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Intra-tumoral bacteria in head and neck cancer: holistic integrative insight

Cancer Biology & Medicine 2025年第02期 113-136页

作者： Yucheng Meng Jiaru Deng Weiwei Deng Zhijun Sun State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Frontier Science Center for Immunology and Metabolism Taikang Center for Life and Medical Sciences Wuhan University Department of Oral & Maxillofacial Head Neck oncology School & Hospital of Stomatology Wuhan University

Intra-tumoral bacteria are pivotal in the initiation and progression of head and neck squamous cell carcinoma(HNSCC), exerting a significant influence on tumor cell biology, immune responses, and the tumor microenvironment(TME). Different types and distribution of bacteria threaten the balance of metabolism and the immune environment of tumor cells. Taking advantage of this disrupted homeostasis, intra-tumoral bacteria stimulate the secretion of metabolites or influence specific immune cell types to produce inflammatory or chemokines, thereby influencing the anti-tumor immune response while regulating the level of inflammation and immunosuppression within the TME. Some intra-tumoral bacteria are used as diagnostic and prognostic markers in clinical practice. Based on the unique characteristics of bacteria, the use of engineered bacteria and outer membrane vesicles for drug delivery and biological intervention is a promising new therapeutic strategy. The presence of intra-tumoral bacteria also makes chemoradiotherapy tolerable, resulting in a poor treatment effect. However, due to the immune-related complexity of intra-tumoral bacteria, there may be unexpected effects in immunotherapy. In this review the patterns of intra-tumoral bacteria involvement in HNSCC are discussed, elucidating the dual roles, while exploring the relevance to anti-tumor immune responses in the clinical context and the prospects and limitations of the use of bacteria in targeted therapy.

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Management of gastrointestinal bleed in the intensive care setting,an updated literature review

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World Journal of Critical Care Medicine 2025年第1期14卷 20-41页

作者： Vignesh K Nagesh Sai Priyanka Pulipaka Ruchi Bhuju Emelyn Martinez Shruthi Badam Gomathy Aarthy Nageswaran Hadrian Hoang-Vu Tran Daniel Elias Charlene Mansour Jaber Musalli Sanket Bhattarai Lokeash Subramani Shobana Tannishtha Sethi Ritvik Sethi Namrata Nikum Chinmay Trivedi Amer Jarri Colin Westman Nazir Ahmed Shawn Philip Simcha Weissman Jonathan Weinberger Ayrton I Bangolo Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Internal Medicine University of Arkansas for Medical SciencesLittle RockAR 72205United States Department of Internal Medicine Hackensack Palisades Medical CenterNorth BergenNJ 07047United States Department of Gastroenterology Hackensack University Medical CenterHackensackNJ 07061United States Department of Pulmonology and Critical Care HCA Florida Bayonet Point HospitalHudsonFL 34667United States Department of hematology&oncology John Theurer Cancer Center at Hackensack University Medical CenterHackensackNJ 07601United States

Gastrointestinal(GI)bleeding is a critical and potentially life-threatening condition frequently observed in the intensive care unit(ICU).This literature review consolidates current insights on the epidemiology,etiology,management,and outcomes of GI bleeding in critically ill *** bleeding remains a significant concern,especially among patients with underlying risk factors such as coagulopathy,mechanical ventilation,and renal *** GI bleeding in the ICU requires a multidisciplinary approach,including resuscitation,endoscopic intervention,pharmacologic therapy,and sometimes surgical *** with enhanced management strategies,GI bleeding in the ICU is associated with considerable morbidity and mortality,particularly when complicated by multi-organ *** review reiterates the need for adequate resuscitation and interventions in managing GI bleeding in critically ill patients,aiming to enhance survival rates and improve the quality of care within the ICU setting.

关键词： Gastrointestinal bleed Varices Variceal bleeding Diverticular bleed Angiodysplasia Ulcer Hemorrhoids Endoscopy Enteroscopy Embolization

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Two treatment methods for hepatocellular carcinoma:Lenvatinib or bevacizumab combined with sintilimab and interventional therapy

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World Journal of Gastroenterology 2025年第10期31卷 164-167页

作者： Fei-Yu Zhao Xiao-Ming Zhang Nian-Song Qian Department of Thoracic oncology Respiratory and Critical Care MedicineThe Eighth Medical Center of People’s Liberation Army General HospitalBeijing 100853China

In their study,Han et al compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and advanced hepatocellular *** triple therapy,which integrates interventional therapy,targeted therapy,and immunotherapy,has emerged as a promising research focus in the treatment of liver ***,it is of utmost significance to select an appropriate combination of interventional therapy,targeted therapy,and immunotherapy for patients suffering from intermediate and advanced liver cancer.

关键词： Hepatocellular carcinoma Bevacizumab Lenvatinib Sintilimab Interventional treatment

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Stir-Fried Semen Armeniacae Amarum Suppresses Aristolochic AcidⅠ-Induced Nephrotoxicity and DNA Adducts

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Chinese Journal of Integrative Medicine 2025年第2期31卷 142-152页

作者： LI Cheng-xian XIAO Xiao-he LI Xin-yu XIAO Da-ke WANG Yin-kang WANG Xian-ling ZHANG Ping LI Yu-rong NIU Ming BAI Zhao-fang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing(100102)China Department of Hepatology Military Institute of Chinese Materiathe Fifth Medical CentreGeneral Hospital of PLABeijing(100039)China National Key Laboratory of Kidney Beijing(100039)China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu(610075)China School of Traditional Chinese Medicine Capital Medical UniversityBeijing(100069)China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing(100039)China Department of Military Patient Management the Fifth Medical Center of PLA General HospitalBeijing(100039)China Department of hematology the Fifth Medical Center of Chinese PLA General HospitalBeijing(100071)China

Objective:To investigate the protective effects of stir-fried Semen Armeniacae Amarum(SAA)against aristolochic acidⅠ(AAⅠ)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et ***:In vitro,HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3(MRP3)were constructed by Lentiviral transduction,and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening *** m RNA,protein expressions,and enzyme activity levels of NAD(P)H quinone dehydrogenase 1(NQO1)and cytochrome P4501A2(CYP1A2)were measured in differentiated Hepa RG *** toxicity after inhibition of AAⅠmetabolite transport was detected using cell counting kit-8 *** vivo,C57BL/6 mice were randomly divided into 5 groups according to a random number table,including:control(1%sodium bicarbonate),AAⅠ(10 mg/kg),stir-fried SAA(1.75 g/kg)and AAⅠ+stir-fried SAA(1.75 and 8.75 g/kg)groups,6 mice in each *** 7 days of continuous gavage administration,liver and kidney damages were assessed,and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined ***:In vivo,combination of 1.75 g/kg SAA and 10 mg/kg AAⅠsuppressed AAⅠ-induced nephrotoxicity and reduced d A-ALI formation by 26.7%,and these detoxification effects in a dose-dependent manner(P<0.01).Mechanistically,SAA inhibited MRP3 transport in vitro,downregulated NQO1 expression in vivo,increased CYP1A2 expression and enzymatic activity in vitro and in vivo,respectively(P<0.05 or P<0.01).Notably,SAA also reduced AAⅠ-induced hepatotoxicity throughout the detoxification process,as indicated by a 41.3%reduction in the number of liver adducts(P<0.01).Conclusions:Stirfried SAA is a novel drug candidate for the suppression of AAⅠ-induced liver and kidney dam

关键词： aristolochic acidⅠ stir-fried Semen Armeniacae Amarum detoxification principles of compatibility metabolic enzymes transporters

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A novel BaEVRless-LV packaging system for the production of lentiviral vectors for clinical-grade CAR-NK cell manufacturing

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Cancer Biology & Medicine 2025年第02期 137-143页

作者： Yinyin Zhang Minghuan Zhang Mengyuan Li Lihong Zong Qian Ye Wen Lei Wenhai Deng Wenbin Qian Department of hematology the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Rong Gu Biotechnology Limited Company Biotherapy Research center the Second Affiliated Hospital Zhejiang University School of Medicine Key Laboratory of Laboratory Medicine Ministry of Education School of Laboratory Medicine and Life Sciences Wenzhou Medical University

Chimeric antigen receptor natural killer (CAR-NK) cell therapy is an alternative immunotherapy that provides robust tumor-eliminating effects without inducing life-threatening toxicities and graft-versus-host disease. CAR-NK cell therapy has enabled the development of “off-the-shelf” products that bypass the lengthy and expensive cell manufacturing process1.

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The therapeutic implications of immunosuppressive tumor aerobic glycolysis

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Cellular & Molecular Immunology 2022年第1期19卷 46-58页

作者： Bradley I.Reinfeld WKimryn Rathmell Tae Kon Kim Jeffrey C.Rathmell Department of Medicine Division of Hematology and OncologyVanderbilt University Medical CenterNashvilleTNUSA

In 2011,Hanahan and Weinberg added“Deregulating Cellular Energetics”and“Avoiding Immune Destruction”to the six previous hallmarks of *** this seminal paper,there has been a growing consensus that these new hallmarks are not mutually exclusive but rather *** following review summarizes how founding genetic events for tumorigenesis ultimately increase tumor cell glycolysis,which not only supports the metabolic demands of malignancy but also provides an immunoprotective niche,promoting malignant cell proliferation,maintenance and *** mechanisms by which altered metabolism contributes to immune impairment are multifactorial:(1)the metabolic demands of proliferating tumor cells and activated immune cells are similar,thus creating a situation where immune cells may be in competition for key nutrients;(2)the metabolic byproducts of aerobic glycolysis directly inhibit antitumor immunity while promoting a regulatory immune phenotype;and(3)the gene programs associated with the upregulation of glycolysis also result in the generation of immunosuppressive cytokines and *** this perspective,we shed light on important considerations for the development of new classes of agents targeting cancer *** types of therapies can impair tumor growth but also pose a significant risk of stifling antitumor immunity.

关键词： cancer metabolism immuno logy glycolysis

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Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 341-347页

作者： Philip J Saylor Division of hematology-oncology Massachusetts General Hospital Cancer Center Boston Massachusetts USA.

Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-K-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed.

关键词： denosumab osteoporosis osteopenia osteoclast RANK (receptor activator of nuclear factor-kappa B) skeletal-relatedevents

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Modulation of B-cell receptor and microenvironment signaling by a guanine exchange factor in B-cell malignancies

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Cancer Biology & Medicine 2016年第2期13卷 277-285页

作者： Wei Liao Sanjai Sharma Division of hematology-oncology Greater Los Angeles VA Healthcare Center UCLA School of Medicine

Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods： N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor （BCR） and chemokine signaling pathways were compared in the Rasgrf-I over-expressing and a control transfected cell line. Results： Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions： This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells.

关键词： B-ceU malignancies mantle cell lymphoma chronic lymphocytic leukemia (CLL) B-cell receptor guanine exchange factorRasgrf- 1 ERK pathway

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Locoregional treatments of metastatic internal mammary node following neoadjuvant chemotherapy

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中华医学杂志(英文版) 2025年第03期

作者： Zhang Jinhui Guan Huajie Song Cailu Liu Lingrui Tang Hailin Wang Jin Department of Breast oncology State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat-Sen University Cancer Center Guangzhou Guangdong China

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Association of image-defined risk factors,tumor resectability,and prognosis in children with localized neuroblastoma

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World Journal of Pediatrics 2019年第6期15卷 572-579页

作者： An-An Zhang Ci Pan Min Xu Xiao-Xia Wang Qi-Dong Ye Yi-Jin Gao Jing-Yan Tang Key Laboratory of Pediatric hematology and oncology Ministry of HealthDepartment of Pediatric Hematology and OncologyShanghai Children's Medical CenterShanghai Jiaotong University School of Medicine(SJTU-SM)ShanghaiChina

Background Although localized neuroblastoma has a good prognosis,some cases have undergone treatment failure or *** from biologic features such as MYCN status,we wondered whether some characteristics of growing tumors are prognostic,such as a well-encapsulated mass without infiltration of vital *** analyzed the diagnostic utility of image-defined risk factors(IDRFs)to predict successful treatment and *** overall goal was to achieve maximum cure rates for patients with localized neuroblastoma through a better understanding of clinical *** We retrospectively reviewed the images of patients with localized neuroblastoma who were enrolled between June 1998 and December 2012 at a single institution in Shanghai,*** categorization regarding IDRFs was available in 67 *** was assessed at diagnosis and after four cycles of neoadjuvant chemotherapy,on *** median follow-up period was 84 months(range: 48-132 months)after *** MRI and CT indicated a total of 177 IDRFs in these 67 *** regression analysis revealed a highly significant negative correlation between the numbers of IDRFs and the possibility of complete removal of *** extension of the tumor,compression of the trachea,and encasement of the main artery in localized neuroblastoma were predictors for incomplete tumor *** to univariate analysis,≥4 IDRFs and intraspinal extension of the tumor were significant indicators of poor *** The number of IDRFs was useful in predicting surgical outcome and event-free *** number of IDRFs should be considered in protocol planning,instead of IDRF presence or absence.

关键词： Image-defined risk factors Localized neuroblastoma Prognosis Surgery

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