The interpretation and review of urothelial carcinoma, 2023 EMSO / 中华泌尿外科杂志

We present a summary of important research in the field of urothelial carcinoma presented at the 2023 European Society for Medical Oncology (ESMO) conference. A total of 53 studies related to urothelial carcinoma were reported, including 6 late-breaking abstract, 7 oral presentations, and 40 poster presentations. Several new treatment options were reported in the non-muscle invasive bladder cancer (NMIBC) field, providing more choices for bacillus Calmette-Guerin (BCG) failing patients. For perioperative systemic treatment of muscle-invasive bladder cancer (MIBC), studies further explored various adaptation of neoadjuvant therapy strategies. For metastatic urothelial carcinoma (mUC), the data on CheckMate-901 and EV-302 studies provided thoughts on first-line treatment options. These studies provide important guidance for clinical practice in the field of urothelial carcinoma.

The Oncolytic Virus Therapy for Non-Small Cell Lung Cancer / 中国生物化学与分子生物学报

Since the oncolytic herpes simplex virus T-VEC was approved in the United States for the treatment of malignant melanoma in 2015, there has been increasing interests in the oncolytic virus therapy. The oncolytic virus therapy also occupies a certain position in the treatment research process of non-small cell lung cancer(NSCLC). Based on the rapid development of genetic engineering and protein engineering, researchers have designed many recombinant oncolytic viruses targeting various specific sites to further improve their targeting and oncolytic effect in order to alleviate symptoms and even cure NSCLC patients. This review introduces the two major classifications of oncolytic viruses, wild type and gene-edited, and how they achieve tumor lysis by specifically targeting and killing tumor cells. We focus on the research progress of oncolytic virus applied alone to treat NSCLC, or combined with chemotherapy, immunotherapies such as chimeric antigen receptor (CAR)-T cell therapy, immune checkpoint inhibitors and other current hot research to treat NSCLC. At the same time, we summarize and discuss the issue of targeted transport, which is of high concern in the academic field of oncolytic virus therapy, and point out that the use of extracellular vesicles as drug carriers has a good potential for development. Finally, we analyze the existing problems and future application prospects in the context of existing basic and clinical studies, to expend new approaches for the treatment of NSCLC, so that it is no longer limited to traditional therapies.

Research Progress of Ferroptosis in Head and Neck Squamous Cell Carcinoma / 肿瘤防治研究

Squamous cell carcinoma of the head and neck (HNSCC) is one of the cancers with the highest incidence rate in the world. Due to the presence of postoperative recurrence and resistance to some chemotherapeutics after the surgery, the prognosis of advanced HNSCC patients is not optimistic. Therefore, it is urgent to improve the efficiency of chemotherapeutics for HNSCC and the prognosis of HNSCC patients. Recent studies have found that ferroptosis has regulatory effect on the growth and proliferation of some types of tumor cells, reducing drug resistance in tumor treatment to a certain extent, and showing great potential in the prevention and treatment of tumors. Therefore, this article will summarize the anti-tumor mechanism of ferroptosis and the current research progress in HNSCC, providing new evidence for the treatment of HNSCC.

Research progress of endoplasmic reticulum targeting drug delivery system for anti-tumor immunotherapy / 药学学报

Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.

Methionine Metabolism and Related Gene Expression Regulation in Cancers / 中国生物化学与分子生物学报

Methionine, an essential amino acid with a variety of physiological functions, plays an important role in the process of metabolic reprogramming of cancer cells. A large number of studies have found that there is dependence on exogenous methionine in different kinds of cancer cells, which is called the Hoffman effect. In vivo, methionine is metabolized through the methionine cycle, linking with the one carbon unit metabolism, folate cycle and the synthesis of many substances such as polyamine, glutathione, cysteine and nucleotide. Abnormity of methionine metabolism often occurs in tumors, accompanied by abnormal gene expression of methionine metabolism related enzymes, including methionine adenosyltransferase (MAT) and methylthioadenosine phosphorylase (MTAP). The abnormal expression of MAT and MTAP can lead to the abnormity of methionine cycle and the salvage pathway, resulting in the decrease of methyl donor S⁃adenosylmethionine (SAM) and the accumulation of methylthioadenosine (MTA) in cancer cells, which is associated with the genesis, progression and metastasis of tumors. Methionine restriction and target therapy derive from the changes of methionine metabolism and related gene expression separately. This review summarizes the changes of methionine⁃ dependent metabolism and the expression regulation of methionine metabolism related genes in cancer cells. Also, the new progress and difficulty in methionine⁃related cancer therapy is introduced. This review may provide new clues for the exploration of cancer therapy.

Targeting DNA damage response in tumor therapy / 中国临床药理学与治疗学

Chemotherapy plays an important role in cancer treatment. With deeply understanding the mechanism of tumorigenesis, different chemotherapeutic drugs have been emerged as initial choices for cancer treatment. However, most patients gradually develop to chemotherapeutic resistance, resulting in failure to initial standard therapy. The mechanisms of chemoresistance are extensively explored. Recent studies indicated intrinsic or acquired alteration of DNA damage repair ability is the key determinant of chemoresistance. In this review, we present deregulation of DNA damage repair pathway in cancers and its involvement contributing to chemoresistance. Furthermore, we discuss strategies to sensitize chemotherapy by targeting at a parallel DNA repair pathway, which become promising approaches to overcome chemotherapeutic resistance.

Advances in inorganic nanomaterials regulated autophagy in cancer treatment / 医学研究生学报

Autophagy represents one of the essential cellular mechanism to maintain homeostasis within cells, performing multiple biological functions during tumorigenesis. Base on the unique physicochemical properties of inorganic nanomaterials, supplemented by easy modification and targeting and so on, they could be used to regulate autophagy, controlling the occurrence and development of tumor and finally achieve treatment. This article primarily reviews the application of several representative inorganic nanomaterials, such as Gold nanoparticles, Silver nanoparticles, Iron oxide nanoparticles, Fullerene C60 nanomaterials, Graphene oxide nanomaterials in regulating autophagy of tumor cells and achieving treatment in recent years.

Cross-talk of GPCRs and RTKs and its effects on oncotherapy / 中国药理学通报

G protein-coupled receptors (GPCRs) are the largest cell surface receptor family, which mediates activities of almost all known cellular response to ligands, including hormones release, neurotransmitters and sensory input.GPCRs can promote development and progression of gastric cancer, colorectal cancer, lung cancer and breast cancer and other tumors.Tyrosine kinase receptors (RTKs) are another important family of membrane receptors, which can regulate cell proliferation, differentiation, migration and survival.Overexpression of RTKs has been found in many cancer cells.Therefore, GPCRs and RTKs are equally important in the clinical treatment of cancer therapeutic.However, GPCRs and RTKs are not independent, and they can use common signal transduction.The present study show that crosstalk between GPCRs and RTKs can facilitate migration of lung epithelial cells, increasing survival of nerve cells and promoting tumor occurrence and development.This article mainly focuses on crosstalk between GPCRs and RTKs and their roles in tumorigenesis and oncotherapy.

Development of new-type locating rod for radiotherapy / 医疗卫生装备

Objective To develop a new type of locating rod with easy installation and high reliability for radiotherapy.Methods The locating rod was composed of a joining beam,two clamping buckles and buckle holders.The joining beam had the length being 530+03 mm.One of the buckles was put at one end of the beam,and the other slided along a stool.An eccentric wheel drove the sliding buckle to determine the space between two buckles,and a returning spring was involved in to enhance the compliance of the sliding buckle.Results The rod gained easy installation and operation,and was compatible with the bed board with the width of 5300 mm.There was no sideslip occurred after locking the rod,and the sideslip shift was not more than 1 mm in case of 20 kgf (1 kgf=9.8 N) lateral traction.Conclnsion The rod has high performances and meets clinical requirements.

Roles of exosomes in tumor diagnosis and treatment / 上海交通大学学报（医学版）

Exosomes are nanosized membrane microvesicles secreted by various living cells.They contain proteins,lipids,RNA,and a variety of other biological macromolecules.Exosomes play an important role in many pathological and physiological processes,such as antigen presentation in the immune system,repair of damaged tissues,and growth and migration of tumors.Tumor-derived or tumor-associated exosomes play a vital role in regulating the occurrence and development of tumors.The analysis and detection of exosomes in tumors is helpful for the early diagnosis of tumors and provide new treatment methods.This article reviews exosomes' origin,composition,and functions in the development,migration,diagnosis,and treatment of tumors and provides new ideas for the treatment of tumors.

Recent progress of aptamer inhibitors targeting c-Met / 中国生化药物杂志

c-Met is one member of the receptor tyrosine kinases (RTKs).It is closely related between the over-expression of c-Met and a wide variety of tumor occurrence, development, invasion, metastasis, prognosis and drug resistance.Therefore, c-Met is a potential target for oncotherapy, and researches on its inhibitors have become a hot spot in the field of tumor treatment.Aptamers targeting c-Met are gained from systematic evolution of ligands by exponential enrichment (SELEX).They can bind to c-Met with high specificity and affinity, resulting in the activation or inhibition of c-Met.We envision that anti-c-Met aptamers would be ideal new c-Met inhibitors after optimization, and could be developed into potential targeted drugs for cancers.

Characterization and evaluation of apoptotic potential of double gene construct pVIVO.VP3.NS1.

Viral gene oncotherapy, targeted killing of cancer cells by viral genes, is an emerging non-infectious therapeutic cancer treatment modality. Chemo and radiotherapy in cancer treatment is limited due to their genotoxic side effects on healthy cells and need of functional p53, which is mutated in most of the cancers. VP3 (apoptin) of chicken infectious anaemia (CIA) and NS1 (Non structural protein 1) of Canine Parvovirus-2 (CPV-2) have been proven to have oncolytic potential in our laboratory. To evaluate oncolytic potential of VP3 and NS1 together these genes needed to be cloned in a bicistronic vector. In this study, both these genes were cloned and characterized for expression of their gene products and its apoptotic potential. The expression of VP3 and NS1 was studied by confocal microscopy and flowcytometry. Expression of VP3 and NS1 in pVIVO.VP3.NS1 transfected HeLa cells in comparison to mock transfected cells indicated that the double gene construct expresses both the products. This was further confirmed by flowcytometry where there was increase in cells expressing VP3 and NS1 in pVIVO.VP3.NS1 transfected group in comparison with the mock control group. The apoptotic inducing potential of this characterized pVIVO.VP3.NS1 was evaluated in human cervical cancer cell line (HeLa) by DNA fragmentation assay, TUNEL assay and Hoechst staning. This double construct was observed to induce apoptosis in HeLa cells.

Design, architecture and application of nanorobotics in oncology.

Oncologists all over the globe, relentlessly research on methodologies for detection of cancer and precise localization of cancer therapeutics with minimal adverse effects on healthy tissues. Since the previous decade, the fast growing research in nanotechnology has shown promising possibilities for achieving this dream of every oncologist.Nanorobots (or nanobots) are typical devices ranging in size from 0.1 to 10 μm and constructed of nanoscale or molecular components. Robots will augment the surgeon’s motor performance, diagnostic capability and sensations with haptics and augmented reality. The article here aims in briefly describing the architecture of the nanorobots and their role in oncotherapy. Although, research into nanorobots is still in its preliminary stages, the promise of such technology is endless.

Cloning and expression analysis of multiple proteins encoding P gene of Newcastle disease virus.

Viral gene oncotherapy is emerging as a biotherapeutic cancer treatment modality based on targeted killing of cancer cells by viral genes. Newcastle disease virus (NDV) has the property to cause selective oncolysis of tumor cells sparing normal cells. NDV has a single stranded negative sense RNA genome, which is 15,186 nucleotide long and consists of six genes, which codes for eight proteins. NDV like other paramyxoviruses has the ability to generate multiple proteins from the P gene. P protein is encoded by an unedited transcript of the P gene, whereas the V and W protein are the results of RNA editing event in which one and two G residues are inserted at a conserved editing site within the P gene mRNA resulting in V and W transcripts, respectively. Although NDV is known to cause oncolysis by triggering apoptosis, the role of different viral proteins in selective oncolysis is still unclear. P gene edited products are known for its anti-apoptotic property in homologous host. In the present study, NDV P gene and its RNA edited products were amplified, cloned, sequenced and in vitro expression was done in HeLa cells. Further constructs were assayed for their apoptosis inducing ability in HeLa cells. Preliminary study suggested that P, V and W proteins are not apoptotic to HeLa cells.

Oncolytic viruses & their specific targeting to tumour cells.

Cancer is one of the major causes of death worldwide. In spite of achieving significant successes in medical sciences in the past few decades, the number of deaths due to cancer remains unchecked. The conventional chemotherapy and radiotherapy have limited therapeutic index and a plethora of treatment related side effects. This situation has provided an impetus for search of novel therapeutic strategies that can selectively destroy the tumour cells, leaving the normal cells unharmed. Viral oncotherapy is such a promising treatment modality that offers unique opportunity for tumour targeting. Numerous viruses with inherent anti-cancer activity have been identified and are in different phases of clinical trials. In the era of modern biotechnology and with better understanding of cancer biology and virology, it has become feasible to engineer the oncolytic viruses (OVs) to increase their tumour selectivity and enhance their oncolytic activity. In this review, the mechanisms by which oncolytic viruses kill the tumour cells have been discussed as also the development made in virotherapy for cancer treatment with emphasis on their tumour specific targeting.

Screening of granulocytes with cancer killing activity and their in vitro anti-tumor effects / 第二军医大学学报

Objective To explore the screening method for granulocytes with cancer killing activity (CKA) and to observe their in vitro anti-tumor effects. Methods (1) Anti-coagulated peripheral whole blood samples were collected from 21 healthy volunteers and were co-cultured with human lung cancer cell line A549. The proliferation activity of cancer cells was observed to screen granulocytes with CKA. (2) The screened granulocytes with CKA was used to treat various tumor cells, CCK-8 method was used to examine the vitality of tumor cells, and the cell apoptosis was detected by Annexin V-FTTC Apoptosis Detection Kit II. (3) The cancer cells were co-cultured using direct contact, Transwell and conditioned medium, and the effects of the three methods on the anti-tumor effect of CKA granulocytes were observed. Results (1) Six granulocyte clones showed noticeable inhibitory effect against A549 cells, and clone 3 had the most potent effect and was marked as CKA granulocyte. (2) The screened CKA granulocytes not only had noticeable inhibitory effects against A549, HepG2 and HeLa cells, but also promoted their apoptosis. (3)The order of the inhibitory efficiencies for the three culture methods from strong to weak was: direct contact > Transwell > conditioned medium. Conclusion CKA granulocytes have noticeable inhibitory effect against some cancer cells, which might be associated with their contact mode with the cancer cells.

Role of centrosome in tumorigenesis and oncotherapy / 基础医学与临床

The centrosome plays a crucial role in the maintaining of cell conformation,mitosis and chromosome seg-regation.It responds to the DNA damage and keeps the genome stability via cross-talking with the intranuclear DNA damage repair system.The apoptosis of tumor cells can be induced through inhibition of the duplication of centro-some.So the inhibitors of centrosomal proteins will be a potential anti-tumor therapy.