People exposed to ionizing radiation (IR) both for diagnostic and therapeutic purposes is constantly increasing. Since the use of IR involves a risk of harmful effects, such as the DNA DSB induction, an accurate determination of this induced DNA damage and a correct evaluation of the risk–benefit ratio in the clinical field are of key relevance. γH2AX (the phosphorylated form of the histone variant H2AX) is a very early marker of DSBs that can be induced both in physiological conditions, such as in the absence of specific external agents, and by external factors such as smoking, heat, background environmental radiation, and drugs. All these internal and external conditions result in a basal level of γH2AX which must be considered for the correct assessment of the DSBs after IR exposure. In this review we analyze the most common conditions that induce H2AX phosphorylation, including specific exogenous stimuli, cellular states, basic environmental factors, and lifestyles. Moreover, we discuss the most widely used methods for γH2AX determination and describe the principal applications of γH2AX scoring, paying particular attention to clinical studies. This knowledge will help us optimize the use of available methods in order to discern the specific γH2AX following IR-induced DSBs from the basal level of γH2AX in the cells.
Precision medicine has driven a major change in the treatment of many forms of cancer. The discovery that each patient is different and each tumor mass has its own characteristics has shifted the focus of basic and clinical research to the singular individual. Liquid biopsy (LB), in this sense, presents new scenarios in personalized medicine through the study of molecules, factors, and tumor biomarkers in blood such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes and circulating tumor microRNAs (ct-miRNAs). Moreover, its easy application and complete absence of contraindications for the patient make this method applicable in a great many fields. Melanoma, given its highly heterogeneous characteristics, is a cancer form that could significantly benefit from the information linked to liquid biopsy, especially in the treatment management. In this review, we will focus our attention on the latest applications of liquid biopsy in metastatic melanoma and possible developments in the clinical setting.
Artificial intelligence (AI), a field of research in which computers are applied to mimic humans, is continuously expanding and influencing many aspects of our lives. From electric cars to search motors, AI helps us manage our daily lives by simplifying functions and activities that would be more complex otherwise. Even in the medical field, and specifically in oncology, many studies in recent years have highlighted the possible helping role that AI could play in clinical and therapeutic patient management. In specific contexts, clinical decisions are supported by “intelligent” machines and the development of specific softwares that assist the specialist in the management of the oncology patient. Melanoma, a highly heterogeneous disease influenced by several genetic and environmental factors, to date is still difficult to manage clinically in its advanced stages. Therapies often fail, due to the establishment of intrinsic or secondary resistance, making clinical decisions complex. In this sense, although much work still needs to be conducted, numerous evidence shows that AI (through the processing of large available data) could positively influence the management of the patient with advanced melanoma, helping the clinician in the most favorable therapeutic choice and avoiding unnecessary treatments that are sure to fail. In this review, the most recent applications of AI in melanoma will be described, focusing especially on the possible finding of this field in the management of drug treatments.
In recent years, medicine has undergone profound changes, strongly entering a new phase defined as the “era of precision medicine”. In this context, patient clinical management involves various scientific approaches that allow for a comprehensive pathology evaluation: from preventive processes (where applicable) to genetic and diagnostic studies. In this scenario, biobanks play an important role and, over the years, have gained increasing prestige, moving from small deposits to large collections of samples of various natures. Disease-oriented biobanks are rapidly developing as they provide useful information for the management of complex diseases, such as melanoma. Indeed, melanoma, given its highly heterogeneous characteristics, is one of the oncologic diseases with the greatest clinical and therapeutic management complexity. So, the possibility of extrapolating tissue, genetic and imaging data from dedicated biobanks could result in more selective study approaches. In this review, we specifically analyze the several biobank types to evaluate their role in technology development, patient monitoring and research of new biomarkers, especially in the melanoma context.
Over the last few decades, the need to reduce and optimize patient medical radiation exposure has prompted the introduction of novel reconstruction algorithms in computed tomography (CT). Against this backdrop, the present study aimed to assess whether reduced radiation dose CT images reconstructed with the new-generation adaptive statistical iterative reconstruction (ASiR-V) maintain the same image quality as that of routine image reconstruction. In addition, the optimization of image quality parameters for the ASiR-V algorithm (e.g., an optimal combination of blending percentage and noise index (NI)) was investigated. An abdominal reference phantom was imaged using the routine clinical protocol (fixed noise index of 18 and 40% ASiR reconstruction). Reduced radiation dose CT scans were performed with varying NI (22, 24, and 30) and using the ASiR-V reconstruction algorithm. Quantitative and qualitative analyses of image noise, contrast, and resolution were performed against NI and reconstruction blending percentages. Our results confirm the ability of the ASiR-V algorithm to provide images of high diagnostic quality while reducing the patient dose. All the parameters were improved in ASiR-V images as compared to ASiR. Both quantitative and qualitative analyses showed that the best agreement was obtained for the images reconstructed using ASiR-V with NI24 and a high percentage of blending (70–100%). This preliminary study results show that ASiR-V allows for a significant reduction in patient dose (about 40%) while maintaining a good overall image quality when appropriate NI (i.e., 24) is used.
Recurrent computed tomography (CT) examination has become a common diagnostic procedure for several diseases and injuries. Though each singular CT scan exposes individuals at low doses of low linear energy transfer (LET) radiation, the cumulative dose received from recurrent CT scans poses an increasing concern for potential health risks. Here, we evaluated the biological effects of recurrent CT scans on the DNA damage response (DDR) in human fibroblasts and retinal pigment epithelial cells maintained in culture for five months and subjected to four CT scans, one every four weeks. DDR kinetics and eventual accumulation of persistent-radiation-induced foci (P-RIF) were assessed by combined immunofluorescence for γH2AX and 53BP1, i.e., γH2AX/53BP1 foci. We found that CT scan repetitions significantly increased both the number and size of γH2AX/53BP1 foci. In particular, after the third CT scan, we observed the appearance of giant foci that might result from the overlapping of individual small foci and that do not associate with irreversible growth arrest, as shown by DNA replication in the foci-carrying cells. Whether these giant foci represent coalescence of unrepaired DNA damage as reported following single exposition to high doses of high LET radiation is still unclear. However, morphologically, these giant foci resemble the recently described compartmentalization of damaged DNA that should facilitate the repair of DNA double-strand breaks but also increase the risk of chromosomal translocations. Overall, these results indicate that for a correct evaluation of the damage following recurrent CT examinations, it is necessary to consider the size and composition of the foci in addition to their number.