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"CAR T-cell therapy in liquid and solid tumors"
Abstract
CAR T cell therapy is a type of immunotherapy that utilizes synthetic, chimeric antigen receptors (CARs) to reprogram T cell antigen specificity and function. These genetically modified T cells are expanded in the lab and then infused into the patient, granting them the ability to fight certain types of diseases such as cancer. CAR T cell therapy has changed the way we view personalized cancer treatment especially in hematologic malignancies, altering the landscape of T cell-based immunotherapy. The MHC-independent CAR-mediated T cell recognition of malignant cells has led to a plethora of targets being tested for a wide variety of tumors. The targeting of CD19, a cell surface molecule expressed on normal B cells as well as in a vast majority of B cell malignancies, and BCMA, expressed on differentiated B cells and cancerous plasma cells, showed great results in the treatment of relapsed or refractory leukemia, lymphoma, and multiple myeloma, with significant clinical responses and high rates of complete remission. Despite the durable remissions in hematologic malignancies, CAR T cell therapy is limited by potentially severe toxicities. Cytokine release syndrome and neurological toxicities are still of great concern to the safety issue following CAR T cell infusion. Treatment of solid tumors using CAR T cell therapy is still a major challenge due to the heterogeneity of such tumors, their physical barriers, and the highly immunosuppressive nature of the solid tumor microenvironment.
TOLIS Rafail
"Difference on glucose profile from Continuous Glucose Monitoring in people with prediabetes vs. normoglycemic individuals: a matched-pair analysis"
Abstract
Background and aims: The glycemic profile of prediabetes, a borderline condition with blood glucose levels higher than normal but not enough to be officially diagnosed as diabetes, derived by continuous glucose monitoring (CGM) is currently unknown. We evaluate the difference of CGM profiles between individuals with prediabetes and matched normoglycemic individuals, including the response to oral glucose tolerance test (OGTT).
Materials and methods: Participants with prediabetes matched for age, sex and body mass index (BMI) with normoglycemic individuals were selected from an ongoing cohort study in Greece. Participants were ≥18 years, without known history of diabetes, no history of severe cardiovascular, liver, kidney, or pancreas diseases. Individuals with FPG levels between 100-124 mg/dL or HbA1c 5.7-6.4% were classified as prediabetes group, whereas participants with FPG <100 mg/dL and HbA1c <5.7% were categorized as normoglycemic. They were instructed to use professional CGM (Envision™ Pro, Medtronic; access to data retrospectively) for two weeks. In the morning of the 2 nd day, a 75g OGTT was performed during fasting state. The primary outcomes were percentages of glucose readings below range (TBR; <54 or <70 mg/dL), in range (TIR; 70-180 mg/dL) and above range (TAR; >180 or >250 mg/dL). Total and incremental areas under the glucose curve (AUC) were calculated between the beginning of the OGTT until two to four hours later. Glucose variability was depicted by the coefficient of variation (CV), standard deviation (SD) and mean amplitude of glucose excursions (MAGE). Wilcoxon sign-ranked test and McNemar mid p-test were employed to detect any differences between matched pairs. Multiple linear regression models were employed to investigate the differences on all outcomes between pre-diabetic and normal participants.
Results: A total of 36 participants (median age 51 years; median BMI 26.4 kg/m 2 ) formed 18 matched pairs. Statistically significant differences were observed for 24-hour TIR (median 98.5% vs. 99.9%, p = 0.013), TAR>180 mg/dl (0.4% vs. 0%, p = 0.0062), and 24-hour mean interstitial glucose (113.8 vs. 108.8 mg/dL, p = 0.0038) between individuals with prediabetes compared to normoglycemic participants. Similarly, there was a statistically significant difference both in daytime and nocturnal percentages of TIR between people with prediabetes and normoglycemic participants (p=0.0273, p=0.0087, respectively). Statistically significant differences favoring the normoglycemic group were found for glycemic variability indexes (median CV 15.2% vs. 11.9%, p = 0.0156; median MAGE 44.3 vs. 33.3 mg/dL, p = 0.0043). Only 10 participants (6 in the prediabetes and 4 in the normoglycemic group) had glucose readings below 70 mg/dL and even fewer had below 54 mg/dL (3 overall; 2 individuals with prediabetes, 1 normoglycemic). In contrast, over 60% of participants with prediabetes had glucose readings greater than 180 mg/dL. Following OGTT, the AUC was significantly lower in normoglycemic compared to the prediabetes group (median 18615.3 vs. 16370.0, p = 0.0347 for total and 4666.5 vs. 2792.7, p = 0.0429 for incremental 2-hour post OGTT).
Conclusion: Our study highlights the different glucose profiles of people with prediabetes compared to normoglycemic individuals. CGM might be helpful in individuals with borderline glucose values for a more accurate classification.
FILIS Panagiotis
"The role of mesenchymal stem cells in the treatment of pelvic floor dysfunction in women"
Abstract
The term ‘’pelvic floor dysfunction’’ refers to all the disorders which are associated with the pelvic floor muscle system. The incidence of these diseases in women is constantly increasing during the last years and is leading to decreased quality of life. The current treatments can be categorized to non-invasive techniques -which often fail to provide a definitive solution- and invasive techniques -which may lead to postoperative complications. It is therefore clear that the development of innovative stem-cell based therapies can be a cornerstone in the treatment of the disease. Stem cells are undifferentiated cells characterized by two unique characteristics: self-renewal capacity and pluripotency and can be derived either from the embryo and fetal tissues or from the adult tissues. Depending on their potential for differentiation, they are classified into totipotent, pluripotent, multipotent, oligopotent and unipotent. The most investigated population of stem cells used for applications in regenerative medicine are mesenchymal stem cells, which are effective in treating many diseases thanks to their properties of migration, tissue repair, immunomodulation and cell death control. Specifically, in the present study, mesenchymal stem cells are the population studied for the treatment of pelvic floor dysfunction since they can act directly to the area of the lesion through migration or indirectly thanks to the paracrine signaling which leads to nutritional and immunomodulatory effects.
Up to date, a massive number of preclinical studies have been performed to investigate the treatment of pelvic floor dysfunction through tissue engineering or secretion products and the results demonstrate the strong ability of tissue regeneration and immune modifications possessed by mesenchymal stem cells. Of course, the small animal models used in preclinical trials only partially mimic the symptoms of the disease, which is why clinical trials are necessary for more valid conclusions. The use of human mesenchymal stem cells in clinical testing is possible thanks to their safe profile, the many sources that can be found and the ease of isolation. Although few, existing clinical trials are enhancing the effectiveness of cell therapy using mesenchymal stem cells for pelvic floor disorders and paving the way for even more studies in the future. The definitive treatment of the disease based on regenerative medicine will be an important achievement of science as it will improve the quality of life of a large number of patients, avoiding the after-surgery discomforts and complications.
LOUKOPOULOS Themistoklis
"Applications of Flow Cytometry in Microbiology"
Abstract
Flow Cytometry is a technology that allows the counting and characterization of molecules and cells that are found in a suspension. It allows the analysis of multiple parameters at once and defines the physical and chemical characteristics of single cells that flow through an optical analysis and digital detection device.A great advantage of flow cytometry is the precise and rapid cell counting, which has ample use in Microbiology, especially when it is combined with other tests like fluorescent staining and immunocytometry, providing us with exact details about the number of living and/or dead microbes, their metabolism, their response to stress and more information about their cell cycle. The most important fact though is that it allows precise gauging of bacterial cell viability, which substantiate the answers on one of the greatest questions of Microbiology. There are applications that appertain to food safety, drinking water viability through online flow cytometry fingerprinting, sewage processing and general protection of the environment. Finally, it’s worth noting that with the use of flow virometry it is possible to identify viruses in the environment, so that in the event of future pandemics (such as the COVID-19 pandemic), it can be a useful tool.
RARRAS Nikolaos
"Capturing the degree of reluctance of the Greek population towards childhood vaccination programs, especially in the period of the new corona virus (COVID 19) pandemic"
Abstract