scholarly journals Analisis dan Strategi Pengendalian Model Matematika Interaksi Sel Kanker Leukemia Mielositik Kronis dan Sel Imunitas

Author(s):  
Nanda Amalia Rahma ◽  
Cicik Alfiniyah ◽  
Windarto Windarto

Leukemia is a disease in the classification of cancer in the blood that is characterized by abnormal growth of blood cells in the bone marrow or lymphoid tissue, and generally occurs in leukocytes or white blood cells. White blood cells that look for types of pathogenic diseases that harm the human body and then damage it are the task of the immune system. This thesis analyzes the mathematical model of chronic myelocytic leukemia cancer cell interactions and immune cells to determine the rate of increase in the population of chronic myelocytic leukemia cancer cells to the effect of immune cells. Based on the analysis of the model obtained two equilibrium points namely the equilibrium point of the extinction of chronic myelocytic leukemia cancer cells (E0) and the equilibrium point of the coexistence of chronic myelocytic leukemia cancer cells (E1). The equilibrium point of extinction will be asymptotically stable, whereas the equilibrium point of coexistence tends to be asymptotically stable using phase fields with the help of MATLAB software. Numerical simulation results show that there is an increase in the number of chronic myelocytic leukemia cancer cell populations and a decrease in the number of vulnerable blood cell populations. When immune cells increase in population, chronic myelocytic leukemia in cancer cells decreases in population but is not significant.

2020 ◽  
Vol 4 (1) ◽  
pp. 197-205 ◽  
Author(s):  
Perrine Remaud ◽  
Jevan Medlock ◽  
Anupam A. K. Das ◽  
David J. Allsup ◽  
Leigh A. Madden ◽  
...  

We report a new approach for separation of blood cancer cells from healthy white blood cells based on cell shape and size recognition by surface functionalised particle imprints.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A635-A635
Author(s):  
Jeffrey Zhang ◽  
Everett Henry ◽  
L Harris Zhang ◽  
Wanying Zhang

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.


2013 ◽  
Vol 2 (3) ◽  
pp. 141
Author(s):  
Muthia Rendra ◽  
Rismawati Yaswir ◽  
Akmal M Hanif

AbstrakLeukemia merupakan penyakit keganasan sel darah yang berasal dari sumsum tulang ditandai oleh proliferasi sel-sel darah putih, dengan manifestasi adanya sel-sel abnormal dalam darah tepi. Pada tahun 2006, leukemia berada pada urutan ke-5 dari keseluruhan penderita kanker di Indonesia. Leukemia kronik merupakan leukemia yang paling sering terjadi pada dewasa dan lanjut usia. Secara umum leukemia kronik diklasifikasikan atas Leukemia Granulositik Kronik (LGK) dan Leukemia Limfositik Kronik (LLK). Leukemia kronik yang perjalanannya lambat dan diiringi oleh gejala yang tidak khas, maka penelitian ini bertujuan untuk mengetahui gambaran laboratorium leukemia kronik di bagian Peyakit Dalam RSUP DR. M. Djamil Padang. Jenis penelitian ini adalah deskriptif retrospektif. Instrumen yang digunakan pada penelitian ini adalah data sekunder yang diperoleh dari Instalasi Rekam Medik RSUP Dr. M. Djamil Padang berupa data pasien leukemia kronik yang dirawat di Bagian Penyakit Dalam RSUP Dr. M. Djamil Padang sejak 1 Januari 2010 – 31 Desember 2012. Hasil penelitian ini menunjukkan bahwa dari 16 kasus leukemia granulositik kronik terdapat 37,5% pasien mengalami anemia sedang, 100% leukositosis, jumlah trombosit dapat menurun, normal, dan meningkat dengan presentase masing-masing 25%, 25%, dan 50%. Gambaran eritrosit sebagian besar normositik anisositosis. Separuh pemeriksaan darah tepi menunjukkan peningkatan persentasi mielosit, 31,25% menunjukkan peningkatan persentasi metamielosit dan eosinofil, serta sebagian besar menunjukkan presentasi blast. Sedangkan gambaran sumsum tulang hiperseluler, penekanan eritropoetik, mielopoetik hiperaktif, dan trombopoetik dalam batas normal. Leukemia limfositik kronik yang terdiri dari 1 kasus menunjukkan gambaran laboratorium berupa anemia sedang, leukositosis, trombositopenia, gambaran eritrosit nomokrom anisositosis, peningkatan jumlah leukosit, peningkatan jumlah limfosit, presentasi smudge cell, dan ditemukan presentasi blast pada darah tepi, tetapi selularitas tidak dapat dinilai.Kata kunci: leukemia kronik, darah tepi, BMPAbstractLeukemia is a malignant disease of blood cells derived from the bone marrow characterized by the proliferation of white blood cells, with the manifestation of the abnormal cells in the peripheral blood. In 2006, leukemia was ranked 5th of all cancer patients in Indonesia. Chronic leukemia is the most common leukemia in adult and the elderly. In general, chronic leukemia classified on chronic myelocytic leukemia (CML) and chronic lymphocytic leukemia (CLL). The onset of chronic leukemia is insidious and accompanied by symptoms that are not typical, this research aims to describe the laboratory findings of chronic leukemia patients treated at Internal Medicine Department of Dr. M. Djamil Hospital Padang.This research is a retrospective descriptive research. The instruments used in this research are the secondary data derived from the Medical Record Departement Dr. M. Djamil Hospital Padang in the form of leukemia chronic patients’ data who were treated in Internal Medicine Department of Dr. M. Djamil Hospital Padang since January 1st 2010 – December 31st 2012. The results of this research showed that of 16 cases of chronic myelocytic leukemia contained 37.5% of the patients had moderate anemia, leukocytosis 100%, platelet count can be decreased, normal, and increased the percentage of each 25%, 25%, and 50%. The morphology of erythrocytes mostly normocytic anisocytosis. Half of peripheral blood examination showed an increase in the percentage of myelocyte, 31.25% showed an increase in the percentage metamyelocyte and eosinophils, as well as most of the shows presentation blast. The bone marrow are hypercellular, compressing erythropoietic, myelopoietic hyperactivity and thrombopoietic mostly normal in number. Chronic lymphocytic leukemia consisting of 1 case shows the laboratory findings are moderate anemia, leukocytosis, thrombocytopenia, the morphology of erythrocyte is normochromic anisocytosis, leukocytes increase in number, increase in the number of lymphocytes, presentations smudge cells, and blast presentation is found in the peripheral blood, but the cellularity not be assessed.Keywords: chronic leukemia, peripheral blood, BMP


Author(s):  
Vidyashree M S

Abstract: Blood Cancer cells forming a tissue is called lymphoma. Thus, disease decreases the cells to fight against the infection or cancer blood cells. Blood cancer is also categorized in too many types. The two main categories of blood cancer are Acute Lymphocytic Lymphoma and Acute Myeloid Lymphoma. In this project proposes a approach that robotic detects and segments the nucleolus from white blood cells in the microscopic Blood images. Here in this project, we have used the two Machine learning algorithms that are k-means algorithm, Support vector machine algorithm. K-mean algorithm is use for segmentation and clustering. Support vector machine algorithm is used for classification. Keywords: k-means, Support vector machine, Lymphoma, Acute Lymphocytic Lymphoma, Machine Learning


2019 ◽  
Author(s):  
Wenfa Ng

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.


2019 ◽  
Vol 10 (2) ◽  
pp. 39-48
Author(s):  
Eman Mostafa ◽  
Heba A. Tag El-Dien

Leukemia is a blood cancer which is defined as an irregular augment of undeveloped white blood cells called “blasts.” It develops in the bone marrow, which is responsible for blood cell generation including leukocytes and white blood cells. The early diagnosis of leukemia greatly helps in the treatment. Accordingly, researchers are interested in developing advanced and accurate automated techniques for localizing such abnormal blood cells. Subsequently, image segmentation becomes an important image processing stage for successful feature extraction and classification of leukemia in further stages. It aims to separate cancer cells by segmenting the microscopic image into background and cancer cells that are known as the region of interested (ROI). In this article, the cancer blood cells were segmented using two separated clustering techniques, namely the K-means and Fuzzy-c-means techniques. Then, the results of these techniques were compared to in terms of different segmentation metrics, such as the Dice, Jac, specificity, sensitivity, and accuracy. The results proved that the k-means provided better performance in leukemia blood cells segmentation as it achieved an accuracy of 99.8% compared to 99.6% with the fuzzy c-means.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lydia Y. Liu ◽  
Vinayak Bhandari ◽  
Adriana Salcedo ◽  
Shadrielle M. G. Espiritu ◽  
Quaid D. Morris ◽  
...  

AbstractWhole-genome sequencing can be used to estimate subclonal populations in tumours and this intra-tumoural heterogeneity is linked to clinical outcomes. Many algorithms have been developed for subclonal reconstruction, but their variabilities and consistencies are largely unknown. We evaluate sixteen pipelines for reconstructing the evolutionary histories of 293 localized prostate cancers from single samples, and eighteen pipelines for the reconstruction of 10 tumours with multi-region sampling. We show that predictions of subclonal architecture and timing of somatic mutations vary extensively across pipelines. Pipelines show consistent types of biases, with those incorporating SomaticSniper and Battenberg preferentially predicting homogenous cancer cell populations and those using MuTect tending to predict multiple populations of cancer cells. Subclonal reconstructions using multi-region sampling confirm that single-sample reconstructions systematically underestimate intra-tumoural heterogeneity, predicting on average fewer than half of the cancer cell populations identified by multi-region sequencing. Overall, these biases suggest caution in interpreting specific architectures and subclonal variants.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 385-385 ◽  
Author(s):  
Charnise Goodings-Harris ◽  
Hui Zhang ◽  
Xuijie Zhao ◽  
Heng Xu ◽  
Omar I Abdel-Wahab ◽  
...  

Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Genome wide association studies by us and others have identified germline genetic variants at the ARID5B locus that strongly influence susceptibility to ALL (Nat Genet 2009, J Clin Oncol 2012). Despite compelling results from these genetic association studies, the molecular mechanisms by which ARID5B contributes to ALL pathogenesis remains largely unknown. ARID5B is a member of the ARID transcription family characterized by a conservative AT rich binding domain, but the physiological functions of ARID5B are poorly understood. Therefore we sought to develop mouse models to comprehensively characterize the roles of ARID5B in normal and malignant hematopoiesis. To this end, we first established a Vav-1 specific Arid5b overexpression (AOE) mouse model. Mice were designed with a tetO element knocked in before the start codon of Arid5b to create an Arid5b tetO mouse. Arid5b tetO mice were then crossed with Vav-1-tTA mice and, overexpression of Arid5b confirmed in the hematopoietic system of progenies with the desired genotype. At 6-8 weeks old complete blood counts (CBC) analysis revealed that AOE mice had a large decrease in white blood cells (WBCs) and a slight reduction in red blood cells (RBCs) and hemoglobin (Hb). We also noted a significant reduction in the bone marrow cellularity of our Arid5b overexpressing mice. To further characterize our AOE mouse model we used flow cytometry to quantify the proportions of mature as well as various stem and progenitor cell populations during hematopoiesis. We found that AOE mice showed an increase in the MegE biased MPP2 (LSK flt3−/CD150+/CD48+) population and a decrease in the lymphoid biased MPP4 (LSK (Flt3+/CD150−/CD48+/−) population. Overexpression of Arid5b resulted in a significant reduction in the proportion of all bone marrow B cell populations (Hardy Fraction A-F) (Figure 1A) and B220+ cells in the spleen. In vitro methylcellulose colony forming assays further revealed a loss of functional pre B lymphoid progenitor in AOE bone marrow. To determine if the hematopoietic defects seen in younger AOE mice was due to a delay in hematopoiesis we aged AOE mice. We found that as we aged AOE mice there was still a reduction in bone marrow cellularity and all bone marrow B cell populations. Surprisingly, as mice were aged we found that AOE mice were prone to sudden death and displayed a dramatic reduction in overall survival when compared to wildtype littermates with a mean survival age of 8 months (Figure 1B). At the time of death, we found that AOE mice presented with severely enlarged spleens. To predict the death of AOE mice we performed ultrasounds to track spleen volume. Based on ultrasounds performed on AOE mice and wildtype littermates, AOE mice spleens become larger than those of their littermates as early as 6 months old, however spleen volume did not predict sudden death. In aged AOE mice, while the spleens were grossly enlarged and contained larger amounts of red pulp and increased Ter119+ cells, there was still a reduction in the proportion of B cells and no increase in the proportions of other white blood cells (Figure 1D). Older AOE mice exhibited anemia, hypergammaglobulinemia, and splenomegaly. By 30 weeks, defects in B cell proportions were seen in the lymph nodes of AOE mice via immunohistochemistry (Figure 1C). Compared to wildtype littermates, AOE mice displayed reduced white blood cells, red blood cells, and platelets (Figure 1D). The anemia was associated with higher reticulocyte numbers and increased serum erythropoietin concentration. The life span of erythrocytes from AOE mice was less than that of wildtype littermates. Together, these results indicated that Arid5b plays an important role in B lymphopoiesis and erythropoiesis. Disclosures No relevant conflicts of interest to declare.


2018 ◽  
Author(s):  
Lydia Y. Liu ◽  
Vinayak Bhandari ◽  
Adriana Salcedo ◽  
Shadrielle M. G. Espiritu ◽  
Quaid D. Morris ◽  
...  

AbstractWhole-genome sequencing can be used to estimate subclonal populations in tumours and this intra-tumoural heterogeneity is linked to clinical outcomes. Many algorithms have been developed for subclonal reconstruction, but their variabilities and consistencies are largely unknown. We evaluated sixteen pipelines for reconstructing the evolutionary histories of 293 localized prostate cancers from single samples, and eighteen pipelines for the reconstruction of 10 tumours with multi-region sampling. We show that predictions of subclonal architecture and timing of somatic mutations vary extensively across pipelines. Pipelines show consistent types of biases, with those incorporating SomaticSniper and Battenberg preferentially predicting homogenous cancer cell populations and those using MuTect tending to predict multiple populations of cancer cells. Subclonal reconstructions using multi-region sampling confirm that single-sample reconstructions systematically underestimate intra-tumoural heterogeneity, predicting on average fewer than half of the cancer cell populations identified by multi-region sequencing. Overall, these biases suggest caution in interpreting specific architectures and subclonal variants.


2019 ◽  
Author(s):  
Wenfa Ng

The immune checkpoint plays an important role in keeping immune cells in check for protecting tissues and organs from attack by the body’s own immune system. Similar concepts also apply in how cancer cells managed to fool immune cells through the surface display of particular antigens that mimic those exhibited by normal body cells. Specifically, cancer cells display antigens that bind to receptors on immune cells that subsequently prevent an attack on the cancer cells. Such binding between cancer antigens and immune cell receptors can be prevented through the use of checkpoint inhibitors antibodies specific for particular receptors on immune cells; thereby, unleashing immune cells to mount an immune response against cancer cells. While demonstrating good remissions in many patients where tumours shrunk substantially after administration of checkpoint inhibitors, cases exist where an overactivated immune system cause harm to organs and tissues culminating in multiple organ failure. Analysis of such toxicity effects of checkpoint inhibitors revealed that generic nature of targeted immune receptor plays a pivotal role in determining extent of side effects. Specifically, if the target immune receptor participates in checkpoints that prevent immune cells from attacking host cells, unleashing such receptors in cancer therapy may have untoward effects on patient’s health. Hence, the goal should be the selection of immune cell receptor specific to cancer cell antigens and which does not bind antigens or ligands displayed by the body’s cells. Such receptors would provide ideal targets for the development of checkpoint inhibitor antibodies for unleashing immune cells against cancer cells. To search for non-generic receptors that bind cancer cell antigens only, a combined computational and experimental approach could be used where ensemble of surface antigens on cancer cells and available receptors on immune cells could be profiled by biochemical assays. Downstream purification of ligands and receptors would provide for both structural elucidation and amino acid sequencing useful for bioinformatic search of homologous sequences. Knowledge of the antigens’ and receptors’ structures and amino acid sequence would subsequently serve as inputs to computational algorithms that models molecular docking events between receptor and antigen. This paves the way for heterologous expression of putative ligand and receptor in cell lines cultured in co-culture format for assessing binding between ligand and receptor, and more importantly, its physiological effects. Ability of immune receptor to bind to ligands on normal cells could also be assessed. Similar co-culture studies could be conducted with cancer cells and different immune cell types to check for reproducibility of observed effect in cell lines. Finally, antibodies could be raised for candidate receptors whose inhibition would not result in systemic attack of immune cells on host cells.


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