scholarly journals Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation

2015 ◽  
Vol 138 (5) ◽  
pp. 1049-1057 ◽  
Author(s):  
Alejandra Martinez de Pinillos Bayona ◽  
Caroline M. Moore ◽  
Marilena Loizidou ◽  
Alexander J. MacRobert ◽  
Josephine H. Woodhams
2005 ◽  
Vol 10 (7) ◽  
pp. 705-714 ◽  
Author(s):  
P. Bartholomä ◽  
Impidjati ◽  
A. Reininger-Mack ◽  
Zhihong Zhang ◽  
H. Thielecke ◽  
...  

One major problem in cancer therapy is the immortality of tumor cells showing an active telomerase, which is responsible for the elongation of the telomeres after each cellular division and the knocking down of apoptotic suppressors. A further phenomenon occurring during cancer therapies is the problem of multicellular resistance. To develop therapeutic anticancer approaches inducing cellular apoptosis, gene-modified biological in vitro systems were established and evaluated for drug screening in a capillary system for a real-time, impedimertic monitoring. Multicellular spheroids of the human breast cancer cell line T-47D clone 11 were transfected with 1) antisense caspase-3 cDNA expression vectors for knocking down the main cell death molecule and 2) sense Bcl-xl cDNA expression vectors for overexpressing the apoptotic suppressor, resulting in more aggressive tumor models. These gene-modified tumor spheroids less sensitive for apoptosis were developed for screening drugs such as methotrexate in tumor spheroid–based biosensor systems via impedance spectroscopy. In this report, it is demonstrated that this could successfully exhibit that this real-time monitoring system with tumor spheroids positioned in a capillary system with a 4-electrode configuration is the most efficient high-content screening module for impedimetric measurements of physiological alterations during gene modification and drug application.


2021 ◽  
Vol 90 ◽  
Author(s):  
Dmitry Alexandrovich Guk ◽  
Olga Olegovna Krasnovskaya ◽  
Elena Kimovna Beloglazkina

2016 ◽  
Vol 52 (18) ◽  
pp. 3631-3634 ◽  
Author(s):  
Ying Tang ◽  
Zhan Wu ◽  
Chong-Hua Zhang ◽  
Xiao-Li Zhang ◽  
Jian-Hui Jiang

An activatable theranostic approach based on self-assembled peptide nanostructures with surface-displayed activatable cytotoxic agents for targeted cancer therapy was developed.


2014 ◽  
Vol 32 (26) ◽  
pp. 2871-2878 ◽  
Author(s):  
Amato J. Giaccia

Traditional cytotoxic agents used in cancer therapy were initially discovered based on their ability to kill rapidly dividing cells. The targets of these early-generation agents were typically one or more aspects of DNA synthesis or mitosis. Thus, dose-limiting toxicities commonly associated with these agents include GI dysfunction, immunosuppression, and other consequences of injury to normal tissues in which cells are replicating under normal physiologic conditions. Although many of these agents still play an important role in cancer therapy when given concurrently with radiation therapy, the major thrust of radiobiology research in the last two decades has focused on discovering tumor-specific traits that might be exploited for more selective targeting that would enhance the efficacy of radiotherapy with less normal tissue toxicity. These newer generation molecular targeted therapies interfere with the growth of tumor cells by inhibiting genes and their protein products that are needed specifically by the tumor for survival and expansion. These agents can be complementary to radiotherapy, a spatially targeted agent. Although there have been extraordinary technical advances in radiotherapy in recent years, we are reaching the limits of improvements that radiotherapy delivery technology can bring and need different approaches. This review will highlight promising new tumor biology–based targets and other novel strategies to reduce normal tissue injury, increase tumor control, and expand the use of radiotherapy to treat widespread metastatic disease.


2019 ◽  
Vol 24 (36) ◽  
pp. 4270-4311 ◽  
Author(s):  
Célia Faustino ◽  
Ana P. Francisco ◽  
Vera M. S. Isca ◽  
Noélia Duarte

The growing incidence of cancer, the toxic side-effects associated with conventional chemotherapeutic agents and the development of multidrug resistance (MDR) drive the search for novel and more effective drugs with multi-target activity and selectivity towards cancer cells. Stilbenes are a group of naturally occurring phenolic compounds of plant origin derived from the phenylpropanoid pathway that may exist as cis- or trans-isomers. Although the trans-isomer is the more common and stable configuration, resveratrol being a representative compound, cis-stilbenes are potent cytotoxic agents that bind to and inhibit tubulin polymerization, destabilizing microtubules. This review summarizes the chemistry and biological evaluation of cytotoxic stilbenes and their synthetic derivatives as promising antimitotic leads for cancer therapy, focusing on the most potent compounds, the combretastatins. Combretastatins isolated from the South African bushwillow Combretum caffrum are among the most potent antimitotic and vascular disrupting agents (VDAs) of natural origin. Preclinical studies have demonstrated their potent antitumor effects in a wide variety of tumors, both in vitro and in vivo, being currently under evaluation in phase 2 and phase 3 clinical trials for several types of solid tumors. Topics covered herein include synthetic medicinal chemistry, modes of action, structure-activity relationships (SAR), preclinical and clinical studies as VDAs in cancer therapy, either as single agents or in combination with cytotoxic anticancer drugs, antiangiogenic agents, or radiation therapy, and development of appropriate formulations based on nanocarriers (e.g., liposomes, nanoemulsions, polymeric, lipid and ceramic nanoparticles, carbon nanotubes) for improved bioavailability and targeted delivery of combretastatins to the tumor vasculature.


In this chapter, cytotoxic chemotherapy is clearly defined as being distinct from targeted immunotherapy. The effect of chemotherapy on the cell cycle is summarized, as well as how different cytotoxic agents can be classified according to their action on the cell. The basic principles of combination chemotherapy regimes are laid out. The use of chemotherapy in curative, palliative, adjuvant, and neo-adjuvant settings is discussed, alongside how chemotherapy can be combined with other treatment modalities. Safe handling and the principles of administration of cytotoxic agents are covered here, as well as the differing routes of administration. There is a discussion of the differing challenges posed by using oral chemotherapy, and there is a section on recognizing and treating extravasation. The chapter concludes by introducing the main types of newer targeted therapies and how they differ in their action, both from each other and also from cytotoxic chemotherapy.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Katrin Sak

Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way.


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