Comparison of patient‐specific internal gross tumor volume for radiation treatment of primary esophageal cancer based separately on three‐dimensional and four‐dimensional computed tomography images

To compare the target volume, position and matching index of the patient‐specific internal gross tumor volume (IGTV) based on three‐dimensional (3D) and four‐dimensional (4D) computed tomography (CT) images for primary esophageal cancer. Twenty‐nine patients with primary thoracic esophageal cancer underwent 3DCT and 4DCT scans during free breathing. IGTVs were constructed using three approaches: combining the gross target volumes from the 10 respiratory phases of the 4DCT dataset to produce IGTV₁₀; IGTV₂ was acquired by combining the two extreme phases; and IGTV_3D was created from the 3DCT‐based gross target volume by enlarging the 95th percentile of motion in each direction measured by the 4DCT. 0.16 cm lateral (LR), 0.14 cm anteroposterior (AP) and 0.29 cm superoinferior (SI) in the upper; 0.18 cm LR, 0.10 cm AP and 0.63 cm SI in the middle; and 0.40 cm LR, 0.58 cm AP and 0.82 cm in the lower thoracic esophagus could account for 95% of respiratory‐induced tumor motion. The centroid position shift between IGTV₁₀ and IGTV₂ was all below 0.10 cm, and less than 0.20 cm between IGTV₁₀ and IGTV_3D. IGTV₁₀ was bigger than IGTV₂; the mean value of matching index for IGTV₂ to IGTV₁₀ was 0.87 ± 0.05, 0.85 ± 0.06 and 0.83 ± 0.05 for upper, middle and distal thoracic esophageal tumors, respectively, and just 0.57 ± 0.11, 0.56 ± 0.13 and 0.40 ± 0.03 between IGTV_3D and IGTV₁₀. 4DCT‐based IGTV₁₀ is a reasonable patient‐specific IGTV for primary thoracic esophageal cancer, and IGTV₂ is considered as an acceptable alternative to IGTV₁₀. However, it seems unreasonable to use IGTV_3D substitute IGTV₁₀.     

Acidic polysaccharide of Panax ginseng regulates the mitochondria/caspase-dependent apoptotic pathway in radiation-induced damage to the jejunum in mice

Owing to its susceptibility to radiation, the small intestine of mice is valuable for studying radioprotective effects. When exposed to radiation, intestinal crypt cells immediately go through apoptosis, which impairs swift differentiation necessary for the regeneration of intestinal villi. Our previous studies have elucidated that acidic polysaccharide of Panax ginseng (APG) protects the mouse small intestine from radiation-induced damage by lengthening villi with proliferation and repopulation of crypt cells. In the present study, we identified the molecular mechanism involved. C57BL/6 mice were irradiated with gamma-rays with or without APG and the expression levels of apoptosis-related molecules in the jejunum were investigated using immunohistochemistry. APG pretreatment strongly decreased the radiation-induced apoptosis in the jejunum. It increased the expression levels of anti-apoptotic proteins (Bcl-2 and Bcl-X_S/L) and dramatically reduced the expression levels of pro-apoptotic proteins (p53, BAX, cytochrome c and caspase-3). Therefore, APG attenuated the apoptosis through the intrinsic pathway, which is controlled by p53 and Bcl-2 family members. Results presented in this study suggest that APG protects the mouse small intestine from irradiation-induced apoptosis through inhibition of the p53-dependent pathway and the mitochondria/caspase pathway. Thus, APG may be a potential agent for preventing radiation induced injuries in intestinal cells during radio-therapy such as in cancer treatment.     

Synthesis of 1,4,5,6-tetrahydropyridazines and pyridazines via transition-metal-free (4 + 2) cycloaddition of alkoxyallenes with 1,2-diaza-1,3-dienes

We developed an economical and practical protocol for the synthesis of 1,4,5,6-tetrahydropyridazines. A diverse range of alkoxyallenes and 1,2-diaza-1,3-dienes undergo (4 + 2) cycloaddition to generate the desired products in excellent yields. The high efficiency, wide substrate scope and good functional group tolerance of this process, coupled with operational simplicity, render the method synthetically attractive. The utility of the cycloaddition is also demonstrated by the preparation of various pyridazines from 1,4,5,6-tetrahydropyridazines.

We developed an economical and practical protocol for the synthesis of 1,4,5,6-tetrahydropyridazines and pyridazines via cyclization of alkoxyallenes and 1,2-diaza-1,3-dienes.

For several years, we have been developing the methodologies of cumulative dienes¹ for the synthesis of heterocyclic compounds.² In the past few decades, allenes have attracted significant attention in organic synthesis.³ By virtue of their reactive and cumulative double bonds, allenes are widely used as valuable C3-feedstocks.⁴ Functional groups at the double bonds of allene moieties strongly influence the reactivities, and thus allow site- and regioselective transformations. For example allenoates, bearing electron-withdrawing substituents (carboxylic ester groups) at the allene moieties, lead to preferred reactions with nucleophiles attacked on the central carbon, and have been thoroughly studied.⁵ Nevertheless, investigations of alkoxyallenes are still limited.⁶ As special enol ethers, alkoxyallenes were frequently employed as strong nucleophiles via deprotonations and metalations.⁷ Moreover, the electronic bias imposed by the alkoxyl groups makes them unique dienophiles; the electron-deficient or electron-rich double bonds could engage in cycloadditions.Recently, Goeke⁸ and Luo⁹et al. developed (4 + 2) annulation of alkoxyallenes with cyclopentadienes and β,γ-unsaturated α-keto esters, respectively (Scheme 1). These established methods employed expensive heavy metals (Au, In), which maybe resulting in the contamination of medicinal products. Accordingly, there is a clear demand for the development of transition-metal-free protocols with high efficiency, operational simplicity, atom economy and general applicability.Open in a separate windowScheme 1Transition-metal-catalyzed (4 + 2) cycloadditions of alkoxyallenes.In 2015, Favi et al. developed (4 + 2) cycloaddition of alkoxyallene with α-halohydrazones (precursors of 1,2-diaza-1,3-dienes), but in which only methoxyallene could be employed as the dienophile (Scheme 2a).¹⁰ The approach allows access to 1,4,5,6-tetrahydropyridazines, which are versatile building blocks and prevalent in a large number of pharmacologically active molecules.¹¹ However, the cyclization suffered from moderate conversion and narrow substrates scope, required long reaction time (up to 7 days) and high stoichiometric ratio of reactants (methoxyallene/Na₂CO₃/α-halohydrazone = 7 : 5 : 1).Open in a separate windowScheme 2(4 + 2) cycloadditions of alkoxyallenes with 1,2-diaza-1,3-dienes.Currently, there is an increased drive to find new ways to maximize synthetic efficiency and minimize waste in chemical and pharmaceutical industries.¹² As part of our group''s continuous interest in cumulene chemistry and transition-metal-free synthesis,¹³ the (4 + 2) annulation of alkoxyallene with 1,2-diaza-1,3-dienes was thus systematically reinvestigated, and in this context, we demonstrate that the cyclization can proceed with a broad range of substrates, producing a wide variety of 1,4,5,6-tetrahydropyridazines in high efficiency. Besides, it was found that these adducts could further convert into pyridazines (Scheme 2b).The investigations began with assaying the (4 + 2) cycloaddition between benzyloxyallene 1a and α-halohydrazone 2a, as shown in

The Interaction Between Amphiphilic Polymer Materials and Guest Molecules: Selective Adsorption and Its Related Applications

The interaction between amphiphilic polymer materials and molecules such as drugs, proteins, and DNA plays one of the key roles for the applications in separation, delivery of drugs, biosensors, and tissue engineering. Thus, the fundamental investigation of this interaction is necessary before some polymer materials can be designed for practical applications. Here, various factors are discussed to determine the interactions between amphiphilic polymer materials and guest molecules. Based on this fundamental understanding, a series of amphiphilic polymer materials with selective adsorption to guest molecules has been developed and widely used for applications in smart separation, temporally controlled release, and patterning of guest molecules, such as dyes, drugs, and proteins.

     

Tea polyphenols and their chemopreventive and therapeutic effects on colorectal cancer

Colorectal cancer(CRC),a multifactorial disease,is usually induced and developed through complex mechanisms,including impact of diet and lifestyle,genomic abnormalities,change of signaling pathways,inflammatory response,oxidation stress,dysbiosis,and so on.As natural polyphenolic phytochemicals that exist primarily in tea,tea polyphenols(TPs)have been shown to have many clinical applications,especially as anticancer agents.Most animal studies and epidemiological studies have demonstrated that TPs can prevent and treat CRC.TPs can inhibit the growth and metastasis of CRC by exerting the antiinflammatory,anti-oxidative or pro-oxidative,and pro-apoptotic effects,which are achieved by modulations at multiple levels.Many experiments have demonstrated that TPs can modulate several signaling pathways in cancer cells,including the mitogen-activated protein kinase pathway,phosphatidylinositol-3 kinase/Akt pathway,Wnt/β-catenin pathway,and 67 kDa laminin receptor pathway,to inhibit proliferation and promote cell apoptosis.In addition,novel studies have also suggested that TPs can prevent the growth and metastasis of CRC by modulating the composition of gut microbiota to improve immune system and decrease inflammatory responses.Molecular pathological epidemiology,a novel multidisciplinary investigation,has made great progress on CRC,and the further molecular pathological epidemiology research should be developed in the field of TPs and CRC.This review summarizes the existing in vitro and in vivo animal and human studies and potential mechanisms to examine the effects of tea polyphenols on CRC.     

Usefulness of autotaxin for the complications of liver cirrhosis

BACKGROUND Autotaxin(ATX) has been reported as a direct biomarker for estimating the evaluation of liver fibrosis. But available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC) are scant.AIM To assess the clinical usefulness of ATX for assessing the complications of LC.METHODS This multicenter, retrospective study was conducted at six locations in Japan. We include patients with LC, n = 400. The ATX level was evaluated separately in men and women because of its high level in female patients. To assess the clinical usefulness of ATX for the complications of LC, the area under the curve(AUC) of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score, albumin-bilirubin(ALBI) score, fibrosis-4 index, and aspartate aminotransferase-to-platelet ratio index.RESULTS The mean age was 68.4 ± 11.4 years, 240 patients(60.0%) were male. A total of 213(53.3%) and 187(46.8%) patients were compensated and decompensated,respectively. The numbers of patients with varix rupture, hepatic ascites, and hepatic encephalopathy were 35(8.8%), 131(32.8%), and 103(25.8%),respectively. The AUCs of ATX in men for hepatic encephalopathy, hepatic ascites, and varix ruptures were 0.853, 0.816, and 0.706, respectively. The AUCs of ATX in women for hepatic encephalopathy, hepatic ascites, and varix rupture were 0.759, 0.717, and 0.697, respectively. The AUCs of ATX in men were higher than those in women, as were all the other biomarkers used to detect encephalopathy and varix ruptures. However, for detecting ascites, the AUC of ALBI in men was more effective than using ATX.CONCLUSION ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.     

A Novel Exploration of a Combination of Gambogic Acid with TiO2 Nanofibers: The Photodynamic Effect for HepG2 Cell Proliferation

As a good photosensitizer, TiO₂ nanomaterials show potential biomedical applications, such as drug carriers or enhancers in photodynamic therapy. In this contribution, novel nanocomposites through the blending of TiO₂ nanofibers with the active compound, gambogic acid (GA), were explored, and the results showed that GA could inhibit cancer cell proliferation in a time-dependent and dose-dependent manner, inducing apoptosis and cell cycle arrest at the G0/G1 phase in HepG2 cells. It is evident that after the GA-TiO₂ nanocomposites were cultured with the cancer cells, the cooperation effect could effectively enhance the cytotoxicity of GA for HepG2 cells. Meanwhile, if activated by UV irradiation, under the presence of GA-TiO₂ nanocomposites, this would lead to significant apoptosis and necrosis for HepG2 cells with a photodynamic therapy (PDT) effect. Associated with the controlled drug-release from these nanocomposites, TiO₂ nanofibers could readily cut down the drug consumption in HepG2 cells and reduce the side-effect for the normal cells and tissue, which may be further utilized in the therapeutic alliance for cancer therapy.