The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most dea... more The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most deaths in the world in the coming years. Less and fewer antibiotics are being produced to kill antibiotic-resistant bacteria. This is because the antibiotic spectrum is about to expire. On the other hand, after these resistant bacteria infect our body, high doses and more effective antibiotics are used to break this resistance gained by the bacteria. However, since these antibiotics affect and kill our healthy microflora, there is a possibility that they may have side effects on our bodies. Mycobacterium tuberculosis bacterium causes Tuberculosis (TB), one of the oldest known human diseases, and it is still one of the most important causes of death, causing two million deaths each year. The resistance of M. tuberculosis bacteria causes the tuberculosis disease to become more insoluble. This thesis aims to show that antibiotic-resistant Mycobacterium smegmatis can be non-resistant with the CRISPR / Cas method in an in-vitro laboratory environment.
Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics... more Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics used today cannot resist this resistance gained by bacteria. The presence of antibiotic-resistant bacteria is shown as a cause of disease that is reported to cause the most deaths in the world in the coming years. Because people resort to the use of more effective antibiotics in high doses to kill these resistant bacteria after they infect our bodies and to counter the resistance they have gained. However, since antibiotics in high doses also affect and kill the healthy microflora of the human body, they are likely to cause side effects and serious problems. Escherichia coli is a bacteria frequently discovered in both human and animal intestines. Some varieties of E. coli can enter the blood from the intestines even though they generally reside in your intestines. Serious sickness might develop as a result. In cases where it mixes with the blood, it can cause many infections such as diarrhoea, respiratory tract problems, urinary tract infections and blood infections, especially in children. Urinary tract and intestinal infections caused by antibiotic-resistant strains of this bacterium, which do not pose a threat to human health under normal conditions, are becoming more common and dangerous. Among the E. coli strains, O157:H7 is the most harmful and deadly strain. The inadequacy of antibiotic treatments applied against resistant bacteria can lead to more deadly results. Fewer and fewer antibiotics are being produced to kill antibioticresistant bacteria because the spectrum of antibiotics is about to run out. The thesis, it is aimed to render antibiotic-resistant E. coli bacteria non-resistant in vitro by using the CRISPR/Cas system, which is the genome editing tool of the 21st century, to prevent all these. Thanks to the CRISPR/Cas system, only methicillin antibiotic-resistant E. coli bacteria will be sensitized or killed without harming the healthy bacteria in the microflora. This project will prove that antibiotic-resistant bacteria, a global health problem, can be sensitized. Thus, CRISPR will be able to use as an alternative antimicrobial agent to antibiotics in the future and will facilitate the production of antimicrobials with CRISPR technology.
Introduction Drug allergy is defined as the ability of the immune system to react to the active s... more Introduction Drug allergy is defined as the ability of the immune system to react to the active substance entering the body. According to the World Allergy Organization, reactions formed through IgE and T cells are considered drug allergies. Drug allergy counts for approximately 10-15% of all undesirable drug reactions according to research (Erkocoglu et al., 2015). Undesirable drug reactions are classified into two groups separate by type A and type B. Type A defined as the 'expected drug reactions' and type B is defined as 'unexpected drug reactions'(Erkocoglu et al., 2015). Type B class contain drug allergies and it is classified according to Gell and Coombs' classification system. The Gell and Coombs classification system have 4 groups. These; Immunoglobulin E (IgE) antibodies such as immediate type reactions (type 1), cytotoxic reactions caused by immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies (type 2), immune complex reactions (type 3) and activation or aggregation of T cells. delayed-type hypersensitivity reactions (type 4) resulting from cellular immune mechanisms (Kilic et al., 2009). The system includes; reaction Type 1, fulminant reactions mediated by (IgE); type 2, cytotoxic reactions mediated by (IgG) or ımmunoglobulin M (IgM) (Kilic et al., 2009), Autoantibodies are formed against the antigenic protein/metabolite structure on the cell surface, and cell lysis occurs by stimulating the complement system in cytotoxic reactions (Kilic et al., 2009). Type 3, The reaction is called the immune complex reaction based on the combination of the antigenic structure of the drug freely in the circulation and the antibodies in the Ig G / M structure against it to form an immunocomplex and accumulate in postcapillary venules (Kilic et al., 2009). Type 4 includes retargeting-type reactions induced by cellular immune systems, such as the recruitment or activation of T cells. Four different subtypes for type 4 reactions. Type 4a involves reactions that are stimulated by Th1 cells and stimulate macrophages and Abstract: Allergy is the reaction of the immune system against the active substance entering the body. Drug allergy is caused by the entry of drug allergens into the body. Drug allergies are examined in two groups, Type A and Type B. Type A describes expected drug reactions and Type B describes unexpected drug reactions. Therefore, drug allergies are in the Type B category. Age, gender, past drug reactions, and genetic polymorphisms are important risk factors for drug allergy. Active drug substances are also particularly important for drug reactions, and drugs containing certain active substances are more prone to allergic reactions. Penicillin, cephalosporin, and fluoroquinolone active ingredients are especially important in beta-lactam antibiotics. At the same time, it is the examination of the use of different drugs belonging to the same group, without experiencing an allergic reaction, with only mild side effects. Especially if we think about the treatment method, CRISPR has been used successfully in various fields in recent years. According to a review study, there was a reduction in the rate of disease progression as a result of cloning research on mice with Type 1 diabetes using CRISPR technology and the disease-specific peptide. This technology may become available in the future by identifying the appropriate peptide group specific to the pharmacological groups for allergic reactions. In terms of diagnostic procedures, provocation tests and immunotherapy are still being studied clinically. As a future aspect of this review, targeted cell or drug content modification using CRISPR may become available for overcoming the allergy.
Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunothera... more Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunotherapeutic approach for cancer treatment. To optimize the production and application of CAR-T cells, we evaluated the in vivo stability and efficacy capacities of CAR-T cells developed under different conditions. In this study, CAR-T cells were activated using Phytohemagglutinin (PHA) or anti-CD3&anti-CD28 and were compared in an in vivo CD19+B-cell cancer model in mouse groups. Our results demonstrated that CAR-T cells activated with PHA exhibited higher stability and anti-cancer efficacy compared to those activated with anti-CD3&anti-CD28. Specifically, CAR19BB-T cells activated with PHA exhibited continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Kaplan–Meier survival analysis revealed prolonged overall survival in the CAR-T cell-treated groups compared to the only tumor group. Furthermore, specific LTR-targeted RT-PCR analysis confirmed the presence of CAR-T cells in the treated groups, with significantly higher levels observed in the CAR19BB-T (PHA) group compared to other groups. Histopathological analysis of spleen, kidney, and liver tissue sections indicated reduced inflammation and improved tissue integrity in the CAR-T cell-treated groups. Our findings highlight the potential benefits of using PHA as a co-stimulatory method for CAR-T cell production, offering a promising strategy to enhance their stability and persistence. These results provide valuable insights for the development of more effective and enduring immunotherapeutic approaches for cancer treatment. CAR-T cells activated with PHA may offer a compelling therapeutic option for advancing cancer immunotherapy in clinical applications.
Every year, millions of drugs are thrown away by consumers, even before their expiration date, as... more Every year, millions of drugs are thrown away by consumers, even before their expiration date, assuming they have deteriorated. We need to see the fact that this has negative repercussions for our country and the world. In addition, when the data of the World Health Organization is examined, when it is considered that approximately 50% of the drugs are used incorrectly or unnecessarily or they are thrown away without even opening the box, we can see that the waste is large. We should not forget that the waste of drugs also brings environmental problems. It is crucial to maintain proper medicine storage conditions and keep out anything that could cause them to deteriorate. The most important factors that play a role in the deterioration of drugs are light, temperature and humidity. If drugs are not stored under appropriate conditions, their chemical structures may change and their effectiveness may decrease or disappear. One of the main factors affecting the deterioration of drugs is that drugs are not kept in the cold chain except for heat, light and humidity. These factors affecting degradation also affect the degradation of DNA. Therefore, it is anticipated that a DNA-based ink will be developed and used in the packaging of drugs, and drug degradation can be followed easily. As a groundbreaking project in the field of health, it is aimed that the person using the drug will be able to notice the deterioration in drugs over time with the DNAINK method. With DNAINK, it is aimed to understand whether the products still maintain their stability effectively, since the text on the drug boxes will be written with DNA ink. The DNA will be fluorescently marked, placed in ink, and injected into the writing on the medicine box. The target is that if the double-stranded DNA is left in conditions such as ultraviolet, light, temperature and humidity for a long time or if it is dependent on time, breaks will occur in the ink containing DNA, and it is aimed to determine the rate of degradation by following these breaks. Against counterfeit drug production, which has become a major health threat in the market, the DNAINK project will additionally develop barcoding technology, an important solution to this problem. Aims to bring Barcoding on the purchased medicine box will help to understand that the medicine came out of the right production place, and to bring a great solution to the health problems experienced due to counterfeit medicine production. With the barcoding technology, it will be possible to monitor whether the purchased drug is fake or not and whether the material deteriorates over time with the DNAINK method. Restriction enzyme analysis will be performed in plasmid DNA design and pHIV-EGFP plasmid will be used at this stage. Then the DNA will be mixed with the ink, and this ink will be subjected to certain tests to measure its stability and effectiveness. Afterwards, it is aimed to reach the desired stage of the project by performing DNA barcode sequencing and analysis. Within the scope of the realization of this project, it is aimed to make it easier to follow the deterioration of the drugs used due to any factor before the expiry date, to protect human health against counterfeit drug production and to guarantee the accuracy of the production site of the used drug.
Purpose of Review Cancer immunotherapy is a treatment made by activating and strengthening the ef... more Purpose of Review Cancer immunotherapy is a treatment made by activating and strengthening the effects of immune system cells that destroy atypical cells like cancer in the body, such as natural killer cells and cytotoxic T lymphocytes. Solid tumors are abnormal tissue masses that usually do not contain areas of cyst or fluid. The cytotoxicity effect of chimeric antigen receptor encoding T (CAR-T) cell on solid tumors needs to be investigated considering the tumor microenvironment, signaling, and cytokine/chemokine release and working mechanism of CAR-T cells of each cancer type. This review aims to discuss new generations of CAR that can be targeted against solid tumors. Recent Findings Considering the findings, this review reports that the mechanism of action that inhibits CAR-T cells includes tumor microenvironment, differentiation efficiency of cells, and tumor antigen heterogeneity, causing impaired anti-cancer action for solid tumors. In this review, the literature was reviewed to propose new-generation CAR-T cells that may show an improved anti-tumor effect against 14 solid tumor types. Summary This review suggests different CAR-T cell approaches against solid tumors. Here, we proposed that there are many different CAR-T cell approaches that are yet to be investigated against solid tumors to show promising anti-tumor capacity.
ABSTRACTIn recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advanceme... more ABSTRACTIn recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advancements and gained clinical approval for use in cancer immunotherapy. CAR, a synthetic receptor integrated into autologous T cells, has yielded highly successful results in patients with leukemia. The significant potential of CAR-T cells has been validated through clinical trials in adult and pediatric cancer treatments. Our therapy developed specifically for CD19-specific Acute Lymphoblastic Leukemia (ALL) has shown promising results in in vitro and in vivo tests. To enhance the response against cancer, provide a bistimulatory effect, and increase stability, we designed two different CAR structures specific to CD19. These designs incorporate the CD28 and 41BB costimulatory domains. Through in vitro analysis, we evaluated the population ratios and cytotoxic activities of Central Memory T cells (TCM) and Stem Cell Memory T cells (TSCM) in CAR-T (CAR1928-T and CAR19BB-T) cells. Our initial des...
Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunothera... more Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunotherapeutic approach for cancer treatment. To optimize the production and application of CAR-T cells, we evaluated the in vivo stability and efficacy capacities of CAR-T cells developed under different conditions. In this study, CAR-T cells were activated using Phytohemagglutinin (PHA) or anti-CD3&anti-CD28 and were compared in an in vivo CD19+B-cell cancer model in mouse groups. Our results demonstrated that CAR-T cells activated with PHA exhibited higher stability and anti-cancer efficacy compared to those activated with anti-CD3&anti-CD28. Specifically, CAR19BB-T cells activated with PHA exhibited continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Kaplan–Meier survival analysis revealed prolonged overall survival in the CAR-T cell-treated groups compared to the only tumor group. Furthermore, specific LTR-targeted RT-PCR analysis confirmed the presence of CAR-T cells in the treated groups, with significantly higher levels observed in the CAR19BB-T (PHA) group compared to other groups. Histopathological analysis of spleen, kidney, and liver tissue sections indicated reduced inflammation and improved tissue integrity in the CAR-T cell-treated groups. Our findings highlight the potential benefits of using PHA as a co-stimulatory method for CAR-T cell production, offering a promising strategy to enhance their stability and persistence. These results provide valuable insights for the development of more effective and enduring immunotherapeutic approaches for cancer treatment. CAR-T cells activated with PHA may offer a compelling therapeutic option for advancing cancer immunotherapy in clinical applications.
Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics... more Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics used today cannot resist this resistance gained by bacteria. The presence of antibiotic-resistant bacteria is shown as a cause of disease that is reported to cause the most deaths in the world in the coming years. Because people resort to the use of more effective antibiotics in high doses to kill these resistant bacteria after they infect our bodies and to counter the resistance they have gained. However, since antibiotics in high doses also affect and kill the healthy microflora of the human body, they are likely to cause side effects and serious problems. Escherichia coli is a bacteria frequently discovered in both human and animal intestines. Some varieties of E. coli can enter the blood from the intestines even though they generally reside in your intestines. Serious sickness might develop as a result. In cases where it mixes with the blood, it can cause many infections such as diarrhoea, respiratory tract problems, urinary tract infections and blood infections, especially in children. Urinary tract and intestinal infections caused by antibiotic-resistant strains of this bacterium, which do not pose a threat to human health under normal conditions, are becoming more common and dangerous. Among the E. coli strains, O157:H7 is the most harmful and deadly strain. The inadequacy of antibiotic treatments applied against resistant bacteria can lead to more deadly results. Fewer and fewer antibiotics are being produced to kill antibioticresistant bacteria because the spectrum of antibiotics is about to run out. The thesis, it is aimed to render antibiotic-resistant E. coli bacteria non-resistant in vitro by using the CRISPR/Cas system, which is the genome editing tool of the 21st century, to prevent all these. Thanks to the CRISPR/Cas system, only methicillin antibiotic-resistant E. coli bacteria will be sensitized or killed without harming the healthy bacteria in the microflora. This project will prove that antibiotic-resistant bacteria, a global health problem, can be sensitized. Thus, CRISPR will be able to use as an alternative antimicrobial agent to antibiotics in the future and will facilitate the production of antimicrobials with CRISPR technology.
Allergy is the reaction of the immune system against the active substance entering the body. Drug... more Allergy is the reaction of the immune system against the active substance entering the body. Drug allergy is caused by the entry of drug allergens into the body. Drug allergies are examined in two groups, Type A and Type B. Type A describes expected drug reactions and Type B describes unexpected drug reactions. Therefore, drug allergies are in the Type B category. Age, gender, past drug reactions, and genetic polymorphisms are important risk factors for drug allergy. Active drug substances are also particularly important for drug reactions, and drugs containing certain active substances are more prone to allergic reactions. Penicillin, cephalosporin, and fluoroquinolone active ingredients are especially important in beta-lactam antibiotics. At the same time, it is the examination of the use of different drugs belonging to the same group, without experiencing an allergic reaction, with only mild side effects. Especially if we think about the treatment method, CRISPR has been used successfully in various fields in recent years. According to a review study, there was a reduction in the rate of disease progression as a result of cloning research on mice with Type 1 diabetes using CRISPR technology and the disease-specific peptide. This technology may become available in the future by identifying the appropriate peptide group specific to the pharmacological groups for allergic reactions. In terms of diagnostic procedures, provocation tests and immunotherapy are still being studied clinically. As a future aspect of this review, targeted cell or drug content modification using CRISPR may become available for overcoming the allergy.
The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most dea... more The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most deaths in the world in the coming years. Less and fewer antibiotics are being produced to kill antibiotic-resistant bacteria. This is because the antibiotic spectrum is about to expire. On the other hand, after these resistant bacteria infect our body, high doses and more effective antibiotics are used to break this resistance gained by the bacteria. However, since these antibiotics affect and kill our healthy microflora, there is a possibility that they may have side effects on our bodies. Mycobacterium tuberculosis bacterium causes Tuberculosis (TB), one of the oldest known human diseases, and it is still one of the most important causes of death, causing two million deaths each year. The resistance of M. tuberculosis bacteria causes the tuberculosis disease to become more insoluble. This thesis aims to show that antibiotic-resistant Mycobacterium smegmatis can be non-resistant with the CRISPR / Cas method in an in-vitro laboratory environment.
Purpose of Review
Cancer immunotherapy is a treatment made by activating and strengthening the ef... more Purpose of Review Cancer immunotherapy is a treatment made by activating and strengthening the effects of immune system cells that destroy atypical cells like cancer in the body, such as natural killer cells and cytotoxic T lymphocytes. Solid tumors are abnormal tissue masses that usually do not contain areas of cyst or fluid. The cytotoxicity effect of chimeric antigen receptor encoding T (CAR-T) cell on solid tumors needs to be investigated considering the tumor microenvironment, signaling, and cytokine/chemokine release and working mechanism of CAR-T cells of each cancer type. This review aims to discuss new generations of CAR that can be targeted against solid tumors.
Recent Findings Considering the findings, this review reports that the mechanism of action that inhibits CAR-T cells includes tumor microenvironment, differentiation efficiency of cells, and tumor antigen heterogeneity, causing impaired anti-cancer action for solid tumors. In this review, the literature was reviewed to propose new-generation CAR-T cells that may show an improved anti-tumor effect against 14 solid tumor types.
Summary This review suggests different CAR-T cell approaches against solid tumors. Here, we proposed that there are many different CAR-T cell approaches that are yet to be investigated against solid tumors to show promising anti-tumor capacity.
In recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advancements and ... more In recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advancements and gained clinical approval for use in cancer immunotherapy. CAR, a synthetic receptor integrated into autologous T cells, has yielded highly successful results in patients with leukemia. The significant potential of CAR-T cells has been validated through clinical trials in adult and pediatric cancer treatments. Our therapy developed specifically for CD19-specific Acute Lymphoblastic Leukemia (ALL) has shown promising results in in vitro and in vivo tests. To enhance the response against cancer, provide a bistimulatory effect, and increase stability, we designed two different CAR structures specific to CD19. These designs incorporate the CD28 and 41BB costimulatory domains. Through in vitro analysis, we evaluated the population ratios and cytotoxic activities of Central Memory T cells (TCM) and Stem Cell Memory T cells (TSCM) in CAR-T (CAR1928-T and CAR19BB-T) cells. Our initial design, CAR1928-T, produced an effective anti-tumor response. With our second design, CAR19BB-T, we not only achieved an anti-tumor effect but also conferred memory capabilities, leading to a comprehensive treatment approach. We demonstrated that CAR-T cells produced using Phytohemagglutinin (PHA) exhibited increased persistence in vitro and in vivo compared to anti-CD3 and anti-CD28 stimulation. The use of PHA to activate CAR19BB-T cells developed a long-lasting and effective CAR-T cell production method in vivo using cancerous animal models. CAR-T cell-treated mice survived tumor-free for up to 60 days, surpassing the survival of mice that received tumors only. Additionally, CAR19BB-T cell production with PHA remained stable over time. These results highlight a novel CAR-T cell production approach with a high-memory T cell profile capable of delaying or preventing cancer relapse. We optimized the method for the production of long-term and effective CAR-T cells and tested it in preclinical experiments. As a result, it was demonstrated that CAR-T cells generated with PHA, when administered as a co-stimulatory dose, can provide continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Preclinical studies have been completed to obtain valuable data for enhancing the long-term effectiveness of CAR-T therapy in clinical trials and transitioning to clinical applications.
The development of genetic modification techniques has led to a new era in cancer treatments that... more The development of genetic modification techniques has led to a new era in cancer treatments that have been limited to conventional treatments such as chemotherapy. intensive efforts are being performed to develop cancer-targeted therapies to avoid the elimination of non-cancerous cells. One of the most promising approaches is genetically modified CAR-T cell therapy. The high central memory T cell (Tcm) and stem cell-like memory T cell (Tscm) ratios in the CAR-T cell population increase the effectiveness of immunotherapy. Therefore, it is important to increase the populations of CAR-expressing Tcm and Tscm cells to ensure that CAR-T cells remain long-term and have cytotoxic (anti-tumor) efficacy. In this study, we aimed to improve CAR-T cell therapy’s time-dependent efficacy and stability, increasing the survival time and reducing the probability of cancer cell growth. To increase the sub-population of Tcm and Tscm in CAR-T cells, we investigated the production of a long-term stable and efficient cytotoxic CAR-T cell by modifications in the cell activation-dependent production using Phytohemagglutinin (PHA). PHA, a lectin that binds to the membranes of T cells and increases metabolic activity and cell division, is studied to increase the Tcm and Tscm population. Although it is known that PHA significantly increases Tcm cells, B-lymphocyte antigen CD19-specific CAR-T cell expansion, its anti-cancer and memory capacity has not yet been tested compared with aCD3/aCD28-amplified CAR-T cells. Two different types of CARs (aCD19 scFv CD8-(CD28 or 4-1BB)-CD3z-EGFRt)-expressing T cells were generated and their immunogenic phenotype, exhausted phenotype, Tcm–Tscm populations, and cytotoxic activities were determined in this study. The proportion of T cell memory phenotype in the CAR-T cell populations generated by PHA was observed to be higher than that of aCD3/aCD28-amplified CAR-T cells with similar and higher proliferation capacity. Here, we show that PHA provides long-term and efficient CAR-T cell production, suggesting a potential alternative to aCD3/aCD28-amplified CAR-T cells.
This thesis is about developing a cancer treatment using a gene therapy approach focused on the p... more This thesis is about developing a cancer treatment using a gene therapy approach focused on the p53 gene, which is responsible for one in six deaths worldwide. When we look at the origins of cancer, we observe tumour suppressor genes that control regular cell activity being expressed and then mis regulated by genetic alterations. Reversing cancer cell tumorigenicity gives vital hints for cancer therapies. Understanding the molecular pathways involved in the loss of tumour suppressor gene activity is a crucial obstacle for cancer treatments. During the project process, axolotl (Ambystoma mexicanum) variations of the p53 gene, known as the cancer resistance gene, were focused on. This is because mutations in the human p53 gene are the most common cause of cancer and increase cancer resistance in the future. The axolotl is an important amphibian with the ability to regenerate. In addition to its regeneration feature, it shows high resistance to cancer formation. Axolotl adults do not undergo metamorphosis and live in water. Despite this situation, it has been observed that it is resistant when exposed to carcinogens. The human p53 gene contains mutation sites in the axolotl p53 gene, which differs from the human p53 gene by 38 amino acids. If the data collected at the end of the study yields the desired findings, it is hoped to develop products with more in-depth research and conduct genetic treatment studies in cancer-cancer resistance.
Every year, millions of drugs are discarded by consumers before they expire, assuming they have d... more Every year, millions of drugs are discarded by consumers before they expire, assuming they have deteriorated. We must recognize that this has negative consequences for our country and the world. Furthermore, when the World Health Organization data is examined, we can see that approximately 50% of the drugs are used incorrectly or unnecessarily, or they are thrown away without even opening the box, indicating that the waste is significant. It is expected that a DNA-based ink will be developed and used in drug packaging, and drug degradation will be easily tracked. As a groundbreaking project in the field of health, the DNAINK method aims to enable drug users to detect the deterioration of drugs over time. Because the text on the drug boxes will be written with DNA ink, the goal of DNAINK is to determine whether the products still maintain their stability effectively. With the DNAINK method and barcoding technology, it will be possible to determine whether a purchased drug is genuine or counterfeit, as well as whether the material deteriorates over time.
The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most dea... more The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most deaths in the world in the coming years. Less and fewer antibiotics are being produced to kill antibiotic-resistant bacteria. This is because the antibiotic spectrum is about to expire. On the other hand, after these resistant bacteria infect our body, high doses and more effective antibiotics are used to break this resistance gained by the bacteria. However, since these antibiotics affect and kill our healthy microflora, there is a possibility that they may have side effects on our bodies. Mycobacterium tuberculosis bacterium causes Tuberculosis (TB), one of the oldest known human diseases, and it is still one of the most important causes of death, causing two million deaths each year. The resistance of M. tuberculosis bacteria causes the tuberculosis disease to become more insoluble. This thesis aims to show that antibiotic-resistant Mycobacterium smegmatis can be non-resistant with the CRISPR / Cas method in an in-vitro laboratory environment.
Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics... more Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics used today cannot resist this resistance gained by bacteria. The presence of antibiotic-resistant bacteria is shown as a cause of disease that is reported to cause the most deaths in the world in the coming years. Because people resort to the use of more effective antibiotics in high doses to kill these resistant bacteria after they infect our bodies and to counter the resistance they have gained. However, since antibiotics in high doses also affect and kill the healthy microflora of the human body, they are likely to cause side effects and serious problems. Escherichia coli is a bacteria frequently discovered in both human and animal intestines. Some varieties of E. coli can enter the blood from the intestines even though they generally reside in your intestines. Serious sickness might develop as a result. In cases where it mixes with the blood, it can cause many infections such as diarrhoea, respiratory tract problems, urinary tract infections and blood infections, especially in children. Urinary tract and intestinal infections caused by antibiotic-resistant strains of this bacterium, which do not pose a threat to human health under normal conditions, are becoming more common and dangerous. Among the E. coli strains, O157:H7 is the most harmful and deadly strain. The inadequacy of antibiotic treatments applied against resistant bacteria can lead to more deadly results. Fewer and fewer antibiotics are being produced to kill antibioticresistant bacteria because the spectrum of antibiotics is about to run out. The thesis, it is aimed to render antibiotic-resistant E. coli bacteria non-resistant in vitro by using the CRISPR/Cas system, which is the genome editing tool of the 21st century, to prevent all these. Thanks to the CRISPR/Cas system, only methicillin antibiotic-resistant E. coli bacteria will be sensitized or killed without harming the healthy bacteria in the microflora. This project will prove that antibiotic-resistant bacteria, a global health problem, can be sensitized. Thus, CRISPR will be able to use as an alternative antimicrobial agent to antibiotics in the future and will facilitate the production of antimicrobials with CRISPR technology.
Introduction Drug allergy is defined as the ability of the immune system to react to the active s... more Introduction Drug allergy is defined as the ability of the immune system to react to the active substance entering the body. According to the World Allergy Organization, reactions formed through IgE and T cells are considered drug allergies. Drug allergy counts for approximately 10-15% of all undesirable drug reactions according to research (Erkocoglu et al., 2015). Undesirable drug reactions are classified into two groups separate by type A and type B. Type A defined as the 'expected drug reactions' and type B is defined as 'unexpected drug reactions'(Erkocoglu et al., 2015). Type B class contain drug allergies and it is classified according to Gell and Coombs' classification system. The Gell and Coombs classification system have 4 groups. These; Immunoglobulin E (IgE) antibodies such as immediate type reactions (type 1), cytotoxic reactions caused by immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies (type 2), immune complex reactions (type 3) and activation or aggregation of T cells. delayed-type hypersensitivity reactions (type 4) resulting from cellular immune mechanisms (Kilic et al., 2009). The system includes; reaction Type 1, fulminant reactions mediated by (IgE); type 2, cytotoxic reactions mediated by (IgG) or ımmunoglobulin M (IgM) (Kilic et al., 2009), Autoantibodies are formed against the antigenic protein/metabolite structure on the cell surface, and cell lysis occurs by stimulating the complement system in cytotoxic reactions (Kilic et al., 2009). Type 3, The reaction is called the immune complex reaction based on the combination of the antigenic structure of the drug freely in the circulation and the antibodies in the Ig G / M structure against it to form an immunocomplex and accumulate in postcapillary venules (Kilic et al., 2009). Type 4 includes retargeting-type reactions induced by cellular immune systems, such as the recruitment or activation of T cells. Four different subtypes for type 4 reactions. Type 4a involves reactions that are stimulated by Th1 cells and stimulate macrophages and Abstract: Allergy is the reaction of the immune system against the active substance entering the body. Drug allergy is caused by the entry of drug allergens into the body. Drug allergies are examined in two groups, Type A and Type B. Type A describes expected drug reactions and Type B describes unexpected drug reactions. Therefore, drug allergies are in the Type B category. Age, gender, past drug reactions, and genetic polymorphisms are important risk factors for drug allergy. Active drug substances are also particularly important for drug reactions, and drugs containing certain active substances are more prone to allergic reactions. Penicillin, cephalosporin, and fluoroquinolone active ingredients are especially important in beta-lactam antibiotics. At the same time, it is the examination of the use of different drugs belonging to the same group, without experiencing an allergic reaction, with only mild side effects. Especially if we think about the treatment method, CRISPR has been used successfully in various fields in recent years. According to a review study, there was a reduction in the rate of disease progression as a result of cloning research on mice with Type 1 diabetes using CRISPR technology and the disease-specific peptide. This technology may become available in the future by identifying the appropriate peptide group specific to the pharmacological groups for allergic reactions. In terms of diagnostic procedures, provocation tests and immunotherapy are still being studied clinically. As a future aspect of this review, targeted cell or drug content modification using CRISPR may become available for overcoming the allergy.
Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunothera... more Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunotherapeutic approach for cancer treatment. To optimize the production and application of CAR-T cells, we evaluated the in vivo stability and efficacy capacities of CAR-T cells developed under different conditions. In this study, CAR-T cells were activated using Phytohemagglutinin (PHA) or anti-CD3&anti-CD28 and were compared in an in vivo CD19+B-cell cancer model in mouse groups. Our results demonstrated that CAR-T cells activated with PHA exhibited higher stability and anti-cancer efficacy compared to those activated with anti-CD3&anti-CD28. Specifically, CAR19BB-T cells activated with PHA exhibited continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Kaplan–Meier survival analysis revealed prolonged overall survival in the CAR-T cell-treated groups compared to the only tumor group. Furthermore, specific LTR-targeted RT-PCR analysis confirmed the presence of CAR-T cells in the treated groups, with significantly higher levels observed in the CAR19BB-T (PHA) group compared to other groups. Histopathological analysis of spleen, kidney, and liver tissue sections indicated reduced inflammation and improved tissue integrity in the CAR-T cell-treated groups. Our findings highlight the potential benefits of using PHA as a co-stimulatory method for CAR-T cell production, offering a promising strategy to enhance their stability and persistence. These results provide valuable insights for the development of more effective and enduring immunotherapeutic approaches for cancer treatment. CAR-T cells activated with PHA may offer a compelling therapeutic option for advancing cancer immunotherapy in clinical applications.
Every year, millions of drugs are thrown away by consumers, even before their expiration date, as... more Every year, millions of drugs are thrown away by consumers, even before their expiration date, assuming they have deteriorated. We need to see the fact that this has negative repercussions for our country and the world. In addition, when the data of the World Health Organization is examined, when it is considered that approximately 50% of the drugs are used incorrectly or unnecessarily or they are thrown away without even opening the box, we can see that the waste is large. We should not forget that the waste of drugs also brings environmental problems. It is crucial to maintain proper medicine storage conditions and keep out anything that could cause them to deteriorate. The most important factors that play a role in the deterioration of drugs are light, temperature and humidity. If drugs are not stored under appropriate conditions, their chemical structures may change and their effectiveness may decrease or disappear. One of the main factors affecting the deterioration of drugs is that drugs are not kept in the cold chain except for heat, light and humidity. These factors affecting degradation also affect the degradation of DNA. Therefore, it is anticipated that a DNA-based ink will be developed and used in the packaging of drugs, and drug degradation can be followed easily. As a groundbreaking project in the field of health, it is aimed that the person using the drug will be able to notice the deterioration in drugs over time with the DNAINK method. With DNAINK, it is aimed to understand whether the products still maintain their stability effectively, since the text on the drug boxes will be written with DNA ink. The DNA will be fluorescently marked, placed in ink, and injected into the writing on the medicine box. The target is that if the double-stranded DNA is left in conditions such as ultraviolet, light, temperature and humidity for a long time or if it is dependent on time, breaks will occur in the ink containing DNA, and it is aimed to determine the rate of degradation by following these breaks. Against counterfeit drug production, which has become a major health threat in the market, the DNAINK project will additionally develop barcoding technology, an important solution to this problem. Aims to bring Barcoding on the purchased medicine box will help to understand that the medicine came out of the right production place, and to bring a great solution to the health problems experienced due to counterfeit medicine production. With the barcoding technology, it will be possible to monitor whether the purchased drug is fake or not and whether the material deteriorates over time with the DNAINK method. Restriction enzyme analysis will be performed in plasmid DNA design and pHIV-EGFP plasmid will be used at this stage. Then the DNA will be mixed with the ink, and this ink will be subjected to certain tests to measure its stability and effectiveness. Afterwards, it is aimed to reach the desired stage of the project by performing DNA barcode sequencing and analysis. Within the scope of the realization of this project, it is aimed to make it easier to follow the deterioration of the drugs used due to any factor before the expiry date, to protect human health against counterfeit drug production and to guarantee the accuracy of the production site of the used drug.
Purpose of Review Cancer immunotherapy is a treatment made by activating and strengthening the ef... more Purpose of Review Cancer immunotherapy is a treatment made by activating and strengthening the effects of immune system cells that destroy atypical cells like cancer in the body, such as natural killer cells and cytotoxic T lymphocytes. Solid tumors are abnormal tissue masses that usually do not contain areas of cyst or fluid. The cytotoxicity effect of chimeric antigen receptor encoding T (CAR-T) cell on solid tumors needs to be investigated considering the tumor microenvironment, signaling, and cytokine/chemokine release and working mechanism of CAR-T cells of each cancer type. This review aims to discuss new generations of CAR that can be targeted against solid tumors. Recent Findings Considering the findings, this review reports that the mechanism of action that inhibits CAR-T cells includes tumor microenvironment, differentiation efficiency of cells, and tumor antigen heterogeneity, causing impaired anti-cancer action for solid tumors. In this review, the literature was reviewed to propose new-generation CAR-T cells that may show an improved anti-tumor effect against 14 solid tumor types. Summary This review suggests different CAR-T cell approaches against solid tumors. Here, we proposed that there are many different CAR-T cell approaches that are yet to be investigated against solid tumors to show promising anti-tumor capacity.
ABSTRACTIn recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advanceme... more ABSTRACTIn recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advancements and gained clinical approval for use in cancer immunotherapy. CAR, a synthetic receptor integrated into autologous T cells, has yielded highly successful results in patients with leukemia. The significant potential of CAR-T cells has been validated through clinical trials in adult and pediatric cancer treatments. Our therapy developed specifically for CD19-specific Acute Lymphoblastic Leukemia (ALL) has shown promising results in in vitro and in vivo tests. To enhance the response against cancer, provide a bistimulatory effect, and increase stability, we designed two different CAR structures specific to CD19. These designs incorporate the CD28 and 41BB costimulatory domains. Through in vitro analysis, we evaluated the population ratios and cytotoxic activities of Central Memory T cells (TCM) and Stem Cell Memory T cells (TSCM) in CAR-T (CAR1928-T and CAR19BB-T) cells. Our initial des...
Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunothera... more Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunotherapeutic approach for cancer treatment. To optimize the production and application of CAR-T cells, we evaluated the in vivo stability and efficacy capacities of CAR-T cells developed under different conditions. In this study, CAR-T cells were activated using Phytohemagglutinin (PHA) or anti-CD3&anti-CD28 and were compared in an in vivo CD19+B-cell cancer model in mouse groups. Our results demonstrated that CAR-T cells activated with PHA exhibited higher stability and anti-cancer efficacy compared to those activated with anti-CD3&anti-CD28. Specifically, CAR19BB-T cells activated with PHA exhibited continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Kaplan–Meier survival analysis revealed prolonged overall survival in the CAR-T cell-treated groups compared to the only tumor group. Furthermore, specific LTR-targeted RT-PCR analysis confirmed the presence of CAR-T cells in the treated groups, with significantly higher levels observed in the CAR19BB-T (PHA) group compared to other groups. Histopathological analysis of spleen, kidney, and liver tissue sections indicated reduced inflammation and improved tissue integrity in the CAR-T cell-treated groups. Our findings highlight the potential benefits of using PHA as a co-stimulatory method for CAR-T cell production, offering a promising strategy to enhance their stability and persistence. These results provide valuable insights for the development of more effective and enduring immunotherapeutic approaches for cancer treatment. CAR-T cells activated with PHA may offer a compelling therapeutic option for advancing cancer immunotherapy in clinical applications.
Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics... more Bacteria are becoming increasingly resistant to antibiotics used in recent years, and antibiotics used today cannot resist this resistance gained by bacteria. The presence of antibiotic-resistant bacteria is shown as a cause of disease that is reported to cause the most deaths in the world in the coming years. Because people resort to the use of more effective antibiotics in high doses to kill these resistant bacteria after they infect our bodies and to counter the resistance they have gained. However, since antibiotics in high doses also affect and kill the healthy microflora of the human body, they are likely to cause side effects and serious problems. Escherichia coli is a bacteria frequently discovered in both human and animal intestines. Some varieties of E. coli can enter the blood from the intestines even though they generally reside in your intestines. Serious sickness might develop as a result. In cases where it mixes with the blood, it can cause many infections such as diarrhoea, respiratory tract problems, urinary tract infections and blood infections, especially in children. Urinary tract and intestinal infections caused by antibiotic-resistant strains of this bacterium, which do not pose a threat to human health under normal conditions, are becoming more common and dangerous. Among the E. coli strains, O157:H7 is the most harmful and deadly strain. The inadequacy of antibiotic treatments applied against resistant bacteria can lead to more deadly results. Fewer and fewer antibiotics are being produced to kill antibioticresistant bacteria because the spectrum of antibiotics is about to run out. The thesis, it is aimed to render antibiotic-resistant E. coli bacteria non-resistant in vitro by using the CRISPR/Cas system, which is the genome editing tool of the 21st century, to prevent all these. Thanks to the CRISPR/Cas system, only methicillin antibiotic-resistant E. coli bacteria will be sensitized or killed without harming the healthy bacteria in the microflora. This project will prove that antibiotic-resistant bacteria, a global health problem, can be sensitized. Thus, CRISPR will be able to use as an alternative antimicrobial agent to antibiotics in the future and will facilitate the production of antimicrobials with CRISPR technology.
Allergy is the reaction of the immune system against the active substance entering the body. Drug... more Allergy is the reaction of the immune system against the active substance entering the body. Drug allergy is caused by the entry of drug allergens into the body. Drug allergies are examined in two groups, Type A and Type B. Type A describes expected drug reactions and Type B describes unexpected drug reactions. Therefore, drug allergies are in the Type B category. Age, gender, past drug reactions, and genetic polymorphisms are important risk factors for drug allergy. Active drug substances are also particularly important for drug reactions, and drugs containing certain active substances are more prone to allergic reactions. Penicillin, cephalosporin, and fluoroquinolone active ingredients are especially important in beta-lactam antibiotics. At the same time, it is the examination of the use of different drugs belonging to the same group, without experiencing an allergic reaction, with only mild side effects. Especially if we think about the treatment method, CRISPR has been used successfully in various fields in recent years. According to a review study, there was a reduction in the rate of disease progression as a result of cloning research on mice with Type 1 diabetes using CRISPR technology and the disease-specific peptide. This technology may become available in the future by identifying the appropriate peptide group specific to the pharmacological groups for allergic reactions. In terms of diagnostic procedures, provocation tests and immunotherapy are still being studied clinically. As a future aspect of this review, targeted cell or drug content modification using CRISPR may become available for overcoming the allergy.
The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most dea... more The presence of antibiotic-resistant bacteria is a disease that is reported to cause the most deaths in the world in the coming years. Less and fewer antibiotics are being produced to kill antibiotic-resistant bacteria. This is because the antibiotic spectrum is about to expire. On the other hand, after these resistant bacteria infect our body, high doses and more effective antibiotics are used to break this resistance gained by the bacteria. However, since these antibiotics affect and kill our healthy microflora, there is a possibility that they may have side effects on our bodies. Mycobacterium tuberculosis bacterium causes Tuberculosis (TB), one of the oldest known human diseases, and it is still one of the most important causes of death, causing two million deaths each year. The resistance of M. tuberculosis bacteria causes the tuberculosis disease to become more insoluble. This thesis aims to show that antibiotic-resistant Mycobacterium smegmatis can be non-resistant with the CRISPR / Cas method in an in-vitro laboratory environment.
Purpose of Review
Cancer immunotherapy is a treatment made by activating and strengthening the ef... more Purpose of Review Cancer immunotherapy is a treatment made by activating and strengthening the effects of immune system cells that destroy atypical cells like cancer in the body, such as natural killer cells and cytotoxic T lymphocytes. Solid tumors are abnormal tissue masses that usually do not contain areas of cyst or fluid. The cytotoxicity effect of chimeric antigen receptor encoding T (CAR-T) cell on solid tumors needs to be investigated considering the tumor microenvironment, signaling, and cytokine/chemokine release and working mechanism of CAR-T cells of each cancer type. This review aims to discuss new generations of CAR that can be targeted against solid tumors.
Recent Findings Considering the findings, this review reports that the mechanism of action that inhibits CAR-T cells includes tumor microenvironment, differentiation efficiency of cells, and tumor antigen heterogeneity, causing impaired anti-cancer action for solid tumors. In this review, the literature was reviewed to propose new-generation CAR-T cells that may show an improved anti-tumor effect against 14 solid tumor types.
Summary This review suggests different CAR-T cell approaches against solid tumors. Here, we proposed that there are many different CAR-T cell approaches that are yet to be investigated against solid tumors to show promising anti-tumor capacity.
In recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advancements and ... more In recent times, chimeric antigen receptor (CAR)-T cell therapy has shown rapid advancements and gained clinical approval for use in cancer immunotherapy. CAR, a synthetic receptor integrated into autologous T cells, has yielded highly successful results in patients with leukemia. The significant potential of CAR-T cells has been validated through clinical trials in adult and pediatric cancer treatments. Our therapy developed specifically for CD19-specific Acute Lymphoblastic Leukemia (ALL) has shown promising results in in vitro and in vivo tests. To enhance the response against cancer, provide a bistimulatory effect, and increase stability, we designed two different CAR structures specific to CD19. These designs incorporate the CD28 and 41BB costimulatory domains. Through in vitro analysis, we evaluated the population ratios and cytotoxic activities of Central Memory T cells (TCM) and Stem Cell Memory T cells (TSCM) in CAR-T (CAR1928-T and CAR19BB-T) cells. Our initial design, CAR1928-T, produced an effective anti-tumor response. With our second design, CAR19BB-T, we not only achieved an anti-tumor effect but also conferred memory capabilities, leading to a comprehensive treatment approach. We demonstrated that CAR-T cells produced using Phytohemagglutinin (PHA) exhibited increased persistence in vitro and in vivo compared to anti-CD3 and anti-CD28 stimulation. The use of PHA to activate CAR19BB-T cells developed a long-lasting and effective CAR-T cell production method in vivo using cancerous animal models. CAR-T cell-treated mice survived tumor-free for up to 60 days, surpassing the survival of mice that received tumors only. Additionally, CAR19BB-T cell production with PHA remained stable over time. These results highlight a novel CAR-T cell production approach with a high-memory T cell profile capable of delaying or preventing cancer relapse. We optimized the method for the production of long-term and effective CAR-T cells and tested it in preclinical experiments. As a result, it was demonstrated that CAR-T cells generated with PHA, when administered as a co-stimulatory dose, can provide continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Preclinical studies have been completed to obtain valuable data for enhancing the long-term effectiveness of CAR-T therapy in clinical trials and transitioning to clinical applications.
The development of genetic modification techniques has led to a new era in cancer treatments that... more The development of genetic modification techniques has led to a new era in cancer treatments that have been limited to conventional treatments such as chemotherapy. intensive efforts are being performed to develop cancer-targeted therapies to avoid the elimination of non-cancerous cells. One of the most promising approaches is genetically modified CAR-T cell therapy. The high central memory T cell (Tcm) and stem cell-like memory T cell (Tscm) ratios in the CAR-T cell population increase the effectiveness of immunotherapy. Therefore, it is important to increase the populations of CAR-expressing Tcm and Tscm cells to ensure that CAR-T cells remain long-term and have cytotoxic (anti-tumor) efficacy. In this study, we aimed to improve CAR-T cell therapy’s time-dependent efficacy and stability, increasing the survival time and reducing the probability of cancer cell growth. To increase the sub-population of Tcm and Tscm in CAR-T cells, we investigated the production of a long-term stable and efficient cytotoxic CAR-T cell by modifications in the cell activation-dependent production using Phytohemagglutinin (PHA). PHA, a lectin that binds to the membranes of T cells and increases metabolic activity and cell division, is studied to increase the Tcm and Tscm population. Although it is known that PHA significantly increases Tcm cells, B-lymphocyte antigen CD19-specific CAR-T cell expansion, its anti-cancer and memory capacity has not yet been tested compared with aCD3/aCD28-amplified CAR-T cells. Two different types of CARs (aCD19 scFv CD8-(CD28 or 4-1BB)-CD3z-EGFRt)-expressing T cells were generated and their immunogenic phenotype, exhausted phenotype, Tcm–Tscm populations, and cytotoxic activities were determined in this study. The proportion of T cell memory phenotype in the CAR-T cell populations generated by PHA was observed to be higher than that of aCD3/aCD28-amplified CAR-T cells with similar and higher proliferation capacity. Here, we show that PHA provides long-term and efficient CAR-T cell production, suggesting a potential alternative to aCD3/aCD28-amplified CAR-T cells.
This thesis is about developing a cancer treatment using a gene therapy approach focused on the p... more This thesis is about developing a cancer treatment using a gene therapy approach focused on the p53 gene, which is responsible for one in six deaths worldwide. When we look at the origins of cancer, we observe tumour suppressor genes that control regular cell activity being expressed and then mis regulated by genetic alterations. Reversing cancer cell tumorigenicity gives vital hints for cancer therapies. Understanding the molecular pathways involved in the loss of tumour suppressor gene activity is a crucial obstacle for cancer treatments. During the project process, axolotl (Ambystoma mexicanum) variations of the p53 gene, known as the cancer resistance gene, were focused on. This is because mutations in the human p53 gene are the most common cause of cancer and increase cancer resistance in the future. The axolotl is an important amphibian with the ability to regenerate. In addition to its regeneration feature, it shows high resistance to cancer formation. Axolotl adults do not undergo metamorphosis and live in water. Despite this situation, it has been observed that it is resistant when exposed to carcinogens. The human p53 gene contains mutation sites in the axolotl p53 gene, which differs from the human p53 gene by 38 amino acids. If the data collected at the end of the study yields the desired findings, it is hoped to develop products with more in-depth research and conduct genetic treatment studies in cancer-cancer resistance.
Every year, millions of drugs are discarded by consumers before they expire, assuming they have d... more Every year, millions of drugs are discarded by consumers before they expire, assuming they have deteriorated. We must recognize that this has negative consequences for our country and the world. Furthermore, when the World Health Organization data is examined, we can see that approximately 50% of the drugs are used incorrectly or unnecessarily, or they are thrown away without even opening the box, indicating that the waste is significant. It is expected that a DNA-based ink will be developed and used in drug packaging, and drug degradation will be easily tracked. As a groundbreaking project in the field of health, the DNAINK method aims to enable drug users to detect the deterioration of drugs over time. Because the text on the drug boxes will be written with DNA ink, the goal of DNAINK is to determine whether the products still maintain their stability effectively. With the DNAINK method and barcoding technology, it will be possible to determine whether a purchased drug is genuine or counterfeit, as well as whether the material deteriorates over time.
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Papers by Gamze Gülden
this resistance gained by bacteria. The presence of antibiotic-resistant bacteria is shown as a cause of disease that is reported to
cause the most deaths in the world in the coming years. Because people resort to the use of more effective antibiotics in high doses
to kill these resistant bacteria after they infect our bodies and to counter the resistance they have gained. However, since antibiotics
in high doses also affect and kill the healthy microflora of the human body, they are likely to cause side effects and serious
problems. Escherichia coli is a bacteria frequently discovered in both human and animal intestines. Some varieties of E. coli can
enter the blood from the intestines even though they generally reside in your intestines. Serious sickness might develop as a result.
In cases where it mixes with the blood, it can cause many infections such as diarrhoea, respiratory tract problems, urinary tract
infections and blood infections, especially in children. Urinary tract and intestinal infections caused by antibiotic-resistant strains
of this bacterium, which do not pose a threat to human health under normal conditions, are becoming more common and
dangerous. Among the E. coli strains, O157:H7 is the most harmful and deadly strain. The inadequacy of antibiotic treatments
applied against resistant bacteria can lead to more deadly results. Fewer and fewer antibiotics are being produced to kill antibioticresistant bacteria because the spectrum of antibiotics is about to run out. The thesis, it is aimed to render antibiotic-resistant E. coli
bacteria non-resistant in vitro by using the CRISPR/Cas system, which is the genome editing tool of the 21st century, to prevent all
these. Thanks to the CRISPR/Cas system, only methicillin antibiotic-resistant E. coli bacteria will be sensitized or killed without
harming the healthy bacteria in the microflora. This project will prove that antibiotic-resistant bacteria, a global health problem,
can be sensitized. Thus, CRISPR will be able to use as an alternative antimicrobial agent to antibiotics in the future and will
facilitate the production of antimicrobials with CRISPR technology.
Cancer immunotherapy is a treatment made by activating and strengthening the effects of immune system cells that destroy atypical cells like cancer in the body, such as natural killer cells and cytotoxic T lymphocytes. Solid tumors are abnormal tissue masses that usually do not contain areas of cyst or fluid. The cytotoxicity effect of chimeric antigen receptor encoding T (CAR-T) cell on solid tumors needs to be investigated considering the tumor microenvironment, signaling, and cytokine/chemokine release and working mechanism of CAR-T cells of each cancer type. This review aims to discuss new generations of CAR that can be targeted against solid tumors.
Recent Findings
Considering the findings, this review reports that the mechanism of action that inhibits CAR-T cells includes tumor microenvironment, differentiation efficiency of cells, and tumor antigen heterogeneity, causing impaired anti-cancer action for solid tumors. In this review, the literature was reviewed to propose new-generation CAR-T cells that may show an improved anti-tumor effect against 14 solid tumor types.
Summary
This review suggests different CAR-T cell approaches against solid tumors. Here, we proposed that there are many different CAR-T cell approaches that are yet to be investigated against solid tumors to show promising anti-tumor capacity.
this resistance gained by bacteria. The presence of antibiotic-resistant bacteria is shown as a cause of disease that is reported to
cause the most deaths in the world in the coming years. Because people resort to the use of more effective antibiotics in high doses
to kill these resistant bacteria after they infect our bodies and to counter the resistance they have gained. However, since antibiotics
in high doses also affect and kill the healthy microflora of the human body, they are likely to cause side effects and serious
problems. Escherichia coli is a bacteria frequently discovered in both human and animal intestines. Some varieties of E. coli can
enter the blood from the intestines even though they generally reside in your intestines. Serious sickness might develop as a result.
In cases where it mixes with the blood, it can cause many infections such as diarrhoea, respiratory tract problems, urinary tract
infections and blood infections, especially in children. Urinary tract and intestinal infections caused by antibiotic-resistant strains
of this bacterium, which do not pose a threat to human health under normal conditions, are becoming more common and
dangerous. Among the E. coli strains, O157:H7 is the most harmful and deadly strain. The inadequacy of antibiotic treatments
applied against resistant bacteria can lead to more deadly results. Fewer and fewer antibiotics are being produced to kill antibioticresistant bacteria because the spectrum of antibiotics is about to run out. The thesis, it is aimed to render antibiotic-resistant E. coli
bacteria non-resistant in vitro by using the CRISPR/Cas system, which is the genome editing tool of the 21st century, to prevent all
these. Thanks to the CRISPR/Cas system, only methicillin antibiotic-resistant E. coli bacteria will be sensitized or killed without
harming the healthy bacteria in the microflora. This project will prove that antibiotic-resistant bacteria, a global health problem,
can be sensitized. Thus, CRISPR will be able to use as an alternative antimicrobial agent to antibiotics in the future and will
facilitate the production of antimicrobials with CRISPR technology.
Cancer immunotherapy is a treatment made by activating and strengthening the effects of immune system cells that destroy atypical cells like cancer in the body, such as natural killer cells and cytotoxic T lymphocytes. Solid tumors are abnormal tissue masses that usually do not contain areas of cyst or fluid. The cytotoxicity effect of chimeric antigen receptor encoding T (CAR-T) cell on solid tumors needs to be investigated considering the tumor microenvironment, signaling, and cytokine/chemokine release and working mechanism of CAR-T cells of each cancer type. This review aims to discuss new generations of CAR that can be targeted against solid tumors.
Recent Findings
Considering the findings, this review reports that the mechanism of action that inhibits CAR-T cells includes tumor microenvironment, differentiation efficiency of cells, and tumor antigen heterogeneity, causing impaired anti-cancer action for solid tumors. In this review, the literature was reviewed to propose new-generation CAR-T cells that may show an improved anti-tumor effect against 14 solid tumor types.
Summary
This review suggests different CAR-T cell approaches against solid tumors. Here, we proposed that there are many different CAR-T cell approaches that are yet to be investigated against solid tumors to show promising anti-tumor capacity.