Roles and application of exosomes in the development,diagnosis and treatment of gastric cancer

As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor angiogenesis.Exosomes transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target cells.In this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human cancer.We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.

Usher syndrome:Genetic diagnosis and current therapeutic approaches

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf population.This genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular areflexia.Among the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset RP.USH type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high frequencies.Conversely,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of life.The dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with society.To date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and CLRN1.These genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional loss.Although non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating USH.Regarding drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in USH.Simultaneously,CI has proven to be critical in the restoration of hearing.This review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et al.Diagnosis and current treatments of USH WJO https://www.wjgnet.com 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and improving patient prognosis.

Presymptomatic Diagnosis and Gene Therapy for Alzheimer’s Disease: Genomic, Therapeutic, and Ethical Aspects—A Systematic Review

Over the past three decades, genomic and epigenetic sciences have identified more than 70 genes involved in the molecular pathophysiology of Alzheimer’s disease (AD). DNA methylation, abnormal histone and chromatin regulation and the action of various miRNAs induce AD. The identification of mutated genes has paved the way for the development of diagnostic kits and the initiation of gene therapy trials. However, despite major advances in neuroscience research, there is yet no suitable treatment for AD. Therefore, the early diagnosis of this neurodegenerative disease raises several ethical questions, including the balance between the principle of non-maleficence and the principle of beneficence. The aims of this research were to present the genomic and ethical aspects of AD, and to highlight the ethical principles involved in its presymptomatic diagnosis and therapy. A systematic review of the literature in PubMed, Google Scholar and Science Direct was carried out to outline the genomic aspects and ethical principles relating not only to the presymptomatic diagnosis of AD, but also to its gene therapy. A total of 16 publications were selected. AD is a multifactorial disease that can be genetically classified into Sporadic Alzheimer’s Disease and Familial Alzheimer’s Disease based on family history. Gene therapy targeting specific disease-causing genes is a promising therapeutic strategy. Advancements in artificial intelligence applications may enable the prediction of AD onset several years in advance. While early diagnosis of AD may empower patients with full decision competence for early decision-making, it also carries implications for the patient’s family members, who are at risk of developing the disease, potentially becoming a source of confusion or anxiety. AD has a significant impact on the life of individuals at risk and their families. Given the absence of disease modifying therapy, genetic screening and early diagnosis for this condition raise ethical issues that must be carefully considered in the context of fundamental bioethical principles, including autonomy, beneficence, non-maleficence, and justice.

Survivin:Potential role in diagnosis,prognosis and targeted therapy of gastric cancer

Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth of these cells. In the case of gastric cancer,survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently,several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis,prognosis and treatment of gastric tumors.

Irritable bowel syndrome: a disease still searching for pathogenesis, diagnosis and therapy

Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient’s quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain (gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome III criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities. Nevertheless, the severity of the patient’s symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms (fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.

Advances in early diagnosis and therapy of pancreatic cancer

BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articles were from CHKD (China Hospital Knowledge Database) RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

Hepatic epithelioid hemangioendothelioma:Update on diagnosis and therapy

With an estimated incidence of only 1-2 cases in every 1 million people,hepatic epithelioid hemangioendothelioma(HEHE)is a rare vascular endothelial cell tumor occurring in the liver and consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix.HEHE is characterized as a low-to-moderate grade malignant tumor and is classified into three types:solitary,multiple,and diffuse.Both the etiology and characteristic clinical manifestations of HEHE are unclear.However,HEHE has a characteristic appearance on imaging including ultrasound,magnetic resonance imaging,and positron emission tomography/computerized tomography.Still,its diagnosis depends mainly on pathological findings,with immunohistochemical detection of endothelial markers cluster of differentiation 31(CD31),CD34,CD10,vimentin,and factor VIII antigen as the basis of diagnosis.Hepatectomy and/or liver transplantation are the first choice for treatment,but various chemotherapeutic drugs are reportedly effective,providing a promising treatment option.In this review,we summarize the literature related to the diagnosis and treatment of HEHE,which provides future perspectives for the clinical management of HEHE.

Role of endoscopic ultrasound in diagnosis and therapy of pancreatic adenocarcinoma

Since its advent more than 20 years ago, endoscopic ultrasound （EUS） has undergone evolution from an experimental to a diagnostic instrument and is now established as a therapeutic tool for endoscopists. Endoscopic ultrasound cannot accurately distinguish benign from malignant changes in the primary lesion or lymph node on imaging alone. With the introduction of the curved linear array echoendoscope in the 2990s, the indications for EUS have expanded. The curved linear array echoendoscope enables the visualization of a needle as it exits from the biopsy channel in the same plane of ultrasound imaging in real time. This allows the endoscopist to perform a whole range of interventional applications ranging from fine needle aspiration （FNA） of lesions surrounding the gastrointestinal tract to celiac plexus block and drainage of pancreatic pseudocyst. This article reviews the current role of EUS and EUS-FNA in diagnosis, staging and interventional application of solid pancreatic cancer.

Primary sclerosing cholangitis: Updates in diagnosis and therapy

Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown origin mostly found in males, and characterized by diffuse inflammation and fibrosis of both intra- and extra-hepatic bile ducts. So far, PSC is considered as an autoimmune hepatobiliary disease. In most cases the progression of PSC towards liver cirrhosis and liver failure is slow but irreversible, and liver transplantation is currently the only definitive treatment. In recent years,PSC has been an area of active research worldwide with great interest in etiology, pathogenesis, diagnosis, and therapeutic options such as hydrophilic ursodeoxycholic acid and immunosuppressive agent tacrolimus. Recent updates on clinical and therapeutic aspects of PSC are discussed in the present review.

Stool antigen tests in the diagnosis of Helicobacter pylori infection before and after eradication therapy

Aim： To evaluate two enzyme immunoassay-based stool antigen tests, Premier Platinum HpSA and Amplified IDEIA HpStAR, and one rapid test, ImmunoCard SLAT! HpSA, in the primary diagnosis of Helicobacter pylon （H pylori） infection and after eradication therapy. METHODS： Altogether 1 574 adult subjects were screened with a whole-blood H pylori antibody test and positive results were confirmed with locally validated serology and ^13C-urea breath test. All 185 subjects, confirmed to be H pylori positive, and 97 H pylorinegative individuals, randomly selected from the screened study population and with negative results in serology and UBT, were enrolled. After eradication therapy the results of 182 subjects were assessed. RESULTS： At baseline, the sensitivity of HpSA and HpStARwas 91.9% and 96.2%, respectively, and specificity was 95.9% for both tests. ImmunoCard had sensitivity of 93.0% but specificity of only 88.7%. After eradication therapy, HpSA and HpStAR had sensitivity of 81.3% and 100%, and specificity of 97.0% and 97.6%, respectively. ImmunoCard had sensitivity of 93.8% and specificity of 97.0%. HpSA, HpStAR, and ImmunoCard had PPV 77%, 80%, and 75%, and NPV 98%, 100%, and 99%, respectively. CONCLUSION： In primary diagnosis, the EIA-based tests performed well. After eradication therapy, negative results were highly accurate for all the three tests. HpStAR had the best overall performance.

Advances and future directions in keloid research:Pathogenesis,diagnosis and personalized treatment strategies

Keloids,which are abnormal manifestations of wound healing,can result in significant functional impairment and aesthetic deformities.The pathogenesis of keloids is multifaceted and complex and influenced by various factors,such as genetics,the environment,and immune responses.The evolution of keloid treatment has progressed from traditional surgical excision to a contemporary combination of therapies including injection and radiation treatments,among others.This article provides a comprehensive review of keloid pathogenesis and treatment,emphasizing the latest advances in the field.Ultimately,this review underscores the necessity for continued research to enhance our understanding of keloid pathogenesis and to devise more effective treatments for this challenging condition.

Recent Progress in Nanoscale Covalent Organic Frameworks for Cancer Diagnosis and Therapy

Covalent organic frameworks(COFs)as a type of porous and crystalline covalent organic polymer are built up from covalently linked and periodically arranged organic molecules.Their precise assembly,welldefined coordination network,and tunable porosity endow COFs with diverse characteristics such as low density,high crystallinity,porous structure,and large specific-surface area,as well as versatile functions and active sites that can be tuned at molecular and atomic level.These unique properties make them excellent candidate materials for biomedical applications,such as drug delivery,diagnostic imaging,and disease therapy.To realize these functions,the components,dimensions,and guest molecule loading into COFs have a great influence on their performance in various applications.In this review,we first introduce the influence of dimensions,building blocks,and synthetic conditions on the chemical stability,pore structure,and chemical interaction with guest molecules of COFs.Next,the applications of COFs in cancer diagnosis and therapy are summarized.Finally,some challenges for COFs in cancer therapy are noted and the problems to be solved in the future are proposed.

Nanotechnology and Nanomedicine: A Promising Avenue for Lung Cancer Diagnosis and Therapy

Lung cancer is a leading cause of cancer-related death worldwide,with a very poor overall five-year survival rate.The intrinsic limitations associated with the conventional diagnosis and therapeutic strategies used for lung cancer have motivated the development of nanotechnology and nanomedicine approaches,in order to improve early diagnosis rate and develop more effective and safer therapeutic options for lung cancer.Cancer nanomedicines aim to individualize drug delivery,diagnosis,and therapy by tailoring them to each patient’s unique physiology and pathological features—on both the genomic and proteomic levels—and have attracted widespread attention in this field.Despite the successful application of nanomedicine techniques in lung cancer research,the clinical translation of nanomedicine approaches remains challenging due to the limited understanding of the interactions that occur between nanotechnology and biology,and the challenges posed by the toxicology,pharmacology,immunology,and largescale manufacturing of nanoparticles.In this review,we highlight the progress and opportunities associated with nanomedicine use for lung cancer treatment and discuss the prospects of this field,together with the challenges associated with clinical translation.

Intestinal anisakiasis treated successfully with conservative therapy:Importance of clinical diagnosis

Intestinal anisakiasis is not only a rare parasitic disease,but is also difficult to diagnose.The symptoms are not specific and are often very severe and abrupt,and the findings of clinical imaging are very remarkable.Therefore,intestinal anisakiasis is often misdiagnosed as acute abdomen or intestinal obstruction and is treated surgically.However,if intestinal anisakiasis could be diagnosed correctly,it is well treated conservatively.We experienced three cases of intestinal anisakiasis,which were diagnosed correctly and treated successfully with conservative therapy.A correct clinical history and imaging interpretation helped us diagnose intestinal anisakiasis correctly and thus treat the patients successfully with conservative therapy.

Liquid biopsy:Precise diagnosis and therapy for cholangiocarcinoma

The following letter to the editor highlights the review titled“Liquid biopsy in cholangiocarcinoma:Current status and future perspective”in World J Gastrointest Oncol 2021;13:332-350.It is necessary to realize individualized therapy to improve the clinical prognosis of patients with cholangiocarcinoma.

Translational research case studies:Development of antibodies for cancer diagnosis and therapy

Antibodies are primary tools in several areas of biomedical sciences, including basic research, diagnostics, and molecular therapeutics. Antibodies are widely used in diagnostic applications for clinical medicine. Analysis of cells and tissues in pathology laboratories includes the use of antibodies on tissue sections. Further, antibodies are making rapid inroads into medical therapeutics, driven by technological evolution from chimeric and humanized to fully human antibodies. The therapeutic antibody market has the potential to reach $30 billion by 2010. Our lab has developed a monoclonal antibody, named Met4 that was raised against the extracellular domain of Met specifically with the goal of measuring Met in FFPE tissues. The Met receptor kinase is expressed on the cell surface of a significant number and variety of human primary solid tumors and in their metastases. The characterization of the Met4 antibody suggests it should possess adequate performance for quantification of Met expression in clinical specimens. We have also generated a fully human Fab fragment against EGFR; conjugated it to taxol as an immuno-chemotherapy agent; and investigated its in vitro antitumor efficacy on EGFR positive A431 epidermoid carcinoma cells.

Nanomedicine:diagnosis to therapy

It can be said that "small technology" becomes a very useful technology and is replacing the classical technology. Nanotechnology is an applied technology relating to management,construction,synthesis of devices in atomic or molecular level that poses the size between 1 and 100 nanometers.In this short article,the author will summarize important advent in nanodiagnosis and nanotherapy then further extrapolate this for the tropical medicine aspect.

Nanomaterials for refining tumor microenvironment and enhancing therapy in head and neck squamous cell carcinoma: a review

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.

Nanomedicine has opened new avenues for cancer diagnosis and therapy

A crucial feature of nanoparticles,such as liposomes,magnetic nanoparticles,quantum dots,metallic nanoparticles,silica nanoparticles,polymersomes and dendrimers etc.,is their higher accumulation in the tumor than in normal tissues1-3.Various nanoparticles have been intensively used as vehicles to deliver

Discussion of diagnosis and therapy strategy for pineal region tumors

Objective To define optimal diagnosis and theraputic strategy of pineal region tumors. Methods Clinicalmaterials of 154 cases with pineal region tumors were analyzed retrospectively. Results The patients with pineal region tumors often complained of increased intracranial pressure and ocular movement deficiency.