrast-enhanced MRI, and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: MRI (3.0T) results of 41 patients with pathologically confirmed periampullary carcinoma were retrospectively assessed. Two radiologists, blinded to histologic type of each tumor, evaluated image findings independently. MRCP image features, enhancement pattern, and apparent diffusion coefficient (ADC) values were analyzed. Independent-sample t-test, chi-square, or Fisher's exact test were used to determine differential image findings between the pancreatobiliary-type and the intestinal-type group. Cohen's κ statistic or interclass correlation coefficient (ICC) were used to evaluate interobserver agreement between two observers. Univariate and multiple logistic regression analysis were performed to identify MRI features with predictive values. RESULTS: On the basis of hematoxylin-eosin staining, 27 patients were classified as having pancreatobiliary-type carcinomas, and 14 patients the intestinal type. The pancreatobiliary-type carcinomas more commonly showed progressive enhancement than the intestinal type (P = 0.003). The minimum ADC (ADCmin ) value of the pancreatobiliary-type group ([0.95 ± 0.21] × 10(-3) mm(2) /s) was significantly lower than the intestinal-type group ([1.10 ± 0.25] × 10(-3) mm(2) /s) (P = 0.047). For interobserver agreement, the κ values and ICCs for all parameters exceeded 0.8, indicating almost perfect agreement. At multiple logistic regression analysis, the enhancement pattern was the only significant independent predictor (P = 0.011, odds ratio [OR] = 0.105). When the enhancement pattern and ADCmin were used in combination, we could identify 70.4% of pancreatobiliary-type and 78.6% of intestinal-type carcinomas. CONCLUSION: Progressive enhancement and low ADCmin values suggest a pancreatobiliary-type periampullary carcinoma.

MRI In rectal cancer: Correlations between MRI features and molecular markers Ki-67, HIF-1α, and VEGF.

PURPOSE: To investigate whether the apparent diffusion coefficient (ADC) values acquired from diffusion-weighted magnetic resonance imaging (DW-MRI) are correlated with molecular markers Ki-67, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in rectal cancer (RC). MATERIALS AND METHODS: Ninety-one patients (64 males and 27 females) diagnosed with rectal cancer underwent 3.0T DW-MRI before any anticancer treatment. DW-MRI was performed using the single-shot echo-planar imaging technique (b = 0 and b = 800 s/mm(2) ). The patients underwent surgery within 1 week after MRI. Ki-67, HIF-1α, and VEGF expression were assessed by immunohistochemistry at both the resected margins and the center of the tumor. RESULTS: We noted that ADC values correlated positively with histology differentiations (r = 0.336, P = 0.001) and negatively with carcinoembryonic antigen level (r = -0.217, P = 0.039) in RC. Both the value and the level of Ki-67 expression were correlated inversely with the ADC values (r = -0.475, P < 0.001 and r = -0.555, P < 0.001). There was a weak negative correlation between HIF-1α expression and the ADC values (r = -0.304, P = 0.003). VEGF expression was correlated inversely with the ADC values of the RCs (r = -0.290, P = 0.005). However, no significant correlation was observed between VEGF expression and the ADC values in pT4 RCs (r = -0.166, P = 0.255). CONCLUSION: Our results suggest that the ADC values on DW-MRI may be used as a measurement of cell proliferation and hypoxia in RC. J. Magn. Reson. Imaging 2016;44:594-600.

[Preliminary Study on the Structural Characteristics of Residue from Rice Straw Burning in Field].

Because of their special structural characteristics, straw burning residues (biochar) have important impacts on the soil carbon sequestration and the transport and transformation behavior of pollutants. In this paper, a series of qualitative and quantitative analysis methods such as scanning electron microscopy (SEM) , X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) have been used to study the basic physical and chemical properties and structural features of rice straw burning residues generating at different incineration intensity in field. The results show that: the basic physical and chemical properties of straw burning residues from field were closely associated with the burning intensity. The higher the burning intensity, the lower the TOC content. Meanwhile, the order degree of carbon atoms in the resulting residue increased. Wherein the fatty component of rice straw burning residues is gradually reduced with the burning intensity while the aromaticity of rice straw burning residues is gradually increased. In addition, the organic components in the straw burning residues from field have more significant contribution to the surface area.

Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: association with response to neoadjuvant therapy and prognosis.

The aim of this study was to determine whether pretreatment status of human epidermal growth factor receptor-2 (HER-2) could predict pathologic response to neoadjuvant chemoradiotherapy (nCRT) and outcomes for patients with locally advanced rectal cancer (LARC). A total of 119 patients diagnosed with LARC received standardized multimodal treatment. Their HER-2 status was determined in pretreatment biopsies by immunohistochemistry (IHC) and FISH. Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. Twenty-two cases in 119 patients assessed as IHC3+ or IHC2+ plus gene-amplified were determined as HER-2 positive. Positive HER-2 status was not associated with any pretreatment clinicopathologic parameters (P > 0.05). HER-2 status could not predict pathologic response to nCRT based on downstaging (P = 0.210) and tumor regression grade (P = 0.085) but it provides us with a trend that HER-2-positive tumors may be resistant to nCRT. Positive HER-2 status was significantly associated with poor 5-year disease-free survival (P = 0.015) and 5-year overall survival (P = 0.026). It can act as a worse prognostic factor for LARC patients.

Affinity purification of binding miRNAs for messenger RNA fused with a common tag.

Prediction of microRNA-mRNA interaction typically relies on bioinformatic methods, but these methods only suggest the possibility of microRNA binding and may miss important interactions as well as falsely predict others. A major obstacle to the miRNA research has been the lack of experimental procedures for the identification of miRNA-mRNA interactions. Recently, a few studies have attempted to explore experimental methods to isolate and identify miRNA targets or miRNAs targeting a single gene. Here, we developed an more convenient experimental approach for the isolation and identification of miRNAs targeting a single gene by applying short biotinylated DNA anti-sense oligonucleotides mix to enhanced green fluorescent protein (EGFP) mRNA which was fused to target gene mRNA. This method does not require a design of different anti-sense oligonucleotides to any mRNA. This is a simple and an efficient method to potentially identify miRNAs targeting specific gene mRNA combined with chip screen.

Mechanism of Cu(II) adsorption inhibition on biochar by its aging process.

Biochar exposed in the environment may experience a series of surface changes, which is called biochar aging. In order to study the effects of biochar aging on Cu(II) adsorption, we analyzed the surface properties before and after biochar aging with scanning electron microscopy (SEM) coupled to an energy-dispersive X-ray spectrometer (EDX) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and then explored the influence of the aging process on Cu(II) adsorption by batch experiments. After the aging process, the oxygen concentration, phenolic hydroxyl groups, aromatic ethers and other oxygen-containing functional groups on the biochar surface increased, while carboxyl groups slightly decreased. Thus, over a range of pH, the cation exchange capacity (CEC) and adsorption capacity of Cu(II) on the aged biochar were smaller than those of new biochar, indicating that when biochar is incubated at constant temperature and water holding capacity in the dark, the aging process may inhibit Cu(II) adsorption. Meanwhile, the dissociation characteristics of oxygen-containing functional groups changed through the aging process, which may be the mechanism by which the biochar aging process inhibits the Cu(II) adsorption. Carboxyl groups became more easily dissociated at low pH (3.3-5.0), and the variation of maximum adsorption capability (qm) of Cu(II) on the old biochar was enlarged. Phenolic hydroxyl groups increased after the aging, making them and carboxyl groups more difficult to dissociate at high pH (5.0-6.8), and the variation of qm of Cu(II) on the aged biochar was reduced.

Multiparametric MRI-based radiomic nomogram for predicting HER-2 2+ status of breast cancer.

Objective: To explore the application of multiparametric MRI-based radiomic nomogram for assessing HER-2 2+ status of breast cancer (BC). Methods: Patients with pathology-proven HER-2 2+ invasive BC, who underwent preoperative MRI were divided into training (72 patients, 21 HER-2-positive and 51 HER-2-negative) and validation (32 patients, 9 HER-2-positive and 23 HER-2-negative) sets by randomization. All were classified as HER-2 2+ FISH-positive (HER-2-positive) or -negative (HER-2-negative) according to IHC and FISH. The 3D VOI was drawn on MR images by two radiologists. ADC, T2WI, and DCE images were analyzed separately to extract features (n = 1906). L1 regularization, F-test, and other methods were used to reduce dimensionality. Binary radiomics prediction models using features from single or combined imaging sequences were constructed using logistic regression (LR) classifier then and validated on a validation dataset. To build a radiomics nomogram, multivariate LR analysis was conducted to identify independent indicators. An evaluation of the model's predictive efficacy was made using AUC. Results: On the basis of combined ADC, T2WI, and DCE images, ten radiomic features were extracted following feature dimensionality reduction. There was superior diagnostic efficiency of radiomic signature using all three sequences compared to either one or two sequences (AUC for training group: 0.883; AUC for validation group: 0.816). Based on multivariate LR analysis, radiomic signature and peritumoral edema were independent predictors for identifying HER-2 2 +. In both training and validation datasets, nomograms combining peritumoral edema and radiomics signature demonstrated an effective discrimination (AUCs were respectively 0.966 and 0. 884). Conclusion: The nomogram that incorporated peritumoral edema and multiparametric MRI-based radiomic signature can be used to effectively predict the HER-2 2+ status of BC.

Boosting Sono-immunotherapy of Prostate Carcinoma through Amplifying Domino-Effect of Mitochondrial Oxidative Stress Using Biodegradable Cascade-Targeting Nanocomposites.

Sono-immunotherapy faces challenges from poor immunogenicity and low response rate due to complex biological barriers. Herein, we prepared MCTH nanocomposites (NCs) consisting of disulfide bonds (S-S) doped mesoporous organosilica (MONs), Cu-modified protoporphyrin (CuPpIX), mitochondria-targeting triphenylphosphine (TPP), and CD44-targeting hyaluronic acid (HA). MCTH NCs efficiently accumulate at the tumor site due to the overexpressed CD44 receptors on the membrane of the cancer cells. Under the function of HAase and glutathione (GSH), MCTH degrades and exposes TPP to deliver CuPpIX to the mitochondrial site and induce a reactive oxygen species (ROS) burst in situ under ultrasound irradiations, thereby causing severe mitochondria dysfunction. This cascade-targeting ability of MCTH NCs not only reinforces oxidative stress in cancer cells but also amplifies immunogenic cell death (ICD) to stimulate the body's immune response and alleviate the tumor immunosuppressive microenvironment. These NCs significantly enhance the infiltration of immune cells into the tumor, particularly CD8+ T cells, for a powerful antitumor sono-immunotherapy. The proposed cascade-targeting strategy holds promise for strengthening sono-immunotherapy for prostate cancer treatment and overcoming the limitations of traditional immunotherapy.

Radiotherapy-induced tumor physical microenvironment remodeling to overcome immunotherapy resistance.

The clinical benefits of immunotherapy are proven in many cancers, but a significant number of patients do not respond well to immunotherapy. The tumor physical microenvironment (TpME) has recently been shown to affect the growth, metastasis and treatment of solid tumors. The tumor microenvironment (TME) has unique physical hallmarks: 1) unique tissue microarchitecture, 2) increased stiffness, 3) elevated solid stress, and 4) elevated interstitial fluid pressure (IFP), which contribute to tumor progression and immunotherapy resistance in a variety of ways. Radiotherapy, a traditional and powerful treatment, can remodel the matrix and blood flow associated with the tumor to improve the response rate of immune checkpoint inhibitors (ICIs) to a certain extent. Herein, we first review the recent research advances on the physical properties of the TME and then explain how TpME is involved in immunotherapy resistance. Finally, we discuss how radiotherapy can remodel TpME to overcome immunotherapy resistance.

Radiomics and Ki-67 index predict survival in clear cell renal cell carcinoma.

OBJECTIVE: To develop and validate predictive models based on Ki-67 index, radiomics, and Ki-67 index combined with radiomics for survival analysis of patients with clear cell renal cell carcinoma. METHODS: This study enrolled 148 patients who were pathologically diagnosed as ccRCC between March 2010 and December 2018 at our institute. All tissue sections were collected and immunohistochemical staining was performed to calculate Ki-67 index. All patients were randomly divided into the training and validation sets in a 7:3 ratio. Regions of interests (ROIs) were segmented manually. Radiomics features were selected from ROIs in unenhanced, corticomedullary, and nephrographic phases. Multivariate Cox models based on the Ki-67 index and radiomics and univariate Cox models based on the Ki-67 index or radiomics alone were built; the predictive power was evaluated by the concordance (C)-index, integrated area under the curve, and integrated Brier Score. RESULTS: Five features were selected to establish the prediction models of radiomics and combined model. The C-indexes of Ki-67 index model, radiomics model, and combined model were 0.741, 0.718, and 0.782 for disease-free survival (DFS); 0.941, 0.866, and 0.963 for overall survival, respectively. The predictive power of combined model was the best in both training and validation sets. CONCLUSION: The survival prediction performance of combined model was better than Ki-67 model or radiomics model. The combined model is a promising tool for predicting the prognosis of patients with ccRCC in the future. ADVANCES IN KNOWLEDGE: Both Ki-67 and radiomics have showed giant potential in prognosis prediction. There are few studies to investigate the predictive ability of Ki-67 combined with radiomics. This study intended to build a combined model and provide a reliable prognosis for ccRCC in clinical practice.