DNA Damage Induced by Ultrasound and Cellular Responses

Ultrasonic technologies pervade the medical field as a long established imaging modality in clinical diagnostics and, with the emergence of targetedhigh-intensity focused ultrasound, as a means of thermally ablating tumors.

Ultrasound (US) causes multiple thermal and non-thermal effects, such as mechanical and chemical stresses, that can result in damage to the cellular membrane and nucleus, leading to transient membrane pores, alterations in gene expression, and cell death, including apoptosis. On the basis of its biological effects US has been proposed as a new drug delivery and molecular targeting tool for cancer therapy. However, the molecular mechanisms involved in US induced cell killing are not yet fully understood. Recently, we have reported that the mechanical effects of US elicit DNA single strand as well as double strand breaking- the most cytotoxic form of DNA damage, which initiates subsequent DNA damage response associated with DNA repair, cell cycle arrest, and cell death. Here in the present study we have focused on one of the most significant biological effects of US, i.e., DNA damage and discussed the underlying mechanisms and a unique cellular response. Read more>>>>>>>>>

A Forecast of Targeting Leukemia Stem Cells by Nanomedicine

Cancer Stem Cells (CSCs) are a subset of cancer cells with self-renewal, differentiation and tumor-initiating properties. They are considered as the leading cause of tumor initiation, promotion, and relapse in most types ofcancers.

Nanomedicine

The first experimental evidence for CSCs was given by Bonnet and Dick in 1997. They found that single CD34+CD38– Acute Myeloid Leukemia (AML) cell was able to initiate AML in NOD-SCID mice. Furthermore, this small subset population was found to be responsible for chemotherapy and radiotherapy resistance because CSCs have enhanced DNA repair ability, enriched anti-apoptotic proteins, improved drug efflux transporters, and are protected in specific microenvironment or niche. Therefore, these leukemia initiating cells (LIC) or leukemia Stem Cells (LSCs) are considered as a critical target for leukemia therapy. Subsequently, CSCs in solid tumors have been identified from brain, prostate, breast, colon, and pancreas cancer. Traditional cancer treatments, such as Chemotherapy and Radiotherapy, are cytotoxic to both normal and cancerous cells, which cause severe side effects, like bone marrow suppression, cardiomyopathy, and neurotoxicity. Read more>>>>>>>>