With approximately one million diagnosed cases and over 700,000 deaths recorded annually, gastric... more With approximately one million diagnosed cases and over 700,000 deaths recorded annually, gastric cancer (GC) is the third most common cause of cancer-related deaths worldwide. GC is a heterogeneous tumor. Thus, optimal management requires biomarkers of prognosis, treatment selection, and treatment response. The Cancer Genome Atlas program sub-classified GC into molecular subtypes, providing a framework for treatment personalization using traditional chemotherapies or biologics. Here, we report a comprehensive study of GC vascular and immune tumor microenvironment (TME)-based on stage and molecular subtypes of the disease and their correlation with outcomes. Using tissues and blood circulating biomarkers and a molecular classification, we identified cancer cell and tumor archetypes, which show that the TME evolves with the disease stage and is a major determinant of prognosis. Moreover, our TME-based subtyping strategy allowed the identification of archetype-specific prognostic biom...
Experimental models of a clinical, pathophysiological context are used to understand molecular me... more Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatmen...
Despite advances in cancer detection and therapy, it has been estimated that the incidence of can... more Despite advances in cancer detection and therapy, it has been estimated that the incidence of cancers will increase, while the mortality rate will continue to remain high, a fact explained by the large number of patients diagnosed in advanced stages when therapy is often useless. Therefore, it is necessary to invest knowledge and resources in the development of new non-invasive biomarkers for the early detection of cancer and new therapeutic targets for better health management. In this review, we provided an overview on the collagen family as promising biomarkers and on how they may be exploited as therapeutic targets in cancer. The collagen family tridimensional structure, organization, and functions are very complex, being in a tight relationship with the extracellular matrix, tumor, and immune microenvironment. Moreover, accumulating evidence underlines the role of collagens in promoting tumor growth and creating a permissive tumor microenvironment for metastatic dissemination. ...
The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens th... more The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Neverthe...
In this study, we analyzed the obstetric factors affecting total nucleated cells (TNC) content of... more In this study, we analyzed the obstetric factors affecting total nucleated cells (TNC) content of cord blood units to establish the criteria for umbilical cord blood (UCB) donor selection in our geographic area. UCB was collected from normal uncomplicated pregnancies. In every case, following data were recorded: (1) gestation length; (2) type of delivery (cesarean or vaginal); and (3) newborn characteristics: weight and sex. For each sample, TNC content, percentage and number of CD34+ cells, and viability were analyzed. The results showed that TNC content increases with cord blood volume, gestational length and newborn weight. The mean blood volume and the mean TNC per unit were 42.37 ± 13.5 ml and 55.49 ± 19.4 × 107, respectively. Stepwise regression analysis revealed a positive and significant correlation (r= 0.89) between these two variables. Meanwhile the CD34+ cell content remains unchanged in deliveries at 32–40 weeks of gestation. The mean CD34+ percentage obtained was 0.37 ±...
Recent findings demonstrated that stem cells could be harvested from a patient and used to repair... more Recent findings demonstrated that stem cells could be harvested from a patient and used to repair his or her own damaged liver. Additionally, stem cells may be manipulated in vitro to induce hepatic differentiation. The current study aims to determine the differentiation efficacy of various liver-specific factors (hepatocyte growth factor, Insulin-Transferrin-Selenium, dexamethasone, and nicotinamide) used for stem cell differentiation into hepatocyte-like cells. Human mesenchymal stem cells were exposed to different media containing these compounds added individually or in various combinations. Hepatic differentiation was assessed via quantitative reverse transcription-polymerase chain reaction and immunocytochemical staining for stemness or liver-specific genes and proteins, including albumin, cytokeratins 18 and 19, HepPar-1, alpha-fetoprotein, and nestin. In addition, functional tests for glycogen storage, urea production, glucose, and albumin synthesis were also performed. The expression profiles of albumin, alpha-fetoprotein, and cytokeratin 19 demonstrated that when hepatocyte growth factor, nicotinamide, or dexamethasone were added individually, incomplete hepatocyte differentiation was achieved; the obtained cell populations contained progenitors that expressed both hepatic (albumin) and biliary (cytokeratin 19) markers, as well as alpha-fetoprotein. Hepatocyte growth factor and nicotinamide were the factors with the most hepatogenic potential. When all factors were added to the culture, cells exhibited features that closely resembled human adult hepatocytes as determined by their gene expression patterns (albumin, HepPar-1, and alpha-fetoprotein, but not cytokeratin 19) and functional testing. These cells with hepatic function may become important tools for liver transplant procedures, liver development studies, and pharmacologic research.
This study aimed to understand gradual biological variations during gastric tumorigenesis, and to... more This study aimed to understand gradual biological variations during gastric tumorigenesis, and to identify the candidate genes that are involved in tumor progression and metastasis. cDNA microarray data were obtained from 10 pair of cancerous and normal adjacent tissue from gastric adenocarcinoma patients. The samples were divided in primary and advanced gastric adenocarcinoma with lymph node metastasis. Validation of the microarray data was accomplished by quantitative RT-PCR on additional 41 samples. The significantly modified genes were grouped in clusters according to their functional annotation, and comparison was done regarding molecular mechanisms involved tumor progression. A total of 136 genes were up-regulated and 96 genes were down-regulated by at least fourfold in tumor tissue. The analysis of gene clusters revealed a complex remodelling of normal gastric epithelium morphology and function associated with the tumorigenesis and metastasis. A large number of proteases are ...
The aim of this study was to investigate the virucid and cytotoxic activity of two hydroalcoholic... more The aim of this study was to investigate the virucid and cytotoxic activity of two hydroalcoholic extracts from French tamarisk (Tamarix gallica) and Milk thistle (Silybum marianum), plants that have been used for their therapeutic effects from ancient times. Each of these extracts was extensively studied for their hepatoprotective and stimulant effects, sometimes with contradictory results. The present study investigates for the first time the antiviral effect and cytoxicity of these extracts using a set of European standardized procedures for the virucidal activity testing in human medicine. Antiviral activity demonstrated by the two extracts complete and sustain our previous results on the hepatoprotective effect of a pharmaceutical product that has both extracts in its composition. Rezumat Scopul prezentului studiu a fost acela de a investiga activitatea virucidă și citotoxică a două extracte hidroalcoolice obținute din cătină roșie (Tamarix gallica) și armurariu (Silybum marian...
The tumor suppressor TP53 gene is one of the commonest mutated genes in colorectal cancer. Beside... more The tumor suppressor TP53 gene is one of the commonest mutated genes in colorectal cancer. Beside somatic mutations, the gene harbors numerous genetic variations that may alter the protein functionality, affecting cancer risk and clinical outcome. Among genetic variations, single nucleotide polymorphisms were investigated in relation to cancer risk, including colorectal cancer susceptibility. The studies revealed that the distribution of polymorphic alleles and their functional relevance varied in a population-dependent manner. In the present work we analyzed the distribution of eleven TP53 genetic variants in a lot of 63 colorectal cancer patients. The polymorphisms with minor allele frequency between 12%-21% and the resulting haplotypes were examined for association with clinicopathological features of colorectal tumors, TP53 somatic mutations and allelic instability at TP53 locus. The polymorphisms rs1625895, rs1042522, rs1642785 and rs17878362 located in intron 6, exon 4, intron...
CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine pr... more CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-be...
Chronic pancreatitis is a progressive inflammatory d isease destroying secretory pancreatic paren... more Chronic pancreatitis is a progressive inflammatory d isease destroying secretory pancreatic parenchyma. Total pancreatectomy and islet autotran splantation (IAT) is a viable option in selected patients in order to decrease mortality and improve hyperglycemia. Duodenum and spleen preserving total pancreatectomy and islet autotransplantation was done in 53 years old woman, with chronic pancreatitis affecting the whole pancreas. Human is let isolation was performed in the Fundeni GMP Laboratory, after informed consent has been obtaine d. Trimmed and cannulated pancreas was distended with enzymatic solution containing: 20U/g pancreas GMP grade NB1 colagenase and 0.6U/ g pancreas neutral protease in HBSS solution by inject ion of cold enzyme solution through the pancreatic duct using a perfusion Biorep system. The digestion was performed using automated method in a Ricordi chamber maintaining temperature between 32 0 C and 38 0 C. Dissociation of the pancreas and appearance of free islet...
Journal of Gastrointestinal and Liver Diseases, 2012
A point mutation (gp130Y757F/Y759F) was identified as being responsible for aberrant activation o... more A point mutation (gp130Y757F/Y759F) was identified as being responsible for aberrant activation of gp130 in mice and associated with gastric adenocarcinoma induction. As a result, we investigated the possible role of key point mutations in Tyr from IL6ST exon 17 that encode for the catalytic domain of gp130, and of its respective activators (IL-6 family member cytokines) in human gastric cancer initiation and development. DNA, protein and plasma from 51 patients with gastric adenocarcinoma have been used in exploring gp130 status. We used sequencing analysis of IL6ST exon 17 in order to identify possible mutations that would lead to constitutive active forms of the receptor. The levels of gp130 activators (IL-6, IL-11, LIF) were analyzed by ELISA in plasma and mucosa of patients with gastric adenocarcinoma. Sequencing analysis did not identify mutations in gp130 key positions (Y759, Y767, Y814, Y905 and Y915). An increased IL-6 and IL-11 level in gastric mucosa was observed, correla...
Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, of... more Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, offering a less invasive and more convenient approach to obtain a time-point image of the tumor burden and its genomic profile. Samples collected from several body fluids, mostly blood, can be used to gain access to circulating tumor cells and DNA, non-coding RNAs, microRNAs, and exosomes, at any moment, offering a dynamic picture of the tumor. For patients with GC, the use of blood-based biopsies may be particularly beneficial since tissue biopsies are difficult to obtain and cause real distress to the patient. With advantages such as repeatability and minimal invasion, it is no wonder that the field of liquid biopsy has received tremendous attention. However, the abundance of studies, involving a wide range of assays with different principles, prevented for the moment the reproducibility of the results and therefore the translation into the clinic of liquid biopsy. In this review, we pre...
The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recogni... more 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.
With approximately one million diagnosed cases and over 700,000 deaths recorded annually, gastric... more With approximately one million diagnosed cases and over 700,000 deaths recorded annually, gastric cancer (GC) is the third most common cause of cancer-related deaths worldwide. GC is a heterogeneous tumor. Thus, optimal management requires biomarkers of prognosis, treatment selection, and treatment response. The Cancer Genome Atlas program sub-classified GC into molecular subtypes, providing a framework for treatment personalization using traditional chemotherapies or biologics. Here, we report a comprehensive study of GC vascular and immune tumor microenvironment (TME)-based on stage and molecular subtypes of the disease and their correlation with outcomes. Using tissues and blood circulating biomarkers and a molecular classification, we identified cancer cell and tumor archetypes, which show that the TME evolves with the disease stage and is a major determinant of prognosis. Moreover, our TME-based subtyping strategy allowed the identification of archetype-specific prognostic biom...
Experimental models of a clinical, pathophysiological context are used to understand molecular me... more Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatmen...
Despite advances in cancer detection and therapy, it has been estimated that the incidence of can... more Despite advances in cancer detection and therapy, it has been estimated that the incidence of cancers will increase, while the mortality rate will continue to remain high, a fact explained by the large number of patients diagnosed in advanced stages when therapy is often useless. Therefore, it is necessary to invest knowledge and resources in the development of new non-invasive biomarkers for the early detection of cancer and new therapeutic targets for better health management. In this review, we provided an overview on the collagen family as promising biomarkers and on how they may be exploited as therapeutic targets in cancer. The collagen family tridimensional structure, organization, and functions are very complex, being in a tight relationship with the extracellular matrix, tumor, and immune microenvironment. Moreover, accumulating evidence underlines the role of collagens in promoting tumor growth and creating a permissive tumor microenvironment for metastatic dissemination. ...
The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens th... more The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Neverthe...
In this study, we analyzed the obstetric factors affecting total nucleated cells (TNC) content of... more In this study, we analyzed the obstetric factors affecting total nucleated cells (TNC) content of cord blood units to establish the criteria for umbilical cord blood (UCB) donor selection in our geographic area. UCB was collected from normal uncomplicated pregnancies. In every case, following data were recorded: (1) gestation length; (2) type of delivery (cesarean or vaginal); and (3) newborn characteristics: weight and sex. For each sample, TNC content, percentage and number of CD34+ cells, and viability were analyzed. The results showed that TNC content increases with cord blood volume, gestational length and newborn weight. The mean blood volume and the mean TNC per unit were 42.37 ± 13.5 ml and 55.49 ± 19.4 × 107, respectively. Stepwise regression analysis revealed a positive and significant correlation (r= 0.89) between these two variables. Meanwhile the CD34+ cell content remains unchanged in deliveries at 32–40 weeks of gestation. The mean CD34+ percentage obtained was 0.37 ±...
Recent findings demonstrated that stem cells could be harvested from a patient and used to repair... more Recent findings demonstrated that stem cells could be harvested from a patient and used to repair his or her own damaged liver. Additionally, stem cells may be manipulated in vitro to induce hepatic differentiation. The current study aims to determine the differentiation efficacy of various liver-specific factors (hepatocyte growth factor, Insulin-Transferrin-Selenium, dexamethasone, and nicotinamide) used for stem cell differentiation into hepatocyte-like cells. Human mesenchymal stem cells were exposed to different media containing these compounds added individually or in various combinations. Hepatic differentiation was assessed via quantitative reverse transcription-polymerase chain reaction and immunocytochemical staining for stemness or liver-specific genes and proteins, including albumin, cytokeratins 18 and 19, HepPar-1, alpha-fetoprotein, and nestin. In addition, functional tests for glycogen storage, urea production, glucose, and albumin synthesis were also performed. The expression profiles of albumin, alpha-fetoprotein, and cytokeratin 19 demonstrated that when hepatocyte growth factor, nicotinamide, or dexamethasone were added individually, incomplete hepatocyte differentiation was achieved; the obtained cell populations contained progenitors that expressed both hepatic (albumin) and biliary (cytokeratin 19) markers, as well as alpha-fetoprotein. Hepatocyte growth factor and nicotinamide were the factors with the most hepatogenic potential. When all factors were added to the culture, cells exhibited features that closely resembled human adult hepatocytes as determined by their gene expression patterns (albumin, HepPar-1, and alpha-fetoprotein, but not cytokeratin 19) and functional testing. These cells with hepatic function may become important tools for liver transplant procedures, liver development studies, and pharmacologic research.
This study aimed to understand gradual biological variations during gastric tumorigenesis, and to... more This study aimed to understand gradual biological variations during gastric tumorigenesis, and to identify the candidate genes that are involved in tumor progression and metastasis. cDNA microarray data were obtained from 10 pair of cancerous and normal adjacent tissue from gastric adenocarcinoma patients. The samples were divided in primary and advanced gastric adenocarcinoma with lymph node metastasis. Validation of the microarray data was accomplished by quantitative RT-PCR on additional 41 samples. The significantly modified genes were grouped in clusters according to their functional annotation, and comparison was done regarding molecular mechanisms involved tumor progression. A total of 136 genes were up-regulated and 96 genes were down-regulated by at least fourfold in tumor tissue. The analysis of gene clusters revealed a complex remodelling of normal gastric epithelium morphology and function associated with the tumorigenesis and metastasis. A large number of proteases are ...
The aim of this study was to investigate the virucid and cytotoxic activity of two hydroalcoholic... more The aim of this study was to investigate the virucid and cytotoxic activity of two hydroalcoholic extracts from French tamarisk (Tamarix gallica) and Milk thistle (Silybum marianum), plants that have been used for their therapeutic effects from ancient times. Each of these extracts was extensively studied for their hepatoprotective and stimulant effects, sometimes with contradictory results. The present study investigates for the first time the antiviral effect and cytoxicity of these extracts using a set of European standardized procedures for the virucidal activity testing in human medicine. Antiviral activity demonstrated by the two extracts complete and sustain our previous results on the hepatoprotective effect of a pharmaceutical product that has both extracts in its composition. Rezumat Scopul prezentului studiu a fost acela de a investiga activitatea virucidă și citotoxică a două extracte hidroalcoolice obținute din cătină roșie (Tamarix gallica) și armurariu (Silybum marian...
The tumor suppressor TP53 gene is one of the commonest mutated genes in colorectal cancer. Beside... more The tumor suppressor TP53 gene is one of the commonest mutated genes in colorectal cancer. Beside somatic mutations, the gene harbors numerous genetic variations that may alter the protein functionality, affecting cancer risk and clinical outcome. Among genetic variations, single nucleotide polymorphisms were investigated in relation to cancer risk, including colorectal cancer susceptibility. The studies revealed that the distribution of polymorphic alleles and their functional relevance varied in a population-dependent manner. In the present work we analyzed the distribution of eleven TP53 genetic variants in a lot of 63 colorectal cancer patients. The polymorphisms with minor allele frequency between 12%-21% and the resulting haplotypes were examined for association with clinicopathological features of colorectal tumors, TP53 somatic mutations and allelic instability at TP53 locus. The polymorphisms rs1625895, rs1042522, rs1642785 and rs17878362 located in intron 6, exon 4, intron...
CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine pr... more CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-be...
Chronic pancreatitis is a progressive inflammatory d isease destroying secretory pancreatic paren... more Chronic pancreatitis is a progressive inflammatory d isease destroying secretory pancreatic parenchyma. Total pancreatectomy and islet autotran splantation (IAT) is a viable option in selected patients in order to decrease mortality and improve hyperglycemia. Duodenum and spleen preserving total pancreatectomy and islet autotransplantation was done in 53 years old woman, with chronic pancreatitis affecting the whole pancreas. Human is let isolation was performed in the Fundeni GMP Laboratory, after informed consent has been obtaine d. Trimmed and cannulated pancreas was distended with enzymatic solution containing: 20U/g pancreas GMP grade NB1 colagenase and 0.6U/ g pancreas neutral protease in HBSS solution by inject ion of cold enzyme solution through the pancreatic duct using a perfusion Biorep system. The digestion was performed using automated method in a Ricordi chamber maintaining temperature between 32 0 C and 38 0 C. Dissociation of the pancreas and appearance of free islet...
Journal of Gastrointestinal and Liver Diseases, 2012
A point mutation (gp130Y757F/Y759F) was identified as being responsible for aberrant activation o... more A point mutation (gp130Y757F/Y759F) was identified as being responsible for aberrant activation of gp130 in mice and associated with gastric adenocarcinoma induction. As a result, we investigated the possible role of key point mutations in Tyr from IL6ST exon 17 that encode for the catalytic domain of gp130, and of its respective activators (IL-6 family member cytokines) in human gastric cancer initiation and development. DNA, protein and plasma from 51 patients with gastric adenocarcinoma have been used in exploring gp130 status. We used sequencing analysis of IL6ST exon 17 in order to identify possible mutations that would lead to constitutive active forms of the receptor. The levels of gp130 activators (IL-6, IL-11, LIF) were analyzed by ELISA in plasma and mucosa of patients with gastric adenocarcinoma. Sequencing analysis did not identify mutations in gp130 key positions (Y759, Y767, Y814, Y905 and Y915). An increased IL-6 and IL-11 level in gastric mucosa was observed, correla...
Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, of... more Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, offering a less invasive and more convenient approach to obtain a time-point image of the tumor burden and its genomic profile. Samples collected from several body fluids, mostly blood, can be used to gain access to circulating tumor cells and DNA, non-coding RNAs, microRNAs, and exosomes, at any moment, offering a dynamic picture of the tumor. For patients with GC, the use of blood-based biopsies may be particularly beneficial since tissue biopsies are difficult to obtain and cause real distress to the patient. With advantages such as repeatability and minimal invasion, it is no wonder that the field of liquid biopsy has received tremendous attention. However, the abundance of studies, involving a wide range of assays with different principles, prevented for the moment the reproducibility of the results and therefore the translation into the clinic of liquid biopsy. In this review, we pre...
The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recogni... more 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.
Uploads