Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy.

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.

A nomogram for predicting hospital mortality of critical ill patients with sepsis and cancer: a retrospective cohort study based on MIMIC-IV and eICU-CRD.

OBJECTIVE: Sepsis remains a high cause of death, particularly in immunocompromised patients with cancer. The study was to develop a model to predict hospital mortality of septic patients with cancer in intensive care unit (ICU). DESIGN: Retrospective observational study. SETTING: Medical Information Mart for Intensive Care IV (MIMIC IV) and eICU Collaborative Research Database (eICU-CRD). PARTICIPANTS: A total of 3796 patients in MIMIC IV and 549 patients in eICU-CRD were included. PRIMARY OUTCOME MEASURES: The model was developed based on MIMIC IV. The internal validation and external validation were based on MIMIC IV and eICU-CRD, respectively. Candidate factors were processed with the least absolute shrinkage and selection operator regression and cross-validation. Hospital mortality was predicted by the multivariable logistical regression and visualised by the nomogram. The model was assessed by the area under the curve (AUC), calibration curve and decision curve analysis curve. RESULTS: The model exhibited favourable discrimination (AUC: 0.726 (95% CI: 0.709 to 0.744) and 0.756 (95% CI: 0.712 to 0.801)) in the internal and external validation sets, respectively, and better calibration capacity than Acute Physiology and Chronic Health Evaluation IV in external validation. CONCLUSIONS: Despite that the predicted model was based on a retrospective study, it may also be helpful to predict the hospital morality of patients with solid cancer and sepsis.

Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.

The malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation and distant metastasis. Anticancer treatments including adjuvant therapies and targeted therapies are effective in eliminating cancer cells but in a limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role in tumor development through changes in macromolecule components, degradation enzymes and stiffness. These variations are under the control of cellular components in tumor tissue via the aberrant activation of signaling pathways, the interaction of the ECM components to multiple surface receptors, and mechanical impact. Additionally, the ECM shaped by cancer regulates immune cells which results in an immune suppressive microenvironment and hinders the efficacy of immunotherapies. Thus, the ECM acts as a barrier to protect cancer from treatments and supports tumor progression. Nevertheless, the profound regulatory network of the ECM remodeling hampers the design of individualized antitumor treatment. Here, we elaborate on the composition of the malignant ECM, and discuss the specific mechanisms of the ECM remodeling. Precisely, we highlight the impact of the ECM remodeling on tumor development, including proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, and immune escape. Finally, we emphasize ECM "normalization" as a potential strategy for anti-malignant treatment.

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.

Head and neck cancer is a malignant tumour with a high mortality rate characterized by late diagnosis, high recurrence and metastasis rates, and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer. Various factors are involved in the occurrence and development of HNSCC, including external inflammatory stimuli and oncogenic viral infections. In recent years, studies on the regulation of cell death have provided new insights into the biology and therapeutic response of HNSCC, such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and recently the newly discovered cuproptosis. We explored how various cell deaths act as a unique defence mechanism against cancer emergence and how they can be exploited to inhibit tumorigenesis and progression, thus introducing regulatory cell death (RCD) as a novel strategy for tumour therapy. In contrast to accidental cell death, RCD is controlled by specific signal transduction pathways, including TP53 signalling, KRAS signalling, NOTCH signalling, hypoxia signalling, and metabolic reprogramming. In this review, we describe the molecular mechanisms of nonapoptotic RCD and its relationship to HNSCC and discuss the crosstalk between relevant signalling pathways in HNSCC cells. We also highlight novel approaches to tumour elimination through RCD.

Short- and medium-term survival of critically ill patients with solid cancer admitted to the intensive care unit.

BACKGROUND: A great increase in the number of patients needs critical care to the intensive care unit (ICU) due to improvements in oncology. The aim of the study was to explore risk factors affecting survival of critically ill patients with solid cancers in ICU. METHODS: The study retrospectively reviewed patients between 2001 and 2012, which were collected by Medical Information Mart for Intensive Care III (MIMIC-III) from the Beth Israel Deaconess Medical Center in Boston, MA, USA. RESULTS: A total of 38,508 adult patients, who were admitted to ICUs and 8,308 (21.6%) were diagnosed as an underlying malignancy; 1,671 and 3,165 adult patients with sold cancer were admitted to surgical ICU (SICU) and medical ICU (MICU), respectively. Patients in SICU had a higher survival rate at the point of 28-, 90-day, and 1-, 3-year than patients in MICU (P<0.001 for all). Multivariate analysis demonstrated that age ≥70, emergency admission, the presence of metastases, Oxford Acute Severity of Illness Score (OASIS) ≥30 and sepsis were independent risk factors affecting 28-day survival in SICU. In MICU, emergency admission, metastatic disease, Sequential Organ Failure Assessment (SOFA) ≥3, Simplified Acute Physiology Score II (SAPS II) ≥39, Acute Physiology Score III (APS III) ≥40, Oxford Acute Severity of Illness Score (OASIS) ≥30, Elixhauser comorbidity index ≥9 and sepsis were independent risk factors for 28-day survival rate. The area under curve (AUC) of the OASIS for predicting ICU mortality was 0.824 [95% confidence interval (CI): 0.805-0.842], which was obviously higher than other scores in SICU. The AUC of the SAPS II for predicting ICU mortality was 0.820 (95% CI: 0.806-0.833), which was slightly higher than other scores in MICU. CONCLUSIONS: Patients with cancer in SICU have longer survival time than patients with cancer in MICU. The prediction of prognosis of critically ill cancer patients can guide treatment and optimize medical resources.

Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.

High Iodine Nutrition May Be a Risk Factor for Cervical Lymph Node Metastasis in Papillary Thyroid Cancer Patients.

PURPOSE: The aim of this study was to retrospectively identify the effect of iodine on the papillary thyroid cancer (PTC) process and investigate the risk clinicopathologic characteristics of cervical lymph node metastasis (CLNM) for achieving a better preventive strategy of PTC. METHODS: Totally 187 patients with CLNM and 279 without CLNM (NCLNM) were enrolled, and their urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured. Logistic regressions were used to reveal the effects of iodine nutrition on the CLNM status of PTC. RESULTS: The levels of thyroid-stimulating hormone (TSH) and thyroglobulin (TG) were higher in the CLNM group than in the NCLNM group. UIC and SIC were positively correlated, and both of them were correlated with TSH, free thyroxine, and TG. The proportions of UIC >300 µg/L and of SIC >90 µg/L were higher in the CLNM than in the NCLNM. Logistic analysis showed that SIC >90 µg/L was an independent predictor for CLNM in PTC. Additionally, age ≥45, female, TG, multifocality, and diameter of cancer invasion >1 cm also affected CLNM status in PTC, and their logistic regression model showed a certain diagnostic accuracy (area under the receiver-operating characteristic curve = 0.72). CONCLUSIONS: Relatively high iodine nutrition seemed to be a significant risk factor for the occurrence of CLNM in PTC and may promote lymphatic metastasis in PTC.

The LncRNA FGD5-AS1/miR-497-5p axis regulates septin 2 (SEPT2) to accelerate cancer progression and increase cisplatin-resistance in laryngeal squamous cell carcinoma.

Aberrant expression or mutation of the Septin gene family is closely associated with cancer progression, and septin 2 (SEPT2) exerts its tumor-promoting effects in multiple cancers, but its role in regulating laryngeal squamous cell carcinoma (LSCC) progression and drug resistance has not been investigated. Based on the published data, the present study identified that SEPT2 promoted cancer progression and increased cisplatin-resistance in LSCC, and a novel LncRNA FGD5-AS1/miR-497-5p axis was crucial for this process. Mechanistically, SEPT2 tended to be enriched in LSCC tissues and cells, and knock-down of SEPT2 inhibited cell proliferation, viability, migration, and tumorigenesis in LSCC cells in vitro and in vivo. Aside from that, SEPT2 overexpression increased cisplatin resistance in LSCC cells. Next, by conducting the dual-luciferase reporter gene system assay, we identified that the LncRNA FGD5-AS1/miR-497-5p axis regulated SEPT2 in LSCC. Specifically, LncRNA FGD5-AS1 sponged miR-497-5p to upregulate SEPT2 in LSCC cells in a competing endogenous RNA (ceRNA) mechanisms-dependent manner. Interestingly, upregulated LncRNA FGD5-AS1 and downregulated miR-497-5p were observed in LSCC tissues and cells, and LncRNA FGD5-AS1 ablation inhibited cancer progression. Also, LncRNA FGD5-AS1 overexpression increased cisplatin-resistance in LSCC by modulating the miR-497-5p/SEPT2 axis. Collectively, we conclude that targeting the LncRNA FGD5-AS1/miR-497-5p/SEPT2 signaling cascade may be an alternative strategy to treat LSCC in the clinic.

The effect of the underlying malignancy on short- and medium-term survival of critically ill patients admitted to the intensive care unit: a retrospective analysis based on propensity score matching.

BACKGROUND: Advances in oncology led to a substantial increase in the number of patients requiring admission to the ICU. It is significant to confirm which cancer critical patients can benefit from the ICU care like noncancer patients. METHODS: An observational retrospective cohort study using intensive care unit (ICU) admissions of Medical Information Mart for Intensive Care III from the Beth Israel Deaconess Medical Center in Boston, MA, USA between 2001 and 2012 was conducted. Propensity score matching was used to reduce the imbalance between two matched cohorts. ICU patients with cancer were compared with those without cancer in terms of patients' characteristics and survival. RESULTS: There were 38,508 adult patients admitted to ICUs during the period. The median age was 65 years (IQR, 52-77) and 8308 (21.6%) had an underlying malignancy diagnosis. The noncancer group had a significant survive advantage at the point of 28-day, 90-day, 365-day and 1095-day after ICU admission compared with cancer group (P < 0.001 for all) after PSM. Subgroup analysis showed that the diagnosis of malignancy didn't decrease 28-day and 90-day survive when patients' age ≥ 65-year, patients in surgical intensive care unit or cardiac surgery recovery unit or traumatic surgical intensive care unit, elective admissions, patients with renal replacement therapy or vasopressor support (P > 0.05 for all). CONCLUSIONS: Malignancy is a common diagnosis among ICU patients. Patients without cancer have a survive advantage compared with patients with cancer in the short- and medium-term. However, in selected groups, cancer critical patients can benefit from the ICU care service like noncancer patients in the short-term.

Prognostic value of platelet distribution width and mean platelet volume in patients with laryngeal cancer.

Aims: To investigate the prognostic relevance of platelet volume indices for survival in laryngeal cancer. Patients & methods: The study included 640 patients with laryngeal cancer. We analyzed the optimal cutoff values through receiver operating characteristic analysis, then analyzed the univariate factor and multivariate variables. Kaplan-Meier curves and log-rank tests were conducted to compare the overall survival (OS) and recurrence-free survival rates between the groups. Results: In multivariate analysis, elevated platelet distribution width (PDW) and PDW/platelet count ratio were significantly correlated with poor prognosis for OS; however, elevated mean platelet volume (MPV) and MPV/platelet count ratio suggested a notable correlation with favorable prognosis for OS. Meanwhile, elevated PDW and decreased MPV were significantly correlated with poor prognosis for recurrence-free survival. Conclusions: Our findings indicate that elevated PDW and decreased MPV could serve as independent biomarkers for worse survival in laryngeal cancer.

A randomized controlled trial comparing the efficacy of tigecycline versus meropenem in the treatment of postoperative complicated intra-abdominal infections.

BACKGROUND: The efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections (cIAIs) is potentially controversial. Here we conducted the non-inferiority study to assess the efficacy and safety of tigecycline versus meropenem in the treatment of postoperative cIAIs. METHODS: Data of abdominal tumor surgery patients with postoperative cIAIs admitted to intensive care unit (ICU) between October 2017 and December 2019 were collected. A prospective, randomized controlled trial was conducted in which 56 eligible patients with cIAIs randomly received intravenous tigecycline or meropenem for 3 to 14 days. Patients and clinicians were not blinded to the group allocation. RESULTS: The total of 56 patients were enrolled, which were divided into 2 groups, one group included 30 patients receiving meropenem and another group included 26 receiving tigecycline therapy. The 2 groups were similar at demographic and baseline clinical characteristics. Microorganisms were isolated from 46 of 56 patients (82.14%), with a total of 107 pathogens were cultured in two groups. The two groups had similar distribution of infecting microorganisms. The primary end point was the clinical response at the end-oftherapy (EOT) visit and upon discharge visit and comprehensive efficacy. The clinical success rates were 83.33%, 76.67% for meropenem versus 76.92%, 88.46% for tigecycline at the EOT visit and upon discharge visit (P>0.05), respectively. Comprehensive efficacy did not significantly differ between two groups either. There were no significant differences in 30-day and 60-day all-cause mortality between two groups (P>0.05). The univariable analysis identified that serum albumin at admission ICU, colorectal cancer on oncology type, postoperative abdominal bleeding were the risk factors for 60-day all-cause mortality. The multivariable analysis showed that postoperative abdominal bleeding were independent predictors of 60-day all-cause mortality. Gastrointestinal disorders and antibacterials-induced Fungal Infection were the most frequently reported adverse events (AEs). The incidence of AEs was similar between meropenem and tigecycline groups (P>0.05). CONCLUSIONS: Taken together, the study demonstrated that tigecycline is as effective and safe as meropenem for postoperative cIAIs in abdominal tumors patients. Tigecycline is non-inferior to meropenem.

Prognostic Significance of Lactate Dehydrogenase in Patients Undergoing Surgical Resection for Laryngeal Squamous Cell Carcinoma.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.

Long noncoding RNA LINC01194 enhances the malignancy of laryngeal squamous cell carcinoma by sponging miR-655 to increase SOX18 expression.

Long noncoding RNAs (lncRNAs) have undergone a comprehensive study for their involvements in tumor treatments. The purpose of our study was to explore the biological effects and regulatory mechanisms of lncRNA LINC01194 (LINC01194) in laryngeal squamous cell carcinoma (LSCC). The levels of LINC01194 in 105 LSCC patients were detected by RT-qPCR. The diagnostic and prognostic value of LINC01194 in LSCC patients were statistically analyzed. The potential functions of LINC01194 in proliferation, apoptosis, and metastasis of LSCC cells were evaluated. The interaction among LINC01194, miR-655 and SOX18 was explored by bioinformatics analysis, luciferase reporter assays and biotinylated RNA pull-down. We found that the expression levels of LINC01194 were highly expressed in LSCC, which was negatively correlated with the clinical outcome of LSCC patients. The area under the ROC curve for LINC01194 was up to 0.8388. Functional assays indicated that LINC01194 knockdown distinctly inhibited LSCC cells proliferation, induced apoptosis, and also attenuated LSCC cells migration and invasion in vitro. Furthermore, we elucidated that LINC01194 promoted SOX18 expression in LSCC cells via functioning as a molecular sponge for miR-655. Overall, based on our findings, LINC01194 served as a tumor promoter and potentially represents a novel prognostic indicator and therapeutic target in LSCC.

Neoadjuvant therapy does not adversely affect the short-term outcome of critically ill cancer patients who underwent surgery.

BACKGROUND: There were conflicting data regarding the effects of neoadjuvant therapy (NT) on the short-term outcomes of critically ill cancer patients. The aim of this study was to investigate whether NT adversely affect the short-term outcomes of critically ill cancer patients who underwent surgery. METHODS: This was a retrospective study which enrolled all critically ill cancer patients who admitted to intensive care unit (ICU) of Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College between September 2017 and September 2018. Patients were divided into two groups: NT group and no NT (nNT) group. The primary outcome was ICU mortality rate. Propensity score analysis and Logistic regression analysis were used to investigate risk factors of ICU death. RESULTS: Hundred and twenty-eight patients received NT and 737 patients did not. The ICU mortality was higher in NT group than that in nNT group (3.9% vs. 1.4%, P=0.041) before propensity score matching analysis. After matching, there were no significant difference in ICU mortality between NT group and nNT group. Univariable logistic analysis demonstrated that a history of coronary heart disease (P=0.008), NT (P=0.041), unplanned admission to ICU (P<0.001), simplified acute physiology score (SAPS) 3 on ICU admission (P<0.001), sequential organ failure assessment (SOFA) on ICU admission (P<0.001), acute kidney injury (P<0.001), and mechanical ventilation (P<0.001) were predictive of ICU death in all 865 patients. Multivariable logistic regression analysis demonstrated that history of coronary heart disease (P=0.010; OR =9.614; 95% CI, 1.731-53.405), SAPS 3 on ICU admission (P=0.026; OR =1.070; 95% CI, 1.008-1.135) and SOFA on ICU admission (P=0.031; OR =1.289; 95% CI, 1.024-1.622) were independent risk factors of ICU death, while NT was not predictive of ICU death (P=0.118). CONCLUSIONS: NT was not a risk factor for ICU death in critically ill cancer patients who underwent surgery.

The 28-day survive for critically ill cancer patients undergoing continuous renal replacement with postoperative acute kidney injure: a retrospective study of 86 cases.

BACKGROUND: Advances in oncology led to a substantial increase in the number of patients requiring admission to the intensive care unit (ICU). It remains controversial to start continuous renal replacement therapy (CRRT) for acute kidney injure (AKI) in critically ill patients with cancer because of the poor outcome and high costs. METHODS: In this retrospective study, we collected data from patients with cancer with postoperative AKI-stage 3 [Kidney Disease: Improving Global Outcomes (KDIGO), 2012] undergoing CRRT in the ICU of Cancer Hospital, Chinese Academy of Medical Sciences from January 2010 to January 2019. Patients were followed up until the time of death or the point of 28-day after ICU admission. Univariate and multivariate analysis was performed to identify risk factors for 28-day survive. RESULTS: Of 8,030 cancer patients after surgical operation admitted by ICU, a total of 86 (1.1%) patients developed postoperative AKI: male/female: 62/24, median age 61 [27-82] years. The number of digestive tract/lung/other types of cancer was 59, 10 and 17, respectively. The median Simplified Acute Physiology Score III (SAPS III) was 65 [49-109] and the median Sequential Organ Failure Assessment (SOFA) score was 6 [1-19]. There were 35 deaths eventually and all the deaths occur within 28 days after ICU admission. Twenty-eight-day survive rate was 57.1%±5.8%. In multivariate cox regression analysis, two risk factors independently affected 28-day survive: SAPS III score ≥65 [hazard ratio (HR): 3.451 (1.272-9.365), P=0.015], the presence of shock at the start of CRRT [HR: 10.262 (2.210-47.660), P=0.003]. The cancer status (P=0.076), cancer types (P>0.05 for both) and neoadjuvant therapy associated with cancer (P=0.949) showed no effects on 28-day survive. CONCLUSIONS: For cancer patients, postoperative AKI-stage 3 is a serious complication with a low 28-day survive rate. Patients with the presence shock at the start of CRRT or SAPS III ≥65 will have a poor 28-day survive. It should be emphasized that the cancer characteristics (status, types or treatment) don't affect 28-day survive.

MicroRNA-429 inhibits bone metastasis in breast cancer by regulating CrkL and MMP-9.

Bone metastasis is common in late-stage breast cancer patients and leads to skeletal-related events that affect the quality of life and decrease survival. Numerous miRNAs have been confirmed to be involved in metastatic breast cancer, such as the miR200 family. Our previous study identified microRNA-429 (miR-429) as a regulatory molecule in breast cancer bone metastasis. However, the effects of miR-429 and its regulatory axis in the metastatic breast cancer bone microenvironment have not been thoroughly investigated. We observed a positive correlation between miR-429 expression in clinical tissues and the bone metastasis-free interval and a negative correlation between miR-429 expression and the degree of bone metastasis. We cultured bone metastatic MDA-MB-231 cells and used conditioned medium (CM) to detect the effect of miR-429 on osteoblast and osteoclast cells in vitro. We constructed an orthotopic bone destruction model and a left ventricle implantation model to examine the effect of miR-429 on the metastatic bone environment in vivo. The transfection experiments showed that the expression levels of V-crk sarcoma virus CT10 oncogene homolog-like (CrkL) and MMP-9 were negatively regulated by miR-429. The in vitro coculture experiments showed that miR-429 promoted osteoblast differentiation and that CrkL promoted osteoclast differentiation. The two animal models showed that miR-429 diminished local bone destruction and distant bone metastasis but CrkL enhanced these effects. Furthermore, CrkL and MMP-9 expression decreased simultaneously in response to increased miR-429 expression. These findings further reveal the possible mechanism and effect of the miR-429/CrkL/MMP-9 regulatory axis in the bone microenvironment in breast cancer bone metastasis.

Long noncoding RNA LINC-PINT regulates laryngeal carcinoma cell stemness and chemoresistance through miR-425-5p/PTCH1/SHH axis.

Functional, noncoding RNA of about 200 nucleotides in length are known as long noncoding RNA (lncRNA). Advances in -omics have revolutionized the information with respect to the coding and noncoding regions of the genome. Several studies have illustrated the role of lncRNA in cell growth and cancer. Profiling and bioinformatic studies of laryngeal cancer has identified LINC-PINT as one of the lncRNA. However, the functional aspects of the deregulation have not been studied in laryngeal tumors. In this study, LINC-PINT expression in normal and tumor tissues were studied. Using a bioinformatic approach, microRNA (miRNA) targets of LINC-PINT and gene targets of the miRNA were determined. The impact of LINC-PINT on cell proliferation and chemoresistance was determined. Further through a set of silencing and re-expression studies phenotype rescue was studied. LINC-PINT expression was downregulated in laryngeal tumors. LINC-PINT targeted miR-425-5p by three sites. miR-425-5p also targeted PTCH1 a protein of the Hedgehog pathway. Downregulation of LINC-PINT was associated with increased cancer stemness and chemoresistance to cisplatin. Our results indicate a probable role of LINC-PINT in the pathology of laryngeal tumors. LINC-PINT re-expression in laryngeal tumors may be explored for reversion of cancer cell stemness and also for rescue of drug resistance phenotype.

Long non-coding RNA AFAP1-AS1/miR-320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance.

AFAP1-AS1 is a long non-coding RNA that is associated with tumorigenesis and poor prognosis in a variety of cancers. We have been suggested that AFAP1-AS1 increases tumorigenesis in laryngeal carcinoma specifically by enhancing stemness and chemoresistance. We assessed AFAP1-AS1 expression in human laryngeal specimens, paired adjacent normal tissues and human HEp-2 cells. Indeed, we found not only that AFAP1-AS1 was up-regulated in laryngeal carcinoma specimens and cells, but also that stemness-associated genes were overexpressed. Silencing of AFAP1-AS1 promoted HEp-2 cell chemoresistance under cisplatin treatment. Expression of AFAP1-AS1 was increased in drug-resistant Hep-2 cells. We then probed the mechanism of AFAP1-AS1 activity and determined that miR-320a was a potential molecular target of AFAP1-AS1. Luciferase reporter and qRT-PCR assays of AFAP1-AS1 and miR-320a levels in human specimens and cell cultures indicated that AFAP1-AS1 negatively regulates miR-320a. To discover the molecular mechanism of miR-320a, we again used the DIANA Tools algorithm to predict its genetic target, RBPJ. After cloning the 3'-untranslated regions (3'-UTR) of RBPJ into a luciferase reporter, we determined that miR-320a did in fact reduce RBPJ mRNA and protein levels. Ultimately, we determined that AFAP1-AS1 increases RBPJ expression by negatively regulating miR-320a and RBPJ overexpression rescues stemness and chemoresistance inhibited by AFAP1-AS1 silencing. Taken together, these results suggest that AFAP1-AS1 can serve as a prognostic biomarker in laryngeal carcinoma and that miR-320a has the potential to improve standard therapeutic approaches to the disease, especially for cases in which cancer cell stemness and drug resistance present significant barriers to effective treatment.

Clinicopathological features and prognosis of malignant peripheral nerve sheath tumor: a retrospective study of 159 cases from 1999 to 2016.

OBJECTIVE: To investigate the clinicopathological features and prognosis of malignant peripheral nerve sheath tumors (MPNST). RESULTS: A total of 159 patients with MPNST were enrolled in the study. The ratio of male to female was 1.04 to 1. The median age was 40 (range: 5-76) years at the time of diagnosis. The 3- and 5-year overall survival rates were 50.0% and 43.0%, respectively. The median follow-up period was 31.0 (range: 2.0-199.0) months. Multivariate analysis showed that AJCC stage and S-100 were independent factors affecting overall survival (p < 0.05 for both). 3- and 5-year tumor-free survival rates for 140 completely resected patients were 40.0% and 34.0%, respectively. Multivariate analysis showed that AJCC stage, S-100 and Ki67 staining were independent factors of tumor-free survival (p < 0.05 for all). MATERIALS AND METHODS: The clinical data of MPNST patients who were treated at Cancer Institute and Hospital, Chinese Academy of Medical Science from January 1999 to January 2016 was retrospectively reviewed. CONCLUSIONS: MPSNT is a highly aggressive tumor with poor prognosis and this study may be useful for prognostic assessment and management decisions. This had been largest documented retrospective study of MPSNT among Chinese populations. Some characteristics were different from those of foreign populations which may suggest the specificity of Chinese patients.