Neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective cohort study.

BACKGROUND: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. MATERIALS AND METHODS: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. RESULTS: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. CONCLUSIONS: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

Phosphorus uptake and rhizosphere properties of alfalfa in response to phosphorus fertilizer types in sandy soil and saline-alkali soil.

Introduction: Phosphorus (P) fertilizer is critical to maintain a high yield and quality of alfalfa (Medicago sativa L.). There are several fertilizer types and soil types in China, and the application of a single type of P fertilizer may not be suitable for present-day alfalfa production. Methods: In order to select the optimal combination of alfalfa and soil type and fertilizer type for improving P utilization efficiency. We conducted a greenhouse pot experiment, calcium superphosphate (SSP), diammonium phosphate (DAP), ammonium polyphosphate (APP), potassium dihydrogen phosphate (KP), and no-fertilizer control treatments were applied to alfalfa in sandy and saline-alkali soils. The response of alfalfa root morphology and rhizosphere processes to different P fertilizers was investigated. Results and discussion: The results showed that shoot biomass of alfalfa was slightly higher in sandy soil than in saline-alkali soil. Shoot biomass of alfalfa increased by 223%-354% in sandy soil under P treatments compared with the control, and total root length increased significantly by 74% and 53% in DAP and SSP treatments, respectively. In saline-alkali soil, alfalfa shoot biomass was significantly increased by 229% and 275% in KP and DAP treatments, and total root length was increased by 109% only in DAP treatment. Net P uptake of alfalfa in DAP treatment was the highest in both soils, which were 0.73 and 0.54 mg plant-1, respectively. Alfalfa shoot P concentration was significantly positively correlated with shoot and root biomass (P < 0.05, 0.01 or 0.001) whereas negatively correlated with acid phosphatase concentration (P < 0.05). Improvement of plant growth and P uptake induced by P fertilizer application was greater in sandy soil than in saline-alkali soil. DAP and KP was the most efficient P fertilizers in both sandy soil and saline-alkali soil.

Transcriptome analysis unveils the mechanisms of lipid metabolism response to grayanotoxin I stress in Spodoptera litura.

Background: Spodoptera litura (tobacco caterpillar, S. litura) is a pest of great economic importance due to being a polyphagous and world-distributed agricultural pest. However, agricultural practices involving chemical pesticides have caused resistance, resurgence, and residue problems, highlighting the need for new, environmentally friendly methods to control the spread of S. litura. Aim: This study aimed to investigate the gut poisoning of grayanotoxin I, an active compound found in Pieris japonica, on S. litura, and to explore the underlying mechanisms of these effects. Methods: S. litura was cultivated in a laboratory setting, and their survival rate, growth and development, and pupation time were recorded after grayanotoxin I treatment. RNA-Seq was utilized to screen for differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to determine the functions of these DEGs. ELISA was employed to analyze the levels of lipase, 3-hydroxyacyl-CoA dehydrogenase (HOAD), and acetyl-CoA carboxylase (ACC). Hematoxylin and Eosin (H & E) staining was used to detect the development of the fat body. Results: Grayanotoxin I treatment significantly suppressed the survival rate, growth and development, and pupation of S. litura. RNA-Seq analysis revealed 285 DEGs after grayanotoxin I exposure, with over 16 genes related to lipid metabolism. These 285 DEGs were enriched in the categories of cuticle development, larvae longevity, fat digestion and absorption. Grayanotoxin I treatment also inhibited the levels of FFA, lipase, and HOAD in the hemolymph of S. litura. Conclusion: The results of this study demonstrated that grayanotoxin I inhibited the growth and development of S. litura. The mechanisms might, at least partly, be related to the interference of lipid synthesis, lipolysis, and fat body development. These findings provide valuable insights into a new, environmentally-friendly plant-derived insecticide, grayanotoxin I, to control the spread of S. litura.

Optimization of the Extraction Strategy for Polyphenols from Pieris Japonica and Evaluation of Its Antioxidant Activity.

Pieris Japonica, belonging to the Rhododendron family, is known for its anti-insect and analgesic properties. Despite previous research, the components and antioxidant activity of Pieris Japonica extract remain unclear. This study aims to identify the optimal extraction process for Pieris Japonica, determine its components, and evaluate its antioxidant capacity. An L9 (34) orthogonal method was employed to optimize the Pieris Japonica extraction process, with the polyphenol content serving as the extraction efficiency index. The extracted components were identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS-MS). Antioxidant activity was assessed via the DPPH test, ABTS radical scavenging test, and FRAP reduction ability test. The optimal extraction process involved soaking Pieris Japonica powder in 60% ethanol with a weight-to-volume ratio of 1:20 (g/mL), followed by eight hours of reflux at 50°C. Under these conditions, the total polyphenol content was 11.2 ± 0.6 mg/g. HPLC/MS-MS revealed that flavonoids were the primary components in the Pieris Japonica extract. The FRAP method determined the total antioxidant capacity to be 1.00 ± 0.05 µmol/mL, while the DPPH method showed a radical scavenging rate of 42.21 ± 4.02%, and the ABTS method yielded a 85.74% scavenging rate, indicating a strong antioxidant activity. The primary components of Pieris Japonica extract were flavonoids, and the extracted plant material exhibited potent antioxidant activity.

A cross-cohort computational framework to trace tumor tissue-of-origin based on RNA sequencing.

Carcinoma of unknown primary (CUP) is a type of metastatic cancer with tissue-of-origin (TOO) unidentifiable by traditional methods. CUP patients typically have poor prognosis but therapy targeting the original cancer tissue can significantly improve patients' prognosis. Thus, it's critical to develop accurate computational methods to infer cancer TOO. While qPCR or microarray-based methods are effective in inferring TOO for most cancer types, the overall prediction accuracy is yet to be improved. In this study, we propose a cross-cohort computational framework to trace TOO of 32 cancer types based on RNA sequencing (RNA-seq). Specifically, we employed logistic regression models to select 80 genes for each cancer type to create a combined 1356-gene set, based on transcriptomic data from 9911 tissue samples covering the 32 cancer types with known TOO from the Cancer Genome Atlas (TCGA). The selected genes are enriched in both tissue-specific and tissue-general functions. The cross-validation accuracy of our framework reaches 97.50% across all cancer types. Furthermore, we tested the performance of our model on the TCGA metastatic dataset and International Cancer Genome Consortium (ICGC) dataset, achieving an accuracy of 91.09% and 82.67%, respectively, despite the differences in experiment procedures and pipelines. In conclusion, we developed an accurate yet robust computational framework for identifying TOO, which holds promise for clinical applications. Our code is available at http://github.com/wangbo00129/classifybysklearn .

Predicting gastric cancer tumor mutational burden from histopathological images using multimodal deep learning.

Tumor mutational burden (TMB) is a significant predictive biomarker for selecting patients that may benefit from immune checkpoint inhibitor therapy. Whole exome sequencing is a common method for measuring TMB; however, its clinical application is limited by the high cost and time-consuming wet-laboratory experiments and bioinformatics analysis. To address this challenge, we downloaded multimodal data of 326 gastric cancer patients from The Cancer Genome Atlas, including histopathological images, clinical data and various molecular data. Using these data, we conducted a comprehensive analysis to investigate the relationship between TMB, clinical factors, gene expression and image features extracted from hematoxylin and eosin images. We further explored the feasibility of predicting TMB levels, i.e. high and low TMB, by utilizing a residual network (Resnet)-based deep learning algorithm for histopathological image analysis. Moreover, we developed a multimodal fusion deep learning model that combines histopathological images with omics data to predict TMB levels. We evaluated the performance of our models against various state-of-the-art methods using different TMB thresholds and obtained promising results. Specifically, our histopathological image analysis model achieved an area under curve (AUC) of 0.749. Notably, the multimodal fusion model significantly outperformed the model that relied only on histopathological images, with the highest AUC of 0.971. Our findings suggest that histopathological images could be used with reasonable accuracy to predict TMB levels in gastric cancer patients, while multimodal deep learning could achieve even higher levels of accuracy. This study sheds new light on predicting TMB in gastric cancer patients.

The effects of free Cys residues on the structure, activity, and tetrameric stability of mammalian uricase.

Mammalian uricases contain four conserved cysteine (Cys) residues, but little is known about their structures and functions. In this study, we first confirmed that all four Cys residues are free and not involved in disulfide bond formation, using canine uricase as a model protein. Cys residues had a greater effect on stability than on activity based on single Cys-to-Ser (serine) substitutions. Circular dichroism (CD) and homology modeling indicated that C188S reduces ß-sheet contents and inter- and intra-subunit hydrophobic interaction, potentially impairing the core tetrameric ß-barrel structure of the tunneling-fold protein, and ultimately decreased the tetrameric stability. Additionally, the inactivation of C188S during the stability tests may be a complex process involving depolymerization followed by irregular aggregation. Double mutations or thiol blockage of Cys188 and Cys195 significantly disrupted the formation and stability of tetrameric uricase, which may be mediated by the free thiols in Cys residues. The present results demonstrated that the free Cys residues are essential for tetrameric formation and stability in mammalian uricase. This implies that free cysteine residues, although not involved in disulfide bonding, may play important structural roles in certain proteins, underscoring the significance of the hydrophobic characteristics of the free thiols in Cys residues. KEY POINTS: • Four Cys residues are not involved in disulfide bonding in mammalian uricase. • The hydrophobicity of free thiols is critical for tetrameric stability in uricase. • Free Cys residues can serve structural roles without involving in disulfide bonds.

MNNMDA: Predicting human microbe-disease association via a method to minimize matrix nuclear norm.

Identifying the potential associations between microbes and diseases is the first step for revealing the pathological mechanisms of microbe-associated diseases. However, traditional culture-based microbial experiments are expensive and time-consuming. Thus, it is critical to prioritize disease-associated microbes by computational methods for further experimental validation. In this study, we proposed a novel method called MNNMDA, to predict microbe-disease associations (MDAs) by applying a Matrix Nuclear Norm method into known microbe and disease data. Specifically, we first calculated Gaussian interaction profile kernel similarity and functional similarity for diseases and microbes. Then we constructed a heterogeneous information network by combining the integrated disease similarity network, the integrated microbe similarity network and the known microbe-disease bipartite network. Finally, we formulated the microbe-disease association prediction problem as a low-rank matrix completion problem, which was solved by minimizing the nuclear norm of a matrix with a few regularization terms. We tested the performances of MNNMDA in three datasets including HMDAD, Disbiome, and Combined Data with small, medium and large sizes respectively. We also compared MNNMDA with 5 state-of-the-art methods including KATZHMDA, LRLSHMDA, NTSHMDA, GATMDA, and KGNMDA, respectively. MNNMDA achieved area under the ROC curves (AUROC) of 0.9536 and 0.9364 respectively on HDMAD and Disbiome, better than the AUCs of compared methods under the 5-fold cross-validation for all microbe-disease associations. It also obtained a relatively good performance with AUROC 0.8858 in the combined data. In addition, MNNMDA was also better than other methods in area under precision and recall curve (AUPR) under the 5-fold cross-validation for all associations, and in both AUROC and AUPR under the 5-fold cross-validation for diseases and the 5-fold cross-validation for microbes. Finally, the case studies on colon cancer and inflammatory bowel disease (IBD) also validated the effectiveness of MNNMDA. In conclusion, MNNMDA is an effective method in predicting microbe-disease associations. Availability: The codes and data for this paper are freely available at Github https://github.com/Haiyan-Liu666/MNNMDA.

Circ_0035381 Regulates Acute Myeloid Leukemia Development by Modulating YWHAZ Expression via Adsorbing miR-582-3p.

Acute myeloid leukemia (AML) is a common hematopoietic disorder. Many circular RNAs (circRNAs) are abnormally expressed in AML, including hsa_circ_0035381 (circ_0035381). Nevertheless, the function and mechanism of circ_0035381 in AML remain mostly unclear. Expression of circ_0035381 was determined by qRT-PCR. The impacts of circ_0035381 on AML cell proliferation, apoptosis, and mitochondrial damage were validated via performing loss-of-function experiments. Targeting relationship was predicted by bioinformatics analysis and verified via dual-luciferase reporter and RNA immunoprecipitation assays. Circ_0035381 was upregulated in AML bone marrow samples and cells. Circ_0035381 downregulation decreased AML cell growth in nude mice and restrained AML cell proliferation and contributed to AML apoptosis and mitochondrial damage in vitro. Circ_0035381 acted as a miR-582-3p sponge, and miR-582-3p downregulation mitigated the impacts of circ_0035381 interference on AML cell proliferation, apoptosis, and mitochondrial damage. MiR-582-3p targeted Tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ), and it restrained AML cell proliferation and facilitated AML cell apoptosis and mitochondrial damage by decreasing YWHAZ expression. Notably, circ_0035381 regulated YWHAZ expression via miR-582-3p. Circ_0035381 knockdown repressed cell proliferation and promoted cell apoptosis and mitochondrial damage via regulating the miR-582-3p/YWHAZ axis in AML.

GSDMD enhances cisplatin-induced apoptosis by promoting the phosphorylation of eIF2α and activating the ER-stress response.

GSDMD is the key effector of pyroptosis, but its non-pyroptosis-related functions have seldom been reported. Here, we report that GSDMD is overexpressed in different types of tumours, including head and neck squamous-cell carcinoma, and it promotes the sensitivity of tumour cells to cisplatin. Unexpectedly, the enhanced cisplatin sensitivity is mediated by apoptosis but not pyroptosis, the well-known function of GSDMD. Furthermore, we found that GSDMD can activate the unfolded protein response by promoting the phosphorylation of eIF2α. Mechanistically, we demonstrated that GSDMD can directly bind to eIF2α and enhance the interaction between eIF2α and its upstream kinase PERK, leading to eIF2α phosphorylation. Consequently, the protein levels of ATF-4 were upregulated, downstream apoptosis-related proteins such as CHOP were activated, and apoptosis was induced. Remarkably, activation of endoplasmic-reticulum (ER) stress induced by GSDMD promotes cell apoptosis during cisplatin chemotherapy, thereby increasing the treatment sensitivity of tumours. Therefore, for the first time, our work reveals an unreported nonpyroptotic function of the classic pyroptosis protein GSDMD: it promotes cell apoptosis during cisplatin chemotherapy by inducing eIF2α phosphorylation and ER stress, which are related to the drug sensitivity of tumours. Our study also indicated that GSDMD might serve as a biomarker for cisplatin sensitivity.

STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma.

STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we found that STEAP3 was aberrantly overexpressed in the nuclei of HCC cells. In a large cohort of clinical HCC tissues, high expression level of nuclear STEAP3 was positively associated with tumor differentiation and poor prognosis (p < 0.001), and it was an independent prognostic factor for HCC patients. In HCC cell lines, nuclear expression of STEAP3 significantly promoted HCC cells proliferation by promoting stemness phenotype and cell cycle progression via RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes. Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback. In summary, our findings support that nuclear expression of STEAP3 plays a critical oncogenic role in the progression of HCC via modulation on EGFR and intracellular signaling, and it could be a candidate for prognostic marker and therapeutic target in HCC.

Rhophilin rho GTPase binding protein 1-antisense RNA 1 (RHPN1-AS1) promotes ovarian carcinogenesis by sponging microRNA-485-5p and releasing DNA topoisomerase II alpha (TOP2A).

Ovarian cancer (OC) is the most common and lethal gynecological cancer worldwide. Long non-coding RNAs (lncRNAs) and sponging microRNAs (miRNAs) serve as key regulators in the biological processes of OC. We sought to evaluate the effect of the RHPN1-AS1-miR-485-5p-DNA topoisomerase II alpha (TOP2A) axis in regulating OC progression. RHPN1-AS1, miR-485-5p, and TOP2A levels in OC tissues and cells were determined by RT-qPCR. The interaction of RHPN1-AS1/miR-485-5p/TOP2A was assessed using luciferase, RNA immunoprecipitation, and RNA pull-down assays. RHPN1-AS1 silencing allowed us to explore its biological function by measuring cell viability, proliferation, migration, invasion, and apoptosis in OC cells. In vivo experiments were performed to verify the in vitro findings. We found that the RHPN1-AS1 and TOP2A levels were significantly enhanced, whereas the miR-485-5p levels were reduced in OC tissues and cells. RHPN1-AS1 silencing attenuated cell growth, facilitated apoptosis in OC cells, and inhibited tumor growth in vivo. Notably, RHPN1-AS1 negatively regulating miR-485-5p promoted the TOP2A expression in OC cells. In conclusion, RHPN1-AS1 sponging miR-485-5p accelerated the progression of OC by elevating TOP2A expression, which makes it a promising target for the treatment of OC patients.

Long non-coding RNA GAS5 knockdown facilitates proliferation and impedes apoptosis by regulating miR-128-3p/FBLN2 axis in ox-LDL-induced THP-1 cells.

BACKGROUND: Long non-coding RNAs (lncRNAs) are found to involve in modulating the development of atherosclerosis (AS). But the molecular mechanism of lncRNA growth-arrest specific transcript 5 (GAS5) in AS is not fully understood. METHODS: QRT-PCR was performed to measure the abundances of GAS5, miR-128-3p and fibulin 2 (FBLN2). Oxidized low-density lipoprotein (ox-LDL)-treated THP-1 cells were employed as cell models of AS. The cell proliferation and apoptosis were analyzed using CCK-8 and Flow cytometry assays, respectively. Levels of all protein were examined by western blot. The interaction among GAS5, miR-128-3p and FBLN2 was confirmed via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: GAS5 was elevated and miR-128-3p was decreased in the serum of patients with AS and ox-LDL-stimulated THP-1 cells. Ox-LDL stimulation inhibited proliferation and induced apoptosis of THP-1 cells. Meanwhile, GAS5 directly targeted miR-128-3p and inversely modulated its expression. Importantly, GAS5 depletion facilitated cell proliferation and impaired apoptosis in ox-LDL-induced THP-1 cells. Additionally, GAS5 augmented FBLN2 expression through sponging miR-128-3p, and miR-128-3p facilitated proliferation and retarded apoptosis of ox-LDL-induced THP-1 cells by targeting FBLN2. CONCLUSION: GAS5 knockdown promoted the growth of ox-LDL-induced THP-1 cells through down-modulating FBLN2 and increasing miR-128-3p, suggesting the potential value of GAS5 for treatment of AS.

Overexpression of gasdermin D promotes invasion of adenoid cystic carcinoma.

OBJECTIVE: To investigate the relationship between gasdermin D (GSDMD) expression and the invasion of adenoid cystic carcinoma (ACC). METHODS: Immunohistochemistry (IHC) was used to examine GSDMD expression in tumours and adjacent non-cancerous (ANC) tissues from 33 patients with salivary ACC patients and in tumour samples from 29 patients with pleomorphic adenoma (PA). Lentiviral infection was used to stably overexpress GSDMD in ACC-LM and ACC-83 cells (GSDMD-ov cells), which were subjected to transwell and scratch tests to assess their invasive abilities compared to control cells. Cells overexpressing GSDMD were treated with siRNA targeting GSDMD, and their invasive ability was subsequently examined. RESULTS: GSDMD expression was significantly higher in ACC tissues than in corresponding ANC tissues (P<0.001). After 24 hours, both the ACC-83 and ACC-LM GSDMD-ov cell lines had more cells that moved through the membrane than did the control cells (P<0.05). For the wound healing experiment, the diameter of the wound in the GSDMD-ov cell lines was smaller than that of the control cells (P<0.001) after 24 hours. The ACC cell lines expressing high GSDMD showed stronger metastatic ability than did the control. CONCLUSION: GSDMD was highly expressed in ACC tissues compared to ANC tissues, and high GSDMD expression promoted the invasion of ACC cells. These findings suggest that GSDMD expression is related to the invasion of ACC. Our data indicate that we may be able to use GSDMD as an indicator of the invasive or metastatic potential of tumour cells in future research.

Correction: Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Inhibition of caspase-3-mediated GSDME-derived pyroptosis aids in noncancerous tissue protection of squamous cell carcinoma patients during cisplatin-based chemotherapy.

The side effects of platinum-based chemotherapy are important factors limiting the survival of oral squamous cell carcinoma (OSCC) patients. Current research suggests that pyroptosis is involved in this process. However, how this mechanism can be used to reduce side effects has not yet been elucidated. In this study, we reported that GSDME was expressed at higher levels in normal tissues than in cancerous tissues in OSCC patients and was the main cause of platinum-based side effects. In an OSCC xenograft model, the inflammatory status and GSDME expression were increased after cisplatin chemotherapy. Cellular experiments showed that higher expression of GSDME was associated with less chemoresistance to cisplatin. A subsequent study demonstrated that cisplatin treatment promotes the maturation of caspase-3, triggers GSDME-mediated pyroptosis and induces cell death. When the amino acid sequence of GSDME cleaved by caspase-3 was mutated, cellular death and pyroptosis induced by cisplatin were significantly inhibited. Moreover, application of vitamin D during cisplatin-based chemotherapy could successfully inhibit GSDME cleavage and pyroptotic cell death in vitro and in vivo. Taken together, our study revealed that vitamin D can inhibit caspase-3-mediated GSDME cleavage and thus reduce normal tissue pyroptosis, relieving chemotherapeutic side effects. Inhibition of systemic GSDME during chemotherapy is currently unachievable. Vitamin D supplementation during chemotherapy in OSCC patients might be able to reduce the process described above and benefit patients. However, additional follow-up clinical studies are needed.

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3.

Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.

Dual energy computed tomography for detection of metastatic lymph nodes in patients with hepatocellular carcinoma.

BACKGROUND: Regional lymph node metastasis in patients with hepatocellular carcinoma (HCC) is not uncommon, and is often under- or misdiagnosed. Regional lymph node metastasis is associated with a negative prognosis in patients with HCC, and surgical resection of lymph node metastasis is considered feasible and efficacious in improving the survival and prognosis. It is critical to characterize lymph node preoperatively. There is currently no consensus regarding the optimal method for the assessment of regional lymph nodes in patients with HCC. AIM: To evaluate the diagnostic value of single source dual energy computed tomography (CT) in regional lymph node assessment for HCC patients. METHODS: Forty-three patients with pathologically confirmed HCC who underwent partial hepatectomy with lymphadenectomy were retrospectively enrolled. All patients underwent dual-energy CT preoperatively. Regional lymph nodes (n = 156) were divided into either a metastatic (group P, n = 52) or a non-metastasis group (group N, n = 104), and further, according to pathology, divided into an active hepatitis (group P1, n = 34; group N1, n = 73) and a non-active hepatitis group (group P2, n = 18; group N2, n = 31). The maximal short axis diameter (MSAD), iodine concentration (IC), normalized IC (NIC), and the slope of the spectral curve (λ HU) of each group in the arterial phase (AP), portal phase (PP), and delayed phase (DP) were analyzed. RESULTS: Analysis of the MSAD, IC, NIC, and λ HU showed statistical differences between groups P and N (P < 0.05) during all three phases. To distinguish benign from metastatic lymph nodes, the diagnostic efficacy of IC, NIC, and λ HU in the PP was the best among the three phases (AP, PP, and DP), with a sensitivity up to 81.9%, 83.9%, and 81.8%, and a specificity up to 82.4%, 84.1% and 84.1%, respectively. The diagnostic value of combined analyses of MSAD with IC, NIC, or λ HU in the PP was superior to the dual energy CT parameters alone, with a sensitivity up to 84.5%, 86.9%, and 86.2%, and a specificity up to 83.0%, 93.6% and 89.8%, respectively. Between groups P1 and P2 and groups N1 and N2, only IC, NIC, and λ HU between groups N1 and N2 in the PP had a statistically significant difference (P < 0.05). CONCLUSION: Dual-energy CT contributes beneficially to regional lymph node assessment in HCC patients. Combination of MSAD with IC, NIC, or λ HU values in the PP is superior to using any single parameter alone. Active hepatitis does not deteriorate the capabilities for characterization of metastatic lymph nodes.