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Gastrointestinal cancer stem cells as targets for innovative immunotherapy

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

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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

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High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients

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World Journal of Gastroenterology 2020年第22期26卷 3024-3033页

作者： Laura Necula Lilia Matei Denisa Dragu ioana Pitica ana iulia neagu Coralia Bleotu Simona Dima irinel Popescu Carmen C Diaconu Mihaela Chivu-Economescu Department of Cellular and Molecular Pathology Stefan S.Nicolau Institute of VirologyBucharest 030304Romania Titu Maiorescu University Faculty of MedicineBucharest 040441Romania Fundeni Clinical institute Bucharest 022328Romania

BACKGROUND Gastric cancer(GC)remains an aggressive malignancy with a high rate of mortality,being the third leading cause of cancer-related death.More than one million newly diagnosed cases and 782685 deaths due to GC were reported in 2018.GC is characterized by limited effective treatment options and the lack of consistent biomarkers for the diagnosis and prognosis of these patients.The discovery of new biomarkers useful in the early diagnosis of GC is mandatory.AiM To evaluate the potential of COL10A1 as a circulating biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.METHODS Plasma and tissue obtained from 49 patients with gastric adenocarcinoma have been used in exploring the expression of COL10A1.Real-time PCR and western blot techniques were used to evaluate COL10A1 level in gastric tumor tissue compared to normal adjacent tissue.The circulating level of COL10A1 was also evaluated by ELiSA in plasma of gastric adenocarcinoma patients.Survival analysis was made in order to evaluate the potential of COL10A1 as a biomarker for the diagnosis and prognosis of gastric adenocarcinoma patients.RESULTS Our results showed a significant increase in COL10A1 gene expression and protein levels in gastric tumor tissue compared to adjacent normal tissue(Pion from the beginning of carcinogenesis,in the early stages,and its increased level remains elevated during cancer progression.A significant increase of COL10A1 plasma level in gastric adenocarcinoma patients was also identified.Moreover,increased COL10A1 plasma level was associated with poor survival of the patients.Plasma COL10A1 performed a diagnostic value in GC with area under the receiver operating characteristic curve(AUC)of 0.9171(P=0.0002),sensitivity of 87.76%,and specificity of 100.0%.Furthermore,this study demonstrated the potential role of plasma COL10A1 in the early detection of GC,as in the early stage,we obtained an AUC of 0.8789(P=0.0030),sensitivity of 81.25%,and specificity of 100

关键词： Gastric cancer COL10A1 Circulating biomarkers Early diagnosis Poor prognosis Tumor stage

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Cancer stem cells: involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics

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World Journal of Gastroenterology 2014年第31期20卷 10790-10801页

作者： Cristiana Pistol Tanase ana iulia neagu Laura Georgiana Necula Cristina Mambet ana-Maria Enciu Bogdan Calenic Maria Linda Cruceru Radu Albulescu Department of Biochemistry-Proteomics Victor Babes National Institute of Pathology Stefan S Nicolau institute of Virology Carol Davila University of Medicine and Pharmacy National institute for Chemical Pharmaceutical Research and Development

Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells(CSCs). in pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs.

关键词： Cancer stem cells Pancreatic cancer Cancer stem ce

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