Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis

Unsymmetrical bisacridines (UAs) represent a novel class of anticancer agents previously synthesized by our group. Our recent studies have demonstrated their high antitumor potential against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, these compounds affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. UAs were shown to undergo metabolic transformations in vitro and in tumor cells. However, the physicochemical properties of UAs, which could possibly affect their interactions with molecular targets, remain unknown. Therefore, we selected four highly active UAs for the assessment of physicochemical parameters under various pH conditions. We determined the compounds’ pK_a dissociation constants as well as their potential to self-associate. Both parameters were determined by detailed and complex chemometric analysis of UV-Vis spectra supported by nuclear magnetic resonance (NMR) spectroscopy. The obtained results indicate that general molecular properties of UAs in aqueous media, including their protonation state, self-association ratio, and solubility, are strongly pH-dependent, particularly in the physiological pH range of 6 to 8. In conclusion, we describe the detailed physicochemical characteristics of UAs, which might contribute to their selectivity towards tumour cells as opposed to their effect on normal cells.     

食管癌患者指甲的红外光谱研究

利用傅里叶红外光谱对正常人,食管癌患者,食管癌术后5个月者的指甲进行了研究。发现他们指甲的红外光谱在频率,强度,峰形等方面均有差异。主要表现在:食管癌患者νs(PO2-)和νas(PO2-)的振动峰均向高波数偏移,术后者回落;癌患者蛋白质C—O基团峰强度增强,术后者峰强度有所减弱,但仍比正常人强;癌患者角蛋白脂质CH2和CH3伸缩振动峰波数有所下降。术后者介于癌患者与正常人之间;食管癌患者角蛋白脂质CH2和CH3弯曲振动峰稍向高波数偏移,术后者恢复至正常人水平;癌患者酰氨Ⅰ带和Ⅱ带都向低波数偏移,术后者介于两者之间。这些差异是应用红外光谱诊断食管癌的基础,表明FTIR光谱在食管癌的早期诊断和快速诊断方面有着十分美好的前景。     

Numerical algorithms for a free boundary problem model of DCIS and a related inverse problem

ABSTRACT

The Ductal carcinoma in situ (DCIS) model has wide applications in the diagnosis of breast cancer, and has been attracted much attention in recent years. In this paper, an effective method has been provided for solving the direct problem of the DCIS model. Moreover, the uniqueness result is established for a kind of inverse problems of DCIS model. Based on the uniqueness theorem, an optimization method has been developed for dealing with the related inverse problem of the DCIS model. The numerical experiments show that the algorithms in this paper are efficient, accurate, robust against noise and fast.     

Molecular design and synthesis of new heterobivalent compounds based on chlorambucil and colchicine

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Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.     

硒对不同水体致癌因子诱发健康人微核的拮抗作用

采用微核检测技术，研究了亚硒酸钠对启东肝癌高发区不同类型饮用水诱发健康人外周血淋巴细胞微核的拮抗作用。结果表明：（１）各实验水体对细胞的毒性作用，宅沟水〉泯沟水〉自来水〉双蒸水。微核率随着实验水体剂量的增加而升高；（２）１ｍｇ／Ｌ的亚硒酸钠浓度对泯沟水，自来水诱发的微核效应有是显的抑制和／或拮抗作用，呈现明显的剂量－效应关系，提示肝癌高发区饮用水体中确存在与肝癌发病相关的致畸因子，补硒确有防与治原     

Investigation on the viscoelasticity of synchronous hepatocellular carcinoma cells

Having made use of the micropipette aspiration technique, we here investigated the viscoelastic properties of hepatocellular carcinoma (HTC) cells from the view of cell cycle. The synchronous G₁ and S phase cells were achieved through thymine-2-desoryriboside and colchicine sequential blockage method and double thymine-2-desoryriboside blockage method, respectively. The synchronization results detected with flow cytometer showed that it could meet the requirements of the experiments nicely. Experimental results were analyzed with a standard linear solid viscoelastic model, in which an elastic element, K₁, is in parallel with a Maxwell element composed of another elastic element, K₂, in series with a viscous element, μ. The results indicated that high K₁, K₂ values and low μ value was the general characteristics of the cells; G₁ phase cells had higher K₁ values and low μ value than S phase cells, which endowed G₁ phase cells with higher elasticity and faster passive deformability than S phase cells. The results maybe also reflected the difference of cytoskeleton between G₁ and S phase cells, and suggested that G₁ phase cells were more suitable for surviving and metastasis in blood circulation than S phase cells.     

胃癌与七种元素关系的分析

57例胃癌癌灶内锌值为(13.740±4.150)×10~(-6),低于癌边缘组织(15.677±4.567)×10~(-6)(P<0.01),亦低于正常组织(15.897±3.580)×10~(-6)(P<0.01)。癌灶铜值为(7.91±6.19)×10~(-6),高于正常组织(5.62±12.01)×10~(-6)(P<0.05),癌灶铜/锌比值亦高于正常组织(P<0.01),但与边缘组织无显著性差异。分化较好的胃腺癌与未分化癌间七种微量元素含量均无显著性差异。这些结果提示,胃癌组织中锌值的降低与铜/锌比值的升高可作为胃癌的辅助诊断指标,而且锌值的检测更具意义。但与分化程度无关。     

Limitations of the Wittig-Horner-type annulation of fluorobutenolide moiety to 3-hydroxyquinoline-2,4(2H,3H)-diones. Novel modifications of the Perkow reaction including fluorinated acyloxy leaving groups

3-(Fluoroacyloxy)quinoline-2,4(1H,3H)-diones react with triethyl phosphite to afford either the product of the Perkow reaction or the corresponding 4-ethoxyquinolin-2(1H)-one. In both reactions, the fluorocarboxylate anion acts as the leaving group. For the corresponding 3-(fluoroiodoacetoxy) derivative this observation precludes the application of the intramolecular Wittig-Horner synthesis to modify quinoline-2,4(1H,3H)-diones by the annulation of a fluorinated but-2-enolide moiety.     

Inhibitory Effect of Anti-HER-2 Anti-CD3 Bi-specific Antibody on the Growth of Gastric Carcinoma

Introduction Gastriccancerisoneofthemostcommonlyen counteredmalignantdiseasesworldwide,especiallyin AsiaandAfrica[1].Thecombinationofoperation,chemotherapyandradiotherapyisusedfortreatinggas triccarcinoma.However,the5yearsurvivalrateof patientsofgastricca…