Background: Cancer is the most prevalent cause of death globally, and radiotherapy is considered the standard of care for most solid tumors, including lung, breast, esophageal, and colorectal cancers and glioblastoma. Resistance to radiation can lead to local treatment failure and even cancer recurrence. Main body: In this review, we have extensively discussed several crucial aspects that cause resistance of cancer to radiation therapy, including radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance of cancer stem cells, modification of cancer cells and their microenvironment, presence of exosomal and non-coding RNA, metabolic reprogramming, and ferroptosis. We aim to focus on the molecular mechanisms of cancer radiotherapy resistance in relation to these aspects and to discuss possible targets to improve treatment outcomes. Conclusions: Studying the molecular mechanisms responsible for radiotherapy resistance and its interactions with the tumor environment will help improve cancer responses to radiotherapy. Our review provides a foundation to identify and overcome the obstacles to effective radiotherapy.
7 January 2023 in Journal of Pharmaceutical Analysis
Neutrophil elastase (NE), a major protease in the primary granules of neutrophils, is involved in microbicidal activity. NE is an important factor promoting inflammation, has bactericidal effects, and shortens the inflammatory process. NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling. However, NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction. Additionally, it plays a complex role in various physiological processes and mediates several diseases. Sivelestat, a specific NE inhibitor, has strong potential for clinical application, particularly in the treatment of coronavirus disease 2019 (COVID-19). This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
The popularity of health concepts and the wave of digitalization have driven the innovation of sensors in the medical field. Such continual development has made sensors progress in the direction of safety, flexibility, and intelligence for continuous monitoring of vital signs, which holds considerable promise for changing the way humans live and even treat diseases. To this end, flexible wearable devices with high performance, such as high sensitivity, high stability, and excellent biodegradability, have attracted strong interest from scientists. Herein, a review of flexible wearable sensors for temperature, heart rate, human motion, respiratory rate, glucose, and pH is highlighted. In addition, engineering issues are also presented, focusing on material selection, sensor fabrication, and power supply. Finally, potential challenges facing current technology and future directions of wearable sensors are also discussed.
Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1α. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications.
The tumour microenvironment is the “hotbed” of tumour cells, providing abundant extracellular support for growth and metastasis. However, the tumour microenvironment is not static and is constantly remodelled by a variety of cellular components, including tumour cells, through mechanical, biological and chemical means to promote metastasis. Focal adhesion plays an important role in cell-extracellular matrix adhesion. An in-depth exploration of the role of focal adhesion in tumour metastasis, especially their contribution at the biomechanical level, is an important direction of current research. In this review, we first summarize the assembly of focal adhesions and explore their kinetics in tumour cells. Then, we describe in detail the role of focal adhesion in various stages of tumour metastasis, especially its key functions in cell migration, invasion, and matrix remodelling. Finally, we describe the anti-tumour strategies targeting focal adhesion and the current progress in the development of some inhibitors against focal adhesion proteins. In this paper, we summarize for the first time that focal adhesion play a positive feedback role in pro-tumour metastatic matrix remodelling by summarizing the five processes of focal adhesion assembly in a multidimensional way. It is beneficial for researchers to have a deeper understanding of the role of focal adhesion in the biological behaviour of tumour metastasis and the potential of focal adhesion as a therapeutic target, providing new ideas for the prevention and treatment of metastases.
The combination of radiation therapy (radiotherapy) with immunotherapy is changing the landscape of cancer treatment. Radiation damage tumor cell DNA through high-energy rays directly causes cell death or growth arrest; Immunotherapy works by boosting a patient’s own immune system’s ability to recognize and destroy cancer cells. The combination of the two not only enhances the local control of the tumor, but may also activate the systemic anti-tumor immune response, transforming the “cold” tumor into a “hot” tumor, thereby improving the survival rate and quality of life of patients. In recent years, this combined treatment approach has shown remarkable efficacy in a variety of cancers, especially non-small cell lung cancer and melanoma, among others. However, how to optimize radiation dose, timing and combination with immunotherapy drugs remains the focus of research. This paper first discusses the effect of radiotherapy on immune system, then analyzes the killing effect of radiotherapy and its mechanism, and finally discusses the latest progress and challenges of the combined application of radiotherapy and immunotherapy. Each section aims to provide clinicians and researchers with an in-depth understanding with a view to optimizing treatment strategies and improving outcomes for cancer patients.