Peripheral CX3CR1+ T cells combined with PD-1 blockade therapy potentiates the anti-tumor efficacy for lung cancer.

Identifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1+ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1- T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1+ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1+ T cells than those in CX3CR1- T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1+ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1+ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1+ T cells as an individual cancer immunotherapy.

Optimization of stope structure parameters by combining Mathews stability chart method with numerical analysis in Halazi iron mine.

When employing the open stope mining method for extracting materials in underground mines, it is necessary for personnel and equipment to operate within a specified range of the goaf area, thus, adoption of appropriate mining parameters in the mining field is crucial for promoting safe production practices. In this study, the Harazi iron mine is taken as the research subject, with theoretical analysis combined with numerical simulation that enables the authors to simulate and analyze the width parameter of the mining field. Theoretical analysis utilizing the Matthew stability chart method confirms that the width of the mining field in Harazi iron mine should not exceed 9 m. Based on this finding, the mechanical response characteristics accompanying the mining process at different widths within the mining field limits are analyzed via the Flac3D numerical analysis software. As a result of this analysis, the optimal width of the mining field in Harazi iron mine is determined to be 8 m. The method utilized in this article provides a rational approach to determining structural parameters of the mining field and can effectively aid in promoting mine safety practices.

Identification and evolution of non-traditional nitrilase from Spirosoma linguale DSM 74 with high hydration activity.

Hydration, a secondary activity mediated by nitrilase, is a promising new pathway for amide production. However, low hydration activity of nitrilase or trade-off between hydration and catalytic activity hinders its application in the production of amides. Here, natural C-terminal-truncated wild-type nitrilase, mined from a public database, obtained a high-hydration activity nitrilase as a novel evolutionary starting point for further protein engineering. The nitrilase Nit-74 from Spirosoma linguale DSM 74 was successfully obtained and exhibited the highest hydration activity level, performing 50.7 % nicotinamide formation and 87.6 % conversion to 2 mM substrate 3-cyanopyridine. Steric hindrance of the catalytic activity center and the N-terminus of the catalytic cysteine residue helped us identify three key residues: I166, W168, and T191. Saturation mutations resulted in three single mutants that further improved the hydration activity of N-heterocyclic nitriles. Among them, the mutant T191S performed 72.7 % nicotinamide formation, which was much higher than the previously reported highest level of 18.7 %. Additionally, mutants I166N and W168Y exhibited a 97.5 % 2-picolinamide ratio and 97.7 % isonicotinamide ratio without any loss of catalytic activity, which did not indicate a trade-off effect. Our results expand the screening and evolution library of promiscuous nitrilases with high hydration activity for amide formation.

The preventive role of the red gingeng ginsenoside Rg3 in the treatment of lung tumorigenesis induced by benzo(a)pyrene.

Red ginseng has been used in traditional medicine for centuries in Asia. In this study, we evaluated four types of red ginseng grown in different areas (Chinese red ginseng, Korean red ginseng A, Korean red ginseng B, and Korean red ginseng C) for their ability to inhibit lung tumor formation and growth induced by the carcinogen benzo(a)pyrene (B(a)P) in A/J mice and found that Korean red ginseng B was the most effective at lowering the tumor load among the four red ginseng varieties. Moreover, we analyzed the levels of various ginsenosides (Rg1, Re, Rc, Rb2, Rb3, Rb1, Rh1, Rd, Rg3, Rh2, F1, Rk1, and Rg5) in four kinds of red ginseng extract and found that Korean red ginseng B had the highest level of ginsenoside Rg3 (G-Rg3), which suggested that G-Rg3 may play an important role in its therapeutic efficacy. This work revealed that the bioavailability of G-Rg3 was relatively poor. However, when G-Rg3 was coadministered with verapamil, a P-glycoprotein inhibitor, the G-Rg3 efflux in Caco-2 cells was lowered, the small intestinal absorption rate of G-Rg3 in the rat models was increased, the concentration levels of G-Rg3 were elevated in the intestine and plasma, and its tumor-preventive abilities in the tumorigenesis rat model induced by B(a)P were also augmented. We also found that G-Rg3 reduced B(a)P-induced cytotoxicity and DNA adduct formation in human lung cells and rescued phase II enzyme expression and activity through Nrf2 pathways, which may be the potential mechanisms underlying the inhibitory effects of G-Rg3 on lung tumorigenesis. Our study showed a potentially vital role of G-Rg3 in targeting lung tumors in murine models. The oral bioavailability of this ginsenoside was augmented by targeting P-glycoprotein, which allowed the molecule to exert its anticancer effects.

Epidermal growth factor receptor inhibitors as adjuvant treatment for patients with resected non-small cell lung cancer harboring EGFR mutation: a meta-analysis of randomized controlled clinical trials.

BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is still under investigation as adjuvant treatment for early-stage disease. Here, we performed a meta-analysis to evaluate the efficacy of adjuvant EGFR-TKI versus non-EGFR-TKI treatment in patients with completely resected non-small cell lung cancer (NSCLC) harboring EGFR mutation. METHODS: Two investigators independently extracted data from databases. A meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in PROSPERO (ID: CRD42022316481). The primary outcome was disease-free survival (DFS) in patients with EGFR mutation, measured as the hazard ratio (HR). Other outcomes (of subgroup analyses) included overall survival (OS) and DFS. RESULTS: After the systematic screening, eight studies with a total of 3098 patients with stage IB-IIIA NSCLC were included. The results show that in patients with EGFR mutation, the DFS in the adjuvant EGFR-TKI group was significantly superior to that in the control group, with a HR of 0.47 (95% confidence interval [CI]: 0.30-0.74; P = 0.001). In subgroup analyses of DFS, the benefit was observed in the EGFR-TKI group versus the chemotherapy group (HR 0.50, 95% CI 0.30-0.84; P = 0.009), the EGFR-TKI combined with chemotherapy group versus the chemotherapy group (HR 0.37, 95% CI 0.16-0.85; P = 0.02), and in stage IIA-IIIA NSCLC (HR 0.45, 95% CI 0.27-0.74; P = 0.002). However, the benefit of DFS did not translate into improved OS in the whole population (HR 0.79, 95% CI 0.54-1.14; P = 0.20). CONCLUSION: EGFR-TKIs prolonged DFS but not OS in patients with completely resected stage II-IIIA NSCLC harboring EGFR mutation. Longer follow-ups and new clinical trials that can result in changes in clinical practice are needed.

PRDX1 stimulates non-small-cell lung carcinoma to proliferate via the Wnt/ß-Catenin signaling.

BACKGROUND: Previous studies have shown that PRDX1 is upregulated in some types of malignant tumors. The role of PRDX1 in non-small-cancer lung carcinoma (NSCLC) remains unclear. This study aims to identify the role of PRDX1 in influencing in-vitro biological functions of NSCLC and the molecular mechanism. METHODS: We collected 50 cases of fresh NSCLC and adjacent non-tumoral tissues for detecting differential expressions of PRDX1 by quantitative real-time polymerase chain reaction (qRT-PCR). Survival time of NSCLC patients, defined as the period from the operation to the latest follow-up or death due to recurrence or metastasis, was recorded for assessing the relationship between PRDX1 and prognosis in NSCLC. Using lentivirus transfection, PRDX1 level was downregulated in NSCLC cells. Subsequently, proliferative and apoptotic abilities, and expression levels of vital genes in the Wnt/ß-Catenin signaling were examined. Finally, the significance of activated Wnt/ß-Catenin signaling during PRDX1-regulated NSCLC proliferation was explored. RESULTS: Using GEPIA database and NSCLC tissues we collected, PRDX1 was detected to be upregulated in NSCLC samples than controls. PRDX1 level was related to tumor staging and prognosis in NSCLC. Knockdown of PRDX1 attenuated proliferative ability and stimulated apoptosis in NSCLC. Protein levels of Wnt5A was downregulated in H1299 and SPC-A1 cells with PRDX1 knockdown. Overexpression of ß-Catenin enhanced proliferative ability and inhibited apoptosis in NSCLC cells with PRDX1 knockdown. CONCLUSIONS: PRDX1 is upregulated in NSCLC samples, and linked to tumor staging and prognosis. It stimulates NSCLC to proliferate by activating the Wnt/ß-Catenin signaling.

Construction of Cordycepin High-Production Strain and Optimization of Culture Conditions.

This study aimed to increase cordycepin production by over-expressing bio-synthetic enzyme genes, including the adenylosuccinate synthase, adenylosuccinate lyase, and 5'-nucleotidase genes. Research data showed that the extracellular and intracellular cordycepin concent of 24 recombinant strains were higher than those of C. militaris WT, indicating that over-expression of key enzyme genes increased cordycepin production. Among them, the CM-adss-5 strain had highest cordycepin production, and the extracellular and intracellular cordycepin concent were 1119.75 ± 1.61 and 65.56 ± 0.97 mg/L, which were 1.26 and 2.61 times that of C. militaris WT. This study also optimized the culture conditions of CM-adss-5 strain through single factor experiments to obtain the best culture conditions. The best culture condition was 25 °C constant temperature, 180-rpm shaking culture, fermentation period 12 days, inoculate amount 5%, initial pH 6, seed age 108 h, and liquid volume 110/250 mL. Then, the extracellular and intracellular cordycepin content of CM-adss-5 strain reached 2581.96 ± 21.07 and 164.08 ± 1.44 mg/L, which were higher by 130.6% and 150.3%, respectively. Therefore, our research provides a way to efficiently produce cordycepin for the development of cordycepin and its downstream products.

Raspberry-like AgBiS2@PVP nanoparticles for enhanced sonodynamic and chemodynamic cancer therapy.

Sonodynamic therapy (SDT) is a non-invasive treatment, preferred by many researchers. Ultrasound is applied to tumor lesions, enriched with a sound sensitizer. The activation of the sound sensitizer produces reactive oxygen species (ROS), which kill the tumor cells. In this study, raspberry-like AgBiS2@PVP nanoparticles (NPs) were prepared, which were modified with polyvinylpyrrolidone (PVP). Finally, AgBiS2@PVP NPs with 261 nm diameter and a suitable band gap were successfully synthesized. These NPs could play a role in SDT by generating ROS when induced by ultrasonic stimulation. Moreover, the AgBiS2@PVP NPs could also catalyze H2O2 in the tumor microenvironment to produce ˙OH, equipping the NPs with chemodynamic therapy (CDT) properties. In vivo and in vitro experiments suggested that, compared to the single treatments, the combination of SDT and CDT had a clearer inhibitory effect on tumor cells.

MOF(Fe)-derived composites as a unique nanoplatform for chemo-photodynamic tumor therapy.

Fe-based metal-organic frameworks (MOFs) can be used for chemodynamic therapy (CDT) for tumors due to their unique Fenton-like effects and porous and biodegradable nature. The adsorption and transport of small molecule drugs by their structure has attracted much attention. Herein, MnO2@NH2-MIL101(Fe)@Ce6-F127 nanoparticles (MNMCF NPs) were synthesized using a facile solvothermal strategy. The small molecule photosensitizer Ce6 was adsorbed by MOFs to improve the biocompatibility of Ce6 and give it high bioavailability when injected intravenously. When the MNMCF NPs reached the tumor site, Fe-based MOFs exhibited Fenton-like properties, producing ˙OH and showing CDT effects. MnO2 could specifically respond to produce O2 in a tumor microenvironment, thereby improving the tumor hypoxia state and enhancing the efficacy of photodynamic therapy (PDT) by Ce6. Both the in vitro and in vivo experiments showed that the MNMCF-guided CDT/PDT combination therapy could effectively ablate tumors without the drawbacks of poor tolerability and potential long-term side effects. Therefore, the prepared MNMCF NPs can be used as promising candidates for synergistic CDT/PDT tumor therapy.

Clinical Correlation of Function and TCR vß Diversity of MAGE-C2-Specific CD8+ T Cell Response in Esophageal Cancer.

Melanoma-associated Ag (MAGE)-C2, an immunogenic cancer germline (testis) Ag, is highly expressed by various tumor cells, thymic medullary epithelial cells, and germ cells. In this study, we aimed to explore the immunologic properties of MAGE-C2-specific CD8+ T cells and the relationship of its TCR ß-chain V region (TCR vß) subfamily distribution to prognosis of patients with esophageal cancer. PBMCs and tumor-infiltrating lymphocytes expanded by CD3/CD28 Dynabeads and MAGE-C2 peptides in vitro resulted in the induction of lysosome-associated membrane protein-1 (LAMP-1 or CD107a) on the cell surface and the production of IFN-γ by MAGE-C2-specific CD8+ T cells. We found differential TCR vß subfamily distribution among flow-sorted CD107a+IFN-γ+ and CD107a-IFN-γ- CD8+ T cells. The proportion of CD107a+ and/or IFN-γ+ tetramer+ CD8+ T cells was lower in patients with lymph node metastasis, late tumor stage, and poorly differentiated state (p < 0.05). T-box transcription factor was positively correlated with CD107a and IFN-γ. Kaplan-Meier analysis showed that patients whose MAGE-C2-specific CD8+ T cells expressed high CD107a and/or IFN-γ had a longer survival time when compared with patients whose MAGE-C2-specific CD8+ T cells expressed low levels of CD107a and/or IFN-γ. Moreover, analysis of TCR vß subfamily distribution revealed that a higher frequency of TCR vß16 in MAGE-C2-specific CD8+ T cells was positively correlated with a better prognosis. These results suggest that the presence of functional MAGE-C2-specific CD8+ T cells had an independent prognostic impact on the survival of patients with esophageal cancer.

Intelligent Bi2Se3@Cu2-xSe heterostructures with enhanced photoabsorption and photoconversion efficiency for tri-modal imaging guided combinatorial cancer therapy by near-infrared â ¡ light.

A novel nanoplatform that supports multimodal imaging has been designed for deep tumor therapy. In this study, Bi2Se3@Cu2-xSe heterojunction nanocomposites with tunable spectral absorption, effective electron-hole separation and high photothermal conversion efficiency were prepared for the combination therapy of phototherapy (PT), chemodynamic therapy (CDT) and radiotherapy (RT). By adjusting the doping ratio, the heterojunction nanoparticles show obvious tunable ability of local surface plasmon resonance and the ability to promote electron-hole separation with significantly enhanced reactive oxygen species production capacity. The band structure and charge density difference calculated by density functional theory further reveal that the change of band gap and the decrease of free carriers can regulate the spectral absorption of nanomaterials and promote electron-hole separation. In addition, the photothermal conversion properties of low carrier density semiconductors are related to their inherent deep level defects. The formation of heterojunctions making the Se atoms deviate from the Bi2Se3 lattice, resulting in more deep level defects and stronger photothermal conversion properties. Meanwhile, this nanoplatform presented features similar to catalase activities and glutathione (GSH) consumption characteristics, which was capable of effectively alleviate the tumor-specific hypoxia environment to enhance the efficacy of O2-dependent photodynamic therapy (PDT) and radiotherapy (RT) and depletion GSH to prevent the reduction of therapeutic efficacy due to the clearance of reactive oxygen species. In addition to therapeutic enhancement, heterojunction nanomaterials have excellent nuclear magnetic resonance imaging (MRI), infrared thermal imaging (IR) and computed tomography (CT) properties due to their significant paramagnetism and excellent photothermal conversion and X-ray attenuation capacities. In conclusion, our findings provide a new strategy for designing multi-function and efficient nanoplatform to treat tumor.

CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy.

Chimeric antigen receptor (CAR) T cells remain unsatisfactory in treating solid tumors. The frequency of tumor-infiltrating T cells is closely related to the good prognosis of patients. Augmenting T cell accumulation in the tumor microenvironment is essential for tumor clearance. To overcome insufficient immune cell infiltration, innovative CAR designs need to be developed immediately. CXCL9 plays a pivotal role in regulating T cell migration and inhibiting tumor angiogenesis. Therefore, we engineered CAR T cells expressing CXCL9 (CART-CXCL9). The addition of CXCL9 enhanced cytokine secretion and cytotoxicity of CAR T cells and endowed CAR T cells with the ability to recruit activated T cells and antiangiogenic effect. In tumor-bearing mice, CART-CXCL9 cells attracted more T cell trafficking to the tumor site and inhibited angiogenesis than conventional CAR T cells. Additionally, CART-CXCL9 cell therapy slowed tumor growth and prolonged mouse survival, displaying superior antitumor activity. Briefly, modifying CAR T cells to express CXCL9 could effectively improve CAR T cell efficacy against solid tumors.

A Nanoarchitectonic Approach Enables Triple Modal Synergistic Therapies To Enhance Antitumor Effects.

Improvement of antitumor effects relies on the development of biocompatible nanomaterials and combination of various therapies to produce synergistic effects and avoid resistance. In this work, we developed GBD-Fe, a nanoformulation that effectively integrated chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT). GBD-Fe used gold nanorods as photothermal agents and encapsulated doxorubicin to amplify Fe3+-guided CDT effects by producing H2O2 and reducing the intracellular glutathione levels. In vitro and in vivo experiments were conducted to demonstrate the enhanced accumulation and antitumor effects of this tripronged therapy under magnetic resonance imaging (MRI) guidance. This tripronged approach of CT/CDT/PTT effectively induced tumor cytotoxicity and inhibited tumor growth in tumor-bearing mice and therefore represents a promising strategy to effectively treat tumors.

Multifunctional phototheranostic nanoplatform based on polydopamine-manganese dioxide-IR780 iodide for effective magnetic resonance imaging-guided synergistic photodynamic/photothermal therapy.

Multifunctional phototheranostics combining diagnostic and therapeutic modalities may provide a revolutionary opportunity for cancer treatment. As a promising tumor phototheranostic molecule, IR780 iodide (IR780) shows excellent photodynamic and photothermal performance under near-infrared laser irradiation; however, its hydrophobicity and instability limit its further use in organisms. This work demonstrates the design and development of a multifunctional nanoplatform (PMIDA, referring to polydopamine (PDA)-manganese dioxide (MnO2)-IR780) for imaging-guided phototherapy. The good biocompatibility of PDA greatly improves the water solubility and photostability of IR780, and its excellent photothermal properties make PMIDA a dual photothermal therapy (PTT). MnO2-induced generation of oxygen in the tumor microenvironment improves the hypoxia effect and photodynamic therapy (PDT) of IR780. Moreover, Mn2+ serves as a decent T1-weighted magnetic resonance imaging (MRI) probe to guide treatment. Notably, in relevant cellular assays, PMIDA shows high photodynamic and photothermal effects contributing to the final therapeutic effect. The MRI-guided PDT/PTT synergistic therapy effect in vivo is demonstrated by precise tumor diagnosis and complete tumor elimination outcomes. Based on these experiments, PMIDA nanoparticles display promising effects in facilitating intravenous injection of IR780 and achieving magnetic resonance imaging (MRI)-guided phototheranostic efficacy for tumor treatment.

Lenvatinib and Cu2-xS nanocrystals co-encapsulated in poly(D,L-lactide-co-glycolide) for synergistic chemo-photothermal therapy against advanced hepatocellular carcinoma.

Lenvatinib (LT) is gradually replacing sorafenib as an alternative targeted drug against advanced hepatocellular carcinoma (HCC). However, the anticancer effects of LT are still limited because of its low cytotoxicity, multidrug resistance (MDR), and tumor relapse. Herein, we constructed a smart biophotonic nanoplatform to overcome the barriers preventing high performance. LT and copper sulfide nanocrystals (Cu2-xS NCs) with excellent photothermal properties in the near-infrared-II (NIR-II) zone were co-encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) through nanoprecipitation. Both in vitro and in vivo evaluations demonstrated that Cu2-xS NCs enhanced the anticancer efficacy of LT, without recurrence. In addition, the presence of copper ions could allow glutathione (GHS) to be consumed and oxygen to be produced, likely suppressing the expression of P-glycoprotein (P-gp) and overcoming the issue of MDR relating to LT. More importantly, synergistic chemo-photothermal therapy with LT and Cu2-xS NCs was more effective than any single therapy or theoretical combination. This nanoplatform is promising for advancing future LT-based treatment strategies for HCC therapy.

Construction of a prognostic model for lung squamous cell carcinoma based on seven N6-methylandenosine-related autophagy genes.

OBJECTIVE: We aimed to construct a novel prognostic model based on N6-methyladenosine (m6A)-related autophagy genes for predicting the prognosis of lung squamous cell carcinoma (LUSC). METHODS: Gene expression profiles and clinical information of Patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) database. In addition, m6A- and autophagy-related gene profiles were obtained from TCGA and Human Autophagy Database, respectively. Pearson correlation analysis was performed to identify the m6A-related autophagy genes, and univariate Cox regression analysis was conducted to screen for genes associated with prognosis. Based on these genes, LASSO Cox regression analysis was used to construct a prognostic model. The corresponding prognostic score (PS) was calculated, and patients with LUSC were assigned to low- and high-risk groups according to the median PS value. An independent dataset (GSE37745) was used to validate the prognostic ability of the model. CIBERSORT was used to calculate the differences in immune cell infiltration between the high- and low-risk groups. RESULTS: Seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, DLC1, ITGB1, PINK1, TP63, and EIF4EBP1. In the training and validation sets, patients in the high-risk group had worse survival times than those in the low-risk group; the areas under the receiver operating characteristic curves were 0.958 and 0.759, respectively. There were differences in m6A levels and immune cell infiltration between the high- and low-risk groups. CONCLUSIONS: Our prognostic model of the seven m6A-related autophagy genes had significant predictive value for LUSC; thus, these genes may serve as autophagy-related therapeutic targets in clinical practice.

Practice, Knowledge, and Attitude of Health Care Providers regarding Cancer Pain Management: A National Survey.

Background: A lack of knowledge and inadequate practices of health care providers (HCPs) are the main obstacles to effective cancer pain management (CPM). The main objective of the study was to evaluate the CPM knowledge, CPM practice, and attitudes towards pharmacists' participation and advanced methods in CPM of physicians, nurses, and pharmacists in China. Methods: An open online survey was adopted using social media software (WeChat) as the platform to conduct a nationwide survey of HCPs involved in CPM in public medical institutions at all levels in China from March to June 2019. Results: A total of 1279 physicians, 2267 nurses, and 1466 pharmacists participated in the survey. Among the three types of professionals, nurses had the highest level of practical ability (61.63 ± 28.99) and best attitudes towards pharmacists' participation and advanced methods in CPM (72.05 ± 33.71) and physicians had the best mastery of CPM-related knowledge (69.60 ± 28.45), while pharmacists performed the worst in these three aspects (50.04 ± 26.69, 61.49 ± 28.95, and 62.07 ± 36.46, respectively). Only 19.69% of the hospitals had a pharmacist to tumor patient ratio ≥1 : 50. Hierarchical analysis showed that passing a good pain management (GPM) ward program and participating in advanced training had positive impacts on the scores of all three parts in the three professions (ptrend <0.05). Conclusions: HCPs' levels of practice, knowledge, and attitudes towards pharmacists and advanced methods of CPM were average in China; however, pharmacists had the worst performance, which demonstrates a need for further improvement. Furthermore, GPM ward programs and advanced trainings are helpful for improving CPM levels.

Blood alkaline phosphatase predicts prognosis of patients with advanced HER2-negative gastric cancer receiving immunotherapy.

BACKGROUND: Immune checkpoint blockade is effective against many cancer types, but few patients achieve a complete response (OR). Therefore, effective prognostic biomarkers are needed for metastatic gastric cancer (GC) patients after immune treatment. The present study assessed the value of hematological parameters as markers of the effectiveness of immune checkpoint blockade among metastatic GC patients. METHODS: This retrospective study included patients with metastatic GC who underwent multiline chemotherapy including at least two courses of immunotherapy between September 2018 and December 2020. Patient and tumor characteristics were tested for prognostic significance by analysis of variance or chi-square test. Kaplan-Meier and Cox analyses were performed to identify factors associated with progression-free survival (PFS). RESULTS: Sixty-one GC patients (mean age 55.61±11.97 years, range 23-80 years, 24 females, and 37 males) were included, and 27, 9 and 25 cases had organ only, peritoneum only, and simultaneous organ and peritoneum metastasis, respectively. Gastrectomy was performed in 24 cases, and there was no operative treatment in the other 37 cases, while all patients received two or more lines of chemotherapy. After immune treatment, 13 patients achieved a partial response (PR), 16 stable disease (SD), and 32 progressive disease (PD). The median PFS was 4.93±3.47 months. An alkaline phosphatase (ALP) level >225 U/L, a lactate dehydrogenase level (LDH) >299 U/L, and a body mass index (BMI) >24 kg/m2 were associated with a short PFS (P=0.01, P=0.008, and P=0.039, respectively). A Cox multivariate proportional hazard model indicated that higher ALP level was a significant prognostic indicator for adverse PFS. CONCLUSIONS: Our data show an ALP cutoff of 225 U/L offered good prognostic sensitivity for HER2-negative metastatic GC. ALP measurement represents a convenient, cost-effective, and relatively sensitive screening tool, and prospective studies involving its evaluation in addition to other biomarkers in metastatic GC patients are indicated.

Using the Diaphragm as a Tracking Surrogate in CyberKnife Synchrony Treatment.

BACKGROUND In this study, we assessed the usefulness of diaphragm surrogate tracking in the design of a respiratory model for CyberKnife Synchrony treatment of lung tumors. MATERIAL AND METHODS Twenty-four patients with lung cancer who underwent stereotactic body radiotherapy with CyberKnife between April and November 2019 were enrolled. Simulation plans for each patient were designed using Xsight lung tracking (XLT) and diaphragm tracking (DT) methods, and tumor visualization tests were performed. The offset consistency at each respiratory phase was analyzed. The relative distance along the alignment center of the superior-inferior (SI) axis in the 2 projections (dxAB), uncertainty (%), and average standard error (AvgStdErr)/maximum standard error (MAXStdErr) were also analyzed. RESULTS Bland-Altman analyses revealed that the average differences±standard deviation (SD) between XLT and DT tracking methods were 0.4±2.9 mm, 0.3±4.35 mm, and -1.8±6.8 mm for the SI, left-right (LR), and anterior-posterior (AP) directions, respectively. These results indicated high consistency in the SI and LR directions and poor consistency in the AP direction. Uncertainty differed significantly between XLT and DT (22.813±5.721% vs 9.384±3.799%; t=-5.236; P=0.0008), but we found no significant differences in dxAB, AvgStdErr, or MAXStdErr. CONCLUSIONS In the majority of cases, motion tracking by XLT and DT was consistent and synchronized in the SI directions, but not in the LR and AP directions. With a boundary margin of 0.3±4.35 mm and 1.8±6.8 mm for the LR and AP directions, DT may contribute to better implementation of CyberKnife Synchrony treatment in patients with lung tumors near the diaphragm that cannot be seen in tumor visualization tests.