Bavya Chandrasekhar;Dona Samuel Karen;Veena Jaganivasan
Journal of Integrative Natural Science
/
v.17
no.1
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pp.13-20
/
2024
Female breast cancer is the fifth highest cause of mortality. Breast cancer is the most prevalent type of cancer in women globally, while it can also affect men. STAT5A plays a role in its development and progression. Given that activation of STAT5a is frequently linked to the growth and progression of tumors, STAT5a has been identified as a possible target for the therapy of several cancers. STAT5A, in particular, has proven to be overexpressed in various breast cancer cell lines and tumors, and it has been associated to the promotion of tumour cell proliferation and survival. STAT5A inhibition has been shown in vitro and in vivo to reduce the development of breast cancer cells. As a result, we have screened compounds from the FDA database that might serve as potential inhibitors of STAT5a through virtual screening, docking, DFT and MD simulation approaches. The drug Nilotinib has shown promising results inhibiting STAT5a. Further, in-vitro analysis will be carried forward to understand the anti-cancer activity.
Khoshtabiat, Laya;Mahdavi, Majid;Dehghan, Gholamreza;Rashidi, Mohammad Reza
Asian Pacific Journal of Cancer Prevention
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v.17
no.9
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pp.4267-4273
/
2016
Previous studies suggested that dithio-carbamates are potent apoptosis and anti-apoptosis inducing agents in various cancer cells. Here, the anti-proliferative and apoptosis inducing effects of a new derivative (2-NDC) from the dithio-carbamate family was examined in human leukemia K562 cells. We use thiazolyl blue tetrazolium bromide (MTT) to measure viability and cell growth inhibition. The 2-NDC showed effects on viability in a dose and time-dependent manner, inhibiting proliferation at concentrations of $10-30{\mu}M$ after 24-48 hours of treatment and increasing values after 72 hours at $40-120{\mu}M$. The cytotoxic effect of the compound was calculated with an $IC_{50}$ of $30{\mu}M$ after 24-hour. Apoptosis induction was confirmed by acridine orange-ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, flow cytometric assessment and also caspase-3 activation assay. Furthermore, enzymes level such as superoxide dismutase (SOD) and catalase (CAT) involved in oxidative stress were evaluated. The results of this study demonstrated insignificant increase of intracellular ROS levels for 24 hours and reduction after 48-72 hours. In addition to reduction of intracellular thiol, caspase-3 like activity was also decreased in a time-dependent manner in cells treated with 2-NDC. Thus 2-NDC can be considered as a good candidate for further pharmaceutical evaluations.
The Journal of the Korean bone and joint tumor society
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v.11
no.1
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pp.54-61
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2005
Purpose: The granulocytic sarcoma which developed in leukemic patients are quite rare and it will have bad prognosis, but it's tumor pathogenesis and also their treatment are not yet established. Through this study we have tried to know their clinical course, prognosis and their end result of recent treatment. Material and Methods: Total 20 patients of granulocytic sarcoma which were developed in total 2,197 leukemic patients from April, 1998 to September, 2004 were treated at the leukemic center and the orthopaedic department of St. Mary's hospital, Catholic University of Korea, and followed them for 1~78 months(average 18 months). Results: Total 20 cases of granulocytic sarcoma was found in 14 cases of total 1,331 acute myelocytic leukemic patients(AML), 4 cases of total 744 of chronic myelocytic leukemic patients(CML), and only one case in total 122 of acute biphenotype of leukemia. And so their occurrence rate in leukmic patients are actually 0.91%, total 20 cases of granulocytic sarcoma in total 2,197 leukemic patients at same period. Their ages are average 28.3 years(4~52 years), and male are predominant(13 cases) than female(7 cases). Single involvement was found in 11 cases but multiple lesions are in 9 cases, and spine, brain, extremities, chest, and pelvic bone are involved in frequency. The granulocytic sarcoma was developed in various stages of the leukemia, ie, 8 cases in complete remission of leukemia, and 12 cases in the treatment process of AML. The pathohistologic evaluation of granulocytic sarcoma was done in 6 cases which was developed in their extremities, and confirmed numerous immature myeloblasts and lymphocytes mixed. The treatment of these granulocytic sarcoma was mainly limited for the treatment of leukemia by Glivac and massive steroid therapy(19cases) and also combined with the bone marrow transplantation(13 cases), but radiation therapy with average 3,500 rads in 15 cases out of total 20 sarcomas was also done, and followed them for average 17.5 months after development of granulocytic sarcomas. Finally their prognosis was so bad that 12 patients(60%) out of total 20 granulocytic sarcoma were dead in 6.5 months after sarcoma developed and we found the granulocytic sarcoma was more fatal if they are developed during the process of CML(mortality: 100%(4/4cases). Conclusion: The prognosis of granulocytic sarcomas in leukemic patients are quite fatal, and much more studies for their pathogenesis and ways of treatment should be performed continuously.
Radiation therapy was the treatment of choice for CML in the past, in the form of SI or radioactive phosphorus. Its use has been replaced to a large extent by various chemotherapeutic agents. Recently SI in CML has been used, both to relieve painful splenomegaly and to take advantage of an indirect effect of SI on unirradiated bone marrow. We have treated 15 CML cases who had a huge spleen during chemotherapy or even after chemotherapy by 6 MV linear accelerator during the past two years at the Division of Radiation Therapy, Kang Nam St. Mary's Hospital, Catholic College. Response to SI has been rated according to the scoring system of Roger W. Byhardt, et al. which evaluated the splenic and hematologic response as well as the response of disease-related systems. According to this scoring system, most patients demonstrated a significant relief of splenomegaly along with improvement of hemogram. And we observed the change of Karnofsky Performance Status after SI, and survival after a confirmative diagnosis and SI.
Ahn, Chul Min;Hwang, Sang Yun;Byun, Min Kwang;Lee, Jin Hyoung;Chung, Wou Young;Moon, Jin Wook;Park, Moo Suk;Min, Yoo Hong;Kim, Se Kyu;Chang, Joon;Kim, Sung Kyu;Kim, Haeryoung;Kim, Hoguen;Kim, Young Sam
Tuberculosis and Respiratory Diseases
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v.57
no.2
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pp.183-187
/
2004
Bronchiolitis obliterans (BO) is a nonspecific inflammatory injury affecting primarily the small airways. Its inflammatory process is characterized by fibrotic obliteration of the lumen of bronchioles. BO can be idiopathic or associated with connective tissue disease, inhaled toxins, infections, drugs, and chronic graft-versus-host-disease (GVHD). Pulmonary complications occur in 40~60% of patients who undergo allogeneic bone marrow transplantation (BMT), causing 10~40% of transplant-related deaths. BO is a characteristic pulmonary complication which occurs usually within a few years after BMT. Documented complications of BO include air-leak syndromes such as pneumomediastinum, subcutaneous emphysema and pneumothorax. We report a case of a 30-year-old male patient with BO due to chronic GVHD after allogenic BMT who presented with recurrent bilateral pneumothoraces.
Kim, Jack-C.;Kim, Young-Hyun;Park, Jin-Il;Kim, Seon-Hee;Choi, Soon-Kyu
Archives of Pharmacal Research
/
v.20
no.3
/
pp.259-263
/
1997
In the preparation of acyclic thymidine nucleoside analogues, $K_2CO_3$(or NaH) treated thymine in DMSO was alkylated with .omega.-chloroalkyl nitrite (Cl-(CH_2)n-CN; n=1, 2, 3, 4) to provide an isomeric mixture of 1-(${\omega}$-cyanoalkyl)thymine (2a-d) and 1,3-bis(${\omega}$-cyanoalkyl)thymine in approximately 5:1 ratios. Reduction of the cyano function 2a-d with $NaBH_{4}/CoCl_{2}$ center dot$ 6H_{2}O$gave the corresponding 1-(${\omega}$aminoalkyl)thymine (3a-d). The newly formed primary amino function in 3a-d was directly reacted with 2-chloroethylisocyanate to afford the 1-[.omega.($N^{I}$-2-chloroethylureido) alkyl]thymine (4a-d) in good yields. Nitrosation of 1-[5-($ N^{I}-2$-chloroethylureido)pentyl] thymine (4d) with glacial acetic acid and dry $NaNO_{2}$-powder in anhydrous $CH_{2}Cl_{2}$gave two types of regioisomeric nitrosoureas, 1-[5-($N^{I}$--chloroethyl-$N^{I}$--nitrosoureido)pentylithymine (5d) and 1-[5-($N^{I}-2$-chloroethyl-N-nitrosoureido)pentyllthymine in approximately 5 :1 ratios. The in vitro cytotoxicity of the synthesized compounds (2a-d, 3a-d, 4a-d and 5a-d) against three cell lines (K-562, P-388 and FM-3A) are measured as $IC^{50}$ values. Compounds 3b and 4c showed moderate activities against all three cell lines, and all other compounds were found to be not active.
Background: Human hepatocellular carcinoma (HCC) is a common liver tumor and the main cause of cancer-related death. Tyrosine kinase inhibitors, such as imatinib and GNF5 which were developed to treat chronic myelogenous leukemia, regulate the progression of various cancers. The aim of this study was to confirm the anti-tumor activity of tyrosine kinase inhibitors through regulation of S-phase kinase-associated protein 2 (Skp2), an important oncogenic factor in various cancer cells, in human hepatocarcinoma SK-HEP1 cells. Methods: Cell viability and colony formation assays were conducted to evaluate the effects of imatinib, GNF5 and GNF2 on the growth of SK-HEP1 cells. Using immunoblot analysis, we assessed change of the activation of caspases, PARP, Akt, mitogen-activated protein kinases, and Skp2/p27/p21 pathway by imatinib and GNF5 in SK-HEP1 cells. Using sh-Skp2 HCC cells, the role of Skp2 in the effects of imatinib and GNF5 was evaluated. Results: Imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells. Treatment of imatinib and GNF5 decreased Skp2 expression and Akt phosphorylation, and increased the expression of p27, p21, and active-caspases in SK-HEP1 cells. In sh-Skp2 HCC cells, cell growth and the expression of Skp2 were inhibited by more than in the mock group treated with imatinib and GNF5. Conclusions: These results suggest that the anti-growth activity of tyrosine kinase inhibitors may be associated with the regulation of p27/p21 and caspases through Skp2 blockage in HCC cells.
Mansouri-Torshizi, Hassan;Saeidifar, Maryam;Ghasemi, Zahra Yekke;Khastan, Mahmood;Divsalar, Adeleh;Saboury, Ali Akbar
Journal of the Korean Chemical Society
/
v.55
no.1
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pp.70-80
/
2011
Two new palladium (II) complexes, [Pd (phen)(pip-dtc)]$NO_3$ and [Pd(phen)(mor-dtc)]$NO_3$, (where phen is 1,10-Phenantroline, pip-dtc is piperidinedithiocarbamate anion and mor-dtc is morpholinedithiocarbamate anion) have been synthesized and characterized by elemental analysis, spectroscopic studies (FT-IR, $^1H$ NMR, UV-Vis) and conductance measurement. In these complexes, the dithiocarbamate ligands coordinate with Pd (II) center as bidentate with two sulfur atoms. These two complexes have been tested against chronic myelogenous leukemia cell line, K562. They show $IC_{50}$ values less than cisplatin and thus the mode of binding of the complexes to calf thymus DNA (CT-DNA) were investigated by ultraviolet difference and fluorescence spectroscopy. They can denature DNA, exhibit cooperative binding and intercalate into DNA. Several binding and thermodynamic parameters are also described.
Yang Kwang Mo;Youn Seon-Min;Jeong Soo-Jin;Jang Ji-Yeon;Jo Wol-Soom;Do Chang-Ho;Yoo Y대-Jin;Shin Young-Cheol;Lee Hyung Sik;Hur Won Joo;Lim Young-Jin;Jeong Min-Ho
Radiation Oncology Journal
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v.21
no.3
/
pp.227-237
/
2003
Purpose: The human chronic myelogenous leukemia cell line, K562, expresses the chimeric bcr-abl oncoprotein, whose deregulated protein tyrosine kinase activity antagonizes via DNA damaging agents. Previous experiments have shown that nanomolar concentrations of herbimycin A (HWA) coupled with X-irradiation have a synergistic effect in inducing apoptosis in the Ph-positive K562 leukemia cell line, but genistein, a PTK inhibitor, is non selective for the radiation-induced apoptosils on $p210^{bcr/abl}$ protected K562 cells. In these experiments, the cytoplasmic signal transduction pathways, the Induction on a number of transcription factors and the differential gene expression in this model were investigated. Materials and Methids: K562 cells in the exponential growth phase were used in this study. The cells were irradiated with 0.5-12 Gy, using a 6 Mev Linac (Clinac 1800, Varian, USA). Immediately after irradiation, the cells were treated with $0.25/muM$ of HMA and $25/muM$ of genistein, and the expressions and the activities of abl kinase, MAPK family, NF- kB, c-fos, c-myc, and thymidine kinase1 (TK1) were examined. The differential gene expressions induced by PTK inhibitors were also investigated. Results: The modulating effects of herbimycin A and genistein on the radiosensitivity of K562 cells were not related to the bcr-abl kinase activity. The signaling responses through the MAPK family of proteins, were not involved either in association with the radiation-induced apoptosis, which is accelerated by HMA, the expression of c-myc was increased. The combined treatment of genistein, with irradiation, enhanced NF- kB activity and the TK1 expression and activity. Conclusion: The effects of HMA and genistein on the radiosensitivity on the K562 cells were not related to the bcr-abl kinase activity in this study, another signaling pathway, besides the WAPK family responses to radiation to K562 cells, was found. Further evaluation using this model will provide valuable information for the optional radiosensitization or radioprotection.
Background: Among the variety of opportunistic infections, pneumonia comprises the major morbidity in immunocompromised patients. Pneumocystis carnii pneumonia (PCP) and cytomegalovirus (CMV) pneumonia are common infectious illness of immunocompromised hosts. Although there are many reports regarding to the co-infection of PCP and CMV diagnosed by bronchoalveolar lavage (BAL) fluid examination, the effects of CMV co-infection on the outcome of PCP is still controversial. The purpose of this investigation is to evaluate the effects of CMV detected by BAL fluid examination on the clinical course of PCP in the immunocompromised patients other than human immunodeficiency virus infection. Method: Ten patients with PCP were enrolled and retrospective analysis of their medical records were done. HIV infected persons were excluded. The PCP was diagnosed by BAL fluid examination with Calcofluor-White staining. CMV was detected in BAL fluid by Shell-vial culture system. Chest radiographic findings were reviewed. We used Fisher's exact test and Mann-Whitney U test for statistical analysis of data. Results: The underlying disorders of patients were idiopathic pulmonary fibrosis (n=1), renal transplantation (n=4), necrotizing vasculitis (n=l), systemic lupus erythematosus (n=1), brain tumor (n=1), chronic myelogenous leukemia (n=1), unidentified (n=1). There were no difference in clinical course, APACHE III score, arterial blood gas analysis, white blood cell count, lymphocyte count, serum albumin concentration, chest radiographic findings and mortality between patients with PCP alone (n=4) and those with CMV co-infection (n=6). Univariate analysis regarding to the factors that associated with mortality of PCP were revealed that the application of mechanical ventilation (p=0.028), the level of APACHE III score (p=0.018) and serum albumin concentration (p=0.048) were related to the mortality of patients with PCP. Conclusion: The clinical course of PCP patients co-infected by CMV were not different from PCP only patients. Instead, accompanied respiratory failure, high APACHE III score and poor nutritional status were associated with poor outcome of PCP.
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