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Chemically oligomerizable TDP-43:a novel chemogenetic tool for studying the pathophysiology of amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第11期17卷 2434-2436页

作者： Kohsuke Kanekura Yoshiaki Yamanaka Tamami Miyagi Masahiko Kuroda department of molecular pathology Tokyo Medical University

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of both upper and lower motor neurons.Most ALS cases are sporadic,but approximately 5-10%of patients have a familial background.To date,more than 30 familial ALS-causative genes have been identified (Maurel et al., 2018).

关键词： sclerosis familial

Purinergic signaling systems across comparative models of spinal cord injury

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Neural Regeneration Research 2022年第3期17卷 2391-2398页

作者： Eva E.Stefanova Angela L.Scott department of pathology and molecular Medicine McMaster UniversityHamiltonONCanada

Within the last several decades,the scientific community has made substantial progress in elucidating the complex pathophysiology underlying spinal cord injury.However,despite the many advances using conventional mammalian models,both cellular and axonal regeneration following spinal cord injury have remained out of reach.In this sense,turning to non-mammalian,regenerative species presents a unique opportunity to identify pro-regenerative cues and chara cterize a spinal cord microenvironment permissive to re-growth.Among the signaling pathways hypothesized to be dysregulated during spinal cord injury is the purinergic signaling system.In addition to its well-known role as energy currency in cells,ATP and its metabolites are small molecule neurotransmitte rs that mediate many diverse cellular processes within the central nervous system.While our unde rstanding of the roles of the purinergic system following spinal cord injury is limited,this signaling pathway has been implicated in all injury-induced secondary processes,including cellular death,inflammation,reactive gliosis,and neural regeneration.Given that the purinergic system is also evolutionarily conserved between mammalian and non-mammalian species,comparisons of these roles may provide important insights into conditions responsible for recovery success.Here,we compare the secondary processes between key model species and the influence of purinergic signaling in each context.As our understanding of this signaling system and pro-regenerative conditions continues to evolve,so does the potential for the development of novel therapeutic interventions for spinal cord injury.

关键词： cell death differenriation glia inflammation neurogenesis proliferation purinergic signaling reactive gliosis regeneration spinal cord injury teleost

Recent advances in gastric cancer early diagnosis

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World Journal of Gastroenterology 2019年第17期25卷 2029-2044页

作者： Laura Necula Lilia Matei Denisa Dragu Ana I Neagu Cristina Mambet Saviana Nedeianu Coralia Bleotu Carmen C Diaconu Mihaela Chivu-Economescu department of cellular and molecular pathology Stefan S.Nicolau Institute of Virology Faculty of Medicine Titu Maiorescu University

Gastric cancer(GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva,stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

关键词： Biomarkers Gastric cancer Early diagnosis Genetic and epigenetic alterations Circulating molecules

New therapeutic options opened by the molecular classification of gastric cancer

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World Journal of Gastroenterology 2018年第18期24卷 1942-1961页

作者： Mihaela Chivu-Economescu Lilia Matei Laura G Necula Denisa L Dragu Coralia Bleotu Carmen C Diaconu department of cellular and molecular pathology Stefan S. Nicolau Institute of Virology Nicolae Cajal Institute Titu Maiorescu University

Gastric cancer(GC) is one of the most lethal and aggressive cancers, being the third cause of cancer related death worldwide. Even with radical gastrectomy and the latest generation of molecular chemotherapeutics, the numbers of recurrence and mortality remains high. This is due to its biological heterogeneity based on the interaction between multiple factors, from genomic to environmental factors, diet or infections with various pathogens. Therefore, understanding the molecular characteristics at a genomic level is critical to develop new treatment strategies. Recent advances in GC molecular classification provide the unique opportunity to improve GC therapy by exploiting the biomarkers and developing novel targeted therapy specific to each subtype. This article highlights the molecular characteristics of each subtype of gastric cancer that could be considered in shaping a therapeutic decision, and also presents the completed and ongoing clinical trials addressed to those targets. The implementation of the novel molecular classification system will allow a preliminary patient selection for clinical trials, a mandatory issue if it is desired to test the efficacy of a certain inhibitor to the given target. This will represent a substantial advance as well as a powerful tool for targeted therapy. Nevertheless, translating the scientific results into new personalized treatment opportunities is needed in order to improve clinical care, the survival and quality of life of patients with GC.

关键词： Gastric cancer molecular classification Immunotherapy Targeted therapy Clinical trials

Murine models based on acute myeloid leukemia-initiating stem cells xenografting

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World Journal of Stem Cells 2018年第6期10卷 57-65页

作者： Cristina Mambet Mihaela Chivu-Economescu Lilia Matei Laura Georgiana Necula Denisa Laura Dragu Coralia Bleotu Carmen Cristina Diaconu cellular and molecular pathology department Stefan S. Nicolau Institute of Virology Nicolae Cajal Institute Titu Maiorescu University

Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.

关键词： Acute myeloid leukemia Leukemia-initiating stem cells Antigen markers Murine models Xenografts

Next-generation sequencing and its clinical application

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Cancer Biology & Medicine 2019年第1期16卷 4-10页

作者： Dahui Qin molecular Diagnostic Laboratory Department of Pathology Moffitt Cancer Center

Next-generation sequencing (NGS) is a new technology used for DNA and RNA sequencing and variant/mutation detection. NGS can sequence hundreds and thousands of genes or whole genome in a short period of time. The sequence variants/mutations detected by NGS have been widely used for disease diagnosis, prognosis, therapeutic decision, and follow up of patients. The capacity of its massive parallel sequencing offers new opportunities for personalized precision medicine.

关键词： NGS DNA capacity

Multiple pathological components in gliosarcoma

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The Journal of Biomedical Research 2021年第5期35卷 408-410页

作者： Nan NJiang Ramiro Larrazabal Waleed Alsunbul Jian-Qiang Lu department of Radiology department of Surgery/Neurosurgery department of pathology and molecular

Dear Editor:Our recent article"Angiosarcomatous component in Glioblastoma:case report and consideration of diagnostic challenge and hemorrhagic propensity"published in The Journal of Biomedical Research[1]demonstrated an interesting case of gliosarcoma with alternating gliomatous and angiosarcomatous components,which on imaging,displayed unique intratumorally piliform enhancement pattern and clinically,exhibited an increased tendency for intraoperative hemorrhage.Indeed,gliosarcoma may be composed of various different pathological components and may dictate the radiological features and clinical presentations that make preoperative diagnosis extremely difficult.

关键词： sarcoma diagnosis pathological

Gastrointestinal cancer stem cells as targets for innovative immunotherapy

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World Journal of Gastroenterology 2020年第14期26卷 1580-1593页

作者： Mihaela Chivu-Economescu Laura G Necula Lilia Matei Denisa Laura Dragu Ana I Neagu Irina Alexiu Coralia Bleotu Carmen Cristina Diaconu department of cellular and molecular pathology Stefan S.Nicolau Institute of VirologyBucharest 030304Romania Nicolae Cajal Institute Titu Maiorescu UniversityBucharest 040441Romania

The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized.Gastrointestinal cancer stem cells(GCSCs)are considered to be responsible for tumor initiation,growth,resistance to cytotoxic therapies,recurrence and metastasis due to their unique properties.These properties make the current therapeutic trials against GCSCs ineffective.Moreover,recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system.Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy.This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells,instead of aiming physically destruction of cancer cells through radio-or chemotherapy.New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens,using innate immune cells like the natural killer and T cells,T-cell chimeric antigen receptor technology,dendritic cell vaccine,or immune checkpoint inhibitors.In this respect,better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.

关键词： Immunotherapy Gastrointestinal cancer Cancer stem cells CAR-T Dendritic cells vaccines Immune checkpoints inhibitors

Barriers to axonal regeneration after spinal cord injury:a current perspective

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Neural Regeneration Research 2022年第1期17卷 85-86页

作者： Jacek M.Kwiecien department of pathology and molecular Medicine Faculty of Health SciencesMcMaster UniversityHamiltonOntarioCanada

Regeneration of long axons after the spinal cord injury(SCI)will benefit patients with extensive traumatic damage to the white matter pathways who experience intolerable,permanent,neurologic deficits even after neuroprotective treatment with anti-inflammatory agents(Kwiecien,2021a).This short paper attempts to synthetize pathologic mechanisms or barriers involved in inhibition of axonal regeneration in the SCI and provides suggestions of therapeutic interventions enabling this regeneration in animal models.

关键词： protective axonal injury