Radiotherapy in the preoperative neoadjuvant treatment of locally advanced rectal cancer.

Radiotherapy and chemotherapy are effective treatments for patients with locally advanced rectal cancer (LARC) and can significantly improve the likelihood of R0 resection. Radiotherapy can be used as a local treatment to reduce the size of the tumor, improve the success rate of surgery and reduce the residual cancer cells after surgery. Early chemotherapy can also downgrade the tumor and eliminate micrometastases throughout the body, reducing the risk of recurrence and metastasis. The advent of neoadjuvant concurrent radiotherapy (nCRT) and total neoadjuvant treatment (TNT) has brought substantial clinical benefits to patients with LARC. Even so, given increasing demand for organ preservation and quality of life and the disease becoming increasingly younger in its incidence profile, there is a need to further explore new neoadjuvant treatment options to further improve tumor remission rates and provide other opportunities for patients to choose watch-and-wait (W&W) strategies that avoid surgery. Targeted drugs and immunologic agents (ICIs) have shown good efficacy in patients with advanced rectal cancer but have not been commonly used in neoadjuvant therapy for patients with LARC. In this paper, we review several aspects of neoadjuvant therapy, including radiation therapy and chemotherapy drugs, immune drugs and targeted drugs used in combination with neoadjuvant therapy, with the aim of providing direction and thoughtful perspectives for LARC clinical treatment and research trials.

Prognostic value of cell-free DNA in cerebrospinal fluid from lung cancer patients with brain metastases during radiotherapy.

BACKGROUND: During the last decades, radiotherapy (RT) for non-small cell lung cancer (NSCLC) with brain metastases (BM) has been developed. However, the lack of predictive biomarkers for therapeutic responses has limited the precision treatment in NSCLC-BM. PATIENTS AND METHODS: In order to find the predictive biomarkers for RT, we investigated the influence of RT on the cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and the frequency of T cell subsets of NSCLC patients with BM. A total of 19 patients diagnosed as NSCLC with BM were enrolled. The CSF from 19 patients and matched plasma samples from 11 patients were collected before RT, during RT, and after RT. The cfDNA from CSF and plasma were extracted, and the cerebrospinal fluid tumor mutation burden (cTMB) was calculated after through next-generation sequencing. The frequency of T cell subsets in peripheral blood was using flow cytometry. RESULTS: The detection rate of cfDNA was higher in CSF compared to plasma in the matched samples. The mutation abundance of cfDNA in CSF was decreased after RT. However, no significant difference was observed in cTMB before and after RT. Although the median intracranial progression-free survival (iPFS) has not yet been reached in patients with decreased or undetectable cTMB, there was a trend that these patients possessed longer iPFS compared to those with stable or increased cTMB (HR 0.28, 95% CI 0.07-1.18, P = 0.067). The proportion of CD4+T cells in peripheral blood was decreased after RT. CONCLUSION: Our study indicates that cTMB can serve as a prognostic biomarker in NSCLC patients with BMs.

Adsorption behaviors and mechanisms of antibiotic norfloxacin on degradable and nondegradable microplastics.

The misuse of both antibiotics and plastics significantly increases the environmental pollution problems associated with these contaminants. Moreover, microplastics can adsorb other pollutants in the environment. However, the mechanisms of antibiotic adsorption by degradable and nondegradable microplastics are not completely understood. In this study, we investigated the environmental behavior of norfloxacin (NOR) using polybutylene succinate (PBS), which is a degradable microplastic, and compared it with conventional microplastics, polystyrene (PS) and polyethylene (PE). The order of adsorption capacity was PS > PBS â‰« PE. The adsorption behavior fitted well with the pseudo-second-order kinetic and Langmuir isotherm models, indicating monolayer adsorption. The process is thermodynamically endothermic and non-spontaneous and is controlled by chemical and physical mechanisms, including π-π conjugation, hydrogen bonds, ion exchange, and electrostatic interactions. The adsorption capacity of microplastics was higher when the solution pH was around the pKa value of NOR than at other pH values. Ionic strength and dissolved organic matter inhibited the adsorption process. For PS and PBS, the amount of NOR adsorbed onto MPs initially decreased and then increased with the increase of coexisting heavy metal ions. Zn2+ and Pb2+ could promote the adsorption of NOR by PE. This study reveals the interaction mechanisms between microplastics and antibiotics and provides a more comprehensive theoretical basis for an ecological environmental risk assessment of different microplastics.

Radiotherapy programs neutrophils to an antitumor phenotype by inducing mesenchymal-epithelial transition.

BACKGROUND: Neutrophils can play a pro-tumor or anti-tumor role depending on the tumor microenvironment. The effects of concurrent treatment with granulocyte colony-stimulating factor (G-CSF) and radiotherapy (RT) on neutrophils have not yet to be described. METHODS: Hypofractionated radiation of 8 Gy ×3 fractions was administered with or without recombinant G-CSF to Lewis lung carcinoma tumor-bearing C57BL/6 model mice. The activation status of cytotoxic T cells in the mice was measured, along with the levels of tumor-associated neutrophils, cytotoxic T cells, and Treg cells. Tumor growth, survival, cytokine expression, and signaling pathways underlying anti-tumor effects of tumor-associated neutrophils after treatment were also studied. To ascertain the effects of concurrent RT and G-CSF on tumor-associated neutrophils, neutrophil depletion was performed. RESULTS: RT affected early neutrophil infiltration, which is the first-line immune response. Subsequently, enhanced accumulation of lymphocytes, particularly CD8 cytotoxic T cells, was observed. Notably, lymphocytic infiltration was inhibited by neutrophil depletion but enhanced by G-CSF treatment. RT generated persistent DNA damage, as evidenced by an accumulation of phosphorylation of histone H2AX (γH2AX), and subsequently triggered inflammatory chemokine secretion. The chemokines CXCL1, CXCL2, and CCL5 were upregulated in both radiation-treated cells and the corresponding supernatants. Neutrophils that were newly recruited after RT improved radiosensitivity by inhibiting epithelial-mesenchymal transition via the reactive oxygen species-mediated PI3K/Akt/Snail signaling pathway, and G-CSF treatment enhanced this effect. CONCLUSIONS: The results of this study suggest that RT activates neutrophil recruitment and polarizes newly recruited neutrophils toward an antitumor phenotype, which is enhanced by the concurrent administration of G-CSF. Mesenchymal-epithelial transition induced by reactive oxygen species accumulation plays a major role in this process. Thus, the polarization of tumor-associated neutrophils might play a role in future cancer immunotherapies.

Genomic analysis of the prognostic effect of tumor-associated neutrophil-related genes across 15 solid cancer types: an immune perspective.

BACKGROUND: Tumor-associated neutrophils (TANs) have been a research hotspot in recent years. However, the role and relevant mechanisms of TANs in the tumor microenvironment (TME) have not yet been elucidated. METHOD: The ribonucleic acid (RNA) expression levels of fucosyltransferase 4 (FUT4) and elastase, neutrophil expressed (ELANE) in samples from The Cancer Genome Atlas (TCGA) (n=4,538) were analyzed. Receiver operating characteristic (ROC) curves were used to calculate the critical cutoff values, and different data were defined as high and low expression. The tumor microenvironment immune type (TMIT) was defined according to the activation state of TAN, and the samples were classified into three TMITs based on their cut-off values. Mutational datasets and overall survival were compared according to the TMITs. RESULTS: The prognostic significance of FUT4, ELANE, and myeloperoxidase (MPO) was different among the 15 cancers, and the prognostic significance of different TMITs varied across the different tumors. Compared with the other groups, TMIT 3 had a favorable prognostic effect, which was most prominent in lung adenocarcinoma (LUAD) [hazard ratio (HR) =0.292, 95% confidence interval (CI): 0.185-0.459, P<0.001]. CONCLUSIONS: Our study demonstrated that highly-activated TANs predicted a favorable prognosis in humans using genomic analyses for the first time. This provides a realistic basis for further exploring the role of TANs in the immune microenvironment and provides real world data for tumor immunotherapy.

The protective effects of granulocyte-macrophage colony-stimulating factor against radiation-induced lung injury.

BACKGROUND: Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Currently, there is no effective treatment for RILI. RILI is associated with chronic inflammation, this injury is perpetuated by the stimulation of chemokines and proinflammatory cytokines. Recent studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a pivotal role in inflammation and fibrosis. This study aimed to investigate the protective effect of GM-CSF against the development of RILI in lung tissue. METHOD: First, a single fraction of radiation at a dose of 16 Gy was targeted at the entire thorax of wild-type (WT) C57BL/6 mice and GM-CSF-/- mice to induce RILI. Second, we detected the radioprotective effects of GM-CSF by measuring the inflammatory biomarkers and fibrosis alteration on radiated lung tissues. Furthermore, we investigated the potential mechanism of GM-CSF protective effects in RILI. RESULTS: The GM-CSF-/- mice sustained more severe RILI than the WT mice. RILI was significantly alleviated by GM-CSF treatment. Intraperitoneally administered GM-CSF significantly inhibited inflammatory cytokine production and decreased epithelial-mesenchymal transition (EMT) in the RILI mouse model. CONCLUSIONS: GM-CSF was shown to be an important modulator of RILI through regulating inflammatory cytokines, which provides a new strategy for the prevention and treatment of RILI.

Enhanced Resistance Switching of Ga2O3 Thin Films by Ultraviolet Radiation.

Conductive filament mechanism can explain major resistance switching behaviors. The forming/deforming of the filaments define the high/low resistance states. The ratio of high/low resistance depends on the characterization of the filaments. In many oxide systems, the oxygen vacancies are important to forming the conductive filaments for the resistance switching behaviors. As ultrawide band gap semiconductor, Ga2O3 has very high resistance for its high resistance state, while its low resistive state has relative high resistance, which normally results in low ratio of high/low resistance. In this letter, we report a high ratio of high/low resistance by ultraviolet radiation. The I-V characteristics of Au/Ti/ß-Ga2O3/W sandwich structure device shows that the HRS to LRS ratio of 5 orders is achieved.

Impact of negative lymph nodes on colon cancer survival and exploring relevant transcriptomics differences through real-world data analyses.

BACKGROUND: The prognostic role and underlying heterogeneity of negative lymph nodes (NLNs) on colon cancer is not well understood. The purpose of this study was to construct NLN-based prognostic models and reveal relevant mechanisms affecting NLNs by analyzing omic data. METHODS: This inception cohort study included 314,398 colon cancer patients from the US Surveillance, Epidemiology, and End Results (SEER) database. Receiver operating characteristic (ROC) curve was used to determine the cut-off of NLNs. Nomograms were constructed and validated using SEER data and the Cancer Genome Atlas (TCGA) data, respectively. The differentially expressed genes (DEGs) were analyzed using edgeR. Enrichment analyses were performed by Metascape. RESULTS: Multivariate analysis confirmed the high NLN had improved cancer-specific survival (CSS) and overall survival (OS) compared to low NLN [hazard ratio (HR) =0.610, 95% confidence interval (CI), 0.601-0.620] for CSS and (HR =0. 682, 95% CI, 0.674-0.690) for OS. Nomograms were established for CSS and OS with the c-statistic 0.790 (95% CI, 0.788-0.792) for CSS and 0.734 (95% CI, 0.732-0.736) for OS. High NLN was associated with less B cell (P=0.002) and macrophage infiltration (P<0.0001), high microsatellite instability (MSI) (OR =4.325, P=0.001), and hypermutation (OR =4.285, P=0.001; high vs. low). Transcriptomics analysis demonstrated histone modifiers were the most significant different biological processes between the high and low NLN group. CONCLUSIONS: The NLN-based models can aid in personalized risk stratification for colon cancer. This study postulates that high NLN may represent a biological subtype with less macrophage infiltration, high MSI status, hypermutation, and histone modifier gene enriched expression, and thus warrants further investigation.

Biocompatible semiconducting polymer nanoparticles as robust photoacoustic and photothermal agents revealing the effects of chemical structure on high photothermal conversion efficiency.

Understanding the relationship between polymer chemical structure and its performance of photoacoustic imaging (PAI) and photothermal therapy (PTT) is important for developing ideal PAI/PTT agents. In this report, four semiconducting polymer nanoparticles (SPNs) with different donor-acceptor architectures are self-assembled for highly effective PAI-guided PTT. In particular, SPN1 with the longest π-conjugation length and the highest mass extinction coefficient which are beneficial for intramolecular charge transfer as well as light harvesting, exhibits the highest photothermal conversion efficiency up to 52.6%. Moreover, the as-prepared SPN1 possess good water-dispersibility, robust size-stability and excellent photothermal properties. Furthermore, the SPN1 not only exhibits a remarkable cancer cell-killing ability but also shows a prominent tumor inhibition capacity. Finally, the as-prepared water-dispersible SPN1 displays good biocompatibility and biosafety, making it a promising candidate for future biomedical applications. Considering the plenty of near-infrared absorbing semiconducting polymer available, our work provides fundamental insights for rational design and preparation of highly efficient SPN-based PAI/PTT agents for cancer theranostics.