Publications by authors named "Orit Uziel"

We hypothesized that via extracellular vesicles (EVs), chronic lymphocytic leukemia (CLL) cells turn endothelial cells into CLL-supportive cells. To test this, we treated vein-derived (HUVECs) and artery-derived (HAOECs) endothelial cells with EVs isolated from the peripheral blood of 45 treatment-naïve patients. Endothelial cells took up CLL-EVs in a dose- and time-dependent manner.

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Although the dynamics of telomeres during the life expectancy of normal cells has been extensively studied, there are still some unresolved issues regarding this research field. For example, the conditions required for telomere shortening leading to malignant transformations are not fully understood. In this work, we mass analyzed DNA of normal and cancer cells for comparing telomere isotopic compositions of white blood cells and cancer cells.

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Background: In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism. The expression of human telomerase reverse transcriptase (hTERT) enables telomere maintenance and provides cancer cells with limitless replicative potential. As such, it may serve as an attractive biomarker for oncogenic activity.

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Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals.

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Multiple myeloma (MM) is the second most common haematological malignancy. Despite the development of new drugs and treatments in recent years, the therapeutic outcomes of patients are not satisfactory. It is necessary to further investigate the molecular mechanism underlying MM progression.

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Physiological and psychological distress may accelerate cellular aging, manifested by shortening of telomere length (TL). The present study focused on TL shortening in anorexia nervosa (AN), an illness combining physiological and psychological distress. For that purpose, we measured TL in 44 female adolescents with AN at admission to inpatient treatment, in a subset of 18 patients also at discharge, and in 22 controls.

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Early detection of tumor cells by identifying universal Tumor Associated Antigens (TAA) can drastically change our diagnostic, theranostic and therapeutic possibilities to cure cancer. Human Telomerase Reverse Transcriptase (hTERT), a hallmark of cancer, could act as an optimal TAA candidate. Here we report about the development of a monoclonal antibody against hTERT peptide (α-hTERT mAb) presented on the surface of cancer cells and its possible applications as a pan-cancer marker.

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Article Synopsis
  • The study examined the levels of hTERT-mRNA in exosomes from the serum of colon cancer patients, Lynch syndrome carriers, and healthy controls to assess its potential as a diagnostic marker.
  • Results showed that colon cancer patients had significantly higher hTERT-mRNA levels compared to healthy individuals, and those with metastatic disease had even higher levels that correlated with CEA levels.
  • The findings also indicated that Lynch syndrome carriers had a higher occurrence of positive hTERT-mRNA in exosomes than controls, suggesting the need for further research to understand its role in cancer development.
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It is now well accepted that cancer cells change their microenvironment from normal to tumor-supportive state to provide sustained tumor growth, metastasis and drug resistance. These processes are partially carried out by exosomes, nano-sized vesicles secreted from cells, shuttled from donor to recipient cells containing a cargo of nucleic acids, proteins and lipids. By transferring biologically active molecules, cancer-derived exosomes may transform microenvironmental cells to become tumor supportive.

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Objectives: Evidence suggests that individuals with physical disability may suffer from psychological distress and accelerated cellular aging, manifested by shortened telomere length (TL), compared with healthy individuals. Studies indicate that high levels of perceived stress and depression may increase the physiological susceptibility and, thus, may contribute to a short TL. However, the moderating role of perceived stress and depression within the relationship between physical disability and TL remains unknown.

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Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists.

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Article Synopsis
  • An amendment to the original paper has been published.
  • The amendment provides updates or corrections to the previous content.
  • You can access the amendment through a link located at the top of the paper.
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Survivors of hematopoietic cell transplantation (HCT) have been shown to exhibit both clinical and biological features of accelerated ageing. Most studies used frailty measures, comorbidities for clinical assessment and several biological assessment of premature ageing. However, these tests are less suitable for age determination of individual patients.

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The wingless and integration site growth factor-5a (Wnt5a) is a ligand of the receptor tyrosine kinase-like orphan receptor-1 (ROR1). Because both Wnt5a and ROR1 are expressed in circulating chronic lymphocytic leukemia (CLL) cells, and because in other cell types, STAT3, which is constitutively activated in CLL, induces Wnt5a signaling, we wondered whether STAT3 induces the expression of Wnt5a in CLL cells. Sequence analysis detected four putative STAT3 binding sites in close proximity to the Wnt5a gene promoter's start codon.

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Objective: evaluation of telomere length change in acutely ill adult patients.

Design: Blood samples were drawn on the first and seventh day of intensive care unit (ICU) stay to assess telomere length using a polymerase chain reaction (PCR)-based technique. Demographic data collected included age, weight, admission diagnosis, baseline laboratory values (pH, C- reactive protein (CRP), serum albumin level, white blood cell count (WBC) count, platelet count), and baseline SOFA and APACHE II scores.

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Objectives: Sleep is necessary for brain function as well as physical and cognitive processes. Sleep disruptions, common with aging, intensify among trauma survivors. Moreover, former prisoners-of-war (ex-POWs) often experience premature aging.

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The importance of telomerase, the enzyme that maintains telomere length, has been reported in many malignancies in general and in multiple myeloma (MM) in particular. Proteasome inhibitors are clinically used to combat effectively MM. Since the mechanism of action of proteasome inhibitors has not been fully described we sought to clarify its potential effect on telomerase activity (TA) in MM cells.

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A ground glass opacity (GGO) lung lesion may represent early stage adenocarcinoma, which has an excellent prognosis upon prompt surgical resection. However, GGO lesions have broad differential diagnoses, including both benign and malignant lesions. Our objective was to study telomere length and telomerase activity in patients with suspected lung cancer in which GGO was the predominant radiographic feature.

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Telomeres (TLs) protect chromosome ends from chromosomal fusion and degradation, thus conferring genomic stability, and play crucial roles in cellular aging and disease. Recent studies have found a correlation between environmental, physiological and even mental stresses on TL dynamics in humans. However, the causal relationship between stress and TL length and the molecular mechanisms underlying that relationship are far from being understood.

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Objectives: Telomere length (TL) is a robust indicator of cellular aging. TL erosion has been associated with exposure to social and traumatic stressors. Loneliness and perceived social support are strongly linked to increased morbidity and mortality, but have yet to be investigated in relation to TL after extreme stress.

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Background: Telomere length (TL) serves as a biomarker of cellular senescence and is a robust predictor of mortality. The association between traumatic stress and TL erosion is rapidly realized, as are the complexities of this relation that include links to posttraumatic stress disorder (PTSD), depression, and psychosocial factors. Nevertheless, the relation between specific stressors in early adulthood and TL in later life, specifically among populations that have undergone extreme stress in early adulthood are largely uninvestigated.

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Exosomes, nano-vesicles secreted from all types of cells in the human body, function as inter-cell communicators. This role of exosomes is fulfilled by their specific content, dependent on the origin of donor cells from which they are secreted. Exosomes contain a plethora of nucleic acids (DNA, RNA and micro RNA), proteins and lipids.

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Background: Telomerase (human telomerase reverse transcriptase (hTERT)) is considered a hallmark of cancer. The aim of our study was to evaluate the feasibility of the detection of hTERT transcripts in serum as a 'pan-cancer' diagnostic method.

Methods: Human telomerase reverse transcriptase mRNA levels were determined in serum and serum-derived exosomes from 133 patients with different malignancies and 45 healthy controls.

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Background: Previous findings have demonstrated the link between trauma, its psychopathological aftermath and cellular aging, as reflected in telomere length. However, as long-term examinations of psychopathology following trauma are scarce, very little is known regarding the repercussions of depression and PTSD trajectories of psychopathology for telomeres. The current study examined the implications of war captivity and depression/PTSD trajectories on telomere length.

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The Popeye domain containing1, also called Bves (Popdc1/Bves), is a transmembrane protein that functions in muscle regeneration, heart rate regulation, hypoxia tolerance, and ischemia preconditioning. The expression of Popdc1/Bves is elevated in cardiomyocytes maintained in serum free defined medium. We hypothesized that Popdc1/Bves is important for cardiomyocyte survival under the stress of serum deprivation and investigated the mechanisms involved.

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