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1.
Ayu ; 43(1): 1-7, 2022.
Article En | MEDLINE | ID: mdl-37554416

Background of the Study: As many as 10 million people have died from cancer globally in 2020, making it the top cause of mortality in the globe. Cancer develops as a result of the multi-stage process by which normal cells convert into tumor cells, progressing from a precancerous lesion to a malignant tumor. By avoiding risk factors and applying existing evidence-based preventative techniques, 30%-50% of malignancies may be averted. In order to avoid cancer, it is essential to know the specific causes of the disease. Nidanas, or etiologies, are well-described in Ayurvedic science. Here, the causes of cancer have been outlined so that the knowledge may be used effectively to avoid the disease. Aims: Identification of cancer etiologies that have been described in classics. Evidence-based understanding of these etiologies and to comprehend the significance of etiologies in cancer prevention. Materials and methods: A thorough evaluation of literature, including ancient Ayurvedic classics, modern medical texts, and articles published in reputable journals, was conducted to meet the study's goals and objectives. Results: According to Ayurveda, there are three distinct phases of tumorigenesis: chronic inflammation, precancerous development, Granthi (a benign glandular swelli ng), and Arbuda (a precancerous tumor) (definite malignancy). A growing body of evidence suggests that the tumor microenvironment, which is predominantly controlled by inflammatory cells, is an essential player in the neoplastic process. Conclusion: Although inflammation is coming into the picture just now in the contemporary world, Ayurveda has described this as a leading cause 5000 years back. It is evident that diet and lifestyle play a crucial role in the etiology of Shoth (inflammation).

2.
Sensors (Basel) ; 21(7)2021 Mar 27.
Article En | MEDLINE | ID: mdl-33801716

Human pose estimation and tracking in real-time from multi-sensor systems is essential for many applications. Combining multiple heterogeneous sensors increases opportunities to improve human motion tracking. Using only a single sensor type, e.g., inertial sensors, human pose estimation accuracy is affected by sensor drift over longer periods. This paper proposes a human motion tracking system using lidar and inertial sensors to estimate 3D human pose in real-time. Human motion tracking includes human detection and estimation of height, skeletal parameters, position, and orientation by fusing lidar and inertial sensor data. Finally, the estimated data are reconstructed on a virtual 3D avatar. The proposed human pose tracking system was developed using open-source platform APIs. Experimental results verified the proposed human position tracking accuracy in real-time and were in good agreement with current multi-sensor systems.


Orientation , Humans , Motion
3.
J Med Chem ; 64(5): 2501-2520, 2021 03 11.
Article En | MEDLINE | ID: mdl-33631934

SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymatic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclinical tumor models, culminating in the identification of the clinical molecule TAK-981.


Antineoplastic Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Neoplasms/drug therapy , Sulfonic Acids/therapeutic use , Sumoylation/drug effects , Ubiquitin-Activating Enzymes/antagonists & inhibitors , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/therapeutic use , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/metabolism , Cell Line, Tumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/metabolism , Humans , Mice , Molecular Structure , Protein Binding , Protein Processing, Post-Translational/drug effects , Structure-Activity Relationship , Sulfonic Acids/chemical synthesis , Sulfonic Acids/metabolism , Ubiquitin-Activating Enzymes/metabolism , Xenograft Model Antitumor Assays
4.
Sensors (Basel) ; 20(18)2020 Sep 18.
Article En | MEDLINE | ID: mdl-32961918

Today, enhancement in sensing technology enables the use of multiple sensors to track human motion/activity precisely. Tracking human motion has various applications, such as fitness training, healthcare, rehabilitation, human-computer interaction, virtual reality, and activity recognition. Therefore, the fusion of multiple sensors creates new opportunities to develop and improve an existing system. This paper proposes a pose-tracking system by fusing multiple three-dimensional (3D) light detection and ranging (lidar) and inertial measurement unit (IMU) sensors. The initial step estimates the human skeletal parameters proportional to the target user's height by extracting the point cloud from lidars. Next, IMUs are used to capture the orientation of each skeleton segment and estimate the respective joint positions. In the final stage, the displacement drift in the position is corrected by fusing the data from both sensors in real time. The installation setup is relatively effortless, flexible for sensor locations, and delivers results comparable to the state-of-the-art pose-tracking system. We evaluated the proposed system regarding its accuracy in the user's height estimation, full-body joint position estimation, and reconstruction of the 3D avatar. We used a publicly available dataset for the experimental evaluation wherever possible. The results reveal that the accuracy of height and the position estimation is well within an acceptable range of ±3-5 cm. The reconstruction of the motion based on the publicly available dataset and our data is precise and realistic.


Computers , Motion , Posture , Actigraphy , Humans , Orientation
5.
Sensors (Basel) ; 19(18)2019 Sep 10.
Article En | MEDLINE | ID: mdl-31510107

Acquisition of 3D point cloud data (PCD) using a laser scanner and aligning it with a video frame is a new approach that is efficient for retrofitting comprehensive objects in heavy pipeline industrial facilities. This work contributes a generic framework for interactive retrofitting in a virtual environment and an unmanned aerial vehicle (UAV)-based sensory setup design to acquire PCD. The framework adopts a 4-in-1 alignment using a point cloud registration algorithm for a pre-processed PCD alignment with the partial PCD, and frame-by-frame registration method for video alignment. This work also proposes a virtual interactive retrofitting framework that uses pre-defined 3D computer-aided design models (CAD) with a customized graphical user interface (GUI) and visualization of a 4-in-1 aligned video scene from a UAV camera in a desktop environment. Trials were carried out using the proposed framework in a real environment at a water treatment facility. A qualitative and quantitative study was conducted to evaluate the performance of the proposed generic framework from participants by adopting the appropriate questionnaire and retrofitting task-oriented experiment. Overall, it was found that the proposed framework could be a solution for interactive 3D CAD model retrofitting on a combination of UAV sensory setup-acquired PCD and real-time video from the camera in heavy industrial facilities.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 220: 117129, 2019 Sep 05.
Article En | MEDLINE | ID: mdl-31141772

A new phthalimide based chemosensor 2-(Pyridin-2-yl-(pyridine-2-ylimino)methyl)isoindoline-1,3-dione (PP3) was synthesized and characterized by IR, LCMS and NMR spectroscopic methods. The metal ions sensing ability of PP3 was examined by naked-eye and UV-Vis absorption techniques. The colorless solution of PP3 turned to yellow upon addition of Cu2+ and a new absorption band appeared at 434 nm. The Job's plot and HR-MS data confirms the formation of a new complex species between PP3 and Cu2+ in 1:1 binding stoichiometry. The sensor PP3 allowed the detection of Cu2+ down to 1.65 µM without any remarkable interference from the other tested metal cations.

7.
Injury ; 49(6): 1104-1107, 2018 Jun.
Article En | MEDLINE | ID: mdl-29704955

INTRODUCTION: Treatment for mid-shaft clavicle fractures has recently seen a paradigm shift towards surgical management. The aim of the study was to compare clinical and functional outcome between plate osteosynthesis and conservative line of management in middle-third clavicle fractures. MATERIAL AND METHODS: A prospective randomized study was conducted on 69 patients with closed displaced clavicle fractures between May 2014 and May 2016. Patients with medial or lateral third clavicle fractures, polytrauma and compound fractures were excluded from the study. Patients treated with plating were in group A (n = 36) while those treated with arm pouch were in group B (n = 33). RESULTS: The mean age of the patient in group A was 32.4 ±â€¯43 and group B was 31.7 ±â€¯26 years. 48 (69.9%) females were involved in the study. History of fall was the most common mechanism of injury affecting 51 (73.9%) patients. All the patients were type 2 B as per the Robinson classification system. The average operative duration was 78.3 ±â€¯12.4 min. Union was seen at 15.6 ±â€¯0.8 in group A and 22.8 ±â€¯0.4 in group B (p < 0.0001). Two (6%) of the patients in group B had non-union. One (2.7%) patient in group A had mal-union. Two (5.5%) patients had plate prominence. One (2.7%) patient had superficial infection. The Constant and Murley scoring at 24 months was 89.42 and 76.24 in group A and group B respectively. CONCLUSION: Plating for displaced mid-shaft clavicle fractures is can lead to better functional and radiological outcomes with minimal complications as compared to the conservative modality of treatment.


Clavicle/injuries , Conservative Treatment , Fracture Fixation, Internal , Fracture Healing/physiology , Fractures, Bone/pathology , Postoperative Complications/physiopathology , Adolescent , Adult , Bone Plates , Clavicle/diagnostic imaging , Female , Fractures, Bone/diagnostic imaging , Fractures, Bone/therapy , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Prospective Studies , Radiography , Treatment Outcome , Young Adult
8.
Dalton Trans ; 46(41): 14201-14209, 2017 Oct 24.
Article En | MEDLINE | ID: mdl-28990631

The pyridine substituted thiourea derivative PTB-1 was synthesized and characterized by spectroscopic techniques as well as by single crystal X-ray crystallography. The metal ion sensing ability of PTB-1 was explored by various experimental (naked-eye, UV-Vis, fluorescence, mass spectrometry and 1H NMR spectroscopy) and theoretical (B3LYP/6-31G**/LANL2DZ) methods. PTB-1 exhibited a highly selective naked-eye detectable color change from colorless to dark brown and UV-Vis spectral changes for the detection of Ag+ with a detection limit of 3.67 µM in aqueous medium. The detection of Ag+ ions was achieved by test paper strip and supported silica methods. In contrast, PTB-1 exhibited a 23-fold enhanced emission at 420 nm in the presence of Hg2+ ions with a nano-molar detection limit of 0.69 nM. Finally, the sensor PTB-1 was applied successfully for the intracellular detection of Hg2+ ions in a HepG2 liver cell line, which was monitored by the use of confocal imaging techniques.


Mercury/analysis , Silver/analysis , Thiourea/analogs & derivatives , Water/chemistry , Crystallography, X-Ray , Hep G2 Cells , Humans , Hydrogen-Ion Concentration , Ions/chemistry , Limit of Detection , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microscopy, Confocal , Molecular Conformation , Pyridines/chemistry , Quantum Theory , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Thiourea/chemistry , Thiourea/metabolism
9.
J Clin Diagn Res ; 11(7): FC06-FC10, 2017 Jul.
Article En | MEDLINE | ID: mdl-28892924

INTRODUCTION: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET) are effective insulin sensitizers used in T2DM. But their efficacy and tolerability needs to be compared in IR associated abnormalities. AIM: To compare the efficacy of PIO and MET in glucocorticoid induced AS, Hepatic Steatosis (HS) and IR in albino rats. MATERIALS AND METHODS: Male Wistar albino rats were randomized into four groups (n=6). Group 1 (Normal control) rats consumed 2% gum acacia orally for 12 days. Group 2 {dexamethasone (DEX) control} rats were administered 2% gum acacia orally for 12 days and DEX (8 mg/kg) intraperitoneally (i.p.) from 7th to 12th day during the study period. Group 3 and 4 (PIO and MET control) rats received oral administration of PIO (45 mg/kg) and MET (1000 mg/kg) for 12 days respectively. Both groups were treated with DEX (8 mg/kg/i.p.) from 7th to 12th day during the study period. On last day, fasting blood was collected and rats were sacrificed by cervical dislocation; aorta and liver tissues were isolated for the histopathological examination. Body weight, liver weight and liver volume were measured. Blood samples were processed for biochemical parameters. The data were analysed by One-way Analysis of variance (ANOVA) followed by Scheffe's multiple comparison post-hoc test. The statistical significance was assumed at p<0.05. RESULTS: Our results established the possible role of DEX in the development of AS and HS. Histopathological examination of Group 2 rats treated with DEX showed a marked lipid accumulation in the aorta and liver. Administration of MET and PIO resulted in partial to complete restoration of DEX induced fatty changes in aorta and liver. Both drugs significantly (p<0.05) prevented the elevation of insulin, lipid, glucose levels, liver weight and liver volume in DEX treated rats. They had significantly (p<0.05) improved body weight and insulin sensitivity. However, PIO was highly significant (p<0.05) compared to MET in reducing DEX induced IR complications. CONCLUSION: These findings suggest that PIO was more effective insulin sensitizer compared to MET in reducing AS, HS and IR induced by glucocorticoids.

10.
Sensors (Basel) ; 17(6)2017 Jun 02.
Article En | MEDLINE | ID: mdl-28574474

Mapping the environment of a vehicle and localizing a vehicle within that unknown environment are complex issues. Although many approaches based on various types of sensory inputs and computational concepts have been successfully utilized for ground robot localization, there is difficulty in localizing an unmanned aerial vehicle (UAV) due to variation in altitude and motion dynamics. This paper proposes a robust and efficient indoor mapping and localization solution for a UAV integrated with low-cost Light Detection and Ranging (LiDAR) and Inertial Measurement Unit (IMU) sensors. Considering the advantage of the typical geometric structure of indoor environments, the planar position of UAVs can be efficiently calculated from a point-to-point scan matching algorithm using measurements from a horizontally scanning primary LiDAR. The altitude of the UAV with respect to the floor can be estimated accurately using a vertically scanning secondary LiDAR scanner, which is mounted orthogonally to the primary LiDAR. Furthermore, a Kalman filter is used to derive the 3D position by fusing primary and secondary LiDAR data. Additionally, this work presents a novel method for its application in the real-time classification of a pipeline in an indoor map by integrating the proposed navigation approach. Classification of the pipeline is based on the pipe radius estimation considering the region of interest (ROI) and the typical angle. The ROI is selected by finding the nearest neighbors of the selected seed point in the pipeline point cloud, and the typical angle is estimated with the directional histogram. Experimental results are provided to determine the feasibility of the proposed navigation system and its integration with real-time application in industrial plant engineering.

11.
Indian J Pathol Microbiol ; 59(2): 216-219, 2016.
Article En | MEDLINE | ID: mdl-27166046

Lichen sclerosus (LS) is a rare disease affecting the skin and the mucous membrane, and it is chronic inflammatory in nature. It occurs in both males and females, but mainly affects females in the fifth or sixth decade of life. It mainly involves the genital and perianal areas but can affect any part of the body and the involvement of the oral mucosa is exceptionally rare, but sometimes it affects only the oral mucosa. It requires differentiating from other lesions of the oral cavity which looks similar to this lesion. In considering the rarity of the reported cases, the present article reports one more case of LS affecting the soft palate in an edentulous 66 year-old male patient.

12.
Scientifica (Cairo) ; 2015: 135298, 2015.
Article En | MEDLINE | ID: mdl-26558136

Background. Recent studies have demonstrated that podoplanin was expressed in some dysplastic lesions adjacent to primary oral cancers suggesting that podoplanin expression may occur in early oral tumorigenesis and lymphangiogenesis and therefore is related to tumor growth. The purpose of this study is to determine the role of podoplanin as a biomarker for cancer risk assessment in oral leukoplakia and correlation of podoplanin expression with grades of oral squamous cell carcinoma (OSCC). Materials and Methods. In the present retrospective study, podoplanin expression was investigated immunohistochemically in 40 patients each of oral leukoplakia and OSCC. The scores were analyzed statistically using one-way ANOVA test followed by Tukey HSD. Results. By applying one-way ANOVA test, there was a highly significant increase of the podoplanin expression from mild to severe dysplasia and from well to poorly differentiated OSCC (P < 0.01). Statistically highly significant difference was present between scores of mild to moderate dysplasia, moderate to severe dysplasia, well to poorly differentiated OSCC, and moderately to poorly differentiated OSCC (Tukey HSD test, P < 0.01). Conclusion. Podoplanin can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions and as a tumor progression biomarker for advanced grades of OSCC.

13.
J Oral Maxillofac Pathol ; 19(2): 270, 2015.
Article En | MEDLINE | ID: mdl-26604518

Lymphomas are the group of neoplasms originating from lymphoreticular system mainly from lymph nodes, among them up to 40% of non-Hodgkin's lymphomas present extra nodally. In oral cavity, lymphomas are least common and account for 3-5% of all malignancies, presenting mainly in older age groups with male predominance. According to Revised European-American Lymphoma classification, among B-cell and T-cell subtypes of non-Hodgkin's lymphomas, diffuse large B-cell lymphoma (DLBCL) is the most common, characterized by diffuse proliferation of large neoplastic B lymphoid cells. Here we present a case report of DLBCL affecting oral cavity involving left buccal vestibule and extending onto the palate, along with its clinical, histopathologic and immunohistochemical features.

14.
Indian Dermatol Online J ; 5(3): 260-5, 2014 Jul.
Article En | MEDLINE | ID: mdl-25165640

Oral submucous fibrosis is a chronic insidious disease and is well-recognized as a premalignant condition. It is a collagen related disorder associated with betel quid chewing and characterized by progressive hyalinization of the submucosa. The oral submucous fibrosis needs to be differentiated from scleroderma showing oral manifestations, as these diseases have different pathogenesis and prognostic aspects. The patients of oral submucous fibrosis can approach the dermatologist. The aim of this article is to present concise overview of the disease and its dermatological relation.

15.
Case Rep Dent ; 2013: 812323, 2013.
Article En | MEDLINE | ID: mdl-23936686

Solitary angiokeratoma of oral mucosa is rare entity. The term Angiokeratoma is used to refer to several lesions, whose common denominator is the presence of dilated blood vessels in association with epidermal hyperplasia. Mucosal involvement, including oral cavity is occasionally found either as a component of the systemic variety, cutaneous involvement or isolated oral involvement. Clinically, the lesion is irregular, whitish to dark brown in color, with female predominance. The etiological factors include injury, trauma, or chronic irritation to the wall of a papillary dermis. Histologically, it is characterized by hyperkeratosis, acanthosis, and dilated vascular spaces with or without organizing thrombi in papillary dermis. The vascular spaces are partly or completely enclosed by elongated ret-ridges. Along with this reporting a case of solitary angiokeratoma affecting tongue in a 38-year-old male patient, along with the literature review is presented.

16.
Rural Remote Health ; 12: 2140, 2012.
Article En | MEDLINE | ID: mdl-22998337

INTRODUCTION: Improving maternal and child health care are two of the Millennium Development Goals of the World Health Organization. India is one of the countries worldwide most burdened by maternal and child deaths. The aim of the study was to describe how families participate in nurse-based antenatal and child health care, and the effect of this in relation to referrals to specialist care, institutional deliveries and mortality. METHODS: The intervention took place in a remote rural area in India and was influenced by Swedish nurse-based health care. A baseline survey was performed before the intervention commenced. The intervention included education program for staff members with a model called Training of Trainers and the establishment of clinics as both primary health centers and mobile clinics. Health records and manuals, and informational and educational materials were produced and the clinics were equipped with easily handled instruments. The study period was between 2006 and 2009. Data were collected from antenatal care and child healthcare records. The Chi-square test was used to analyze mortality differences between years. A focus group discussion and a content analysis were performed. RESULTS: Families' participation increased which led to more check-ups of pregnant women and small children. Antenatal visits before 16 weeks among pregnant women increased from 32 to 62% during the period. Women having at least three check-ups during pregnancy increased from 30 to 60%. Maternal mortality decreased from 478 to 121 per 100 000 live births. The total numbers of children examined in the project increased from approximately 6000 to 18 500 children. Infant mortality decreased from 80 to 43 per 1000 live births. Women and children referred to specialist care increased considerably and institutional deliveries increased from 47 to 74%. CONCLUSION: These results suggest that it is possible in a rural and remote area to influence peoples' awareness of the value of preventive health care. The results also indicate that this might decrease maternal and child mortality. The education led to a more patient-friendly encounter between health professionals and patients.


Health Knowledge, Attitudes, Practice , Health Plan Implementation , Maternal-Child Health Centers , Practice Patterns, Nurses' , Prenatal Care/methods , Rural Health Services , Adult , Child, Preschool , Cooperative Behavior , Family Health/education , Family Planning Services , Female , Focus Groups , Humans , India , Infant , Infant Mortality/trends , Interprofessional Relations , Maternal Mortality/trends , Maternal-Child Health Centers/standards , Maternal-Child Health Centers/statistics & numerical data , Obstetrics/education , Obstetrics/standards , Organizational Objectives , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Pregnancy , Professional-Patient Relations , Rural Health Services/standards , Sweden , Workforce
17.
Lung India ; 27(3): 170-2, 2010 Jul.
Article En | MEDLINE | ID: mdl-20931040

Endobronchial hamartoma is a rare benign tumor of lung that may present with symptoms of airway obstruction with wheezing, stridor, recurrent pneumonia or atelectasis. We report a case of a patient with endobronchial hamartoma, recurrent pneumonia, who presented to us with sputum smear and culture positive pulmonary tuberculosis. He was treated with antitubercular treatment and endobronchial hamartoma was resected completely by diode laser through fiberoptic bronchoscope.

19.
Biometals ; 20(2): 177-84, 2007 Apr.
Article En | MEDLINE | ID: mdl-16900397

In this experimental study, we investigated whether L-ascorbic acid has any influence on the blood antioxidant defense system, lipid peroxidation and hematological parameters of the albino rats exposed to nickel sulfate(NiSO4). Twenty four adult rats were divided into four groups of six animals in each group. The control rats were untreated and comprised Group I. Group II rats were administered nickel sulfate (2.0 mg/100 g b.wt.; intraperitonially, i.p.). Group II rats were treated orally L-ascorbic acid (50 mg/100 g b.wt.) and Group IV rats were given both nickel sulfate and L-ascorbic acid simultaneously on alternate days until the tenth dose. The hematological parameters were assessed: red blood corpuscle counts, packed cell volume %, hemoglobin concentration, white blood corpuscle counts and platelets count decreased significantly and clotting time increased significantly in nickel treated rats. We also observed increase malondialdehyde (MDA) and decrease glutathione level (GSH) in erythrocytes of nickel treated rats. The activities of erythrocyte antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were significantly increased in rats treated with nickel sulfate. Simultaneously treatment of L-ascorbic acid exhibited a possible protective role on the toxic effect of nickel sulfate on the hematological values, erythrocyte MDA and GSH concentrations as well as antioxidant enzymatic defense system.


Antioxidants/metabolism , Ascorbic Acid/metabolism , Erythrocytes/drug effects , Irritants/pharmacology , Nickel/pharmacology , Animals , Erythrocytes/metabolism , Injections, Intraperitoneal , Lipid Peroxidation , Male , Rats , Rats, Wistar
20.
Mol Cancer Ther ; 5(12): 3052-61, 2006 Dec.
Article En | MEDLINE | ID: mdl-17172407

Strains within the genus Salinospora have been shown to produce complex natural products having antibiotic and antiproliferative activities. The biochemical basis for the cytotoxic effects of salinosporamide A has been linked to its ability to inhibit the proteasome. Synthetically accessible salinosporamide A (ML858) was used to determine its biochemical and biological activities and to compare its effects with those of bortezomib. ML858 and bortezomib show time- and concentration-dependent inhibition of the proteasome in vitro. However, unlike bortezomib, which is a reversible inhibitor, ML858 covalently binds to the proteasome, resulting in the irreversible inhibition of 20S proteasome activity. ML858 was equipotent to bortezomib in cell-based reporter stabilization assays, but due to intramolecular instability is less potent in long-term assays. ML858 failed to maintain levels of proteasome inhibition necessary to achieve efficacy in tumor models responsive to bortezomib. Our results show that ML858 and bortezomib exhibit different kinetic and pharmacologic profiles and suggest that additional characterization of ML858 is warranted before its therapeutic potential can be fully appreciated.


Antineoplastic Agents/pharmacology , Boronic Acids/pharmacology , Lactones/pharmacology , Protease Inhibitors/pharmacology , Proteasome Inhibitors , Pyrazines/pharmacology , Pyrroles/pharmacology , Animals , Antineoplastic Agents/chemistry , Binding, Competitive , Boronic Acids/chemistry , Bortezomib , Drug Stability , Female , HT29 Cells , HeLa Cells , Humans , Lactones/chemistry , Mice , Mice, Nude , Mice, SCID , Protease Inhibitors/chemistry , Proteasome Endopeptidase Complex/metabolism , Pyrazines/chemistry , Pyrroles/chemistry , Xenograft Model Antitumor Assays
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