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Search Results: 1 - 10 of 326746 matches for " Suresh S. Ramalingam "
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Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions
Rossella Marullo, Erica Werner, Natalya Degtyareva, Bryn Moore, Giuseppe Altavilla, Suresh S. Ramalingam, Paul W. Doetsch
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081162
Abstract: Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy.
The Combination of RAD001 and NVP-BEZ235 Exerts Synergistic Anticancer Activity against Non-Small Cell Lung Cancer In Vitro and In Vivo
Cheng-Xiong Xu,Yikun Li,Ping Yue,Taofeek K. Owonikoko,Suresh S. Ramalingam,Fadlo R. Khuri,Shi-Yong Sun
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020899
Abstract: The phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit PI3K, mTOR or both are currently under development. The mTOR allosteric inhibitor, RAD001, and the PI3K/mTOR dual kinase inhibitor, BEZ235, are examples of these agents. We were interested in developing strategies to enhance mTOR-targeted caner therapy. In this study, we found that BEZ235 alone effectively inhibited the growth of rapamycin-resistant cancer cells. Interestingly, the combination of sub-optimal concentrations of RAD001 and BEZ235 exerted synergistic inhibition of the growth of human lung cancer cells along with induction of apoptosis and G1 arrest. Furthermore, the combination was also more effective than either agent alone in inhibiting the growth of lung cancer xenografts in mice. The combination showed enhanced effects on inhibiting mTOR signaling and reducing the expression of c-Myc and cyclin D1. Taken together, our results suggest that the combination of RAD001 and BEZ235 is a novel strategy for cancer therapy.
Statistical learning methods as a preprocessing step for survival analysis: evaluation of concept using lung cancer data
Madhusmita Behera, Erin E Fowler, Taofeek K Owonikoko, Walker H Land, William Mayfield, Zhengjia Chen, Fadlo R Khuri, Suresh S Ramalingam, John J Heine
BioMedical Engineering OnLine , 2011, DOI: 10.1186/1475-925x-10-97
Abstract: A small set of clinical variables (CVs) for stage-1 non-small cell lung cancer patients was used to evaluate an approach for using SL methods as a preprocessing step for survival analysis. A stochastic method of training a probabilistic neural network (PNN) was used with differential evolution (DE) optimization. Survival scores were derived stochastically by combining CVs with the PNN. Patients (n = 151) were dichotomized into favorable (n = 92) and unfavorable (n = 59) survival outcome groups. These PNN derived scores were used with logistic regression (LR) modeling to predict favorable survival outcome and were integrated into the survival analysis (i.e. Kaplan-Meier analysis and Cox regression). The hybrid modeling was compared with the respective modeling using raw CVs. The area under the receiver operating characteristic curve (Az) was used to compare model predictive capability. Odds ratios (ORs) and hazard ratios (HRs) were used to compare disease associations with 95% confidence intervals (CIs).The LR model with the best predictive capability gave Az = 0.703. While controlling for gender and tumor grade, the OR = 0.63 (CI: 0.43, 0.91) per standard deviation (SD) increase in age indicates increasing age confers unfavorable outcome. The hybrid LR model gave Az = 0.778 by combining age and tumor grade with the PNN and controlling for gender. The PNN score and age translate inversely with respect to risk. The OR = 0.27 (CI: 0.14, 0.53) per SD increase in PNN score indicates those patients with decreased score confer unfavorable outcome. The tumor grade adjusted hazard for patients above the median age compared with those below the median was HR = 1.78 (CI: 1.06, 3.02), whereas the hazard for those patients below the median PNN score compared to those above the median was HR = 4.0 (CI: 2.13, 7.14).We have provided preliminary evidence showing that the SL preprocessing may provide benefits in comparison with accepted approaches. The work will require further evalu
Synthesis, Optical and Dielectric Properties of Tris-Glycine Zinc Chloride (TGZC) Single Crystals  [PDF]
S. Suresh, D. Arivuoli
Journal of Minerals and Materials Characterization and Engineering (JMMCE) , 2011, DOI: 10.4236/jmmce.2011.106039
Abstract: Non-linear optical materials find wide range of applications in the fields of opto-electronics, fiber optic communication, computer memory devices etc. Tris-Glycine Zinc Chloride (TGZC) is one of the NLO materials exhibiting more efficiency. In the present study Tris-Glycine Zinc Chloride were grown is single crystal form using slow evaporation technique. Single crystal X-ray diffraction analysis reveals that the crystal belongs to orthorhombic system with the space group Pbn21. The optical absorption studies show that the crystal is transparent in the entire visible region with a cut off wavelength of 250 nm. The optical band gap is found to be 4.60 eV. The dependence of extinction coefficient (K) and refractive index (n) on the wavelength has also been reported. Force constants (k) were calculated using FTIR spectral analysis which shows higher values of k for COO and C=O stretching vibrations. The dielectric studies show that the dielectric constant and dielectric loss decrease exponentially with frequency at different temperatures (35℃, 55℃, 75℃ and 95℃).
Growth, Optical, Mechanical and Dielectric Properties of Glycine Zinc Chloride NLO Single Crystals  [PDF]
S. Suresh, D. Arivuoli
Journal of Minerals and Materials Characterization and Engineering (JMMCE) , 2011, DOI: 10.4236/jmmce.2011.1012086
Abstract: Single crystals of Glycine Zinc Chloride (GZC) were grown from aqueous solution by slow evaporation technique. Single crystal X-ray diffraction analysis reveals that the crystal belongs to orthorhombic system with the space group Pna21.The optical transmission study reveals the transparency of the crystal in the entire visible region and the cut off wavelength has been found to be 230 nm. The optical band gap is found to be 3.40eV. The transmittance of GZC crystal has been used to calculate the refractive index (n), the extinction coefficient (K) and the real er and imaginary ei components of the dielectric constant. Mechanical studies were carried out on the as grown crystal. Dielectric constant and dielectric loss measurements were carried out at different temperatures and frequencies. Photoconductivity measurements carried out on the grown crystal reveal the negative photoconducting nature.
Sudha Ramalingam,Akila R. S.
Socio-Legal Review , 2010,
Abstract: In this insightful article, Sudha Ramalingam and R.S. Akila highlight the apathy of the State machinery, judiciary and the civil society towards the increasing violations of the right to life through encounter killings. Tracing the history of response to encounter killings, the authors illustrate how perpetrators of this extra-legal deprivation of life and liberty are glorified in news media, revered by the State and civil society, and thus enjoy immunity from the clutches of the criminal justice system. The situation prevalent in a relatively stable Tamil Nadu is especially highlighted in order to demonstrate the falsity of the assumption that encounter killings are widespread only in conflict-ridden states. The willingness of society to acquiesce while the law of the court is replaced with the law of the street is attributed to the lack of faith of civil society in the criminal justice system. The authors lament the proliferation and acceptance of these extra-legal killings in a constitutional democracy like India, labelling the same to be unacceptable.
ZnO Nanobelts: An Efficient Catalyst for Synthesis of 5-Arylidine-2,4-Thiazolidinediones and 5-Arylidine-Rhodanines  [PDF]
Jagir S. Sandhu, Suresh  
International Journal of Organic Chemistry (IJOC) , 2012, DOI: 10.4236/ijoc.2012.223042
Abstract: A facile preparation of ZnO nanobelts by chemical precipitation technique and its utility as catalyst in Knoevenagel condensation of 2,4-thiazolidinedione/rhodanine has been described. X-ray diffraction and transmission electron microscopy techniques revealed the formation ZnO nanobelts. Scanning electron microscopic observations indicate that the lengths of nanobelts are ranging from a few hundreds of micrometers to a few millimeters. Its use for the condensation of aldehydes and active methylene compounds under solvent free reaction condition at 90℃ afforded the corresponding products in excellent yields in minute time.
Robinow syndrome
Suresh S
Indian Journal of Orthopaedics , 2008,
Abstract: Robinow syndrome is a rare autosomal recessive mesomelic dwarfism with just more than 100 cases reported in the literature so far. The lower extremity is spared with skeletal deformity usually confined to the forearm, hand, and the dorsal spine. Diagnosis is made easily in the early childhood by the typical "fetal facies" appearance, which disappears to a certain extent as the patient grows. The author reports two cases of this entity with vertebral segmentation defects, rib fusion, and typical severe brachymelia and facial features.
Type 4 capitellum fractures: Diagnosis and treatment strategies
Suresh S
Indian Journal of Orthopaedics , 2009,
Abstract: Background: Fractures of the capitellum are rare injuries of the elbow usually seen in the adolescents. This fracture is often missed in the emergency room if a proper radiograph is not available. Recent reports have described many modalities of treatment favoring headless screw for fixation. The facility for headless screw fixation, however, is not available in most centers. This paper presents the diagnosis and management of type 4 capituller fractures (Mckee) with gadgets available in a district hospital. Materials and Methods: Between 2004 and 2007 three patients with right sided type IV capetullar fracture were treated in a district hospital. There were two boys aged 15 and 17 and one 33 years old lady. In one case, the fracture was missed in the emergency room. A double arc sign in the lateral views of the X-rays of the elbow was seen in all the cases. In each case a preoperative CT scan was done and a diagnosis of Mckee type IV fracture of the capitellum was made. Under tourniquet, using extended lateral approach, open reduction and internal fixation was done using 4mm partially threaded AO cancellous screws (n=2) and 2.7 mm AO screws (n=1), under vision from posterior to anterior direction from the posterior aspect of lateral condyle of humerus avoiding articular penetration. Results: All the fractures united uneventfully. At the end of one year follow-up, two cases had excellent elbow function; implants were removed and there were no signs of AVN or arthritis. The third case had good elbow ROM at 11 months without AVN. Conclusion: Double arc sign on lateral X-rays of the elbow along with pre-operative CT scan evaluation is important to avoid a missed diagnosis and analysis of type IV capitellur fracture. Fixation with non-cannulated ordinary AO screws using extended Kocher′s lateral approach has given good results.
Management of "floating elbow" in children
Suresh S
Indian Journal of Orthopaedics , 2007,
Abstract: Background: Supracondylar fractures associated with ipsilateral forearm fractures, aptly termed as "floating elbow" is a rare injury in children after a fall from height. The various authors report their results with conservative treatment of one or both injury to aggressive emergency operative fixation of both components. Materials and Methods: During a period of three years, the author managed four cases of floating elbow in children. All cases were managed by closed reduction and pinning of both components of the injury. Results: All patients recovered full elbow range of motion at three months followup and were rated as excellent as per modified Flynn′s criteria. None of the patients developed cubitus varus deformity, complications related to the pins or delayed union. Conclusions: Early closed reduction and K wire fixation of both components of this injury gives better stability and prevents development of complications like compartment syndrome and elbow deformities.
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