Systematic Review of Toxicity Profiles on Nano-TiO2 for Cancer Therapy

@#Introduction: With the increasing clinical use of titanium dioxide nanoparticles (nano-TiO2), a better understanding of their safety in the human use is critical. The present study aims to review the potential application of nano-TiO2 as targeted cancer therapy based on their toxicity risk which highly dependent on their physio-chemical properties. Methods: This review was performed based on PRISMA-P protocol that begin with literature searching on the selected databases; PubMed, Springer Link, Science Direct and general search engine; Google Scholar from 2013 to 2018. Studies retrieved by the pre-determined keywords (titanium dioxide nanoparticles, toxicity, genotoxicity, cytotoxicity, targeted cancer therapy) that assessed toxicity risk of nano-TiO2 in cancer therapeutics were included. Results: The search retrieved 252 articles. Assessment of eligibility by application of inclusion criteria yielded 14 articles. Nano-TiO2 induced cytotoxicity and genotoxicity in dose and time-dependent manner killing the cancerous cells. All studies used primary particles size < 100 nm with mean of 39.38 and standard deviation of 30.47 which is lower than the mean denoting diameter distribution from selected studies are concentrated from the mean. Conclusion: This review suggest that TiO2 nanoparticles can be considered as an ideal candidate for drug-delivery vehicle for targeted cancer therapy by specifically tailored their physio-chemical properties of this nanoparticles according to desired target site and functions to ensure its optimal efficacy.

The Use of Normal Stem Cells and Cancer Stem Cells for Potential Anti-Cancer Therapeutic Strategy

BACKGROUND: Despite recent advance in conventional cancer therapies including surgery, radiotherapy, chemotherapy, and immunotherapy to reduce tumor size, unfortunately cancer mortality and metastatic cancer incidence remain high. Along with a deeper understanding of stem cell biology, cancer stem cell (CSC) is important in targeted cancer therapy. Herein, we review representative patents using not only normal stem cells as therapeutics themselves or delivery vehicles, but also CSCs as targets for anti-cancer strategy. METHODS: Relevant patent literatures published between 2005 and 2017 are discussed to present developmental status and experimental results on using normal stem cells and CSCs for cancer therapy and explore potential future directions in this field. RESULTS: Stem cells have been considered as important element of regenerative therapy by promoting tissue regeneration. Particularly, there is a growing trend to use stem cells as a target drug-delivery system to reduce undesirable side effects in non-target tissues. Noteworthy, studies on CSC-specific markers for distinguishing CSCs from normal stem cells and mature cancer cells have been conducted as a selective anti-cancer therapy with few side effects. Many researchers have also reported the development of various substances with anticancer effects by targeting CSCs from cancer tissues. CONCLUSION: There has been a continuing increase in the number of studies on therapeutic stem cells and CSC-specific markers for selective diagnosis and therapy of cancer. This review focuses on the current status in the use of normal stem cells and CSCs for targeted cancer therapy. Future direction is also proposed.

Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy

Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention. p38 is a unique MAPK family member that contains a PDZ motif at its C-terminus and interacts with a PDZ domain-containing protein tyrosine phosphatase PTPH1. This PDZ-coupled binding is required for both PTPH1 dephosphorylation and inactivation of p38 and for p38 phosphorylation and activation of PTPH1. Moreover, the p38/PTPH1 complex can further regulate their substrates phosphorylation and dephosphorylation, which impacts Ras transformation, malignant growth and progression, and therapeutic response. This review will use the p38/PTPH1 signaling network as an example to discuss the potential of targeting the kinase/phosphatase signaling complex for development of novel targeted cancer therapy.

Research Progress of Aptamer-Functionalized Agents for Targeted Cancer Therapy / 中国药学杂志

Ideal preparation of cancer therapy could specifically target to tumor cells, serving as safe and effective drug delivery system. With peculiar molecular recognition ability, aptamers become the most promising biological target molecules. This review was based on representative literatures, and the data was summarized and analyzed. It summarizes the latest research progress of aptamers modified targeted tumor preparation in the past five years from tethered way and carriers type, and the existing problems are analyzed and prospected.

Terapias moleculares dirigidas en los pacientes con cáncer: logros y perspectivas / Molecular therapeutics in patients with cancer unresponsive to conventional treatments

Los avances recientes en la patogénesis molecular del cáncer han permitido descubrir y desarrollar estrategias basadas en la utilización de moléculas con actividad biológica específicas o terapias moleculares dirigidas (TMD). El cáncer es un proceso complejo debido a la acumulación de mutaciones y alteraciones en el genoma. Las células tumorales parecen depender de una continua desregulación de una o varias vías de señalamiento intracelular. El conocimiento integral de estas vías logrará descifrar la biología de trasfondo de la mayoría de los cánceres. Las tecnologías de punta en genómica y proteómica pueden ayudar a identificar la respuesta in vitro e in vivo del intervensionismo de las TMD, las cuales comprenden agentes que bloqueando los oncogenes o las vías oncogénicas de señalamientos, pueden secundariamente detener la carcinogénesis y la progresión tumoral. Revisamos los conceptos de adicción oncogénica, de rúbrica de la vía oncogénica, algunas tecnologías, los resultados obtenidos con TMD en pacientes con cáncer que no responde a tratamiento convencional, y las limitaciones y perspectivas de esta nueva estrategia. Potencialmente, la TMD conseguirá mayor desarrollo a través de identificar un número progresivo de oncogenes blanco-moleculares y sus correspondientes agentes bloqueadores. Se requiere mejorar los criterios de diseño, ejecución y valoración clínicos en la aplicación de protocolos con terapias moleculares dirigidas.

Recent advances and insights into the molecular pathogenesis of cancer provide unprecedented opportunities for discovery and development of molecularly target-therapeutic (MTT) strategies. Cancer is a complex process due to accumulation of multiple mutations and alterations in the genoma. Tumor cells seem to rely heavily on the continued deregulation of one or more signaling pathways. Complete identification on cell signaling deregulations have provided greater understanding on the biology that underlies most cancers. High-throughput technologies in genomics and proteomics can help to detect the response in vitro and in vivo of targeted MTT effects. Cancer MTT are drugs blocking specific oncogenes or oncogenic signaling pathways and can secondary block off the growth and spreading involved in carcinogenesis and tumor progression. In this paper we revised concepts of oncogene addiction, oncogenic pathways signature and commented the high-tech technologies related to their study. Also we revised the favorable clinical results using new MTT strategies for hard-to-treat cancers in the last year, and the limitations and perspectives to achieve more effective targeted cancer therapy results. Identification of a progressive number of molecularly targeted oncogenes and their corresponding blocking agents will give cancer MTT strategies great potential for development in the next years. Novel biologic endpoints and innovative clinical designs are also required to the successful application of the therapies.

Hyperthermic Cancer Therapy and Its Mechanism / 日本補完代替医療学会誌

We have reported that heat as well as X-rays induced <i>p53</i>-centred signal transduction. The p53 molecule determines the fate of cells, especially apoptosis. Wild-type (wt) <i>p53 </i>cells are resistant to heat as compared with the mutated-type (m) <i>p53 </i>cells. Apoptosis is efficiently induced in the wt<i>p53</i> cells by heat through the activation of Bax and Caspase-3, not but m<i>p53</i> cells. Therefore, we proposed that wt<i>p53</i> patients would be more suitable for hyperthermic therapy than m<i>p53</i> patients. To enhance apoptosis in m<i>p53</i> cells, however, we succeeded the establishing new cancer therapies against m<i>p53</i> cells using chemical chaperon therapy with glycerol and peptide therapy with p53 C-terminal peptide. In addition, we applied siRNA or gene therapy with <i>p53</i>-targeted genes to m<i>p53</i> and <i>p53</i>-deficient cells. It is our hope to show that these new therapies prove more effective as cancer therapies as soon as possible.<br>

RNA interference mediated inhibition of epidermal growth factor receptor expression and its significance in different human cancer cell lines / 中国癌症杂志

Background and purpose:The epidermal growth factor receptor (EGFR) is commonly overexpressed in a variety of solid tumors, and has important roles in cancer pathogenesis and progression. EGFR thus provides a rational target for cancer therapy. We studied siRNA-mediated inhibition of epidermal growth factor receptor expression and its biologic effects in different human cancer cell lines (A431, HeLa and SPC-A-1). Methods:Cells were transfected with chemically synthesized siRNA-EGFR. EGFR mRNA was quantified by real-time PCR and was detected by immunofluorescence staining and flow cytometry. The biologic effects on cell growth were assessed by colony-formation assay.Results:siRNA-EGFR significantly decreased mRNA level of EGFR by 73.9 %, 44.6 % and 57.7 %, protein expression of EGFR by 77.0 %, 61.3 % and 65.2 %, and reduced colony number by 27.2 %, 53.9 % and 59.1 % in A431, HeLa and SPC-A-1, respectively.Conclusions:Our data suggested that RNA interference could downregulate EGFR and inhibit colony forming ability and EGFR expression at mRNA/protein levels in human cancer cell lines with different pathological types. siRNA could be one of the promising strategies in future targeted cancer therapy.