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What images are coming to your mind when you think about sustainable and qualified life? The main picture drawn is healthcare. Many people suffer from cancer; more than 18.1 million people were diagnosed with cancer and 9.6 million people died from cancer worldwide in 2018. Therefore many diagnosis and treatment strategies that are shaped and regulated by biomedicine approaches have been developed to solve this problem. Biomedicine is an interdisciplinary science to understand the interaction of biological, chemical, and physiological principles. These principles should be brought together to be applicable and sustainable for qualified life. Drug discovery and combination therapy using nanocarriers and natural compounds are being innovated as new approaches and opportunities for cancer treatment. Theoretically and practically, there is no limit to the development of new biomedicinal tools for personalized medicine in cancer. Therefore personalized medicine plays an important role for reaching successful therapy with low cost. By discovering the diverse potential of biomedicine, we can provide better healthcare in the world.

WOS: 000514819900002, PubMed: 31833715, Objective: Acute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases. Materials and Methods: the cytotoxic and apoptotic effects of methylstat and doxorubicin on HL-60 cells were detected by MTT cell viability assay, double staining of treated cells with annexin-V/propidium iodide, and caspase-3 activity assay. Mitochondrial activity was analyzed using JC-1 dye. the expression levels of the BCL2 and BCL2L1 anti-apoptotic genes in HL-60 cells were determined using real-time polymerase chain reaction (PCR). Lastly, the cytostatic effect was determined by cell cycle analysis. Results: in our research, cytotoxic, cytostatic, and apoptotic effects of methylstat on human HL-60 cells were investigated. Cytotoxic and cytostatic analyses revealed that methylstat decreased cell proliferation in a dose-dependent cytotoxic manner and arrested HL-60 cells in the G2/M and S phases. Methylstat also induced apoptosis through the loss of mitochondria! membrane potential and increases in caspase-3 enzyme activity. the expression levels of BC12and BCL2L1 were also decreased according to real-time PCR results. Finally, the combination of methylstat with doxorubicin resulted in synergistic cytotoxic effects on HL-60 cells. Conclusion: Taken together, these results demonstrate that methylstat may be a powerful candidate as a drug component of AML treatment protocols., Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [BIDEB 2209-A], The National Scholarship Program granted this project for undergraduate scientists supported by the Scientific and Technological Research Council of Turkey (BIDEB 2209-A). We are grateful to Prof. Udo Oppermann for supplying us with methylstat from the University of Oxford (United Kingdom). the authors acknowledge the assistance of the Bioengineering and Biotechnology Application and Research Center staff of Izmir Institute of Technology. We are deeply thankful to Miray Unlu, PhD student, for her assistance with the apoptotic assays.

Cancer cells divide continuously without any control, rendering immortal cells. These changes cause the dynamic instability in their genomes. Therefore each cancer cell in a tumor mass has various changes for specific tumor types. Their differences should be diagnosed on the basis of mutated genes and/or proteins. After the detection of alterations in cancer cells based on the techniques and instruments of biomedicine, personalized therapy continues with preexisting drug implementations. Personalized therapy broadens the borders with circulating tumor cells causing the metastasis in distant regions, developing specific gene therapies, novel targeted drugs, and immunotherapeutics for eliminating cancerous cells precisely. Within this context, biomedicine helps humankind to merge the biological and physiological knowledge to clinical practice. In this chapter, we aimed to clarify attitudes in biomedicine from molecular changes from single tumor cells to in vivo studies to find the best therapy for a cancer patient.

Flavonoids are a family of polyphenolic photochemical that are naturally found in plants. Flavonoids have been widely studied due to the curiosity of scientists about the implementation of nature to human health. These experimental and epidemiological studies showed that flavonoids have beneficial effects such as antioxidation, antiinflammation, antiplatelet, antiallergic, antiaging, antidiabetic, and anticarcinogenic activity. They can also interact with and regulate cellular proteins, transcription factors, and signaling enzymes at the molecular level. Cancer is one of the most common problems in human health and millions of people die due to cancer every year. Due to the lack of completely efficient therapies for most cancer patients, new approaches should be discovered. Flavonoids have been investigated and many studies have confirmed their importance as a therapy option in many diseases. In this chapter we review the use of flavonoids as therapeutical agents and prevention for cancer, including the recent studies as well as future perspectives in the field.

Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.

As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.

Background In this study, we aimed to determine synergistic apoptotic and cytotoxic effects of methylstat and bortezomib on U266 and ARH77 multiple myeloma (MM) cells. Methods Cytotoxic effects of the drugs were demonstrated by MTT cell proliferation assay while apoptotic effects were examined by loss of mitochondrial membrane potential (MMP) by JC-1 MMP detection kit, changes in caspase-3 enzyme activity and Annexin-V apoptosis assay by flow cytometry. Expression levels of apoptotic and antiapoptotic genes were examined by qRT-PCR. Results Our results showed that combination of methylstat and bortezomib have synergistic antiproliferative effect on MM cells as compared to either agent alone. These results were also confirmed by showing synergistic apoptotic effects determined by increased loss of mitochondrial membrane potential and increased caspase-3 enzyme activity and relocation of phosphotidyleserine on the cell membrane by Annexin-V/PI double staining. Combination of bortezomib with methylstat arrested cells at the S phase of the cell cycle. Methylstat treatment caused upregulation of FASLG, NGFR, TNF, TNFRS10B and TNFRS1B apoptotic genes and downregulation of AKT1, AVEN, BAG1 BCL2L2 and RELA antiapoptotic genes in a dose and time dependent manner. Conclusion In conclusion, our data suggested that bortezomib in combination with methylstat decreased cell proliferation and induced apoptosis significantly in U266 and ARH77 cells. When supported with in vivo analyses, methylstat might be considered as a potential new agent for the treatment of MM.

Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.

Aim: The aim of this study is to evaluate and compare therapeutic effects of mesenchymal stem cell (MSCs) and osteoprotegerin (OPG) gene transfer applications on inhibition and/or repair of orthodontically induced inflammatory root resorption (OIIRR). Materials and methods: Thirty Wistar rats were divided into four groups as untreated group (negative control), treated with orthodontic appliance group (positive control), MSCs injection group, and OPG transfected MSCs [gene therapy (GT) group]. About 100g of orthodontic force was applied to upper first molar teeth of rats for 14 days. MSCs and transfected MSC injections were performed at 1st, 6th, and 11th days to the MSC and GT group rats. At the end of experiment, upper first molar teeth were prepared for genetical, scanning electron microscopy (SEM), fluorescent microscopy, and haematoxylin eosin-tartrate resistant acid phosphatase staining histological analyses. Number of total cells, number of osteoclastic cells, number of resorption lacunae, resorption area ratio, SEM resorption ratio, OPG, RANKL, Cox-2 gene expression levels at the periodontal ligament (PDL) were calculated. Paired t -test, Kruskal–Wallis, and chi-square tests were performed. Results: Transferred MSCs showed marked fluorescence in PDL. The results revealed that number of osteoclastic cells, resorption lacunae, resorption area ratio, RANKL, and Cox-2 were reduced after single MSC injections significantly ( P < 0.05). GT group showed the lowest number of osteoclastic cells ( P < 0.01), number of resorption lacunae, resorption area ratio, and highest OPG expression ( P < 0.001). Conclusions: Taken together all these results, MSCs and GT showed marked inhibition and/or repair effects on OIIRR during orthodontic treatment on rats.

Tumors progress in a specific area, which supports its development, spreading or shrinking in time with the presence of different factors that effect the fate of the cancer cells. This specialized site is called "tumor microenvironment" and has a composition of heterogenous materials. The immune cells are also residents of this stromal, cancerous, and inflammatory environment, and their types, densities, or functional differences are one of the key factors that mediate the fate of a tumor. T cells as a vital part of the immune system also are a component of tumor microenvironment, and their roles have been elucidated in many studies. In this review, we focused on the immune system components by focusing on T cells and detailed T helper cell subsets in tumor microenvironment and how their behaviors affect either the tumor or the patient's outcome.

Chronic myeloid leukemia (CML) is characterized by the accumulation of Philadelphia chromosome-positive (Ph+) myeloid cells. Ph+ cells occur via a reciprocal translocation between the long arms of chromosomes 9 and 22 resulting in constitutively active Bcr-abl fusion protein. Tyrosine kinase inhibitors (TKIs) are used against the kinase activity of Bcr-abl fusion protein for the effective treatment of CML. However, the development of drug resistance, directed by different genetic mechanisms, is the major problem of clinical applications of TKIs. These mechanisms include mutations in the TKI binding site of Bcr-abl, overexpression of Bcr-abl, overexpression of ATP binding cassette transporters, aberrant ceramide metabolism, inhibition of apoptosis, and changes in expression levels of microRNAs. Recently, many studies have focused on understanding the molecular mechanisms of drug resistance in cancer while targeting therapies providing reversal of resistance. Cancer stem cells also have roles in tumor initiation, maintenance, progression, metastasis, and drug resistance. Uncovering the mechanisms of drug resistance can provide more efficient treatment of cancer since these findings may provide novel targets for a complete cure. In this review, we discuss recent findings on the mechanisms of multidrug resistance and its reversal in CML.

Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromosomal abnormalities, oncogene activation and growth factor dysregulation. Chemotherapy is the most commonly used treatment strategy in MM. However, MM is a difficult disease to treat because of its marked resistance to chemotherapy. MM has been shown to be commonly multidrug resistance (MDR)-negative at diagnosis and associated with a high incidence of MDR expression at relapse. This review deals with the molecular aspects of MM, drug resistance mechanisms during treatment and also possible new applications for overcoming drug resistance.

peripheral blood smear. After viral, infectious, rheumatologic tests were normal, we applied bone marrow aspiration and biopsy and it was normocellular. We determined PNH clon at the flaer test. Then, we started to eculizumab therapy. He has been treated with eculizumab for two years. And also he has been treated 1200 mg eculizumab every 12 days for twenty months. In the last hemogram wbc: 3300 mm3, hgb: 6.2 g/dl, plt: 2000 mm3. He had a lot of transfusions during two years. He has no donor for allogeneic stem cell transplantation. We are still looking for unrelated donor for him. Conclusion: Eculizumab therapy has been shown to reduce the need for blood transfusion in patients with PNH.

Background: Pomegranate is also named Punica granatum native to Asia which contains a number of bioactive compounds such as phenolics, flavonoids ellagitannins and minerals. Previous studies have reported the anticarcinogenic effects of Pomegranate via inducing apoptosis and inhibition of cell proliferation in various cancer types. Purpose: In this study, we aimed to identify the cytotoxic and apoptotic effects of pomegranate extracts on U266 multiple myeloma cells. Methods: The cytotoxic effects of P. granatum leave, stem and flower on U266 cells were conducted via MTT cell proliferation assay. Then, apoptotic effects of P. granatum leave, stem and flower extracts on U266 cells were tested by loss of mitochondrial membrane potential and location of phosphotidylserine. Cell cycle analysis by flow cytometry was also performed to obtain cell populations in different phases by flow cytometry. Results: P. granatum extracts inhibited proliferation on U266 cells in a dose-dependent manner. We determined 87-, 88-, and 82% decreases in proliferation of U266 cells exposed to 500 μg/ml P. granatum leave, 500 μg/ml P.granatum stem and 100μg/ml P. granatum flower extracts for 72 hours, respectively, as compared to untreated cells. Annexin-V analysis revealed that there were 13-, 17-, and 19 fold increases in apoptotic cell population of U266 exposed to 500-, 750-, and 1000 μg/ml P. granatum leave extract, 16and 27 fold increases in apoptotic cell population exposed to 750-, and 1000 μg/ml P. granatum stem extract whereas 1.6and 3.5 fold increases in apoptotic cells exposed to 50 and 100 μg/ml P. granatum flower extract for 72 hours, respectively, as compared to control group cells. Loss of mitochondrial membrane potential analyses also confirmed apoptosis results. Summary/conclusion: These results documented cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells. Pomegranate induced apoptosis through deformation of mitochondrial membrane potential and increasing cell cycle arrests.

Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.