Small Molecular Gemcitabine Prodrugs for Cancer Therapy

Gemcitabine as a pyrimidine nucleoside analog anticancer drug has high efficacy for a broad spectrum of solid tumors. Gemcitabine is activated within tumor cells by sequential phosphorylation carried out by deoxycytidine kinase to mono-, di-, and triphosphate nucleotides with the last one as the active form. But the instability, drug resistance and toxicity severely limited its utilization in clinics. In the field of medicinal chemistry, prodrugs have proven to be a very effective means for elevating drug stability and decrease undesirable side effects including the nucleoside anticancer drug such as gemcitabine. Many works have been accomplished in design and synthesis of gemcitabine prodrugs, majority of which were summarized in this review.

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European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects

Frontiers in Oncology ◽

10.3389/fonc.2019.00640 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

Tej H. Patel ◽

Lucas Norman ◽

Steven Chang ◽

Sina Abedi ◽

Catherine Liu ◽

...

Keyword(s):

Drug Resistance ◽

Side Effects ◽

Anticancer Drug ◽

Differential Responses ◽

Mtdna Variants

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Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

Current Medicinal Chemistry ◽

10.2174/0929867325666180719145819 ◽

2020 ◽

Vol 27 (13) ◽

pp. 2118-2132 ◽

Cited By ~ 5

Author(s):

Aysegul Hanikoglu ◽

Hakan Ozben ◽

Ferhat Hanikoglu ◽

Tomris Ozben

Keyword(s):

Oxidative Stress ◽

Drug Resistance ◽

Side Effects ◽

Cancer Therapy ◽

Tumor Cells ◽

Anticancer Drugs ◽

Chemotherapeutic Agents ◽

Oxidation Reactions ◽

Hybrid Compounds ◽

Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

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Recent Advances in the Rational Drug Design Based on Multi-target Ligands

Current Medicinal Chemistry ◽

10.2174/0929867327666200102120652 ◽

2020 ◽

Vol 27 (28) ◽

pp. 4720-4740 ◽

Cited By ~ 3

Author(s):

Ting Yang ◽

Xin Sui ◽

Bing Yu ◽

Youqing Shen ◽

Hailin Cong

Keyword(s):

Drug Resistance ◽

Clinical Practice ◽

Side Effects ◽

Drug Design ◽

Rational Drug Design ◽

Health Conditions ◽

Pharmacokinetic Parameters ◽

Single Target ◽

Rational Drug ◽

Huge Challenge

Multi-target drugs have gained considerable attention in the last decade owing to their advantages in the treatment of complex diseases and health conditions linked to drug resistance. Single-target drugs, although highly selective, may not necessarily have better efficacy or fewer side effects. Therefore, more attention is being paid to developing drugs that work on multiple targets at the same time, but developing such drugs is a huge challenge for medicinal chemists. Each target must have sufficient activity and have sufficiently characterized pharmacokinetic parameters. Multi-target drugs, which have long been known and effectively used in clinical practice, are briefly discussed in the present article. In addition, in this review, we will discuss the possible applications of multi-target ligands to guide the repositioning of prospective drugs.

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Knowledge, attitude, and practice of pharmacy and medical students regarding self-medication, a study in Zabol University of Medical Sciences; Sistan and Baluchestan province in south-east of Iran

BMC Medical Education ◽

10.1186/s12909-020-02374-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mahmoud Hashemzaei ◽

Mahdi Afshari ◽

Zahra Koohkan ◽

Ali Bazi ◽

Ramin Rezaee ◽

...

Keyword(s):

Drug Resistance ◽

Medical Students ◽

Side Effects ◽

Drug Information ◽

Significant Risk ◽

Disease Recurrence ◽

Medical Sciences ◽

Self Medication ◽

Attitude And Practice ◽

Knowledge Attitude And Practice

Abstract Background Self-medication is defined as using medicinal products to treat the disorders or symptoms diagnosed by oneself. Although informed self-medication is one of the ways to reduce health care costs, inappropriate self-treatment can pose various risks including drug side effects, recurrence of symptoms, drug resistance, etc. The purpose of this study was to investigate the knowledge, attitude, and practice of pharmacy and medical students toward self-medication. Methods This study was conducted in Zabol University of Medical Sciences in 2018. Overall, 170 pharmacy and medical students were included. A three-part researcher-made questionnaire was designed to address the students’ knowledge, attitude, and practice. Statistical analysis was performed in SPSS 25 software. Results According to the results, 97 (57.1%) students had carried out self-medication within the past 6 months. Overall, the students self-medicated on average 4.2 ± 2.9 times per year. Self-medication was more common in male students (65.4%, P = 0.043). Cold was the most common ailment treated with self-medication (93.2%), and antibiotics (74.4%) were the most commonly used drugs. The primary information sources used by the students were their previous prescriptions (47.4%). Pharmacy students had a higher level of drug information (P < 0.001). There was a statistically significant association between the level of drug information and the tendency for self-medication (P = 0.005). Disease recurrence was the most common negative complication of self-medication. Conclusion There is a need to educate pharmacy and medical students regarding self-medication and its side effects. The high prevalence of self-medication and the overuse of antibiotics can pose a significant risk of drug resistance.

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Design and synthesis of periodic mesoporous organosilica materials with a multi-compartment structure

RSC Advances ◽

10.1039/c5ra16497d ◽

2015 ◽

Vol 5 (109) ◽

pp. 89397-89406 ◽

Cited By ~ 1

Author(s):

Chun Xiang Cynthia Lin ◽

Siddharth Jambhrunkar ◽

Pei Yuan ◽

Chun Hui Clayton Zhou ◽

George Xiu Song Zhao

Keyword(s):

Anticancer Drug ◽

Release Rate ◽

Slow Release ◽

Drug Carrier ◽

High Loading ◽

Loading Capacity ◽

Periodic Mesoporous Organosilica ◽

Design And Synthesis ◽

Mesoporous Organosilica ◽

Organosilica Materials

Multi-compartment periodic mesoporous organosilica materials show desirable properties as anticancer drug carrier with high loading capacity and slow release rate.

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Cellular uptake of drug loaded spider silk particles

Biomaterials Science ◽

10.1039/c6bm00435k ◽

2016 ◽

Vol 4 (10) ◽

pp. 1515-1523 ◽

Cited By ~ 13

Author(s):

Martina B. Schierling ◽

Elena Doblhofer ◽

Thomas Scheibel

Keyword(s):

Drug Resistance ◽

Side Effects ◽

Cellular Uptake ◽

Spider Silk ◽

Medical Therapies

Medical therapies are often accompanied by not-wanted side-effects or, even worse, targeted cells can develop drug resistance leading to an ineffective treatment. Here, it was shown that drugs can be efficiently delivered into and released within cells when spider silk particles were used as a carrier.

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Cathepsin L inhibition suppresses drug resistance in vitro and in vivo: a putative mechanism

AJP Cell Physiology ◽

10.1152/ajpcell.00082.2008 ◽

2009 ◽

Vol 296 (1) ◽

pp. C65-C74 ◽

Cited By ~ 35

Author(s):

Xin Zheng ◽

Fei Chu ◽

Pauline M. Chou ◽

Christine Gallati ◽

Usawadee Dier ◽

...

Keyword(s):

Drug Resistance ◽

Cancer Cell ◽

Trichostatin A ◽

Cathepsin L ◽

Active Form ◽

Cancer Resistance ◽

Protease Inhibition ◽

Resistance To Chemotherapy

Cathepsin L is a lysosomal enzyme thought to play a key role in malignant transformation. Recent work from our laboratory has demonstrated that this enzyme may also regulate cancer cell resistance to chemotherapy. The present study was undertaken to define the relevance of targeting cathepsin L in the suppression of drug resistance in vitro and in vivo and also to understand the mechanism(s) of its action. In vitro experiments indicated that cancer cell adaptation to increased amounts of doxorubicin over time was prevented in the presence of a cathepsin L inhibitor, suggesting that inhibition of this enzyme not only reverses but also prevents the development of drug resistance. The combination of the cathepsin L inhibitor with doxorubicin also strongly suppressed the proliferation of drug-resistant tumors in nude mice. An investigation of the underlying mechanism(s) led to the finding that the active form of this enzyme shuttles between the cytoplasm and nucleus. As a result, its inhibition stabilizes and enhances the availability of cytoplasmic and nuclear protein drug targets including estrogen receptor-α, Bcr-Abl, topoisomerase-IIα, histone deacetylase 1, and the androgen receptor. In support of this, the cellular response to doxorubicin, tamoxifen, imatinib, trichostatin A, and flutamide increased in the presence of the cathepsin L inhibitor. Together, these findings provided evidence for the potential role of cathepsin L as a target to suppress cancer resistance to chemotherapy and uncovered a novel mechanism by which protease inhibition-mediated drug target stabilization may enhance cellular visibility and, thus, susceptibility to anticancer agents.

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LASER 532-NM ND:YAG PICOSECOND IN TREATMENT OF SOLAR LENTIGO AND EPHELIDES

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2020.5.10 ◽

2020 ◽

pp. 72-77

Author(s):

Ha Bui Manh ◽

Thanh Le Thai Van

Keyword(s):

Side Effects ◽

Key Words ◽

Descriptive Study ◽

Patient Evaluation ◽

High Efficacy ◽

Mild Pain ◽

Solar Lentigo ◽

Pre Treatment ◽

532 Nm

Aims: To evaluate the efficacy, side effects of laser 532-nm Nd:YAG picosecond in treating solar lentigo and ephelides at HCMC hospital of dermato-venereology. Objectives and Method: Prospective - descriptive study. There were 43 patients dealing with solar lentigo and ephelides treated with laser 532-nm Nd:YAG picosecond. Each patient went through 3 treatments with one month interval, three months follow up for delayed side effects and recurrent. Evaluating the treatment by MI, VLCS, self-patient evaluation with 5 grades scale. Evaluating side effects of the treatment by 5 grade Wong-Baker scale. Collected data were analysed with SPSS.20.0. Results: Based on MI at the end of the study, the effectiveness of the treatment gained 81.4% good, 16.3% average and 2.3% bad. Self-patient evaluation revealed 76.7% good, 20.9% average and 2.3% bad. VLCS of post-treatment reduced 7.44 ± 2.14 unit compares with of pre-treatment. Recently after treatment, 100% patients had erythema and mild pain in 5 grade Wong-Baker scale, 20.9% had mild edema, 2.3% had post imflammatory hyperpigmentation (PIH). Two ephelides cases recurred 3 months after treatment (4.6%). Conclusions: Laser 523-nm Nd:YAG picosecond has high efficacy and less side effects in treating solar lentigo and ephelides. Key words: solar lentigo, ephelides, laser 532-nm Nd:YAG picosecond

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Exploiting vulnerabilities in cancer signalling networks to combat targeted therapy resistance

Essays in Biochemistry ◽

10.1042/ebc20180016 ◽

2018 ◽

Vol 62 (4) ◽

pp. 583-593 ◽

Cited By ~ 9

Author(s):

Peter T. Harrison ◽

Paul H. Huang

Keyword(s):

Drug Resistance ◽

Targeted Therapy ◽

Kinase Inhibitors ◽

Effective Means ◽

Deep Understanding ◽

Therapy Resistance ◽

Resistance Mechanisms ◽

Precision Oncology ◽

First Line ◽

Clinical Responses

Drug resistance remains one of the greatest challenges facing precision oncology today. Despite the vast array of resistance mechanisms that cancer cells employ to subvert the effects of targeted therapy, a deep understanding of cancer signalling networks has led to the development of novel strategies to tackle resistance both in the first-line and salvage therapy settings. In this review, we provide a brief overview of the major classes of resistance mechanisms to targeted therapy, including signalling reprogramming and tumour evolution; our discussion also focuses on the use of different forms of polytherapies (such as inhibitor combinations, multi-target kinase inhibitors and HSP90 inhibitors) as a means of combating resistance. The promise and challenges facing each of these polytherapies are elaborated with a perspective on how to effectively deploy such therapies in patients. We highlight efforts to harness computational approaches to predict effective polytherapies and the emerging view that exceptional responders may hold the key to better understanding drug resistance. This review underscores the importance of polytherapies as an effective means of targeting resistance signalling networks and achieving durable clinical responses in the era of personalised cancer medicine.

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