Cathepsin B-responsive nanodrug delivery systems for precise diagnosis and targeted therapy of malignant tumors

The tumor microenvironment(TME)significantly influences cancer evolution and therapeutic efficacy.Targeting biofunctional molecules to the TME has long been appreciated as a means of raising local drug concentrations and reducing systemic toxicities.The booming nanotechnology field has realized the importance of cathepsin B to derive a variety of intelligent enzyme-responsive nanosized drug delivery systems(nanoDDS)to improve treatment responses and clinical outcomes.In this tutorial review,after introducing the molecular structure and physiological/pathological functions of cathepsin B,the outstanding achievements of cathepsin B-responsive nanoplatforms in the precise diagnosis,targeted therapy,and synergistic theranostics of malignant tumors are systematically described.Finally,the challenges of enzyme-substrate incompatibility,low diagnostic sensitivity,mass production and biocompatibility of multifunctional nanoDDS are considered in order to successfully promote them to clinical applications.

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.

Real-world treatment patterns of gastrointestinal neuroendocrine tumors: A claims database analysis

AIM To describe real-world treatment patterns of gastrointestinal neuroendocrine tumors(GI NET).METHODS In this retrospective cohort study,we used 2009-2014 data from 2 United States commercial claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included somatostatin analogues(SSA),cytotoxic chemotherapy(CC),targeted therapy(TT),interferon(IF) and combinations. We identified patients at least 18 years of age,with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who initiated pharmacologic treatment from 7/1/09-6/30/14. A 6 mo clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment or the study end date,whichever was first.RESULTS We identified 2258 newly treated GI NET patients: mean(SD) age was 55.6 years(SD = 9.7),47.2% of the patients were between 55 and 64 years,and 48.8% were female. All regions of the United States were represented. 59.6% started first-line therapy with SSA monotherapy(964 with octreotide LAR,380 with octreotide SA,and 1 with lanreotide),33.3% CC,3.6% TT,and 0.5% IF. The remainder received combinations. Mean follow up was 576 d. Overall mean first-line therapy duration was 361 d(449 d for SSA,215 for CC,267 for TT). 58.9% of patients had no pharmacological treatment beyond first line. The most common secondline was combination therapy with SSA. In graphical pattern analysis,there was no clear pattern visible after first line therapy.CONCLUSION In this study,60% of patients initiated treatment with SSA alone or in combination. The relatively long time to discontinuation suggests possible sustained effectiveness and tolerability.

Progress in research of liver surgery in China

INTRODUCTIONLiver surgery,was started in the late 1950s in Chinaand has developed rapidly in the past 40 years.The study on the diagnosis and treatment of primaryliver cancer in China underwent four stages:①Inthe 1950s,the anatomical study of the liver lay asolid foundation for liver resection.①In

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

The 2023 update of the Chinese Society of Clinical Oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision medicine.These updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer patients.Key revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric cancer.For advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)patients.Additionally,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer.The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

Highly variable biodistribution of ^(68)Ga labeled somatostatin analogues ^(68)Ga-DOTA-NOC and ^(68)Ga-DOTA-TATE in neuroendocrine tumors: clinical implications for somatostatin receptor directed PET/CT

Background:Somatostatin receptor(SSTR)-targeted positron emission tomography/computed tomography(PET/CT)imaging has risen to the forefront for neuroendocrine tumor(NET)detection and management,yet the variability of significant uptake variability(SUV)as a semiquantitative measure of disease detection and tumor response to treatment has not been fully explored.Methods:We assess the reproducibility and interscan variability of SUV metrics of normal tissue and NET in serial^(68)Ga-DOTA-NOC and^(68)Ga-DOTA-TATE PET imaging to clinically monitor disease state.Eighty-one patients were enrolled in this retrospective study.Results:Both primary and metastatic hepatic lesions demonstrated SUV(SUVmean 16.5±8.0).The median SUVmean was 16 for the spleen,9.7 for the pituitary,12.6 for the adrenal glands,and 4.8 for the liver.The normal pituitary gland demonstrates focal homogenous uptake with SUVmax range of 4.5–23.The adrenal gland showed uptake with SUVmax range of 4.1–29.4,which is more than two times greater than liver uptake(SUVmean range,2.3–12.4).Highest physiological uptake seen in the spleen(average SUVmean of 17.3,range of 5.4–34.4).Conclusions:The highly variable nature of regional SUVmean and SUVmax in both physiologic tissue and lesions suggests the need for incorporation of more reliable quantitative measures for clinical decision making.

中枢神经系统多层菊花团的胚胎性肿瘤诊疗研究进展

近年随着脑肿瘤分子生物学的发展,具有不同组织形态的富含神经毡和真菊形团的胚胎性肿瘤、髓上皮瘤及室管膜母细胞瘤归属于同一分子实体,统称为多层菊花团的胚胎性肿瘤(embryonal tumor with multilayered rosettes,ETMR)。这些肿瘤的罕见性和更新给诊断和治疗带来了挑战。文章主要对ETMR的临床表现、影像特点、诊断及临床研究情况进行回顾分析,以期为临床管理提供指导帮助。对ETMR的临床特点及诊断治疗的研究情况进行文献综述。典型的组织学特点联合分子生物学改变,可以更好地诊断ETMR。目前ETMR的治疗建议主要基于小型、主要是回顾性患者队列的数据。普遍推荐最大安全切除,适应年龄和风险的放疗、化疗为ETMR主要治疗手段,早期放疗可能改善预后。

21世纪以来胃癌治疗进展及未来展望

胃癌作为中国发病率及死亡率均位居前列的恶性肿瘤,具有异质性高、预后差等特点。进入21世纪,随着基因组学、腹腔镜微创技术、靶向治疗及免疫治疗的迅速发展,胃癌诊疗水平取得了长足进步。本文总结21世纪以来胃癌防治领域中的重要研究进展,并对未来进行展望,期待在胃癌早期筛查、诊断和精准治疗方面取得更大进步和突破,进一步提高患者的总生存率,将胃癌转变为可以控制的“慢性病”。

透明质酸修饰血清白蛋白纳米粒在肿瘤诊疗中的研究进展

传统检测和治疗肿瘤的方法存在局限性,如靶向性不足、灵敏度有限等。科学家们开发出的一种新型纳米系统,即利用透明质酸修饰血清白蛋白构建一种生物相容性和降解性都得到改善的纳米系统,有望提供一种新的肿瘤诊疗方法。此外,该纳米系统还具有独特的双重靶向效应,可间接提高肿瘤成像的灵敏度和治疗的准确性。本文旨在探讨透明质酸血清白蛋白纳米粒在肿瘤成像诊断、治疗和治疗一体化应用中的最新研究进展,并指出现阶段仍面临的挑战及须解决的问题,进而为抗肿瘤靶向纳米制剂的开发提供理论依据及方法指导。

循环肿瘤细胞检测在非小细胞肺癌诊疗中的研究进展

非小细胞肺癌(NSCLC)是最常见的肺癌类型,确诊时绝大多数患者已处于疾病晚期,因此对NSCLC早期诊断、实时监测以及预后评估非常必要。目前对于NSCLC的检测手段多种多样,但很难确诊及评估预后。循环肿瘤细胞(CTCs)指从肿瘤原发灶或转移灶脱落并侵入至外周血循环的肿瘤细胞,作为液体活检的一种新形式被广泛应用于各大转移性疾病的诊断及预后评估。近年来,CTCs在NSCLC诊疗中展现了广阔的应用前景,如协助早期诊断、评估治疗效果、监测患者预后。

纳米递送系统线粒体靶向策略在肿瘤诊疗中的应用

肿瘤是危害人类健康的重大疾病之一。目前用于肿瘤治疗的方法有手术治疗、化学药物治疗、放射治疗等。然而,传统的治疗方法存在治疗效果不佳、易引发多药耐药、毒副作用大等缺点,仍需进一步探索新的肿瘤治疗靶点和策略。线粒体作为细胞的能量转换器,被认为是肿瘤、心血管和神经性疾病新药设计的最重要靶点之一。纳米药物递送载体具有易被主动靶向基团修饰的特点,可实现细胞乃至细胞器的精准靶向给药。本文从抑制肿瘤细胞增殖、促进肿瘤细胞凋亡、抑制肿瘤复发与转移、诱导细胞自噬等方面综述了线粒体靶向纳米载体在肿瘤诊疗中的应用。

三苯基膦盐在肿瘤诊断和治疗中的应用

针对靶向亚细胞器的治疗是肿瘤治疗的一个新兴研究方向,其机理是通过损伤亚细胞器或影响亚细胞器周围的环境,使细胞凋亡.而在众多的亚细胞器中,线粒体是亚细胞的能量工厂,可以为亚细胞的各项生命活动提供能量,因此靶向线粒体治疗是亚细胞器治疗的热点之一.此外,线粒体还参与细胞分化、细胞信息传递和细胞凋亡等过程.诱导线粒体损伤或者影响线粒体内表达物质的正常供应关系,对亚细胞生存状态有巨大的影响.三苯基膦(TPP)盐可以利用线粒体膜电位差来实现线粒体靶向功能,是最广为接受和应用较多的线粒体靶向小分子.为了进一步增加其功能的多样性,往往会在TPP烷基链的尾端进行设计,实现肿瘤的高效诊断和治疗.文章综述了近年来TPP盐在肿瘤诊断和治疗领域中的研究进展,以及在未来所面对的挑战.

Results of the Management of Gastrointestinal Stromal Tumors (GIST): About 6 Cases at the Vichy Hospital Center (France)

The aim of our study was to analyze the results of surgical management of gastrointestinal stromal tumors (GIST) at the Vichy Hospital Center. Methodology: Between 2010 and 2020, the data of 6 patients operated at the Vichy Hospital Center for GIST were analyzed. The parameters studied were: age, sex, antecedents, discovery circumstances, imagery, surgical procedure, anatomopathological data, the follow-up and the morbidity-mortality. Results: There were 5 men and one woman with an average age of 72.16 years [58 - 80 years]. The average time of evolution was 8 months (0 - 14 months). The diagnosis was fortuitous in 2 cases. Atypical abdominal pain was the main symptom in 3 cases. One case was received in a clinical picture of peritoneal irritation syndrome. Echo-endoscopy with biopsy specimen histology made it possible to make the diagnosis in 5 cases and the surgical specimen in 1 case. The fusiform type was the predominant histological form. The stomach was the most common location. The average size of GISTs was 7.3 × 4 cm with a positive C Kit in all patients. Neoadjuvant chemotherapy was performed on one patient. Surgery was curative and was done laparoscopically on 4 patients. Adjuvant chemotherapy based on Imatinib at a rate of 400 mg/d in 3 patients was initiated. One patient presented a fistula of the esophagus-jejunal anastomosis on D6 post operation controlled by a drainage and an antibiotic therapy. Mortality was zero. During the surgery, all of the patients were followed up with surgeon, oncologist. Conclusion: GISTs are the most common mesenchymal tumors of the digestive tract with a preferential gastric location. Laparoscopic surgery, with advances in molecular biology and the introduction of targeted therapy has improved the management of these tumors in terms of morbidity and mortality.

The Chinese Society of Clinical Oncology(CSCO):Clinical guidelines for the diagnosis and treatment of gastric cancer,2021

There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.

The Chinese Society of Clinical Oncology(CSCO):clinical guidelines for the diagnosis and treatment of gastric cancer

China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.

Long-term complete response in metastatic poorly-differentiated neuroendocrine rectal carcinoma with a multimodal approach: A case report

BACKGROUND Neuroendocrine gastrointestinal tumors(NETs)are rare and have different natural behaviors.Surgery is the gold standard treatment for local disease while radiotherapy has been demonstrated to be ineffective.Poorly differentiated neuroendocrine carcinomas(NECs)represent only 5%-10%of digestive NETS.Due to aggressive growth and rapid metastatic diffusion,early diagnosis and a multidisciplinary approach are mandatory.The role of surgery and radiotherapy in this setting is still debated,and chemotherapy remains the treatment of choice.CASE SUMMARY A 42-year-old male with an ulcerated bleeding rectal lesion was diagnosed with a NEC G3(Ki67 index>90%)on May 2015 and initially treated with 3 cycles of first-line chemotherapy,but showed early local progressive disease at 3 mo and underwent sphincter-sparing open anterior low rectal resection.In September 2015,the first post-surgery total-body computed tomography(CT)scan showed an early pelvic disease relapse.Therefore,systemic chemotherapy with FOLFIRI was started and the patient obtained only a partial response.This was followed by pelvic radiotherapy(50 Gy).On April 2016,a CT scan and 18F-fluorodeoxy-glucose positron emission tomography imaging showed a complete response(CR)of the pelvic lesion,but pathological abdominal inter-aortocaval lymph nodes were observed.Due to disease progression of abdominal malignant nodes,the patient received radiotherapy at 45 Gy,and finally obtained a CR.As of January 2021,the patient has no symptoms of relapse and no late toxicity after chemotherapy or radiotherapy.CONCLUSION This case demonstrates how a multimodal approach can be successful in obtaining long-term CR in metastatic sites in patients with high grade digestive NECs.

Gastrointestinal Stromal Tumors in the 21^stCentury

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal lesions accounting for only 0.2% of all gastrointestinal neoplasms. These tumors arise from the interstitial cells of Cajal, with mutations described in proto-oncogenes such as KIT, PDGFRA, DOG-1, and SDH. The majority of these lesions are asymptomatic, thus the true incidence remains unknown. While patients typically undergo initial endoscopy, CT scan and/or MRI, findings are often nonspecific and require a biopsy to identify the tumor. As such, immunohistochemical evaluation is the gold-standard for the accurate diagnosis of GIST. Though surgical excision remains the gold-standard for curative management, the discovery of imatinib, a tyrosine kinase inhibitor (TKI), has revolutionized the treatment of GIST in the 21st?century as a “prototype” of molecular targeted therapy for solid tumors. Risk assessment for recurrence divides these tumors into low and high-risk categories. In the latter, a role for adjuvant therapy with TKI confers a significantly better prognosis than previously observed. However, secondary mutations conferring drug resistance remain an ongoing challenge for management, as few alternative treatment options are available for patients intolerant/refractory to TKI therapy. In this review, we summarize the epidemiology, molecular pathogenesis, clinical presentation, diagnosis, pathology features, management options, and prognostic features of GISTs.

融合基因在唾液腺肿瘤中的研究进展

唾液腺肿瘤是常见的口腔颌面部肿瘤且具有异质性,无法手术、复发和转移的患者治疗选择非常有限,而融合基因的发现为其诊疗开辟了新途径。融合基因编码新的融合癌蛋白或异位表达的正常/截短的癌蛋白,其主要靶标是转录辅助活化因子、酪氨酸激酶受体以及参与生长因子信号和细胞周期调节的转录因子,其中一些靶标或由这些靶标激活的途径是可靶向的。随着进一步迈入精准医疗和靶向治疗时代,更全面的分子分析将为各种唾液腺肿瘤的诊断、分子发病机制提供新的见解、为常规治疗效果不佳的患者提供更多的治疗选择。该文回顾了唾液腺良恶性肿瘤中融合基因类型、功能作用及靶向药物研究进展,旨在为融合基因在唾液腺肿瘤中的诊断、机制研究及临床治疗提供新的方向。

血小板:肿瘤诊断与治疗的新兴靶点

血小板是肿瘤发生发展过程中的重要参与者,能够通过构建炎性微环境、促进血管生成和介导肿瘤免疫逃逸,直接或间接地影响肿瘤生长和转移进程。随着肿瘤微环境的动态变化,血小板的数量、体积和分子组学也发生相应改变,提示血小板相关的生物标志物具有反映肿瘤负荷演变的巨大潜力。基于血小板对肿瘤发生发展的促进效应,血小板被视为肿瘤生物治疗的重要靶点。靶向抑制血小板功能可以显著控制肿瘤的发生发展并改善患者的预后。此外,血小板对肿瘤组织具有较强的亲和能力。应用靶向血小板或血小板功能模拟的思路研发抗肿瘤靶向制剂以有效地增加纳米药物的肿瘤靶向性和生物相容性,是提高肿瘤靶向治疗效率的新兴策略。本文聚焦于血小板与肿瘤之间的复杂相互作用,在总结作用机制的基础上,对血小板相关的肿瘤标志物和抗肿瘤靶向治疗进行了重点阐述。

微小RNA-31在肿瘤中的作用研究进展

微小RNA-31 (miR-31)是在动物和人体组织中广泛存在的一种多功能miRNA,可调控靶基因的表达并参与细胞增殖、分化和凋亡等生理、病理过程。miR-31与肿瘤的发生发展密切相关。miR-31可作为抑癌或促癌基因表达于各个肿瘤中,并在肿瘤细胞增殖、侵袭和迁移等多个生物学过程中发挥重要作用。因此,miR-31有望成为恶性肿瘤的新型生物标志物和治疗靶点。本文就miR-31在恶性肿瘤中的作用机制、治疗预后等方面的研究进展进行综述,以期为恶性肿瘤的早期诊断及个性化治疗提供策略。