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Article ; Online: ScMO(BO

Ma, Ruru / Xu, Dongdong / Yang, Yun / Su, Xin / Lei, Binghua / Yang, Zhihua / Pan, Shilie

Dalton transactions (Cambridge, England : 2003)

2017 Volume 46, Issue 43, Page(s) 14839–14846

Abstract: Two new isostructural rare-earth oxyborates ScMO(BO ...

Abstract	Two new isostructural rare-earth oxyborates ScMO(BO
Language	English
Publishing date	2017-11-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/c7dt03172f
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Article ; Online: Large optical polarizability causing positive effects on the birefringence of planar-triangular BO

Zhou, Xinyuan / Huang, Junben / Cai, Gemei / Zhou, Hengwei / Huang, Yineng / Su, Xin

Dalton transactions (Cambridge, England : 2003)

2020 Volume 49, Issue 10, Page(s) 3284–3292

Abstract: ... In this work, taking a series of borates with only planar-triangular BO ...

Abstract	The structure-property relationship of photoelectric functional materials has been recognized as a hot topic. The study of the inner link between the band gaps and birefringence of optical materials is extremely crucial for the design and creation of novel optical devices, but still remains rather unexplored. In this work, taking a series of borates with only planar-triangular BO
Language	English
Publishing date	2020-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/d0dt00155d
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Article ; Online: Automatic multi-class intertrochanteric femur fracture detection from CT images based on AO/OTA classification using faster R-CNN-BO method.

Yoon, Sun-Jung / Hyong Kim, Tae / Joo, Su-Bin / Eel Oh, Seung

Journal of applied biomedicine

2020 Volume 18, Issue 4, Page(s) 97–105

Abstract: Intertrochanteric (IT) femur fractures are the most common fractures in elderly people, and they lead to significant morbidity, mortality, and reduced quality of life. The different types of fractures require a careful definition to ensure accurate ... ...

Abstract	Intertrochanteric (IT) femur fractures are the most common fractures in elderly people, and they lead to significant morbidity, mortality, and reduced quality of life. The different types of fractures require a careful definition to ensure accurate surgical planning and reduce the operation time, healing time, and number of surgical failures. In this study, a deep learning-based automatic multi-class IT fracture detection model was developed using computed tomography (CT) images and based on the AO/OTA classification method. The original CT image was resized and rearranged according to the fracture location and an unsharp masking filter was applied. A multi-class classification of nine different types of IT fractures and no fracture was performed using the faster regional-convolutional neural network (R-CNN). Bayesian optimization was also implemented to determine the optimal hyperparameter values for the faster R-CNN algorithm. In our proposed model, IT fractures classified into two classes showed an average accuracy of 0.97 ± 0.02, which was 0.90 ± 0.02 when classified into ten classes. Additionally, the detected region of interest from our proposed model showed minimum root mean square error and intersection over union values of 16.34 ± 47.01 pixels and 0.87 ± 0.12, respectively. In the future, our proposed automatic multi-class IT femur fracture detection model could allow clinicians to identify the fracture region and diagnose different types of femur fractures faster and more accurately. This will increase the probability of correct surgical treatment and minimize postoperative complications.
MeSH term(s)	Aged ; Bayes Theorem ; Femur/diagnostic imaging ; Hip Fractures/surgery ; Humans ; Neural Networks, Computer ; Quality of Life ; Tomography, X-Ray Computed
Language	English
Publishing date	2020-09-22
Publishing country	Poland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2171142-2
ISSN	1214-0287 ; 1214-0287
ISSN (online)	1214-0287
ISSN	1214-0287
DOI	10.32725/jab.2020.013
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Article ; Online: Targeting autophagy enhances BO-1051-induced apoptosis in human malignant glioma cells.

Chu, Pei-Ming / Chen, Li-Hsin / Chen, Ming-Teh / Ma, Hsin-I / Su, Tsann-Long / Hsieh, Pei-Chen / Chien, Chian-Shiu / Jiang, Bo-Hua / Chen, Yu-Chih / Lin, Yi-Hui / Shih, Yang-Hsin / Tu, Pang-Hsien / Chiou, Shih-Hwa

Cancer chemotherapy and pharmacology

2012 Volume 69, Issue 3, Page(s) 621–633

Abstract: Purpose: BO-1051 is an N-mustard derivative that is conjugated with DNA-affinic 9-anilinoacridine ... Since BO-1051 was reported to have strong anticancer activity, we investigated the effect and underlying ... mechanism of BO-1051 in human glioma cell lines.: Methods: Human glioma cell lines U251MG and U87MG were ...

Abstract	Purpose: BO-1051 is an N-mustard derivative that is conjugated with DNA-affinic 9-anilinoacridine. Since BO-1051 was reported to have strong anticancer activity, we investigated the effect and underlying mechanism of BO-1051 in human glioma cell lines. Methods: Human glioma cell lines U251MG and U87MG were studied with BO-1051 or the combination of BO-1051 and autophagic inhibitors. Growth inhibition was assessed by MTT assay. Apoptosis was measured by annexin V staining followed by flow cytometry and immunoblotting for apoptosis-related molecules. Induction of autophagy was detected by acridine orange labeling, electron microscopy, LC3 localization and its conversion. Transfection of shRNA was used to determine the involvement of Beclin1 in apoptotic cell death. Results: MTT assay showed that BO-1051 suppressed the viability of four glioma cell lines (U251MG, U87MG, GBM-3 and DBTRG-05MG) in a dose-dependent manner. The IC(50) values of BO-1051 for the glioma cells were significantly lower than the values for primary neurons cultures and normal fibroblast cells. Moreover, BO-1051 not only induced apoptotic cell death, but also enhanced autophagic flux via inhibition of Akt/mTOR and activation of Erk1/2. Importantly, suppression of autophagy by 3-methyladenine or bafilomycin A1 significantly increased BO-1051-induced apoptotic cell death in U251MG and U87MG cells. In addition, the proportion of apoptotic cells after BO-1051 treatment was enhanced by co-treatment with shRNA against Beclin1. Conclusions: BO-1051 induced both apoptosis and autophagy, and inhibition of autophagy significantly augmented the cytotoxic effect of BO-1051. Thus, a combination of BO-1051 and autophagic inhibitors offers a potentially new therapeutic modality for the treatment of malignant glioma.
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Autophagy/drug effects ; Blotting, Western ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Culture Techniques ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Glioma/drug therapy ; Glioma/metabolism ; Glioma/pathology ; Humans ; MAP Kinase Signaling System/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Microscopy, Electron, Transmission ; Microscopy, Fluorescence ; Microscopy, Phase-Contrast ; Molecular Structure ; Nitrogen Mustard Compounds/chemistry ; Nitrogen Mustard Compounds/pharmacology ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; TOR Serine-Threonine Kinases/antagonists & inhibitors
Chemical Substances	Antineoplastic Agents ; BO-1051 ; Nitrogen Mustard Compounds ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2012-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-011-1747-0
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Article ; Online: BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models.

Ambati, Srikanth R / Shieh, Jae-Hung / Pera, Benet / Lopes, Eloisi Caldas / Chaudhry, Anisha / Wong, Elissa W P / Saxena, Ashish / Su, Tsann-Long / Moore, Malcolm A S

Oncotarget

2016 Volume 7, Issue 28, Page(s) 43062–43075

Abstract: ... in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death in a concentration and ... time dependent manner in sarcoma cell lines. BO-1055 had potent activity (submicromolar IC50) against ... in osteosarcoma (IC50 >10μM) cell lines. BO-1055 exhibited a wide therapeutic window compared to other DNA ...

Abstract	DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; γ-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death in a concentration and time dependent manner in sarcoma cell lines. BO-1055 had potent activity (submicromolar IC50) against Ewing sarcoma and rhabdomyosarcoma, intermediate activity in DSRCT (IC50 = 2-3μM) and very weak activity in osteosarcoma (IC50 >10μM) cell lines. BO-1055 exhibited a wide therapeutic window compared to other DNA damaging drugs. BO-1055 induced more DNA double strand breaks and γH2AX expression in cancer cells compared to benign cells. BO-1055 showed inhibition of tumor growth in A673 xenografts and caused tumor regression in cyclophosphamide resistant patient-derived Ewing sarcoma xenografts and A204 xenografts. Combination of BO-1055 and irinotecan demonstrated synergism in Ewing sarcoma PDX models. Potent activity on sarcoma cells and its relative lack of toxicity presents a strong rationale for further development of BO-1055 as a therapeutic agent.
Language	English
Publishing date	2016-07-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.9657
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Article: [A reconstructed B. Fragilis-derived recombinant α-galactosidase developed for human blood type B→O conversion].

Gao, Hong-Wei / Li, Su-Bo / Bao, Guo-Qiang / Tan, Ying-Xia / Wang, Ling-Yan / Jin, Si-Hu / Wang, Ying-Li / Ji, Shou-Ping / Gong, Feng

Zhongguo shi yan xue ye xue za zhi

2011 Volume 19, Issue 2, Page(s) 503–507

Abstract: This study was aimed to prepare a reconstructed B. Fragilis-derived recombinant α-galactosidase developed for human B to O blood group conversion. Based on the construction of recombinant E. Coli (DE3) which can express α-galactosidase, the inducing time ...

Abstract	This study was aimed to prepare a reconstructed B. Fragilis-derived recombinant α-galactosidase developed for human B to O blood group conversion. Based on the construction of recombinant E. Coli (DE3) which can express α-galactosidase, the inducing time and inducer concentration were optimized for high expression of α-galactosidase. Then, the expression products in supernatant were purified by cation and anion exchange column chromatography. The purified α-galactosidase was used to treat B group red blood cells in phosphate buffer (pH 6.8) for 2 hours to prepare O group red blood cells. The results showed that the optimal inducing conditions for α-galactosidase expression were IPTG 0.1 mmol/L, 37°C and 2 hours. The specific enzyme activity of purified protein increased from 0.42 U/mg to 2.1 U/mg as compared with pre-purification. And, the conditions of B to O blood group conversion were 26°C, pH 6.8 (neutral pH condition) and 2 hours. Moreover, 225 µg of the enzyme could converse 1 ml B red blood cells to O completely. It is concluded that the technology of expression and purification of recombinant α-galactosidase has been established, and the purified protein can converse B red blood cells to O completely, which means that an effective enzyme conversing B red blood cells to O has been obtained.
MeSH term(s)	ABO Blood-Group System/immunology ; Bacteroides fragilis/enzymology ; Cloning, Molecular ; Escherichia coli/metabolism ; Humans ; Recombinant Proteins/biosynthesis ; alpha-Galactosidase/biosynthesis
Chemical Substances	ABO Blood-Group System ; Recombinant Proteins ; alpha-Galactosidase (EC 3.2.1.22)
Language	Chinese
Publishing date	2011-04
Publishing country	China
Document type	English Abstract ; Journal Article
ZDB-ID	2404306-0
ISSN	1009-2137
ISSN	1009-2137
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Zs.A 6603: Show issues

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Article ; Online: Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms.

Kuo, Ching-Ying / Chou, Wen-Cheng / Wu, Chin-Chung / Wong, Teng-Song / Kakadiya, Rajesh / Lee, Te-Chang / Su, Tsann-Long / Wang, Hui-Chun

Oncotarget

2015 Volume 6, Issue 28, Page(s) 25770–25783

Abstract: ... the function of novel water-soluble N-mustard BO-1055 (ureidomustin) in DNA damage response and repair ... mechanisms. As expected, BO-1055 induces ATM and ATR-mediated DNA damage response cascades, including ... that cell survival sensitivity to BO-1055 is comparable to that of mitomycin C. Both compounds require ...

Abstract	Alkylating agents are frequently used as first-line chemotherapeutics for various newly diagnosed cancers. Disruption of genome integrity by such agents can lead to cell lethality if DNA lesions are not removed. Several DNA repair mechanisms participate in the recovery of mono- or bi-functional DNA alkylation. Thus, DNA repair capacity is correlated with the therapeutic response. Here, we assessed the function of novel water-soluble N-mustard BO-1055 (ureidomustin) in DNA damage response and repair mechanisms. As expected, BO-1055 induces ATM and ATR-mediated DNA damage response cascades, including downstream Chk1/Chk2 phosphorylation, S/G2 cell-cycle arrest, and cell death. Further investigation revealed that cell survival sensitivity to BO-1055 is comparable to that of mitomycin C. Both compounds require nucleotide excision repair and homologous recombination, but not non-homologous end-joining, to repair conventional cross-linking DNA damage. Interestingly and unlike mitomycin C and melphalan, MGMT activity was also observed in BO-1055 damage repair systems, which reflects the occurrence of O-alkyl DNA lesions. Combined treatment with ATM/ATR kinase inhibitors significantly increases BO-1055 sensitivity. Our study pinpoints that BO-1055 can be used for treating tumors that with deficient NER, HR, and MGMT DNA repair genes, or for synergistic therapy in tumors that DNA damage response have been suppressed.
MeSH term(s)	Animals ; Antineoplastic Agents, Alkylating/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors ; Ataxia Telangiectasia Mutated Proteins/metabolism ; CHO Cells ; Cell Death/drug effects ; Cricetulus ; DNA Damage ; DNA Modification Methylases/metabolism ; DNA Repair ; DNA Repair Enzymes/metabolism ; Dose-Response Relationship, Drug ; Drug Synergism ; HEK293 Cells ; Humans ; MCF-7 Cells ; Melphalan/pharmacology ; Mitomycin/pharmacology ; Nitrogen Mustard Compounds/pharmacology ; Phenylurea Compounds/pharmacology ; Protein Kinase Inhibitors/pharmacology ; RNA Interference ; Recombinational DNA Repair ; S Phase Cell Cycle Checkpoints/drug effects ; Signal Transduction/drug effects ; Time Factors ; Transfection ; Tumor Suppressor Proteins/metabolism
Chemical Substances	1-(3-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-3-(4-(bis(2-chloroethyl)amino)phenyl)urea ; Antineoplastic Agents, Alkylating ; Nitrogen Mustard Compounds ; Phenylurea Compounds ; Protein Kinase Inhibitors ; Tumor Suppressor Proteins ; Mitomycin (50SG953SK6) ; DNA Modification Methylases (EC 2.1.1.-) ; MGMT protein, human (EC 2.1.1.63) ; ATM protein, human (EC 2.7.11.1) ; ATR protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; DNA Repair Enzymes (EC 6.5.1.-) ; Melphalan (Q41OR9510P)
Language	English
Publishing date	2015-09-22
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.4514
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Article ; Online: Determination of tissue distribution of potent antitumor agent ureidomustin (BO-1055) by HPLC and its pharmacokinetic application in rats.

Chien, Shin-I / Yen, Jiin-Cherng / Kakadiya, Rajesh / Chen, Ching-Huang / Lee, Te-Chang / Su, Tsann-Long / Tsai, Tung-Hu

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2013 Volume 917-918, Page(s) 62–70

Abstract: Ureidomustin hydrochloride (BO-1055) was designed as a water-soluble nitrogen-mustard ...

Abstract	Ureidomustin hydrochloride (BO-1055) was designed as a water-soluble nitrogen-mustard, which exhibited potent anticancer activity and was selected as a candidate for preclinical studies. However, up to date, there is rarely an easy and economic method to quantize ureidomustin in the biological samples. The aim of this study is to develop a simple yet valid quantization method to tackle this challenge. Here we present a combined high-performance liquid chromatography with photodiode array (HPLC-PDA) method in quantizing the ureidomustin in the plasma and various organs of Sprague-Dawley rats. The method was validated in terms of precision, accuracy, and extraction recovery. Furthermore, the established method was applied to study pharmacokinetics of ureidomustin in the rat's plasma and verified via a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Calibration curves of the plasma and organ samples were falling at the range between 0.5-50μg/mL and 0.1-50μg/mL (r(2)≥0.999 and CV≤±15%), respectively. The limits of detection (LOD) were 0.1μg/mL for plasma samples and 0.05μg/mL for organ samples, while the detection limits of quantification (LOQ) were 0.5μg/mL for plasma samples and 0.1μg/mL for organ samples. The average recovery of ureidomustin was about 83%. These results demonstrated a linear pharmacokinetic pattern at dosages of 10 and 30mg/kg. The pharmacokinetic data revealed that ureidomustin was best fitted to a two-compartment model with a rapid distribution phase and a slow elimination phase. Besides, after a short intravenous administration time at the dose of 10mg/kg, ureidomustin was found to be quickly distributed to all organs in rats, accumulated mainly in the kidney, and only a limited amount was detected in the brain.
MeSH term(s)	Animals ; Antineoplastic Agents/blood ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacokinetics ; Chromatography, High Pressure Liquid/methods ; Limit of Detection ; Male ; Nitrogen Mustard Compounds/blood ; Nitrogen Mustard Compounds/chemistry ; Nitrogen Mustard Compounds/pharmacokinetics ; Phenylurea Compounds/blood ; Phenylurea Compounds/chemistry ; Phenylurea Compounds/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry/methods ; Tissue Distribution
Chemical Substances	1-(3-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-3-(4-(bis(2-chloroethyl)amino)phenyl)urea ; Antineoplastic Agents ; Nitrogen Mustard Compounds ; Phenylurea Compounds
Language	English
Publishing date	2013-02-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2012.12.025
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Zs.A 813: Show issues

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Article ; Online: Autophagy inhibition enhances apoptosis triggered by BO-1051, an N-mustard derivative, and involves the ATM signaling pathway.

Chen, Li-Hsin / Loong, Che-Chuan / Su, Tsann-Long / Lee, Yi-Jang / Chu, Pei-Ming / Tsai, Ming-Long / Tsai, Ping-Hsin / Tu, Pang-Hsien / Chi, Chin-Wen / Lee, Hsin-Chen / Chiou, Shih-Hwa

Biochemical pharmacology

2011 Volume 81, Issue 5, Page(s) 594–605

Abstract: In a previous study, BO-1051, an N-mustard linked with a DNA-affinic molecule, was shown to target ... as well as the underlying mechanism, of BO-1051. We found that BO-1051 simultaneously induced apoptosis ... and autophagy in hepatocellular carcinoma cell lines. DNA double strand breaks induced by BO-1051 ...

Abstract	In a previous study, BO-1051, an N-mustard linked with a DNA-affinic molecule, was shown to target various types of cancer cell lines. In the present study, we aimed to investigate the cytotoxicity, as well as the underlying mechanism, of BO-1051. We found that BO-1051 simultaneously induced apoptosis and autophagy in hepatocellular carcinoma cell lines. DNA double strand breaks induced by BO-1051 activated the ATM signaling pathway and subsequently resulted in caspase-dependent apoptosis. When autophagy was inhibited in its early or late stages, apoptosis was significantly enhanced. This result indicated autophagy as a cytoprotective effect against BO-1051-induced cell death. We further inhibited ATM activation using an ATM kinase inhibitor or ATM-specific siRNA and found that while apoptosis was blocked, autophagy also diminished in response to BO-1051. We not only determined a signaling pathway induced by BO-1051 but also clarified the linkage between DNA damage-induced apoptosis and autophagy. We also showed that BO-1051-induced autophagy acts as a cytoprotective reaction and downstream target of the ATM-signaling pathway. This research revealed autophagy as a universal cytoprotective response against DNA damage-inducing chemotherapeutic agents, including BO-1051, cisplatin, and doxorubicin, in hepatocellular carcinoma cell lines. Autophagy contributes to the remarkable drug resistance ability of liver cancer.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Ataxia Telangiectasia Mutated Proteins ; Autophagy/drug effects ; Carcinoma, Hepatocellular ; Cell Cycle Proteins/physiology ; Cell Line, Tumor ; DNA Damage ; DNA-Binding Proteins/physiology ; Humans ; Liver Neoplasms ; Nitrogen Mustard Compounds/pharmacology ; Protein-Serine-Threonine Kinases/physiology ; Signal Transduction ; Tumor Suppressor Proteins/physiology
Chemical Substances	Antineoplastic Agents ; BO-1051 ; Cell Cycle Proteins ; DNA-Binding Proteins ; Nitrogen Mustard Compounds ; Tumor Suppressor Proteins ; ATM protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2011-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2010.12.011
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Zs.A 19: Show issues

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Article ; Online: The novel DNA alkylating agent BO-1090 suppresses the growth of human oral cavity cancer in xenografted and orthotopic mouse models.

Sanjiv, Kumar / Su, Tsann-Long / Suman, Sharda / Kakadiya, Rajesh / Lai, Tsung-Ching / Wang, Hsuan-Yao / Hsiao, Michael / Lee, Te-Chang

International journal of cancer

2012 Volume 130, Issue 6, Page(s) 1440–1450

Abstract: ... and on in vivo xenografts. Among them, BO-1090, bis(hydroxymethyl)-3a-aza-cyclopenta[a]indene ... Following DNA damage, BO-1090 induced G1/S-phase arrest and apoptosis in oral cancer cell lines ... The therapeutic potential of BO-1090 was tested in mice that received a xenograft of oral cavity cancer cell lines ...

Abstract	Oral cancer is the fourth-most common cause of death in males and overall the sixth-most common cause of cancer death in Taiwan. Surgery, radiotherapy and chemotherapy combined with other therapies are the most common treatments for oral cavity cancer. Although cisplatin, 5-fluorouracil and docetaxel are commonly used clinically, there is no drug specific for oral cavity cancer. Here, we demonstrated that derivatives of 3a-aza-cyclopenta[a]indene, a class of newly synthesized alkylating agents, may be drugs more specific for oral cancer based on its potent in vitro cytotoxicity to oral cancer cells and on in vivo xenografts. Among them, BO-1090, bis(hydroxymethyl)-3a-aza-cyclopenta[a]indene derivative, targeted DNA for its cytotoxic effects as shown by inhibition of DNA synthesis (bromodeoxyuridine-based DNA synthesis assay), induction of DNA crosslinking (alkaline gel shift assay), and induction of DNA single-stranded breaks (Comet assay) and double-stranded breaks (γ-H2AX focus formation). Following DNA damage, BO-1090 induced G1/S-phase arrest and apoptosis in oral cancer cell lines. The therapeutic potential of BO-1090 was tested in mice that received a xenograft of oral cavity cancer cell lines (SAS or Cal 27 cells). Intravenous injection of BO-1090 significantly suppressed tumor growth in comparison to control mice. BO-1090 also significantly reduced the tumor burden in orthotopic mouse models using SAS cells. There was no significant adverse effect of BO-1090 treatment with this dosage based on whole blood count, biochemical enzyme profiles in plasma and histopathology of various organs in mouse. Taken together, our current results demonstrate that B0-1090 may have potential as a treatment for oral cavity cancer.
MeSH term(s)	Alkylating Agents/pharmacology ; Animals ; Antineoplastic Agents/pharmacology ; CHO Cells ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Cycle Checkpoints/drug effects ; Cell Growth Processes/drug effects ; Cell Line ; Cell Line, Tumor ; Cricetinae ; DNA/drug effects ; DNA Damage ; Fibroblasts/drug effects ; G1 Phase/drug effects ; Humans ; KB Cells ; Mice ; Mouth Neoplasms/drug therapy ; Mouth Neoplasms/genetics ; Mouth Neoplasms/pathology ; S Phase/drug effects
Chemical Substances	Alkylating Agents ; Antineoplastic Agents ; DNA (9007-49-2)
Language	English
Publishing date	2012-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.26142
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In stock of ZB MED Cologne/Königswinter

Order via subito

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Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito