Ling Qi

Bio: Ling Qi is an academic researcher from Harbin Medical University. The author has contributed to research in topics: Pyroptosis & Cancer cell. The author has an hindex of 3, co-authored 7 publications receiving 46 citations.

The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer

Abstract: Apoptosis has long been recognized as a mechanism that kills the cancer cells by cytotoxic drugs. In recent years, studies have proved that pyroptosis can also shrink tumors and inhibit cells proliferation. Both apoptosis and pyroptosis are caspase-dependent programmed cell death pathways. Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death. When GSDME is highly expressed, the active caspase-3 cuts it and releases the N-terminal domain to punch holes in the cell membrane, resulting in cell swelling, rupture, and death. When the expression of GSDME is low, it will lead to the classical mechanism of tumor cell death, which is apoptosis. More interestingly, researchers have found that GSDME can also be located upstream of caspase-3, connecting extrinsic, and intrinsic apoptotic pathways. Then, promoting caspase-3 activation, and forming a self-amplifying feed-forward loop. GSDME-mediated pyroptosis is correlated with the side effects of chemotherapy and anti-tumor immunity. This article mainly reviews the caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer, to provide new strategies and targets for cancer treatment.

Pyroptosis, a new bridge to tumor immunity

Abstract: Pyroptosis refers to the process of gasdermin (GSDM)-mediated programmed cell death (PCD) and our understanding of pyroptosis has expanded beyond the cells and is known to involve extracellular responses. Recently, there has been an increasing interest in pyroptosis due to its emerging role in activating the immune system. In the meantime, pyroptosis-mediated therapies, which use the immune response to kill cancer cells, have also achieved notable success in a clinical setting. In this review, we discuss that the immune response induced by pyroptosis activation is a double-edged sword that affects all stages of tumorigenesis. On the one hand, the activation of inflammasome-mediated pyroptosis and the release of pyroptosis-produced cytokines alter the immune microenvironment and promote the development of tumors by evading immune surveillance. On the other hand, pyroptosis-produced cytokines can also collect immune cells and ignite the immune system to improve the efficiency of tumor immunotherapies. Pyroptosis is also closely with several immune checkpoints, especially programmed death-1 (PD-1) or programmed death- ligand 1 (PD-L1). In this review, we mainly focused on our current understanding of the interplay between the immune system and tumors that process through pyroptosis and debate about their use as potential therapeutic targets.

Caspase-8: A key protein of cross-talk signal way in "PANoptosis" in cancer.

Abstract: Cysteinyl aspartate specific proteinase (Caspase)-8 has long been considered a promoter of apoptosis and part of the mechanism by which cytotoxic drugs kill cancer cells. With the continuous exploration of the types of programmed cell death, an increasing number of studies have confirmed that caspase-8 plays an important role in cancer. Recently, scholars have proposed the term "PANoptosis," which mainly includes three programmed cell death modes, namely pyroptosis, apoptosis and necroptosis. In addition to mediating endogenous apoptotic pathways, caspase-8 can also participate in the cleavage of gasdermin (GSDM) family proteins to induce pyroptosis. Furthermore, the expression of enzymatically inactive caspase-8 (C362S) can cause embryonic lethality and inflammatory tissue destruction in mice by inducing necroptosis and pyroptosis. Therefore, the activation and deletion of caspase-8 enzyme activity, as well as the knockout of the coding gene, are closely related to "PANoptosis." In addition, caspase-8 can also improve the tumor microenvironment and enhance tumor antiimmunity. Studies have shown that caspase-8 is also associated with tumor growth and invasion, angiogenesis and metastasis, therapeutic resistance and poor clinical outcomes. Therefore, it is very important to measure the cancer-promoting and anticancer effects of caspase-8 and find a balance, and to study its role in the effect of "PANoptosis" in depth. This article reviews the role of caspase-8 in "PANoptosis" in cancer to provide new strategies and targets for cancer.

A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer.

Abstract: Ovarian cancer (OC) is a highly malignant gynaecological tumour that has a very poor prognosis. Pyroptosis has been demonstrated in recent years to be an inflammatory form of programmed cell death. However, the expression of pyroptosis-related genes in OC and their correlations with prognosis remain unclear. In this study, we identified 31 pyroptosis regulators that were differentially expressed between OC and normal ovarian tissues. Based on these differentially expressed genes (DEGs), all OC cases could be divided into two subtypes. The prognostic value of each pyroptosis-related gene for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 7-gene signature was built and classified all OC patients in the TCGA cohort into a low- or high-risk group. OC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Utilizing the median risk score from the TCGA cohort, OC patients from a Gene Expression Omnibus (GEO) cohort were divided into two risk subgroups, and the low-risk group had increased overall survival (OS) time (P = 0.014). Combined with the clinical characteristics, the risk score was found to be an independent factor for predicting the OS of OC patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched and that the immune status was decreased in the high-risk group. In conclusion, pyroptosis-related genes play important roles in tumour immunity and can be used to predict the prognosis of OCs.

The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer

Abstract: Apoptosis has long been recognized as a mechanism that kills the cancer cells by cytotoxic drugs. In recent years, studies have proved that pyroptosis can also shrink tumors and inhibit cells proliferation. Both apoptosis and pyroptosis are caspase-dependent programmed cell death pathways. Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death. When GSDME is highly expressed, the active caspase-3 cuts it and releases the N-terminal domain to punch holes in the cell membrane, resulting in cell swelling, rupture, and death. When the expression of GSDME is low, it will lead to the classical mechanism of tumor cell death, which is apoptosis. More interestingly, researchers have found that GSDME can also be located upstream of caspase-3, connecting extrinsic, and intrinsic apoptotic pathways. Then, promoting caspase-3 activation, and forming a self-amplifying feed-forward loop. GSDME-mediated pyroptosis is correlated with the side effects of chemotherapy and anti-tumor immunity. This article mainly reviews the caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer, to provide new strategies and targets for cancer treatment.

Photodynamic Therapy for the Treatment and Diagnosis of Cancer–A Review of the Current Clinical Status

Abstract: Photodynamic therapy (PDT) has been used as an anti-tumor treatment method for a long time and photosensitizers (PS) can be used in various types of tumors. Originally, light is an effective tool that has been used in the treatment of diseases for ages. The effects of combination of specific dyes with light illumination was demonstrated at the beginning of 20th century and novel PDT approaches have been developed ever since. Main strategies of current studies are to reduce off-target effects and improve pharmacokinetic properties. Given the high interest and vast literature about the topic, approval of PDT as the first drug/device combination by the FDA should come as no surprise. PDT consists of two stages of treatment, combining light energy with a PS in order to destruct tumor cells after activation by light. In general, PDT has fewer side effects and toxicity than chemotherapy and/or radiotherapy. In addition to the purpose of treatment, several types of PSs can be used for diagnostic purposes for tumors. Such approaches are called photodynamic diagnosis (PDD). In this Review, we provide a general overview of the clinical applications of PDT in cancer, including the diagnostic and therapeutic approaches. Assessment of PDT therapeutic efficacy in the clinic will be discussed, since identifying predictors to determine the response to treatment is crucial. In addition, examples of PDT in various types of tumors will be discussed. Furthermore, combination of PDT with other therapy modalities such as chemotherapy, radiotherapy, surgery and immunotherapy will be emphasized, since such approaches seem to be promising in terms of enhancing effectiveness against tumor. The combination of PDT with other treatments may yield better results than by single treatments. Moreover, the utilization of lower doses in a combination therapy setting may cause less side effects and better results than single therapy. A better understanding of the effectiveness of PDT in a combination setting in the clinic as well as the optimization of such complex multimodal treatments may expand the clinical applications of PDT.

Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment.

Abstract: In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.

Photodynamic Therapy—An Up-to-Date Review

Abstract: The healing power of light has attracted interest for thousands of years. Scientific discoveries and technological advancements in the field have eventually led to the emergence of photodynamic therapy, which soon became a promising approach in treating a broad range of diseases. Based on the interaction between light, molecular oxygen, and various photosensitizers, photodynamic therapy represents a non-invasive, non-toxic, repeatable procedure for tumor treatment, wound healing, and pathogens inactivation. However, classic photosensitizing compounds impose limitations on their clinical applications. Aiming to overcome these drawbacks, nanotechnology came as a solution for improving targeting efficiency, release control, and solubility of traditional photosensitizers. This paper proposes a comprehensive path, starting with the photodynamic therapy mechanism, evolution over the years, integration of nanotechnology, and ending with a detailed review of the most important applications of this therapeutic approach.