Browsing by Subject "carcinogenesis"
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Item Immunolocalizations of VEGF, its receptors flt-1, KDR and TGF-β's in epithelial ovarian tumors(2006) Inan S.; Vatansever S.; Celik-Ozenci C.; Sanci M.; Dicle N.; Demir R.Objective: Angiogenesis is an essential factor for growth, differentiation, invasion and metastasis of tumors. In this study, we aimed to evaluate the immunolocalizations of vascular endothelial growth factor (VEGF), its receptors flt-1, KDR/flk-1, and transforming growth factor-beta's (TGF-β) in epithelial ovarian tumors, utilizing indirect immunohistochemistry to understand the role of the angiogenic events in ovarian neoplasia. Methods: Tissue blocks from 40 patients who had ovarian pathology (borderline serous-mucinous tumor and malignant serous-mucinous adenocarcinoma of the ovary) were included in this study. All formalin-fixed, paraffin-embedded tissue sections were stained with hematoxylin-eosin or primary antibodies against VEGF, flt-1, KDR/flk-1, TGF-β1, TGF-β2 and TGF-β3 using the avidin-biotin-peroxidase method. H-SCORE, a semi-quantitative grading system, was used to compare immunohistochemical staining intensities. Results: Positive VEGF immunoreactivity was concentrated in the epithelial and stromal parts of all the ovarian samples and the endothelial cells in the stroma were also stained. Increased immunoreactivity of VEGF was observed in malignant ovarian adenocarcinomas compared to the borderline tumors of the ovary. VEGF receptors, flt-1 and KDR/flk-1 immunoreactivities were detected not only in vascular endothelial cells, but also in tumor cells at malignant sites. Immunoreactivities of VEGF and its receptors were coexpressed in tumor cells of the ovarian carcinoma. While immunoreactivities of TGF-β1 and TGF-β2 were both overexpressed in malignant ovarian carcinomas, immunoreactivity of TGF-β3 was still mild. Conclusion: Our results suggest that overexpression of VEGF, its receptors flt-1, KDR/flk-1 and TGF-β interaction may play an important role in the ovarian cancer biology, with potential effects on tumor growth and angiogenesis. New therapeutic strategies using VEGF and TGF-β antagonists could obtain an additional approach to the treatment ovarian carcinoma by inhibiting angiogenesis.Item Overcoming drug resistance in hormone-and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination(2010) Cengiz E.; Karaca B.; Kucukzeybek Y.; Gorumlu G.; Gul M.K.; Erten C.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose-and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array® (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated C3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers. © Springer Science+Business Media B.V. 2009.Item The role of circadian rhythm genes in cancer; [Kanserde sirkadiyan ritim genlerinin rolü](2011) Atmaca H.; Uzunoǧlu S.Circadian (In Latin: Circa=around, Diem=day) rhythm describes the processes of 24 hour oscillations in the living systems. At the cellular level, circadian rhythm is controlled by a molecular network with positive and negative feedbacks. The known critical elements in the positive feedback loop are Clock and Bmal1; the ones in complementary negative feedback are mainly Period and Cryptochrome genes. In cancer, which is an important health problem today, dysregulation of circadian rhythm is an important risk factor. In this review, circadian rhythm genes involved in cell proliferation, apoptosis, DNA repair, metabolism, detoxification and response to DNA damage and their roles in cancer development are summarized.Item Prevalence of prostate cancer in high boron-exposed population: A community-based study(Humana Press Inc., 2011) Müezzinoğlu T.; Korkmaz M.; Neşe N.; Bakırdere S.; Arslan Y.; Ataman O.Y.; Lekili M.We investigated the possible relationship between boron exposure and prostate cancer (PCa) for men living and being employed at boron mines in villages with rich boron minerals. Out of 456 men studied, 159 were from villages with rich boron sources and boron levels in drinking water of >1 mg L -1 and these men formed the study group, while 63 from villages with rich boron sources and boron levels in drinking water of <1 mg L -1 were enrolled into control group 1. A further 234 subjects from other villages with no boron mines were considered as control group 2. Prostate specific antigen (PSA) levels could be obtained from a total of 423 men. Urinary boron concentration as an indicator of boron exposure in 63 subjects, prostatic volumes by transrectal ultrasonography in 39 subjects, and prostatic biopsies in 36 subjects were obtained for study and control groups. The daily boron exposure was calculated according to urinary boron levels. Although there was no significant difference among the groups in terms of total PSA levels, the number of subjects with tPSA ≥2.5 and tPSA ≥10.0 ng dL -1 prostatic volumes in men whose prostates were biopsied (p<0.012) was significantly lower in the study group as compared with those in the control group 2. These results suggested that high exposure to boron might have an implication within the prostatic cellular processes related to hyperplasia and carcinogenesis, even though we did not find a statistically significant association between PCa and boron exposure. © Springer Science+Business Media, LLC 2011.Item Nonmelanoma Skin Cancer of the Head and Neck: Prevention(2012) Oghan F.; Eskiizmir G.; Unlu H.; Cingi C.The importance and effectiveness of prevention efforts and strategies for skin cancers are reviewed. Topical sunscreens and their proper use are presented. Topical and ingested forms of natural, synthetic, or biologic chemical agents that are potentially efficacious for chemoprevention are listtdldted and discussed. © 2012 Elsevier Inc.Item Effects of porcine pancreatic enzymes on the pancreas of hamsters. Part 2: Carcinogenesis studies(2012) Nozawa F.; Yalniz M.; Saruc M.; Standop J.; Egami H.; Pour P.M.Context Our previous study suggested that porcine pancreatic extract in hamsters with peripheral insulin resistance, normalizes insulin output, islet size and pancreatic DNA synthetic rate. It also inhibited the growth of human pancreatic cancer cells in nude mice. Objective To examine the potential value of the porcine pancreatic extract in controlling pancreatic carcinogenesis in this model, the present experiment was performed. Design Hamsters were fed a high fat diet and four weeks later when insulin resistance emerges, they were divided into two groups. One group received 1 g/kg BW of porcine pancreatic extract in drinking water and the other group received tap water. One week later, when insulin output normalizes in porcine pancreatic extract-treated hamsters, a single subcutaneous injection of N-nitrosobis-(2-oxopropyl) amine (BOP) at a dose of 40 mg/kg BW was given to all hamsters. The experiment was terminated at 43 weeks after the porcine pancreatic extract treatment. The number and size of pancreatic tumors, blood glucose, insulin, amylase and lipase levels, the average size of islets and the number of insulin cells/islets were determined. Results The incidence of pancreatic cancer was significantly lower in the porcine pancreatic extract group (P=0.043), as well as the plasma insulin level and the size of the islets in the porcine pancreatic extract group were significantly lower (P<0.001) than in the control group. No significantly differences were found in the glucose level between the groups. Conclusion These results show that porcine pancreatic extract has a potential to inhibit pancreatic cancer growth.Item Cancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids(Spandidos Publications, 2014) Oktem G.; Sercan O.; Guven U.; Uslu R.; Uysal A.; Goksel G.; Ayla S.; Bilir A.Cancer stem cells (CSCs) have the ability to self-renew similar to normal stem cells. This process is linked with metastasis and resistance to chemotherapy and radiotherapy. In the present study, we constructed an in vitro differentiation model for CSCs. CSCs isolated and proliferated for one passage were maintained as monolayers or spheroid-forming cells with serum included media for differentiation process. Differentiation of adhesion molecules and cellular ultrastructural properties were investigated and compared in both monolayer and spheroid cultures. CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with the remaining heterogeneous cancer cell bulk population. Microarray-based gene expression analysis was applied to determine genes with differential expression and protein expression levels of candidates were analyzed by immunohistochemistry. Electron microscopy showed detailed analysis of morphology. TGFβ1 was found to be significantly upregulated in monolayer CSCs. High expression levels of VCAN, COL7A1, ITGβ3, MMP16, RPL13A, COL4A2 and TIMP1 and low expression levels of THBS1, MMP1 and MMP14 were detected when CSCs were maintained as serum-grown prostate CSC spheroids. Immunohistochemistry supported increased immunoreactivity of TGFβ1 in monolayer cultures and VCAN in spheroids. CSCs were found to possess multipotential differentiation capabilities through upregulation and/or downregulation of their markers. TGFβ1 is a triggering molecule, it stimulates versican, Col7A1, ITGβ3 and, most importantly, the upregulation of versican was only detected in CSCs. Our data support a model where CSCs must be engaged by one or more signaling cascades to differentiate and initiate tumor formation. This mechanism occurs with intracellular and extracellular signals and it is possible that CSCc themselves may be a source for extracellular signaling. These molecules functioning in tumor progression and differentiation may help develop targeted therapy.Item Chronic actinic damage of facial skin(Elsevier Inc., 2014) Bilaç C.; Şahin M.T.; Öztürkcan S.Chronic actinic damage of the skin manifests itself as extrinsic skin aging (photoaging) and photocarcinogenesis. During the last decade, substantial progress has been made in understanding cellular and molecular mechanisms of photoaging. DNA photodamage and ultraviolet-generated reactive oxygen species are the initial events that lead to most of the typical histologic and clinical manifestations of chronic photodamage of the skin. Chronic actinic damage affects all layers of the skin. Keratinocytes, melanocytes, fibroblasts, and endothelial cells are altered by ultraviolet radiation and can result in numerous changes in human skin, particularly the skin of fair-skinned individuals. These changes include actinic keratosis, thickening and wrinkling, elastosis, telengiectasia, solar comedones, diffuse or mottled hyperpigmentation, and skin cancers. There are many options in the treatment of changes caused by chronic actinic damage. The most effective measure of prevention of the photoaging and photocarcinogenesis is sun protection. © 2014 Elsevier Inc.Item Possible relations between oxidative damage and apoptosis in benign prostate hyperplasia and prostate cancer patients(IOS Press BV, 2014) Kosova F.; Temeltaş G.; Arı Z.; Lekili M.Cancer has been described as the twentieth century plague, and is a very common health problem. It has been reported that ROS and ROS products play a key role in cancer and that oxidative damage is effective in apoptosis initiation. In this study we aimed to evaluate the relationship between MDA (malondialdehyde), DNA damage (8-hydroxyguanine, 8-OH-dG), and caspase-3 in BHP and prostate cancer patients. Twenty male patients with prostate cancer and 20 male patients with benign prostate hyperplasia were included into this study. The MDA (nanomole), DNA damage (nanograms per millilitre), and caspase-3 (nanograms per millilitre) levels were measured in prostate cancer and benign prostate hyperplasia using Elisa kits (Millipore Corporation, Billerica, MA, USA). In the prostate cancer group, serum MDA (30.96± 9.25) and DNA damage (4.42±0.36) levels were significantly raised (p <0.05) when compared to the benign prostate hyperplasia group (24.05±8.06, 3.99±0.54). However, in the prostate cancer group, serum caspase-3 (2.36±0.82) levels were statistically significantly lowered (p <0.05) compared with the benign prostate hyperplasia group (3.15±1.04). We observed that altered prooxidant, DNA damage levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that, although the triggering of these changes is unknown, changes in the levels of MDA, DNA damage, and caspase-3 in the blood are related to prostatic carcinoma development. In addition, it would be appropriate to conduct new studies with a large number of patients at different stages. © International Society of Oncology and BioMarkers (ISOBM) 2013.Item Alteration in methylation pattern of retinoblastoma 1 gene promotor region in intestinal metaplasia with or without helicobacter pylori and gastric cancer patients(Wroclaw University of Medicine, 2016) Boyacioglu S.O.; Kasap E.; Yuceyar H.; Korkmaz M.Background. Helicobacter pylori, intestinal metaplasia (IM), and gene methylation play important roles in gastric carcinogenesis. However, the association among H. pylori infection, IM, gastric cancer (GC), and gene methylation is not fully understood. Cell cycle control involving retinoblastoma 1 (RB1) gene is one of the main regulatory pathways reported to be altered in gastric carcinogenesis. Objectives. The purpose of this research is to assess the methylation status of RB1 gene in GC and IM with or without H. pylori infection, and to discuss the possible role of H. pylori-induced RB1 gene methylation in the mechanism of gastric carcinogenesis. Material and Methods. The methylation profile of RB1 gene was analyzed by sodium bisulfite modification and methylation-specific PCR in GC (n = 24), IM patients with H. pylori positive (n = 20) and negative (n = 20), and control subjects (n = 20). Results. According to methylation levels in RB1 gene; the high correlation values were detected between H. pylori positive-IM group and GC group, and between H. pylori positive-IM and H. pylori negative-IM groups (p < 0.05). No correlations between H. pylori negative-IM and GC groups and between GC and control groups were detected in methylation status of RB1 gene. Conclusions. High methylation levels in RB1 gene in H. pylori positive individuals may suggest an elevated risk of gastric cancer occurrence. © Copyright by Wroclaw Medical University.Item Review of the health effects of berries and their phytochemicals on the digestive and immune systems(Oxford University Press, 2018) Govers C.; Kasikci M.B.; van der Sluis A.A.; Mes J.J.Berries are generally considered beneficial to health. This health-promoting potential has mainly been ascribed to berries' phytochemical and vitamin content, and little attention has been paid to the potential benefits of berries for the digestive tract, despite this being the first point of contact. In vivo studies that described the health effects of berries on individual parts of the digestive tract (ie, the mouth, esophagus, stomach, small and large intestine, microbiome, and immune system) were reviewed. Immune effects were included because a large part of the immune system is located in the intestine. Beneficial health effects were mainly observed for whole berry extracts, not individual berry components. These effects ranged from support of the immune system and beneficial microbiota to reduction in the number and size of premalignant and malignant lesions. These results demonstrate the potency of berries and suggest berries can serve as a strong adjuvant to established treatments or therapies for a variety of gastrointestinal and immune-related illnesses. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved.Item Loss of Wasl improves pancreatic cancer outcome(American Society for Clinical Investigation, 2020) Hidalgo-Sastre A.; Desztics J.; Dantes Z.; Schulte K.; Ensarioglu H.K.; Bassey-Archibong B.; Öllinger R.; Engleiter T.; Rayner L.; Einwächter H.; Daniel J.M.; Altaee A.S.A.; Steiger K.; Lesina M.; Rad R.; Reichert M.; Von Figura G.; Siveke J.T.; Schmid R.M.; Lubeseder-Martellato C.Several studies have suggested an oncogenic role for the neural Wiskott-Aldrich syndrome protein (N-WASP, encoded by the Wasl gene), but thus far, little is known about its function in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed in silico analysis of WASL expression in PDAC patients and found a correlation between low WASL expression and prolonged survival. To clarify the role of Wasl in pancreatic carcinogenesis, we used 2 oncogenic Kras-based PDAC mouse models with pancreas-specific Wasl deletion. In line with human data, both mouse models had an increased survival benefit due to either impaired tumor development in the presence of the tumor suppressor Trp53 or the delayed tumor progression and senescent phenotype upon genetic ablation of Trp53. Mechanistically, loss of Wasl resulted in cell-autonomous senescence through displacement of the N-WASP binding partners WASP-interacting protein (WIP) and p120ctn; vesicular accumulation of GSK3β, as well as YAP1 and phosphorylated β-catenin, which are components of the destruction complex; and upregulation of Cdkn1a(p21), a master regulator of senescence. Our findings, thus, indicate that Wasl functions in an oncogenic manner in PDAC by promoting the deregulation of the p120-catenin/β-catenin/p21 pathway. Therefore, strategies to reduce N-WASP activity might improve the survival outcomes of PDAC patients. © 2020, American Society for Clinical Investigation.Item Synthesis and apoptotic activities of new 2(3H)-benzoxazolone derivatives in breast cancer cells(Bentham Science Publishers, 2020) Erdag E.; Becer E.; Mulazim Y.; Vatansever H.S.; Kabadayı H.; Kesanli B.Background: 2(3H)-Benzoxazolone derivatives are preferential structural blocks in pharmacological probe designing with the possibility of modifications at various positions on the core structure. Benzoxazolones showed various biological activities such as analgesics, anti-inflammatory and anti-cancer. Objective: In the present work, we have prepared new Mannich bases of 2(3H)-benzoxazolone derivatives and evaluated their cytotoxicities and proapoptotic properties in MCF-7 breast cancer cell line. Methods: The structures of these compounds were characterized by FT-IR, elemental analysis,1H and13C NMR. Cytotoxicities of all the target compounds were investigated by MTT assay. Apoptotic properties of compounds were evaluated by immunocytochemistry using antibodies against caspase-3, cytochrome-c, FasL, and also TUNEL assay. Results: These two novel compounds, 1 and 2, both have the same piperazine substituent on the nitrogen atom of benzoxazolone and the main difference in the structures of these compounds is the presence of Cl substituent at the 5-position of the benzoxazolone ring. MTT results showed that compounds 1 and 2 were effective in terms of reduction of cell viability at 100µM and 50µM concentration for 48h, respectively. As a result of im-munohistochemical staining, Fas L and caspase-3 immunoreactivities were significantly increased in MCF-7 cells after treatment with compound 1. Additionally, caspase-3 and cytochrome-c immunoreactivities were also increased significantly in MCF-7 cells after treatment with compound 2. The number of TUNEL positive cells was significantly higher in MCF-7 cells when compared with the control group after treatment with both compounds 1 and 2. Conclusion: It could be concluded that N-substituted benzoxazolone derivatives increase potential anti-cancer effects and they could be promising novel therapeutic agents for chemotherapy. © 2021 Bentham Science Publishers.Item Senescence-mediated anticancer effects of quercetin(Elsevier Inc., 2022) Özsoy Gökbilen S.; Becer E.; Vatansever H.S.Cellular senescence plays a key role in aging and age-related disease initiation. It is a highly dynamic and multistep process that can be stimulated by various stimuli, including cellular stress, DNA damage, telomere shortening, and oncogene activation. Also, senescence is a potent antitumor mechanism, by preventing the proliferation of cancerous cells. However, some of the senescent cells have apoptosis resistance and can cause recurrence in cancer. A new class of drugs termed senolytics selectively kill and eliminate senescent cells. In recent years, natural compounds such as quercetin have been discovered to be effective as senolytic agents. Quercetin is a phytochemical that has strong antioxidant properties and pro-apoptotic effects and has been investigated for many years. Additionally, it has great potential to be used as a senolytic agent. According to preclinical and early-phase clinical data of senolytic agent research, quercetin administration appears to be effective in preventing or alleviating cancer formation. In this paper, we review the importance of cellular senescence in carcinogenesis and the effects of quercetin on senescence, as well as quercetin's potential effects as a pro-apoptotic agent and suppressor of cancer cell proliferation. © 2022 Elsevier Inc.Item Transcriptomic analysis of plasma exosomes provides molecular information of response to cabazitaxel treatment in men with metastatic castration-resistant prostate cancer(John Wiley and Sons Inc, 2023) Vardaki I.; Özcan S.S.; Fonseca P.; Lin S.-H.; Logothetis C.J.; Yachnin J.; Ullen A.; Panaretakis T.Background: Prostate cancer is the second most common cancer type and the second most common cancer-related cause of death in men. Cabazitaxel, a next-generation taxane, shows favorable toxicity profile and is effective in docetaxel-resistant tumors. Despite initial responses, in most cases, prostate cancer patients acquire resistance to cabazitaxel. There is a need to identify molecular markers that can monitor and predict treatment response. Methods: We performed transcriptional exosome profiling (Human Transcriptome Array-HTA 2.0) from the plasma of 19 patients with castration-resistant prostate cancer at baseline and in patients after one cycle of cabazitaxel (C1). The patients were stratified in two groups (responders and nonresponders) according to their clinical response to cabazitaxel. Gene set enrichment analysis and ingenuity pathway analysis platforms were used for gene and pathway analysis. Results: We detected molecular differences in the exosomes from two groups of patients (nonresponders vs. responders) at baseline in pathways related to prostate cancer, oncogenic signaling, cytoskeleton, and immune system. In nonresponders, we found enrichment of cytoskeleton related gene (Stathmin-1 and ITSN1) that have been associated with resistance to cabazitaxel. Monitoring of exosomal transcripts after the first cycle of treatment revealed changes in pathways associated with response to treatment. Conclusions: Sequential transcriptional profiling of plasma-derived exosomes reveals differential expression of genes that may reflect resistance to cabazitaxel treatment and therapy response. © 2023 Wiley Periodicals LLC.Item Resveratrol modulates miRNA machinery proteins in different types of colon cancer cells(De Gruyter Open Ltd, 2024) Becer E.; Madencioğlu S.; Kabadayı H.; Vatansever H.S.Objectives: Resveratrol (RSV) is a stilbenoid compound that shows anticancer activity in many cancer cells. Exosomes might affect carcinogenesis and the development of colorectal cancer by affecting communication between tumor cells in the tumor microenvironment via their cargo content miRNA. The aim of this study is to determine the effect of RSV on the expression of Dicer, Ago2, eIf2α, CD-9, CD-63, and exosomal miRNA levels in COLO320 and COLO741 colon cancer cell lines. Methods: The MTT method was used for cell growth and cytotoxicity in both COLO320 and COLO741 cell lines. Dicer, Ago2, eIF2α, CD-9, and CD-63 antibodies were used for the immunocytochemical evaluation. Total miRNA analysis was performed using a miRCURY Exosome Isolation Kit. Results: As a result of immunocytochemical staining, increased CD-63 immunoreactivity was observed in RSV-treated COLO320 cells vs. RSV-treated COLO-741 cells. Dicer immunoreactivity increased after the RSV treatment in COLO320 cells. Higher eIF2α immunoreactivity was observed in RSV-treated COLO741 cells compared to both COLO741 control cells and RSV-treated COLO320 cells. Non-significant decreases were observed in miRNA concentration in RSV-treated COLO320 and COLO741 cells compared to control group cells. Conclusions: RSV could increase miRNA biogenesis in COLO320 cancer cells and decrease it in COLO741 cancer cells. © 2023 the author(s), published by De Gruyter.Item The Prognostic Impact of Tumor Microenvironment and Checkpoint Blockade-Associated Molecules (PD-1, PD-L1, CD163 and CD14) in Nodal Diffuse Large B-cell Lymphoma, NOS(Springer, 2024) Atmış Ö.; Neşe N.; Aydoğdu İ.; Alaca İ.; Mavili H.S.; İşisağ A.It is aimed to determine expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), CD163 and CD14 in diffuse large B-cell lymphomas (DLBCL), and whether these markers may predict prognosis in DLBCL cases. A total of 52 nodal DLBCL, NOS cases with no known extranodal involvement at the time of diagnosis were evaluated. PD-1, PD-L1, CD163, and CD14 were studied by immunohistochemistry. The relationships between the results and clinical and laboratory prognostic markers were investigated. It was observed that patients with PD-1 expression < 5 positive cells/HPF had worse overall survival. No significant relationship was found between survival and PD-L1, CD163 and CD14 expressions. In addition, cases that are > 60 years of age, that have Eastern Cooperative Oncology Group (ECOG) performance score ≥ 2, stage IV disease, high International Prognostic Index score score (≥ 3), elevation of LDH, low albumin level, low hemoglobin level, low peripheral blood lymphocyte count, high peripheral blood neutrophil/lymphocyte ratio, high peripheral blood platelet/lymphocyte ratio were found to have worse overall survival. It was concluded that in patients with low number of PD-1 positive tumor-infiltrating lymphocytes have low survival rates and therefore PD-1 expression may be useful in indicating prognosis. © The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2023.