Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Phytochelatin-Mediated Cultivar-Dependent Cd Accumulations of Lactuca sativa and Implication for Cd Pollution-Safe Cultivars Screening.

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.

Proteomic and Biochemical Evidence Involving Root Cell Wall Biosynthesis and Modification, Tricarboxylic Acid Cycle, and Glutathione Metabolism in Cultivar-Dependent Cd Accumulation of Water Spinach (Ipomoea aquatica).

Proteomic analysis and biochemical tests were employed to investigate the critical biological processes responsible for the different cadmium (Cd) accumulations between two water spinach (Ipomoea aquatica) cultivars, QLQ and T308. QLQ, with lower shoot Cd accumulation and translocation factor than T308, possessed higher expression of cell wall biosynthesis and modification proteins in roots, together with higher lignin and pectin contents, higher pectin methylesterase activity, and lower pectin methylation. The results demonstrated that QLQ could more effectively restrict root-to-shoot Cd translocation by compartmentalizing more Cd in root cell walls. In contrast, T308 showed higher expression of the tricarboxylic acid (TCA) cycle, glutathione (GSH) metabolism, and heavy metal transporter proteins, accompanied by higher GSH content and glutathione S-transferase (GST) and glutathione reductase (GR) activity, which accelerated Cd uptake and translocation in T308. These findings revealed several critical biological processes responsible for cultivar-dependent Cd accumulation in water spinach, which are important for elucidating Cd accumulation and transport mechanisms in different cultivars.

Screening of the proteins related to the cultivar-dependent cadmium accumulation of Brassica parachinensis L.

Cultivar-dependent cadmium (Cd) accumulation was principal in developing Cd-pollution safe cultivars (PSCs). Proteins related to different Cd accumulations of the low-Cd-accumulating (SJ19) and high-Cd-accumulating (CX4) cultivars were investigated by iTRAQ analysis. Higher Cd bioaccumulation factors and translocation factor in CX4 than in SJ19 were consistent with the cultivar-dependent Cd accumulations. The Cd uptake was promoted in CX4 due to its higher expression of Cd-binding proteins and the lower expression of Cd-efflux proteins in roots. What's more, significantly elevated thiol groups (PC2 and PC3) in CX4 under Cd stress might contribute to the high Cd accumulation in roots and the root-to-shoot translocation of Cd-PC complex. Up-regulated proteins involved in cellulose biosynthesis and pectin de-esterification in SJ19 enhanced the Cd sequestration of root cell walls, which was considered as the predominant strategy for reducing Cd accumulation in shoots. The present study provided novel insights in the cultivar-dependent Cd accumulation in shoots of B. parachinensis.

Regulation effects of naringin on diesel particulate matter-induced abnormal airway surface liquid secretion.

BACKGROUND: PM2.5 is closely related to the incidence and mortality of respiratory diseases. Diesel particulate matter (DPM) is the main component of particulate air pollution and an important source of PM2.5. HYPOTHESIS/PURPOSE: This study mainly explored the effect of DPM on airway surface liquid (ASL) secretion and the regulation of naringin in this process, to evaluate therapeutic potentials of naringin for the treatment of abnormal secretion of the respiratory tract caused by PM2.5. METHODS: The concentration of lysozyme was measured by Lysozyme Assay Kit. Total protein content was determined by the BCA Protein Assay Kit. The concentration of cAMP and MUC5AC, expressions of CFTR, AQP1, and AQP5 proteins were measured by ELISA. Expressions of CFTR, AQP1 and AQP5 mRNA were determined by qPCR. Amount of CFTR on the cell membrane was determined by immunofluorescence. RESULTS: The in vitro and in vivo studies had indicated that DPM could inhibit ASL secretion and increased the viscosity of the liquid. Naringin had the functions to attenuate DPM-induced injury, reduce liquid viscosity by reducing MUC5AC and total protein secretion, increase DPM-induced CFTR, AQP1, and AQP5 mRNA and protein expression, positively regulate apical CFTR insertion and promote CFTR activation by increasing intracellular cAMP. CONCLUSION: These results demonstrated that naringin had regulating effects on the DPM-induced abnormal secretion of the respiratory tract.

Toxicity of cadmium and its health risks from leafy vegetable consumption.

Cadmium (Cd) is a highly toxic heavy metal and has spread widely in the environment in recent decades. This review summarizes current knowledge about Cd contamination of leafy vegetables, its toxicity, exposure, health risks, and approaches to reducing its toxicity in humans. Leafy vegetable consumption has been identified as a dominant exposure pathway of Cd in the human body. An overview of Cd pollution in leafy vegetables as well as the main sources of Cd is given. Notable estimated daily intakes and health risks of Cd exposure through vegetable consumption for humans are revealed in occupational exposure areas and even in some reference areas. Vegetable consumption is one of the most significant sources of exposure to Cd, particularly in occupational exposure regions. Therefore, numerous approaches have been developed to minimize the accumulation of Cd in leafy vegetables, among which the breeding of Cd pollution-safe cultivars is one of the most effective tools. Furthermore, dietary supplements from leafy vegetables perform positive roles in alleviating Cd toxicity in humans with regard to the effects of essential mineral elements, vitamins and phytochemicals taken into the human body via leafy vegetable consumption.

Effects of phosphorus on chemical forms of Cd in plants of four spinach (Spinacia oleracea L.) cultivars differing in Cd accumulation.

In order to clarify how cadmium (Cd) chemical forms in planta relate to the genotype difference in Cd accumulation of spinach (Spinacia oleracea L.), two low-Cd and two high-Cd cultivars were compared under a hydroponic experiment with two concentrations of Cd (8.98 or 44.71 µmol Cd L(-1)). The concentrations of phosphorus in the hydroponic system were also adjusted to two levels (0.5 and 1.0 mmol L(-1)) to investigate the influence of phosphorus on the forms and accumulation of Cd in the tested cultivars. Average Cd concentrations in shoots were 8.50-10.06 mg kg(-1) for high-Cd cultivars and 6.11-6.64 mg kg(-1) for low-Cd cultivars a under lower Cd treatment and were as high as 24.41-31.35 mg kg(-1) and 19.65-25.76 mg kg(-1), respectively, under a higher treatment. Phosphorus significantly decreased Cd accumulation in the tested cultivars, and the effect had superiority over the cultivar alternation under higher Cd stress. Cadmium in the NaCl-extractable fraction of the plant tissues showed the greatest relationship to genotype difference of Cd accumulation. The difference in the capacity to binding Cd into F HAc, F HCl, or F Residue was another important mechanism involving in the genotype difference in Cd accumulation of spinach. Among them, average proportion of Cd in F HAc in low-Cd cultivars was higher than that in high-Cd cultivars in association with the effect of phosphorus.

Effects of phosphorus supplied in soil on subcellular distribution and chemical forms of cadmium in two Chinese flowering cabbage (Brassica parachinensis L.) cultivars differing in cadmium accumulation.

Differences in the subcellular distribution and chemical speciation of Cd between two Chinese flowering cabbage (Brassica parachinensis L.) cultivars, Lubao70 (LB70, low-Cd cultivar) and ChixinNO.4 (CX4, high-Cd cultivar) were investigated under various soil Cd and P treatments. Subcellular fractionation of Cd-containing tissues showed that a higher proportion of Cd was bound to the cell wall fraction of LB70 than that of CX4, indicating that Cd compartment functioned better in LB70. Compared to CX4, LB70 had lower proportions of Cd in inorganic form and water-soluble form, but higher proportions of Cd in proteins/pectates integrated form, implying that the low Cd accumulation in LB70 is associated with the low in vivo mobility of Cd. In both cultivars, shoot and root Cd concentration and translocation of Cd from the roots to the shoots obviously decreased with increasing soil P level. It was found that phosphorus (P) played important roles in Cd uptake and translocation via the processes involved in bonding Cd to the cell wall fraction and forming Cd-phosphate complexes. It is suggested that use of low-Cd cultivars in conjunction with P supply is a much useful way to reduce the pollution risk of Cd in the food chain.

[Cropping patterns of Bupleurum chinense in semi-arid region of Loess Plateau].

Field experiments were conducted to investigate the suitable cropping patterns of grain crops and medical plant Bupleurum chinense in the semi-arid region of the Loess Plateau. Three cropping patterns were designed, including corn-Bupleurum chinense intercropping (corn/Bupleurum chinense), wheat followed by soybean-Bupleurum chinense intercropping (wheat-soybean/Bupleurum chinense), and sequential planting of Bupleurum chinense (wheat-Bupleurum chinense). Of the three patterns, wheat-soybean/Bupleurum chinense was the best in economic yields and ecological benefits. Among the cultivars (cv. Lingchuan, Zuoquan and Wanrong) of Bupleurum chinense tested, the cv. Wanrong originated from relatively high temperature region exhibited the highest yield, while the cv. Zuoquan originated from relatively low temperature region had the lowest one, indicating that introducing Bupleurum chinense cultivars from the areas with higher temperature to lower temperature areas could increase their yield. The cropping pattern of wheat-soybean/Bupleurum chinense was the most effective one, with the yield being 11.6% and 16.8% higher than that of corn/Bupleurum chinense and wheat-Bupleurum chinense, respectively.

Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: a preliminary report.

INTRODUCTION: We describe our experience with sorafenib and sunitinib in the treatment of chemotherapy-refractory advanced penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: Between May 2008 and June 2009, 6 advanced penile cancer patients were treated with sorafenib or sunitinib in our center. All of them had previously received at least two chemotherapy regimens. Tumor responses were evaluated by radiologic assessment and serum SCC antigen change. Immunohistochemical staining of CD34 and Ki-67 was performed in 3 paired tumor tissues before and after treatment. RESULTS: In the 6 patients, 1 partial response and 4 stable diseases were observed. Three patients showed pain response and had an improvement in quality of life. After molecular-targeted therapies, reduction in microvessel density and Ki-67 labeling index was observed in paired specimens. Serum SCC antigen levels were decreased in 5 patients after 1 week of medication. The patient who achieved partial response had an SCC antigen reduction of nearly 95% after treatment with sunitinib. Serious adverse events were fatal infection and rupture of the femoral vessel, which were unlikely related to the medication. CONCLUSIONS: The feasibility and activity of sorafenib and sunitinib in our series suggest that this approach may be a promising alternative in chemotherapy-refractory advanced penile SCC.