Hepatoid adenocarcinoma of the lung with PD-L1 expression and the response to anti-PD-1 therapy: a case report.

Hepatoid adenocarcinoma of the lung (HAL) is extremely rare; a standardized treatment strategy for HAL has not been established. The prognosis of patients with unresectable HAL is extremely poor. Here, we reported a 64-year-old male patient with unresectable alpha-fetoprotein-producing HAL who showed moderate harboring programmed death ligand 1 (PD-L1) expression and no targetable driver mutations. The patient was treated with brain radiotherapy, multiple lines of chemotherapies, and PD-1 inhibitor and achieved a survival rate of 9 months. The patient finally died because of the progression of brain metastasis. The case report provides valuable information for the treatment strategy development of advanced HAL patients and reminds us of the therapeutic particularity of brain metastasis.

Chemometrics and antioxidant activity assisted nontargeted metabolomics for the identification of ginger species.

An ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry method was developed for the separation and identification of phenols, organic acids, flavonoids and curcumin in different species of ginger. The parameters affecting the separation and response of liquid chromatography, including the stationary phase and mobile phase, were systematically investigated and optimized. To further identify the differential metabolites in the six types of samples, a chemometric approach was introduced. Principal component analysis, cluster analysis and partial least squares discriminant analysis were used to identify the major components in the samples and to compare the compositional differences between the various samples. In addition, antioxidant experiments were designed to investigate the differences in antioxidant activity among the six ginger samples. The method showed good linearity (R2 ≥0.9903), satisfactory precision (RSD% ≤ 4.59 %), low LOD (0.35-25.86 ng/mL) and acceptable recovery (78-109 %) and reproducibility (RSD% ≤ 4.20 %). Therefore, the method has great potential for application in the compositional analysis and quality control of ginger.

Effect of EGFR-TKIs combined with craniocerebral radiotherapy on the prognosis of EGFR-mutant lung adenocarcinoma patients with brain metastasis: A propensity-score matched analysis.

Background and Purpose: Epidermal growth factor receptor (EGFR)-mutant lung cancers are associated with a high risk of developing brain metastases (BM). Craniocerebral radiotherapy is a cornerstone for the treatment of BM, and EGFR-TKIs act on craniocerebral metastases". However, whether EGFR-TKIs combined with craniocerebral radiotherapy can further increase the efficacy and improve the prognosis of patients is unclear. This study aimed to evaluate the difference in efficacy between targeted-therapy alone and targeted-therapy combined with radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM. Materials and Methods: A total of 291 patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutations were enrolled in this retrospective cohort study. Propensity score matching (PSM) was conducted using a nearest-neighbor algorithm (1:1) to adjust for demographic and clinical covariates. Patients were divided into two groups: EGFR-TKIs alone and EGFR-TKIs combined with craniocerebral radiotherapy. Intracranial progression-free survival (iPFS) and overall survival (OS) were calculated. Kaplan-Meier analysis was used to compare iPFS and OS between the two groups. Brain radiotherapy included WBRT, local radiotherapy, and WBRT+Boost. Results: The median age at diagnosis was 54 years (range: 28-81 years). Most patients were female (55.9%) and non-smokers (75.5%). Fifty-one pairs of patients were matched using PSM. The median iPFS for EGFR-TKIs alone (n=37) and EGFR-TKIs+craniocerebral radiotherapy (n=24) was 8.9 and 14.7 months, respectively. The median OS for EGFR-TKIs alone (n=52) and EGFR-TKIs+craniocerebral radiotherapy (n=52) was 32.1 and 45.3 months, respectively. Conclusion: In EGFR-mutant lung adenocarcinoma patients with BM, targeted therapy combined with craniocerebral radiotherapy is an optimal treatment.

Microwave ablation of non-small cell lung cancer tumors changes plasma levels of cytokines IL-2 and IFN-γ.

Background: Combined therapy with immune checkpoint inhibitors (ICIs) and microwave ablation (MWA) is known to improve outcome in non-small cell lung cancer (NSCLC). However, the mechanism underlying the synergistic effect of these two treatments is unknown. Tumor immune microenvironment is known to affect the efficacy of ICI. Therefore, in the present study, we evaluated changes in the levels of peripheral cytokines at 48 h and 1-month post-ablation in patients with NSCLC. Materials and Methods: A total of 44 patients with primary NSCLC were retrospectively enrolled. All patients underwent MWA of the primary tumors. Plasma samples were collected pre- and post-ablation to examine the levels of various cytokines, including interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor (TNF)-α, and interferon-gamma (IFN-γ). Results: Although the levels of the majority of cytokines remained within normal range, levels of IL-2 and IFN-γ were significantly decreased at 48 h post-ablation and increased at 1-month post-ablation. In the subgroup analyses, changes in IL-2 and IFN-γ levels were commonly identified. Moreover, the Eastern Cooperative Oncology Group status, sex, pathology type, tumor site, and tumor size were associated with cytokines' levels pre-ablation or post-ablation. Conclusion: MWA of NSCLC tumors influenced the plasma levels of cytokines IL-2 and IFN-γ.

TRIM3 facilitates estrogen signaling and modulates breast cancer cell progression.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. More than 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha-negative breast cancer, which is more aggressive and has a shorter survival time, ER alpha-positive breast cancer could benefit from endocrine therapy. Selective estrogen receptor modulators, such as tamoxifen, are widely used in endocrine therapy. Approximately half of ER alpha-positive breast cancer patients will eventually develop endocrine resistance, making it a major clinical challenge in therapy. Thus, decoding the throughput of estrogen signaling, including the control of ER alpha expression and stability, is critical for the improvement of breast cancer therapeutics. METHODS: TRIM3 and ER alpha protein expression levels were measured by western blotting, while the mRNA levels of ER alpha target genes were measured by RT-PCR. A CCK-8 assay was used to measure cell viability. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling activity was accomplished with luciferase assays, RT-PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect ER alpha protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the ER alpha protein. RESULTS: In our current study, we found that TRIM3, an E3 ligase, can promote ER alpha signaling activity and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and migration, while unbiased RNA sequencing data indicated that TRIM3 is required for the activity of estrogen signaling on the -genome-wide scale. The immunoprecipitation assays indicated that TRIM3 associates with ER alpha and promotes its stability, possibly by inducing K63-linked polyubiquitination of ER alpha. In conclusion, our data implicate a nongenomic mechanism by which TRIM3 stabilizes the ER alpha protein to control ER alpha target gene expression linked to breast cancer progression. CONCLUSION: Our study provides a novel posttranslational mechanism in estrogen signaling. Modulation of TRIM3 expression or function could be an interesting approach for breast cancer treatment. Video abstract.

Dynamic changes in the systemic immune-inflammation index predict the prognosis of EGFR-mutant lung adenocarcinoma patients receiving brain metastasis radiotherapy.

BACKGROUND: The systemic immune-inflammation index (SII) has recently emerged as a predictor of survival in non-small cell lung cancer patients. There is also tight correlation between radiotherapy and immune status, and brain metastases (BM) radiotherapy is an important treatment in patients with BM from lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations. Hence, this study aimed to present the prognostic value of SII and its dynamic changes during BM radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM. METHODS: Patients with EGFR-mutant lung adenocarcinoma who received BM radiotherapy between November 2011 and April 2021 were included in this retrospective study. The SII was calculated using data acquired within 1 week before the start of radiation treatment and 1 week before its completion. According to the cutoff value of SII before radiation treatment determined using receiver operating characteristic curve analyses, we divided the patients into a high group and a low group. Patients were further classified into high-high, high-low, low-low, and low-high groups based on dynamic changes in SII. Prognostic values of the SII and other factors were determined using the Kaplan-Meier method, as well as univariate and multivariate Cox analysis. RESULTS: A total of 202 patients met the inclusion criteria, and the median overall survival (OS) of the entire cohort was 36 months. According to the SII cutoff of 859.79, an SII value below this cutoff was associated with longer OS (hazard ratio 0.6653, 95% confidence interval 0.4708-0.9402, P < 0.05). The patients in the low-low group, whose SII within 1 week before the start and end of BM radiotherapy were below the cutoff, had a median OS of 55.2 months, which was significantly longer than the OS in all other groups (P < 0.05). Univariate and multivariate analyses confirmed that dynamic SII change (P = 0.032), Lung-molGPA (P < 0.001), and thoracic radiation (P = 0.048) were independently correlated with OS. CONCLUSIONS: The SII and its dynamic change may have a prognostic value in patients with EGFR-mutant lung adenocarcinoma treated with BM radiotherapy.

OsTGAL1 suppresses the resistance of rice to bacterial blight disease by regulating the expression of salicylic acid glucosyltransferase OsSGT1.

Many TGA transcription factors participate in immune responses in the SA-mediated signaling pathway in Arabidopsis. This study identified a transcription factor OsTGAL1, which is induced upon infection by Xoo. Overexpression of OsTGAL1 increased the susceptibility of rice to Xoo. Plants overexpressing OsTGAL1 could affect the expression of many SA signaling-related genes. OsTGAL1 was able to interact with the promoter of OsSGT1, which encodes a key enzyme for SA metabolism. The transcript of OsSGT1 was induced by Xoo and this responsive expression was further increased in plants overexpressing OsTGAL1. OsSGT1 knockout lines had enhanced resistance to Xoo, and knocking out OsSGT1 in plants overexpressing OsTGAL1 blocked the susceptibility caused by OsTGAL1. Altered expression levels of several OsPRs in all the transgenic plants demonstrated that SA-mediated signaling had been affected. Furthermore, we identified an oxidoreductase of CC-type glutaredoxin, OsGRX17, which interacted with OsTGAL1. OsGRX17 reduced the regulation of OsTGAL1 on OsSGT1, and this may be due to its redox modulation. Thus, our results demonstrate that OsTGAL1 negatively regulates resistance to Xoo by its effects on SA metabolism via the activation of OsSGT1, which provides valuable targets for plant breeders in developing new cultivars that are resistant to Xoo.

Immunomodulatory role of metalloproteases in cancers: Current progress and future trends.

Metalloproteinases (MPs) is a large family of proteinases with metal ions in their active centers. According to the different domains metalloproteinases can be divided into a variety of subtypes mainly including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteases (ADAMs) and ADAMs with Thrombospondin Motifs (ADAMTS). They have various functions such as protein hydrolysis, cell adhesion and remodeling of extracellular matrix. Metalloproteinases expressed in multiple types of cancers and participate in many pathological processes involving tumor genesis and development, invasion and metastasis by regulating signal transduction and tumor microenvironment. In this review, based on the current research progress, we summarized the structure of MPs, their expression and especially immunomodulatory role and mechanisms in cancers. Additionally, a relevant and timely update of recent advances and future directions were provided for the diagnosis and immunotherapy targeting MPs in cancers.

lncRNA TINCR facilities bladder cancer progression via regulating miR­7 and mTOR.

Long non­coding RNAs (lncRNAs) have been implicated in various human malignancies, but the molecular mechanism of lncRNA TINCR ubiquitin domain containing (TINCR) in bladder cancer remains unclear. The present study found that the expression of TINCR was significantly increased in bladder cancer tissues and cell lines, when compared with that in adjacent normal tissues and normal urinary tract epithelial cell line SV­HUC­1, respectively. Moreover, the high expression of TINCR was associated with tumor metastasis and advanced tumor, node, metastasis stage, as well as reduced overall survival rates of patients with bladder cancer. Further investigation revealed that microRNA (miR)­7 was negatively mediated by TINCR in bladder cancer cells. Silencing of TINCR expression significantly increased miR­7 expression and reduced bladder cancer cell proliferation, migration and invasion, while knockdown of miR­7 expression reversed the inhibitory effects of TINCR downregulation on bladder cancer cells. mTOR was then identified as a target gene of miR­7 in bladder cancer, and it was demonstrated that overexpression of mTOR reversed the inhibitory effects of miR­7 on bladder cancer cells. In conclusion, this study suggests that TINCR/miR­7/mTOR signaling may be a potential therapeutic target for bladder cancer.

Endostar continuous intravenous infusion combined with S-1 and oxaliplatin chemotherapy could be effective in treating liver metastasis from gastric cancer.

OBJECTIVE: Endostar is a new vascular epithelial inhibitor, which is reported to be effective in treating liver metastasis from gastric cancer. However, the optimal therapeutic regimen of Endostar remains unclear. Thus, our study aimed to examine the efficacy and safety of Endostar continuous intravenous infusion combined with S-1 and oxaliplatin (SOX) chemotherapy in treating such patients. PATIENTS AND METHODS: A total of sixty patients with liver metastasis from gastric cancer admitted in our department were enrolled. The experimental group (n = 30) was treated with Endostar continuous intravenous infusion combined with SOX regimen chemotherapy, and the control group (n = 30) received SOX regimen chemotherapy alone. All patients received at least two cycles of treatment. The objective effective rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse reactions were recorded and compared. RESULTS: The ORR of the experimental group and control group was 63.3% and 43.3% (P = 0.046), respectively. The DCR of the experimental group and the control group was 86.7% and 73.3% (P = 0.034). The median PFS in the experimental group was longer than that in the control group (15.3 months vs. 12 months). There was no significant difference in the incidence of common adverse reactions such as gastrointestinal reaction, bone marrow suppression, and cardiac toxicity between the two groups. No death was observed in the study period. CONCLUSION: Continuous infusion of Endostar combined with SOX chemotherapy could be recommended for the treatment of liver metastasis from gastric cancer due to its high effective rate, and Endostar did not increase the incidence of adverse reactions.

Ectopic expression of B and T lymphocyte attenuator in gastric cancer: a potential independent prognostic factor in patients with gastric cancer.

It has been confirmed that B and T lymphocyte attenuator (BTLA; also known as CD272) is a novel co--inhibitory molecule that exhibits a critical role in restraining cell-mediated antitumor immunity. The present study aimed to investigate the expression and prognostic significance of BTLA in gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed to investigate BTLA expression in gastric cancer tissues and normal mucosal tissues. In total, 123 pathologically confirmed specimens were obtained from stage IIIa gastric cancers. A correlation test, Kaplan-Meier curves, and a Cox proportional hazards regression model were used to analyze the data. No BTLA staining in the normal tissues was found, while BTLA-stained gastric carcinoma cells were detected in 75.6% (93/123) of the gastric cancer specimens. High expression levels of BTLA were detected in 31.7% (39/123) of the specimens, while low expression levels were detected in 68.3% (84/123) of the specimens. High BTLA expression levels were associated with shorter survival time, as confirmed by univariate and multivariate analyses. These findings provide a basis for the concept that high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer.

4-(2,4-Dichloro-phen-yl)-5,5-dimethyl-2-(3-silatranyl-propyl-mino)-1,3,2-dioxa-phospho-rinane 2-oxide.

In the title compound, C(20)H(31)Cl(2)N(2)O(6)PSi, the dioxaphospho-rinane ring adopts a cis conformation. The silatrane fragment forms a cage-like structure in which there exists an intra-molecular Si-N donor-acceptor bond. In the crystal, centrosymmetrically related mol-ecules are linked by pairs of N-H⋯O hydrogen bonds into inversion dimers, generating rings with graph-set motif R(2) (2)(8). The dimers are further connected into ribbons parallel to the a axis by inter-molecular C-H⋯O hydrogen bonds.

[Absorption mechanism of oxysophocarpine across Caco-2 cell monolayer mode].

OBJECTIVE: To investigate the absorption mechanism of oxysophocarpine across Caco-2 cell monolayer model. METHOD: The safety concentration of oxysophocarpine in Caco-2 cell was first selected by using MTT method. Then the Caco-2 cell monolayers drug transport model was assigned to study the bi-direction transport mechanism of oxysophocarpine by evaluating the influent factors such as time, concentration, pH, P-gp inhibitor of verapamil, on its absorption characterization. RESULT: In the Caco-2 cell monolayer model, the transport volume was correlated positively with the time and concentration of oxysophocarpine, and affected by pH value. Verapamil had no influence on its transport since the transport of oxysophocarpine from apical (AP) to basolateral (BL) was similar to the transport from basolateral to apical. CONCLUSION: The intestinal absorption mechanism of oxysophocarpine was deduced as passive transference by Caco-2 cell monolayer model.

[Simultaneous determination of alpha-pinene, beta-pinene, eucalyptol and alpha-terpineolin in essential oil from Alpinia officinarum Hance by GC].

OBJECTIVE: To establish a method for simultaneous determination of alpha-pinene, beta-pinene, eucalyptol and alpha-terpineolin in essential oil from Alpinia officinarum by GC. METHOD: The essential oil was extracted by steam distillation. The determination was carried on with capillary column DB-1 (0.25 mm x 30 m, 0.25 microm). Temperature programs: 50 degrees C (hold 2 min) programmed to 130 degrees C (hold 3 min) at 8 degrees C x min(-1). The detector was FID. Inlet temperature was 230 degrees C. The detector temperature was 250 degrees C. Carrying gas was nitrogen (1.2 mL x min(-1)), split injection was conducted with split ratio of 10:1. Injection volumn was 1 microL. RESULT: The linear ranges of alpha-pinene, beta-pinene, eucalyptol and alpha-terpineolin were 0.009-0.090 (r = 0.999 8), 0.009-0.091 (r = 0.999 8), 0.060 4-0.604 (r = 0.999 7) and 0.037 4-0.374 g x L(-1) (r = 0.999 5), respectively. The average recoveries (n = 9) of a-pinene, beta-pinene, eucalyptol and alpha-terpineolin were 96.2% (RSD 0.8%) and 96.7% (RSD 1.1%), 98.7% (RSD 1.1%) and 96.7% (RSD 2.2%), respectively. CONCLUSION: The developed method is simple, quick and accurate, which is helpful to control the quality of A. officinarum.

[Effects of forest and swamp on hydrochemical characteristics of streams].

With the upper reaches of Gongbiela River in the northeast part of Xiaoxing' an Mountains as test area, this paper studied the hydrochemical characteristics of the streams in forest and swamp during the period of June - September 2004. The results indicated that the hydrochemistry of forest and swamp streams belonged to calcium-bicarbonate type I (C1(Ca)). The pH value, mineralization rate, total hardness, and HCO3(-), SO4(2-), Ca(2+), Mg(2+) and Fe concentrations of forest streams were lower than those of swamp streams, while the concentrations of total N, total P, Cl-, K+, and Na+ were in adverse. In both of the streams, the contents of heavy metal elements such as Fe, Mn, Cu, Zn, Cd, Hg and Pb were lower than the class I in Environmental Quality Standards for Surface Water (EQSSW) of China. The concentrations of total N and P in forest streams were (0.27 +/- 0.04) mg x L(-1) and (0.040 +/- 0.005) mg x L(-1), respectively, being significantly higher than those ((0.21 +/- 0.02) mg x L(-1) and (0.025 +/- 0.004) mg x L(-1)) in swamp streams. Swamp wetland had a stronger ability in depositing and adsorbing N and P, with more NH4(+) -N adsorbed than NO3(-) -N, and also had a stronger ability on the reduction and release of Fe, with the Fe content ((0.26 +/- 0.05) mg x L(-1)) in its streams obviously higher than that in forest streams.