Ultra-pH-sensitive sensor for visualization of lysosomal autophagy, drug-induced pH alteration and malignant tumors microenvironment

2021 ◽  
pp. 130393
Author(s):  
Tao Zhang ◽  
Fangjun Huo ◽  
Weijie Zhang ◽  
Jianbin Chao ◽  
Caixia Yin
Keyword(s):  
Malignant Tumors ◽  
Ph Sensitive ◽  
Drug Induced ◽  
Sensitive Sensor

scholarly journals IN VITRO AND IN VIVO EVALUATION OF 2-CHLOROE THYLN ITROSOUREA DERIVATIVES AS ANTITUMOR AGENTS

2015 ◽  
Vol 37 (1) ◽  
pp. 23-29
Author(s):  
A Sen ◽  
K K Goswami ◽  
A Mallick ◽  
A K Saxena ◽  
U Sanyal ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Agents ◽  
Malignant Tumors ◽  
Optimum Dose ◽  
Mouse Tumor ◽  
Drug Induced ◽  
In Vivo Evaluation ◽  
Liver And Kidney

Aim: To evaluate potential of Naphthal-NU, Napro-NU and 5-Nitro-naphthal-NU, 2-chloroethylnitrosourea compounds with substituted naphthalimide in the pre-clinical studies. Materials and Methods: In vitro cytotoxicity of three nitrosoureas was determined in human and mouse tumor cell lines by MTT assays. In vivo anti-tumor potential was evaluated in Sarcoma-180 (S-180) and Ehrlich’s carcinoma (EC) solid tumors. Apoptosis in S-180 cells was analyzed by using Annexin V-Propidium Iodide (PI). Histological analysis of liver and kidney was performed at optimum dose (50 mg/kg). Expression status of CD4+, CD8+ and CD25+ cells in treated mouse were also examined. Results: Significant tumor growth retardation by the compounds was noted in early and advanced disease groups, as the life span of drug treated mice increased considerably. Drug induced killing was observed by induction of apoptosis. Naphthal-NU and 5-Nitro-naphthal-NU were effective to normalize the tumor induced structural abnormalities of liver and kidney. The compounds have no immunotoxic effect on CD4+ and CD8+ T cells and down regulate CD4+CD25+ regulatory T cells. Conclusion: Overall data holds promise for the antitumor activity with lower toxicity of the compounds that can be utilized for the treatment of human malignant tumors.

5-Fluorouracil-loaded Self-assembled pH-sensitive Nanoparticles as Novel Drug Carrier for Treatment of Malignant Tumors

2006 ◽  
Vol 14 (3) ◽  
pp. 377-382 ◽  
Author(s):  
Liang LIU ◽  
Ping JIN ◽  
Ming CHENG ◽  
Guoliang ZHANG ◽  
Fengbao ZHANG
Keyword(s):  
Malignant Tumors ◽  
Drug Carrier ◽  
Ph Sensitive ◽  
Self Assembled ◽  
Novel Drug

scholarly journals Design, Synthesis, and Characterization of Schiff Base Bond-Linked pH-Responsive Doxorubicin Prodrug Based on Functionalized mPEG-PCL for Targeted Cancer Therapy

Polymers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1127 ◽  
Author(s):  
Yinglei Zhai ◽  
Xing Zhou ◽  
Zhiqiang Zhang ◽  
Lei Zhang ◽  
Dianyu Wang ◽  
...  
Keyword(s):  
Side Effects ◽  
Malignant Tumors ◽  
Drug Carrier ◽  
In Vitro Release ◽  
Average Diameter ◽  
In Vitro Cytotoxicity ◽  
Ph Sensitive ◽  
Ph Responsive ◽  
Design Synthesis

The side effects of doxorubicin (DOX) extremely limit its application in the treatment of malignant tumors. Nano-sized polymeric drugs based on the acidic microenvironment of tissular- or intra- tumor have attracted ample attention because of their potential in reducing side effects. In this research, an amphiphilic diblock copolymer based on poly (ethylene glycol) (PEG) and functionalized polycaprolactone (PCL) was synthesized and utilized as the drug carrier. DOX was chemically conjugated with the polymer via acid-cleavable imine bonds to obtain a novel pH-sensitive DOX prodrug (mPEG-PCL-Imi-DOX). mPEG-PCL-Imi-DOX (24.2 wt % DOX content) formed micelles with an average diameter of 125 nm through a simple solvent evaporation method. The in vitro release profile demonstrated that DOX release of the prodrug micelles was pH-responsive and able to be accelerated with the decrease of pH. In vitro cytotoxicity assay tests revealed that the pH-sensitive DOX prodrug micelles exhibited relatively lower toxicity and similar antitumor efficacy towards MCF-7 cells compared with free DOX. Hence, the DOX prodrug micelles with imine bonds can offer a carrier with great potential for chemo-therapeutics.

Blockade of histone deacetylase 6 protects against cisplatin-induced acute kidney injury

2018 ◽  
Vol 132 (3) ◽  
pp. 339-359 ◽  
Author(s):  
Jinhua Tang ◽  
Yingfeng Shi ◽  
Na Liu ◽  
Liuqing Xu ◽  
Xiujuan Zang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Histone Deacetylase ◽  
Malignant Tumors ◽  
Inflammatory Diseases ◽  
Kidney Injury ◽  
Histone Deacetylase 6 ◽  
Drug Induced ◽  
Sod Activity ◽  
Kidney Injury Molecule 1 ◽  
E Cadherin

Histone deacetylase 6 (HDAC6) has been shown to be involved in various pathological conditions, including cancer, neurodegenerative disorders and inflammatory diseases. Nonetheless, its specific role in drug-induced nephrotoxicity is poorly understood. Cisplatin (dichlorodiamino platinum) belongs to an inorganic platinum – fundamental chemotherapeutic drug utilized in the therapy of various solid malignant tumors. However, the use of cisplatin is extremely limited by obvious side effects, for instance bone marrow suppression and nephrotoxicity. In the present study, we utilized a murine model of cisplatin-induced acute kidney injury (AKI) and a highly selective inhibitor of HDAC6, tubastatin A (TA), to assess the role of HDAC6 in nephrotoxicity and its associated mechanisms. Cisplatin-induced AKI was accompanied by increased expression and activation of HDAC6; blocking HDAC6 with TA lessened renal dysfunction, attenuated renal pathological changes, reduced expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, and decreased tubular cell apoptosis. In cultured human epithelial cells, TA or HDAC6 siRNA treatment also inhibited cisplatin-induced apoptosis. Mechanistic studies demonstrated that cisplatin treatment induced phosphorylation of AKT and loss of E-cadherin in the nephrotoxic kidney, and administration of TA enhanced AKT phosphorylation and preserved E-cadherin expression. HDAC6 inhibition also potentiated autophagy as evidenced by increased expression of autophagy-related gene (Atg) 7 (Atg7), Beclin-1, and decreased renal oxidative stress as demonstrated by up-regulation of superoxide dismutase (SOD) activity and down-regulation of malondialdehyde levels. Moreover, TA was effective in inhibiting nuclear factor-κ B (NF-κB) phosphorylation and suppressing the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Collectively, these data provide strong evidence that HDAC6 inhibition is protective against cisplatin-induced AKI and suggest that HDAC6 may be a potential therapeutic target for AKI treatment.

Differential pH‐sensitive sensor with DC electrode‐offset compensation

2017 ◽  
Vol 53 (4) ◽  
pp. 251-253 ◽  
Author(s):  
K.H. Lee ◽  
D. Lee ◽  
J. Yoon ◽  
O. Kwon ◽  
J. Lee
Keyword(s):  
Ph Sensitive ◽  
Sensitive Sensor ◽  
Offset Compensation

scholarly journals Molecular Initiating Events Associated with Drug-Induced Liver Malignant Tumors: An Integrated Study of the FDA Adverse Event Reporting System and Toxicity Predictions

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 944
Author(s):  
Kota Kurosaki ◽  
Yoshihiro Uesawa
Keyword(s):  
Adverse Event ◽  
Reporting System ◽  
Malignant Tumors ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Drug Event ◽  
Drug Induced ◽  
Event Reporting ◽  
Nonalcoholic Fatty Liver ◽  
Drug Classes

Liver malignant tumors (LMTs) represent a serious adverse drug event associated with drug-induced liver injury. Increases in endocrine-disrupting chemicals (EDCs) have attracted attention in recent years, due to their liver function-inhibiting abilities. Exposure to EDCs can induce nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, which are major etiologies of LMTs, through interaction with nuclear receptors (NR) and stress response pathways (SRs). Therefore, exposure to potential EDC drugs could be associated with drug-induced LMTs. However, the drug classes associated with LMTs and the molecular initiating events (MIEs) that are specific to these drugs are not well understood. In this study, using the Food and Drug Administration Adverse Event Reporting System, we detected LMT-inducing drug signals based on adjusted odds ratios. Furthermore, based on the hypothesis that drug-induced LMTs are triggered by NR and SR modulation of potential EDCs, we used the quantitative structure–activity relationship platform for toxicity prediction to identify potential MIEs that are specific to LMT-inducing drug classes. Events related to cell proliferation and apoptosis, DNA damage, and lipid accumulation were identified as potential MIEs, and their relevance to LMTs was supported by the literature. The findings of this study may contribute to drug development and research, as well as regulatory decision making.

Current management approach of Cancer in Ayurveda

2017 ◽  
Vol 2 (3) ◽  
Author(s):  
Archana Kashid
Keyword(s):  
Malignant Tumors ◽  
Integrated Approach ◽  
Normal Function ◽  
The Body ◽  
Arterial System ◽  
Management Approach ◽  
Drug Induced ◽  
Health Maintenance ◽  
Organ Systems ◽  
Natural Drugs

Ayurveda, the oldest Indian indigenous medicine system of plant drugs is known from very early times for preventing or suppressing various tumors using these natural drugs. In Ayurvedic concept, according to Charaka and Sushruta Samhitas, Cancer is described as inflammatory or non-inflammatory swelling and mentioned either as Granthi (minor neoplasm) or Arbuda (major neoplasm). The nervous system (Vata), the venous system (Pitta) and the arterial system (Kapha) are three basics of Ayurveda and very important for normal body function. In malignant tumors all three systems get out of control (Tridoshas) and lose mutual coordination that causes tissue damage, resulting critical condition. Tridoshas cause excessive metabolic crisis resulting in proliferation. The modern cancer therapy which is known to burdened by drug-induced toxic side effects hoping perfect cure of disease form the complementary and alternative medicine system. The main goal of Ayurvedic therapy is to find the ultimate cause of an illness while the therapeutic approach of Ayurveda is divided into four categories as Prakrutisthapana Chikitsa (health maintenance), Rasayana Chikitsa, (restoration of normal function), Roganashani Chikitsa (disease cure) and Naishthiki Chikitsa (spiritual approach). Commonly used herbal decoctions reported in Ayurveda are made of multiple herbs possessing great potential for a cancer cure; scientifically these formulations work on multiple biochemical pathways and influence different organ systems all together and nourish the body as a whole by supporting body‘s deference systems. Now it is important to raise awareness and encourage implementation of Ayurvedic therapies for combating cancer and suggest an integrated approach in tumor management and treatment.

Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques

2006 ◽  
Vol 182 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Dmitrii I. Potapenko ◽  
Margaret A. Foster ◽  
David J. Lurie ◽  
Igor A. Kirilyuk ◽  
James M.S. Hutchison ◽  
...  
Keyword(s):  
Real Time ◽  
Ph Sensitive ◽  
Real Time Monitoring ◽  
Drug Induced ◽  
Low Field ◽  
Induced Changes

scholarly journals TYMS 3′-UTR Polymorphism: A Novel Association with FOLFIRINOX-Induced Neurotoxicity in Pancreatic Cancer Patients

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 77
Author(s):  
Marina Emelyanova ◽  
Ilya Pokataev ◽  
Igor Shashkov ◽  
Elena Kopantseva ◽  
Vladimir Lyadov ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Recessive Model ◽  
Ductal Adenocarcinoma ◽  
Hematological Toxicity ◽  
Drug Induced ◽  
Novel Association ◽  
Substantial Risk ◽  
The Common ◽  
Grade 3 ◽  
The Impact

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy that has the worst 5-year survival rate of all of the common malignant tumors. Surgery, chemotherapy, and/or chemoradiation remain the main tactics for PDAC treatment. The efficacy of chemotherapy is often compromised because of the substantial risk of severe toxicities. In our study, we focused on identification of polymorphisms in the genes involved in drug metabolism, DNA repair and replication that are associated with inter-individual differences in drug-induced toxicities. Using the microarray, we genotyped 12 polymorphisms in the DPYD, XPC, GSTP1, MTHFR, ERCC1, UGT1A1, and TYMS genes in 78 PDAC patients treated with FOLFIRINOX. It was found that the TYMS rs11280056 polymorphism (6 bp-deletion in TYMS 3′-UTR) predicted grade 1–2 neurotoxicity (p = 0.0072 and p = 0.0019, according to co-dominant (CDM) and recessive model (RM), respectively). It is the first report on the association between TYMS rs11280056 and peripheral neuropathy. We also found that PDAC patients carrying the GSTP1 rs1695 GG genotype had a decreased risk for grade 3–4 hematological toxicity as compared to those with the AA or AG genotypes (p = 0.032 and p = 0.014, CDM and RM, respectively). Due to relatively high p-values, we consider that the impact of GSTP1 rs1695 requires further investigation in a larger sample size.

Early Development of Drug-Induced Hepatic Necrosis

1971 ◽  
Vol 29 ◽  
pp. 576-577
Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser
Keyword(s):  
Early Development ◽  
Hepatic Necrosis ◽  
Screening Tests ◽  
Dense Matrix ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Drug Induced ◽  
Hepatocellular Damage ◽  
Sprague Dawley Rats ◽  
Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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