Search

Background The conventional Papanicolaou-stained cervical smear is the most common screening test for cervical cancer. The sensitivity of the test in detecting abnormal cells is 67–75% in various studies. Owing to the volume of smears at cancer screening centres, significant man-hours are expended in the test. We have developed a software program for identification of foci of abnormal cells from conventional smears. We have chosen the convolutional neural network (CNN) model for its efficacy in image classification. Methods A total of 1838 microphotographs from cervical smears, containing 1301 ‘normal’ foci and 537 ‘abnormal’ foci were included in the study. The data set was split into training, testing and validation sets. A CNN was developed in the Python programming language. The CNN was trained with the training and testing set. At the end of training, 94.64% accuracy was achieved in the testing set. The CNN was then run on the validation set (441 images). Results The CNN showed 94.28% sensitivity, 96.01% specificity, 91.66% positive predictive value and 97.30% negative predictive value. The CNN could recognise normal squamous cells, overlapping cells, neutrophils and debris and classify the focus appropriately. False positives were reported when the CNN failed to recognise overlapping cells (2.7% microphotographs). It could correctly label cell clusters with high nuclear cytoplasmic ratio and hyperchromasia. In 1.8% of microphotographs, a false negative was reported. Conclusion The CNN showed 95.46% diagnostic accuracy, suggesting potential use in screening.

In recent days, vanadium complexes and nanoparticles have received sustainable attention owing to their vast applications in different fields. In the present study, we report a facile approach for the synthesis of irregular dumbbell shaped vanadium pentoxide nanoparticles (V2O5 NPs: 30-60 nm) via the polyol-induced microwave irradiation process along with calcination. The as-synthesized nanoparticles were characterized using various physico-chemical techniques (e.g. XRD, TEM, FT-IR, DLS and XPS). The cell viability assay showed that V2O5 NPs could efficiently inhibit the proliferation of different cancer cells (B16F10, A549, and PANC1), depicting their anti-proliferative activity. However, V2O5 NPs did not exert significant cytotoxicity to the normal cells (CHO, HEK-293 and NRK-49F), suggesting their biocompatible nature. Interestingly, these nanoparticles inhibited the proliferation and migration of the endothelial cells (HUVECs and EA.hy926) and disrupted the blood vasculature in a chick embryo model, indicating their anti-angiogenic properties. The mechanistic study revealed that the effective internalization of V2O5 NPs generated intracellular reactive oxygen species (ROS) which in turn up-regulated p53 protein and down-regulated survivin protein in cancer cells, leading to the apoptosis process. Furthermore, the administration of V2O5 NPs to melanoma bearing C57BL6/J mice significantly increased their survivability as compared to the control untreated tumor bearing mice, exhibiting the therapeutic potential of the nanoparticles against melanoma. Additionally, the in vivo toxicity study demonstrated no toxic effect in mice upon sub-chronic exposure to V2O5 NPs. Altogether, we strongly believe that V2O5 NPs could intrinsically provide a new direction for alternative therapeutic treatment strategies for melanoma and other cancers by employing their anti-angiogenic properties in the future.

Aim: Study aims to investigate the effect of cigarette smoking on cancer-related transformation in oral epithelial cells of smokers through evaluating the alteration in Wnt/β-catenin and MAPK pathways. Materials & methods: Exfoliated oral epithelial cells were collected from 138 subjects and categorized into nonsmokers, smokers and clinically diagnosed precancer and cancer patients. Real-time quantitative PCR was performed to detect the fold changes of related genes. Expressions of biomarkers were assessed using immunofluorescence and western blot. Results: Study shows significant (p

Tobacco smoking is considered as one of the major risk factors for development of oral cancer. In vitro studies indicate that cigarette smoke initiates transformation of epithelial cells toward development of oral cancer through altering mitochondrial metabolic pathways. However the present in vitro models need to be improved to correlate these molecular changes with epithelial transformations. In present study, we investigated the association of mitochondrial metabolic events with oral cancer progression under cigarette smoke extract (CSE). In this regard, an in vitro model of oral keratinocyte cell line (MOE1A) was developed by exposing them with different concentrations of CSE. Alterations in cellular phenomena were confirmed by Fourier-transform infrared spectroscopy (FTIR) study, which indicated changes in important functional groups of CSE-induced oral cells. Enhanced reactive oxygen species (ROS) of exposed cells altered the mitochondrial metabolic activities in terms of increased mitochondrial mass and DNA content. Further, mitochondrial heme-metabolism was investigated and real-time PCR study showed altered expression of important genes like ALAS1, ABCB6, CPOX, FECH, HO-1. Both transcriptomic and proteomic studies showed up- and down-regulation of important biomarkers related to cellular cancer progression. Overall data suggest that CSE alters mitochondrial heme metabolic pathway and initiates cancer progression through modifying cellar biomarkers in oral epithelial cells.

Autofluorescence imaging is an emerging method for detection of cancer associated risks, depending on the variation in autofluorescence property of normal and cancer cells. In the present study, autofluorescence images of cervical cell were assessed for early cervical cancer risk prediction. For classification of cervical epithelial cells collected from normal and clinically diagnosed cancer patients, a set of spectral texture features (SPTF) were extracted from 2-dimensional (2-D) Fourier transform of autofluorescence images. To discriminate the normal and the abnormal cells, SPTFs were evaluated by two 1-D functions, i.e., radial function and angular function, accumulated from the frequency spectrum. The classification was assessed by four different types of support vector machines (SVMs), namely, Linear SVM, Quadratic SVM, Cubic SVM, and Gaussian SVM. The best accuracy was achieved by Gaussian SVM (0.95) with a sensitivity of 0.90 and specificity of 0.88. The overall accuracy of all the classifiers was more than 0.82. This experiment was also evaluated by receiver operating characteristics (ROC) curve and area under ROC curve (AUC) of each classifier, which reveals the comparative results for this database.

Context: Cervical cancer is the second most common cancer in women. The liquid based cervical cytology (LBCC) is a useful tool of choice for screening cervical cancer. Aims: To train a convolutional neural network (CNN) to identify abnormal foci from LBCC smears. Settings and Design: We have chosen retrospective study design from archived smears of patients undergoing screening from cervical cancer by LBCC smears. Materials and Methods: 2816 images, each of 256 × 256 pixels, were prepared from microphotographs of these LBCC smears, which included 816 “abnormal” foci (low grade or high grade squamous intraepithelial lesion) and 2000 ‘normal’ foci (benign epithelial cells and reactive changes). The images were split into three sets, Training, Testing, and Evaluation. A convolutional neural network (CNN) was developed with the python programming language. The CNN was trained with the Training dataset; performance was assayed concurrently with the Testing dataset. Two CNN models were developed, after 20 and 10 epochs of training, respectively. The models were then run on the Evaluation dataset. Statistical Analysis Used: A contingency table was prepared from the original image labels and the labels predicted by the CNN. Results: Combined assessment of both models yielded a sensitivity of 95.63% in detecting abnormal foci, with 79.85% specificity. The negative predictive value was high (99.19%), suggesting potential utility in screening. False positives due to overlapping cells, neutrophils, and debris was the principal difficulty met during evaluation. Conclusions: The CNN shows promise as a screening tool; however, for its use in confirmatory diagnosis, further training with a more diverse dataset will be required.

Oral cancer is a major healthcare problem and accounts for approximately 40% of cancer risk. It is evident that the detection of oral cancer at an early stage can markedly improve the survival rate. Though several invasive ‘gold standard’ methods continue to be practiced clinically, non-invasive detection modalities look promising for early oral cancer risk assessment. Exfoliative cytology is one such method in which the desquamated cells are collected from the oral epithelium and examined under microscope. However, the main challenge in automated quantification arises here on the formation of cellular clump during the smear preparation. In this chapter, the role of computational advances in segmentation of overlapping cells is illustrated. A computational model, based on Voronoi-based hybrid active contour method, is proposed for segmenting the overlapping oral epithelial cells.

Critical limb ischemia (CLI) is a severe type of peripheral artery disease (PAD) which occurs due to an inadequate supply of blood to the limb extremities. Patients with CLI often suffer from extreme cramping pain, impaired wound healing, immobility, cardiovascular complications, amputation of the affected limb and even death. The conventional therapy for treating CLI includes surgical revascularization as well as restoration of angiogenesis using growth factor therapy. However, surgical revascularization is only suitable for a small percentage of CLI patients and is associated with a high perioperative mortality rate. The use of growth factors is also limited in terms of their poor therapeutic angiogenic potential, as observed in earlier clinical studies which could be attributed to their poor bio-availability and non-specificity issues. Therefore, to overcome the aforesaid disadvantages of conventional strategies there is an urgent need for the advancement of new alternative therapeutic biomaterials to treat CLI. In the past few decades, various research groups, including ours, have been involved in developing different pro-angiogenic nanomaterials. Among these, zinc oxide nanoflowers (ZONFs), established in our laboratory, are considered one of the more potent nanoparticles for inducing therapeutic angiogenesis. In our earlier studies we showed that ZONFs promote angiogenesis by inducing the formation of reactive oxygen species and nitric oxide (NO) as well as activating Akt/MAPK/eNOS cell signaling pathways in endothelial cells. Recently, we have also reported the therapeutic potential of ZONFs to treat cerebral ischemia through their neuritogenic and neuroprotective properties, exploiting angio-neural cross-talk. Considering the excellent pro-angiogenic properties of ZONFs and the importance of revascularization for the treatment of CLI, in the present study we comprehensively explore the therapeutic potential of ZONFs in a rat hind limb ischemia model (established by ligating the hind limb femoral artery), an animal model that mimics CLI in humans. The behavioral studies, laser Doppler perfusion imaging, histopathology and immunofluorescence as well as estimation of serum NO level showed that the administration of ZONFs could ameliorate ischemia in rats at a faster rate by promoting therapeutic angiogenesis to the ischemic sites. Altogether, the present study offers an alternative nanomedicine approach employing ZONFs for the treatment of PADs.

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

Background Surgical site infections (SSIs) are among the most common healthcare-associated infections. Under-nutrition is an important risk factor for SSIs and can lead to delayed wound healing and longer hospital stays. Oral nutritional supplements are prescribed to reduce the risk of infection and improve health status, but data from randomised controlled trials (RCTs) have shown mixed results. Thus, the objective of our planned systematic review is to evaluate oral nutritional supplements on preventing SSIs in adult surgical patients Methods RCTs conducted in adult surgical patients who receive oral nutritional support will be included. The primary outcome will be the incidence of SSIs (within 30 days of surgery or within 90 days for joint replacement surgery). Secondary outcomes will be changes in nutritional status, mortality, health-related quality of life and costs. Literature searches will be conducted in several electronic databases (from inception onwards): MEDLINE, Embase, CINAHL and The Cochrane Central Register of Controlled Trials (CENTRAL). Grey literature will be identified through searching clinical trial registers and dissertation databases. Two reviewers will independently screen all citations, full-text articles and abstract data. The study methodological quality (or bias) will be appraised using the Cochrane risk of bias tool. If feasible, we will conduct random effects meta-analysis where appropriate. Discussion This systematic review will evaluate the evidence for pre- and post-surgical intervention with oral nutritional supplements in adults. Findings from this planned review may inform subsequent nutritional interventions for hospitalised patients who undergo surgery. Systematic review registration PROSPERO CRD42020140954

Neuritogenesis, a complex process of the sprouting of neurites, plays a vital role in the structural and functional restoration of cerebral ischemia-injured neuronal tissue. Practically, there is no effective long-term treatment strategy for cerebral ischemia in clinical practice to date due to several limitations of conventional therapies, facilitating the urgency to develop new alternative therapeutic approaches. Herein, for the first time we report that pro-angiogenic nanomaterials, zinc oxide nanoflowers (ZONF), exhibit neuritogenic activity by elevating mRNA expression of different neurotrophins, following PI3K/Akt-MAPK/ERK signaling pathways. Further, ZONF administration to global cerebral ischemia-induced Fischer rats shows improved neurobehavior and enhanced synaptic plasticity of neurons via upregulation of Neurabin-2 and NT-3, revealing their neuroprotective activity. Altogether, this study offers the basis for exploitation of angio-neural cross talk of other pro-angiogenic nano/biomaterials for future advancement of alternative treatment strategies for cerebral ischemia, where neuritogenesis and neural repair are highly critical.

Background &amp, Aims: ARID1A is postulated to be a tumor suppressor gene owing to loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role in pancreatic pathogenesis is not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of its direct functional role in PDAC, using a combination of GEM model and PDAC cell lines. Methods: Pancreas-specific mutant Arid1a-driven GEM model (Ptf1a-Cre, KrasG12D, Arid1af/f or &ldquo, KAC&rdquo, ) was generated by crossing Ptf1a-Cre, KrasG12D (&ldquo, KC&rdquo, ) mice with Arid1af/f mice and characterized histologically with timed necropsies. Arid1a was also deleted using CRISPR-Cas9 system in established human and murine PDAC cell lines to study the immediate effects of Arid1a loss in isogenic models. Cell lines with or without Arid1a expression were developed from respective autochthonous PDAC GEM models, compared functionally using various culture assays, and subjected to RNA-sequencing for comparative gene expression analysis. DNA damage repair was analyzed in cultured cells using immunofluorescence and COMET assay. Results: Retention of Arid1a is critical for early progression of mutant Kras-driven pre-malignant lesions into PDAC, as evident by lower Ki-67 and higher apoptosis staining in &ldquo, as compared to &ldquo, mice. Enforced deletion of Arid1a in established PDAC cell lines caused suppression of cellular growth and migration, accompanied by compromised DNA damage repair. Despite early development of relatively indolent cystic precursor lesions called intraductal papillary mucinous neoplasms (IPMNs), a subset of &ldquo, mice developed aggressive PDAC in later ages. PDAC cells obtained from older autochthonous &ldquo, mice revealed various compensatory (&ldquo, escaper&rdquo, ) mechanisms to overcome the growth suppressive effects of Arid1a loss. Conclusions: Arid1a is an essential survival gene whose loss impairs cellular growth, and thus, its expression is critical during early stages of pancreatic tumorigenesis in mouse models. In tumors that arise in the setting of ARID1A loss, a multitude of &ldquo, mechanisms drive progression.

BACKGROUND Corneal ulcer is one of the leading causes of ocular morbidity in developing country. Early diagnosis and targeted therapy is indispensable. Sociodemographic variables along with predisposing factors plays a major role in its development and clinicopathological correlation in diagnosis is very much helpful in diagnosis and subsequent management. The aim of the study is to identify the epidemiological factors and causative organism of the suppurative corneal ulcer. MATERIALS AND METHODS In this observational cross-sectional study, after taking proper history, patients with suppurative corneal ulcer are examined for clinical diagnosis. Applying sterile method of swab collection from the ulcer for standard microbiological examination (staining, culture) swabs are taken for predetermined laboratory investigations. Sociodemographic variables (age, gender, occupation) relevant injury history, microbiological data are tabulated for statistical calculations. RESULTS After application of inclusion and exclusion criteria wiling 81 patients, M:F=55:26 were assessed. Major number of patients (n=61, 75.30%) are middle aged between 33-62 years of age. Occupation played a major role as evidenced by 44.44% (n=36) contribution from agricultural workers (tea garden worker, pineapple farmer, other agricultural worker) followed by household worker (n=13, 16.05%). Positive history of prior corneal injury is common in fungal corneal ulcer (n=22, 51.16%) as well as in bacterial (n=8, 66.66%). Among the prior corneal injury associated fungal ulcer vegetative matter injury in 15 patients (32.60%), while in bacterial variety, it is 5 (10.86%) in number. In laboratory investigations, pure fungal growths are found in 37 patients (45.68%), while pure bacterial are 12 in number (14.81%). A good number (n=8, 9.81%) shows mixed infection. Culture negative ulcers are good in number (n=24, 29.63%) among which 6 (7.47%) are microscopically positive. The sensitivity and specificity of clinical diagnosis of fungal corneal ulcer are 84.61% and 72.41% respectively with a high correlation between clinical and microbiological diagnosis of fungal corneal ulcer (either smear positive or culture positive and a quiet high positive predictive value for clinical diagnosis (84.61%). But, in case of bacterial corneal ulcer, the positive predictive value is 41.37%, while negative predictive value is 84.61% in our study. CONCLUSION Middle-aged agricultural workers are more prone to develop corneal ulcer and fungal corneal ulcers are more prevalent in this region of India than bacterial. History of prior corneal injury is a major risk factor. Fungal corneal ulcers have high correlation between clinical and microbiological diagnosis than bacterial.

Dysregulation in mitochondrial dynamics has been associated with several diseases including cancer. Present study assessed the alteration in mitochondrial fission protein (Drp1) in oral epithelial cells collected from clinically confirmed pre-cancer and cancer patients and further correlates it with the cellular apoptosis signaling. Results indicate the ROS accumulation in OSCC patients is accompanied by several changes including increase in mitochondrial mass, expression of mitochondrial fission protein (Drp1) and alteration in apoptotic signaling. The positive co-relation has been observed between the expressions of anti-apoptotic Bcl-2proteinswith mitochondrial fission protein Drp1. Higher mitochondrial fission in oral cancer cells was also correlated with the increased expression of cell cycle marker CyclinD1 indicating highly proliferative stage of oral cancer cells. The clinical correlation can be extended to develop biomarker for diagram and program in oral cancer management.

FTIR spectroscopy and Raman spectroscopy of biological analytes are increasingly explored as screening tools for early detection of cancer. In the present study, an integrated analysis of the FTIR and Raman spectra obtained from exfoliated cells is adopted to improve discrimination of normal, pre-cancerous and cancerous conditions. Multiple spectra were obtained from 13 normal, 13 pre-cancer and 10 cancer patients in both modes. Compared to normal patients, significant differences were observed at 1550, 1580, 1640, 2370, 2330, 2950-3000 and 3650-3750 cm-1 (FTIR) and 520, 640, 785, 827, 850, 935, 1003, 1175, 1311 cm-1 and 1606 cm-1 (Raman) vibrations of the other two. The increase in DNA, protein and lipid content with malignancy was more clearly elucidated by examining both spectra. Principal component analysis (PCA)-linear discriminant analysis (LDA) with 10-fold cross validation of the FTIR and Raman spectral data sets showed efficient discrimination between normal and pathological conditions while overlapping was seen between the two pathologies. The PCA-LDA model of the dual spectra yielded a classification accuracy of 98% in comparison with either FTIR (85%) or Raman (82%) in a spectrum-wise comparison. In the patient-wise approach (mean of all spectra from a patient), the overall classification efficiency was 73%, 80% and 87% for FTIR, Raman and integrated spectral approaches respectively. Moreover, the efficiency of the integrated FTIR-Raman PCA-LDA model as a prediction tool was tested to screen susceptible individuals (11 cigarette smokers) using the dual spectra acquired from these individuals. The study presents proof-of-concept for adopting a large-scale, follow-up trial of the approach for mass screening purposes.

Two different silica based (MSU-2 and MCM-41) curcumin loaded mesoporous materials V3 and V6 were synthesized and characterized by several physico-chemical techniques. Release kinetic study revealed the slow and sustained release of curcumin from those materials in blood simulated fluid (pH: 7.4). The materials V3 and V6 were found to be biocompatible in non-cancerous CHO cell line while exhibiting significant cytotoxicity in different cancer cells (human lung carcinoma cells: A549, human breast cancer cells: MCF-7, mouse melanoma cells: B16F10) compared to pristine curcumin indicating the efficacy of the mesoporous silica materials based drug delivery systems (DDSs). The generation of intracellular reactive oxygen species (ROS) and down regulation of anti-apoptotic protein leading to the induction of apoptosis were found to be the plausible mechanisms behind the anti-cancer activity of these DDSs. These results suggest that curcumin-loaded drug delivery system may be successfully employed as an alternative treatment strategy for cancer therapeutics through a nanomedicine approach in near future.

Teratoma is a germ cell tumor common in anterior mediastinum but intrapulmonary location is rare. Gonadal and extra-gonadal primary site needs to be ruled out first to call the tumor as intrapulmonary teratoma. Here, we report a case of benign intrapulmonary cystic teratoma in a 28 year old female who presented with left sided chest pain and shortness of breath and was initially provisionally diagnosed to have hydatid cyst in lung.

Background: The adequacy of haemodialysis in patients of type 2 diabetes mellitus with chronic kidney disease stage 5 depends on several clinical as well as laboratory parameters. Previous studies from Western literature have identified several clinical and laboratory markers for predicting adequacy of dialysis. There is a dearth of literature regarding the same in Indian patient populace. Authors aimed to find correlation, if any, between glycemic control and adequacy of dialysis in this cohort of patients.Methods: A set of 200 patients of type 2 diabetes mellitus who have undergone hemodialysis at a tertiary care hospital were included in the study. Random blood sugar (RBS), Glycated hemoglobin (HbA1c) were measured at admission. After 4 hours of dialysis, the urea reduction ratio (URR) and Kt/V was measured for each patient. The correlation coefficient as well as linear equation of the association between these variables were calculated. Standard statistical method and software were used in the process.Results: The study revealed a linear negative correlation between the variables RBS, HbA1c and URR as well as Kt/V. This suggests the importance of pre dialysis glycemic control in patients undergoing hemodialysis.Conclusions: Authors formulate the hypothesis that glycated hemoglobin and random blood sugar at admission correlate well with the outcome and adequacy of dialysis in patients of stage 5 chronic kidney disease undergoing haemodialysis. Good glycemic control (HbA1c

Introduction: The Pap stained cervical smear is a screening tool for cervical cancer. Commercial systems are used for automated screening of liquid based cervical smears. However, there is no image analysis software used for conventional cervical smears. The aim of this study was to develop and test the diagnostic accuracy of a software for analysis of conventional smears. Materials and Methods: The software was developed using Python programming language and open source libraries. It was standardized with images from Bethesda Interobserver Reproducibility Project. One hundred and thirty images from smears which were reported Negative for Intraepithelial Lesion or Malignancy (NILM), and 45 images where some abnormality has been reported, were collected from the archives of the hospital. The software was then tested on the images. Results: The software was able to segregate images based on overall nuclear: cytoplasmic ratio, coefficient of variation (CV) in nuclear size, nuclear membrane irregularity, and clustering. 68.88% of abnormal images were flagged by the software, as well as 19.23% of NILM images. The major difficulties faced were segmentation of overlapping cell clusters and separation of neutrophils. Conclusion: The software shows potential as a screening tool for conventional cervical smears; however, further refinement in technique is required.

Oral cancer is one of the biggest health care burdens in the Indian subcontinent (40% of the cancer risk). In most of the cases, it is evident that, like any other cancer, oral cancer is usually detected at advanced stages, which considerably reduce the survival rates. Hence, early detection of cancer is of utmost importance to enhance the survival rates. Among various carcinogenic agents, tobacco smoking has detrimental effect on oral cancer. So routine screening of habitual smokers may improve the early detection possibilities. In this chapter, an attempt has been taken to analyze the importance of computer-aided diagnosis in early cancer monitoring. In our previous study, we have shown the application of SVM to detect the precancer risk in habitual smokers by classifying them on the basis of selected features. Along with morphological features in previous study, the texture features were extracted by GLCM method. However, in many cases, ambiguous results had been obtained by this method. So, in the proposed work, we have used LBP method for extraction of texture features and the performance measures are calculated in terms of sensitivity, specificity, and accuracy in order to improve the diagnostic accuracy. According to our study, the LBP method is proved as better feature extractor as classification accuracy has been improved. To classify habitual smoker in comparison to nonsmoker and precancer by SVM method, the present study is 91.66% sensitive, 87.3% specific, and 88.33% accurate.

Recent trends in medical imaging enable overcoming the limitations of noninvasive histological assessment and subjectivity concerns in diagnosis of several diseases. These advancements are complemented by computer-assisted diagnosis (CAD) algorithms to further enhance accuracy of diagnosis. CAD algorithms are able to monitor the prognosis of chronic diseases like cancer. Among different cancer types, prostate cancer is the most common cancer in men. Early diagnosis of this cancer is known to significantly enhance the survival rate of patients. In this chapter, a CAD algorithm has been presented for sonoelastography images, which is an ultrasound-based imaging technique that determines cancers through analyzing tissue elasticity. Fourier and wavelet-based transformations were used to classify the images after segmenting them into affected and unaffected regions based on the ground truth information obtained from clinician. Classification rate of a maximum of 97% was obtained using the stationary wavelet transform (SWT) method, whereas 94%, 96%, and 61% were obtained with fast Fourier transform (FFT), discrete wavelet transform (DWT), and spatial domain, respectively. The proposed study shows that sonoelastography images can be used for diagnosis of prostate cancer by applying wavelet technique.

In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future.

Metabolic alterations of oral epithelial cells under oxidative stress are important signatures for early diagnosis of oral cancer. Amongst different metabolic alterations, non-invasive photo-diagnostic methods have been extensively used for determining cellular heme metabolism and accumulation of protoporphyrin IX (PpIX) under administration of suitable photosensitizer. In this study, we report these metabolic alterations by direct analysis of oral exfoliated cells obtained from individuals with prolonged smoking habit without the exogenous administration of any photosensitizer. The relative expression level of relevant biomolecules of study groups were compared with clinically diagnosed and histopathologically confirmed leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC) patients. The energy imbalance and variation in 'redox ratio' were examined through spectroscopic studies which showed an increasing trend (p < 0.001) in smokers to OSCC groups in comparison to nonsmoker control. Gene expression of important intermediates of the heme metabolic pathway (viz. 5-aminolevulinate synthase 1 (ALAS1), Ferrochelatase (FECH), hemeoxygenase 1 (HO-1) and ATP binding cassette subfamily G member 2 (ABCG2)) which affect production of PpIX was assessed. Relative mRNA level of ALAS1 and HO1 was upregulated whereas mRNA level of other genes (viz. FECH and ABCG2) were found to be downregulated in smokers as well as in cancer groups. Outcome of different spectroscopic studies on exfoliated cells (viz. fluorescence, atomic absorption and Fourier transform infrared spectroscopy) corroborated with the expression of biomarkers related to cellular endogenous metabolism related to heme cycle. This study indicates significant alterations in endogenous metabolic products, and cellular functional groups in oral epithelial cells among the study groups. Our study reports a strong possibility of diagnosis of early cancer signatures amongst habitual smokers by direct and non-invasive assessment of metabolic status of oral epithelial cells without exogenous administration of photosensitizers. The knowledge accrued from the study may guide clinicians in precise detection of precancer trend in the susceptible population through a noninvasive rapid screening method.

Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis. The macropinocytic uptake of nab-paclitaxel induced macrophage immunostimulatory (M1) cytokine expression and synergized with IFNγ to promote inducible nitric oxide synthase expression in a TLR4-dependent manner. Nab-paclitaxel was internalized by tumor-associated macrophages in vivo, and therapeutic doses of nab-paclitaxel alone, and in combination with gemcitabine, increased the MHCII+CD80+CD86+ M1 macrophage population. These data revealed an unanticipated role for nab-paclitaxel in macrophage activation and rationalized its potential use to target immune evasion in pancreatic cancer. Cancer Immunol Res; 5(3); 182–90. ©2017 AACR.

Introduction: Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disease where assessment of disease activity is essential for management of patient. Currently, many composite scoring systems are used for evaluation of disease activity but they are mainly clinical-based. As several haematological parameters are altered due to systemic inflammatory process in RA, this study was intended to evaluate role of common haematological parameters to assess disease activity in RA. Aim: To find out the association of disease activity of Rheumatoid Arthritis (RA) with platelet count, Mean Platelet Volume (MPV) and Haemoglobin (Hb) level so that these costeffective haematological parameters can be used as additional factors to assess disease activity. Materials and Methods: This hospital based cross-sectional study was done on newly diagnosed patients of RA along with age and sex matched healthy control population. Patients suffering from malignancies, renal failure, diabetes mellitus or RA patients on drug therapy were excluded. Clinically, disease activity of RA was measured using DAS 28-3 Score (Modified Disease Activity Score using three variables- tender joint count, swollen joint count and ESR). Haematological parameters were measured by automated cell counter. Results: Total 80 cases were selected (60 female and 20 male). 48 patients with high disease activity (DAS 28-3>5.1) were labelled as Group-A and 32 with low to moderate disease activity (DAS 28-3 ≤5.1) as Group- B. Mean platelet count of patients of group A and group B were 4.53 lac/cmm and 2.17 lac/cmm respectively (p

Increasing incidents of diabetes (mellitus) induced non-healing lower extremity wounds and disease associated amputations have raised significant concerns related to quality of life of afflicted patients. High glucose level in diabetic wounds inhibits the transactivation of angiogenesis related molecules resulting delayed healing progression. Present study investigates the impact of a natural medicine like honey in angiogenesis of non-healing diabetic lower limb wounds. Quantitative assessment of different vessel parameters was performed on in vitro CAM model for validation of angiogenic potential of honey. Further the upregulation of angiogenesis related prime molecular markers like HIF-1α, VEGFA, VEGFR2 is under the therapeutic intervention of honey indicated improved angiogenesis which in turn promote the healing rate. These results may facilitate in determining the healing impact of this natural product in treatment of diabetic wounds and it may also help in developing alternative cost effective therapeutic modality.

The degree of increase in foetal haemoglobin (HbF) synthesis in haematological malignancies may be associated with the degree of malignancy. The aim of the present study was to quantify HbF levels in various childhood haematological malignancies and also, to ascertain its prognostic significance by comparing the results with the already established standard prognostic factors. Newly diagnosed cases of haematological malignancies in the paediatric age group were included in the study. HbF levels were estimated in each case of the study group along with HbF levels of control group comprising healthy children of same age group. The estimation was done by HPLC and Modified Betke's method. 50 cases of newly diagnosed haematological malignancies were studied out of which most of the cases were of acute lymphoblastic leukaemia (ALL) [n = 30(60 %)] followed by acute myeloid leukaemia (AML) [n = 8(16 %)], Hodgkin's lymphoma [n = 7(14%)], non-Hodgkin's lymphoma [n = 5(10 %)]. Raised HbF levels were found in 43.3 % cases of ALL (13/30) and 37.5 % cases of AML (3/8). No significant rise in HbF level was found in cases of lymphomas. There was correlation between raised HbF level and poor prognostic factors in cases of ALL but no such correlation was found in cases of AML. HbF levels are often elevated in childhood leukaemias as compared to childhood lymphomas. Thus, the concentration of HbF in acute childhood leukaemia may be considered as a prognostic factor.

Curcumin, because of its distinguishing ability to inhibit activation of transcription factor linked to chemoresistance and drug transporters, is now being co-administered with various potent anti-cancer drugs. In the present study, we report on such potentiating capabilities of curcumin in anti-angiogenic cancer therapy. With a view to simultaneously deliver curcumin and doxorubicin to tumor vasculature in anti-angiogenic cancer therapy, herein we report on the design & synthesis of a tumor vasculature targeting pegylated RGDK-lipopeptide. We show that curcumin & doxorubicin co-encapsulated within the liposomes of the presently described pegylated RGDK-lipopeptide exhibit synergism in inhibiting proliferation, invasion and migration of both tumor and endothelial cells presumably by inhibiting proliferation and metastasis related genes both at mRNA & protein levels. Pronounced tumor growth inhibition was observed in mice treated with formulations containing both the drugs. Tumor growth inhibition was found to be 2-3 folds less in mice treated with formulations containing only curcumin or only doxorubicin. The presently described liposomal system is expected to find future use for simultaneously delivering potentially any combinations of hydrophilic and hydrophobic potent small molecule cancer therapeutics to tumor vasculature in anti-angiogenic cancer therapy.

A series of meso-substituted thienyl BODIPY analogues (1, 1a–g) have been designed and synthesized. Among those, compounds 1c, 1d and 1e show biocompatibility towards endothelial cells whereas 1c and 1d show significant cytotoxicity towards cancerous cells. The formation of intracellular reactive oxygen species (ROS) and the activation of the apoptotic protein may be a plausible mechanism for the anti-proliferative nature of 1c and 1d. Additionally, compounds 1c, 1d, and 1e fluoresce inside the cancer cells. The combined results suggest the future theranostic (therapeutics + diagnostics) applications of 1c and 1d in cancer diseases.

Increasing number of Phase I/II clinical studies have demonstrated clinical potential of curcumin for treatment of various types of human cancers. Despite significant anti-tumor efficacies and bio-safety profiles of curcumin, poor systemic bioavailability is retarding its clinical success. Efforts are now being directed toward developing stable formulations of curcumin using various drug delivery systems. To this end, herein we report on the development of a new tumor vasculature targeting liposomal formulation of curcumin containing a lipopeptide with RGDK-head group and two stearyl tails, di-oleyolphosphatidylcholine (DOPC) and cholesterol. We show that essentially water insoluble curcumin can be solubilized in fairly high concentrations (~500 μg/mL) in such formulation. Findings in the Annexin V/Propidium iodide (PI) binding based flow cytometric assays showed significant apoptosis inducing properties of the present curcumin formulation in both endothelial (HUVEC) and tumor (B16F10) cells. Using syngeneic mouse tumor model, we show that growth of solid melanoma tumor can be inhibited by targeting such liposomal formulation of curcumin to tumor vasculature. Results in immunohistochemical staining of the tumor cryosections are consistent with tumor growth inhibition being mediated by apoptosis of tumor endothelial cells. Findings in both in vitro and in vivo mechanistic studies are consistent with the supposition that the presently described liposomal formulation of curcumin inhibits tumor growth by blocking VEGF-induced STAT3 phosphorylation in tumor endothelium. To the best of our knowledge, this is the first report on inhibiting tumor growth through targeting liposomal formulation of curcumin to tumor vasculatures.

Evaluating molecular attributes in association with its epithelial and sub-epithelial changes of oral sub-mucous fibrosis is meaningful in exploring the plausibility of an epithelio-mesenchymal transition (EMT) and malignant potentiality of this pathosis. In this study histopathological and histochemical attributes for basement membrane and connective tissue in biopsies of oral sub-mucous fibrosis (n = 55) and normal oral mucosa (n = 16) were assessed and expressions of p63, E-cadherin, β-catenin, N-cadherin and TWIST were analyzed immunohistochemically. The p63 and its isoforms (TA and ∆N), PARD3, E-cadherin and β-catenin were also assessed transcriptomically by q-PCR and EMT players like TWIST1, ZEB1, MMP9 and micro-RNA 205 were searched in gene expression microarrays. Oral epithelium demonstrating impairment in progressive maturation in oral sub-mucous fibrosis concomitantly experienced an increase in basement membrane thickness and collagen deposition along with alteration in target molecular expressions. In comparison to non-dysplastic conditions dysplastic stages exhibited significant increase in p63 and p63∆N expressions whereas, E-cadherin and β-catenin exhibited loss from the membrane with concurrent increase in cytoplasm. Further the N-cadherin and TWIST were gained remarkably along with the appearance of nuclear accumulation features of β-catenin. The microarray search had noticed the up-regulation of TWIST1, ZEB1 and MMP9 along with down regulation of micro-RNA 205. The simultaneous increase in basement membrane thickness and sub-epithelial collagen deposition were the plausible indicators for increased matrix stiffness with expected impact on oral epithelial functional homoeostasis. This was corroborated with the increase in expressions of epithelial master regulator p63 and its oncogenic isoform (∆N) along with membranous loss of E-cadherin (EMT hallmark) and its associate β-catein and gain of mesenchymal markers like N-cadherin and TWIST. These also became indicative for the induction of epithelial to mesenchymal transitional mechanism in oral sub-mucous fibrosis when connoted here with the relevant modulation in expressions of EMT regulators.

The paper deals with the analyses of the atmospheric vertical potential gradient (PG) from the ground for 90 fair weather days during 2006–2009 measured at Kolkata (Lat: 22.56°N). The variations of PG have been studied extensively to investigate their values during monsoon and winter seasons. Higher values of PG at Kolkata are observed due to higher abundance of pollutant particles. The observed PG are compared with the results of Potsdam station (Lat: 52°N) and Johannesburg station (Lat: 26°S), with 9 years data and 2 years data respectively. The correlations studies are carried out among PG, PDC (Point Discharge Current) as well as negative and positive carrier conductivities. The corresponding correlation coefficients are obtained as 0.93, −0.842 and −0.844.

Precise histopathological localization of E-cadherin and p63 is of immense importance in understanding the integrity of oral mucosal stratified epithelium in normal and diseased conditions. Necessarily immunohistochemical imaging should have minimum bleaching impact on the dyes and ability to produce clear and crisp images. Here ApoTome provides an alternative with metal halide light source and structured illumination under the assistance of grids, along with integrated image processing modality to generate crisp images with digital interface. The current study demonstrates the applicability of such microscopic system in capturing fluorescence images of immunohistochemical sections of normal and precancerous biopsies in respect to the expression of p63 and E-cadherin in the epithelial cells. The ApoTome images localize the nuclear and membranous expressions of p63 and E-cadherin, respectively, with remarkable specificity. The findings on E-cadherin expression have enormous diagnostic significance as these images clearly differentiate the early and advanced stages of oral submucous fibrosis based on their cytoplasmic and membranous location. Thus, this study clearly depicts a remarkable performance of ApoTome with diagnostic significance.

Absorption and effectiveness of vaginally administered misoprostol tablets may vary according to the medium in which it is placed. This study was directed to compare the outcomes of vaginal administrations of acetic acid-moistened misoprostol tablets with those of dry tablets for induction of second-trimester abortion. A randomized comparative trial where 322 women at 13–20 weeks gestation, requiring medical abortion, were randomly assigned to vaginal administration of either acetic acid-moistened or dry misoprostol tablets with a dose schedule of 400 μg three-hourly, up to a maximum five doses over 24 h. The same doses were repeated for another 24 h in nonresponders. Primary outcome measure was complete abortion rate at 24 and 48 h, and the secondary outcome measures were induction–abortion interval, failure rate and side effects. A difference of 15% in success rates at 24 h was used to calculate the sample size required with a power of 0.8 at the 5% significance level. No statistically significant differences in the complete abortion rates were observed at 24 h (70.95 vs. 68.71%, P = 0.675) and at 48 h (86.49 vs. 84.35%, P = 0.604) when both groups were compared. The difference in mean induction–abortion interval was also statistically insignificant between the groups (12.5 ± 1.6 vs. 12.8 ± 1.5 h, P = 0.97). Other outcome measures were also comparable in both groups. Moistening misoprostol tablets with 5% acetic acid before vaginal application creates no difference in outcomes when compared with those after the vaginal application of dry tablets for the termination of second-trimester pregnancy.

In a randomised control study, we evaluated the efficacy of intravenous low-dose magnesium sulphate for the management of eclampsia. A total of 144 women with eclampsia were divided into a study group and a control group of 72 women each. The study group received 0.75 g/h of magnesium sulphate intravenously after a loading intravenous dose of 4 g and the control group was given the standard intramuscular regimen as advocated by Pritchard. The primary outcome measure was recurrence rate of the seizures. The secondary outcome measures were development of magnesium toxicity if any, and maternal and perinatal outcomes. The difference in the incidence of fit recurrence was statistically insignificant when both groups were compared (7.46% vs 8.57%, p = 0.939). The total dose of magnesium sulphate was significantly lower in the intravenous group (p0.0001), in which no patient developed magnesium toxicity. Low-dose intravenous magnesium sulphate was found to be as effective as the standard intramuscular regimen, while maintaining a high safety margin.

The assessment of malignant potential of oral submucous fibrosis grades vis-à-vis their progression towards malignancy is associated with expression of possible multiple molecular markers.To analyse p63, E-cadherin and CD105 expression in this premalignant pathosis with a view to unravel and understand the expression of these molecules as markers.The oral mucosal biopsies (normal, oral submucous fibrosis with and without dysplasia) were studied with routine HE, and by immunohistochemistry for p63, E-cadherin and CD105 expression. p63 was assessed as percentage of positive nuclei. E-cadherin expression was estimated through (i) distance between basement membrane and E-cadherin expression initiation point, (ii) ratio between epithelial thickness and epithelial thickness displaying E-cadherin, and (iii) E-cadherin intensity variation along the expression path. CD105 expression was assessed qualitatively.The p63+ cells were highest in severely dysplastic tissues followed by other dysplastic grades, normal oral mucosa and non-dysplastic conditions. However, the p63+ cells displayed the feature of progressive maturation only in normal mucosa. There was a loss of membranous E-cadherin in basal layers of all diseased conditions; it was highest in severe dysplasia. There was significant variation (p0.0001) in E-cadherin intensity within and between the tissues (normal and diseased). CD105 expression increased abruptly in dysplasia.The malignant potential of this pre-cancerous condition is likely to be correlated with an increase in p63 and CD105 expression and a concomitant loss of membranous E-cadherin. This may lead to marker identification through greater validation.

Introduction: Fine-needle aspiration cytology (FNAC) for identification of papillary carcinoma thyroid is a moderately sensitive and specific modality. The present machine learning tools can correctly classify images into broad categories. Training software for recognition of papillary thyroid carcinoma on FNAC smears will be a decisive step toward automation of cytopathology. Aim: The aim of this study is to develop an artificial neural network (ANN) for the purpose of distinguishing papillary carcinoma thyroid and nonpapillary carcinoma thyroid on microphotographs from thyroid FNAC smears. Subjects and Methods: An ANN was developed in the Python programming language. In the training phase, 186 microphotographs from Romanowsky/Pap-stained smears of papillary carcinoma and 184 microphotographs from smears of other thyroid lesions (at ×10 and ×40 magnification) were used for training the ANN. After completion of training, performance was evaluated with a set of 174 microphotographs (66 – nonpapillary carcinoma and 21 – papillary carcinoma, each photographed at two magnifications ×10 and ×40). Results: The performance characteristics and limitations of the neural network were assessed, assuming FNAC diagnosis as gold standard. Combined results from two magnifications showed good sensitivity (90.48%), moderate specificity (83.33%), and a very high negative predictive value (96.49%) and 85.06% diagnostic accuracy. However, vague papillary formations by benign follicular cells identified wrongly as papillary carcinoma remain a drawback. Conclusion: With further training with a diverse dataset and in conjunction with automated microscopy, the ANN has the potential to develop into an accurate image classifier for thyroid FNACs.

SummaryIn a prospective comparative study we screened 112 women with a past history either of pre-eclampsia, eclampsia, recurrent abortion, IUGR, IUFD or abruptio placentae, with no apparent aetiology and a demographically matched cohort of 106 women having a past history of uncomplicated pregnancy outcome for the presence of antiphospholipid antibodies (aPL) and their significance. In the former group, the prevalence of aPL ranged from 10–46.87% compared with 8.49% in the later group. In women with the presence of aPL, the incidence of pre-eclampsia, early onset pre-eclampsia and abruptio placentae were 25%, 14.58% and 18.75%, respectively. In the same group, the abortion rate was 25% and live-birth rate was 64.58% with IUFD rate of 10.42%. Fetal morbidity rates were also higher in the mothers with aPL positivity, the incidence of IUGR was 27.08% and oligohydramnios was 33.33% in them. All these complications were statistically significant when compared with those of aPL negative mothers.

Background Food allergy may be defined as an immunoglobulin E-mediated immune response to food proteins. Such studies have previously not been done in Calcutta, India. The present study was therefore undertaken to record the sensitivity to commonly consumed foods in patients with allergic rhinitis and asthma.Materials and methods A survey of 800 patients (410 males and 390 females) reporting to the Allergy Unit of the Institute of Child Health, Calcutta, were selected for the study conducted from May 2006 to April 2007. Respiratory allergic patients in the age group of 5 to 60 years were evaluated using a standard questionnaire, and skin prick test was performed using common food and aeroallergens.Results/Conclusions Out of the 684 patients with a history of food allergy, most of them, that is, 338, are in the age group 16 to 40 years, 192 of them were in the age group 41 to 60 years, and 154 were in the age group 5 to 15 years. Most of the patients with food allergy had asthma (65.05%), rhinitis and asthma (20.03%), and skin allergies (4.97%), such as itching, eczema, and urticaria. The foodstuffs that were found to elicit symptoms of hypersensitivity were egg, milk, wheat, pulses, vegetables, fishes, and fruits.The patients aged between 16 and 40 years (male-female ratio, 1:1.19) were mostly sensitive to prawn, brinjal, banana, ladyfinger, papaya, wheat, and egg. The age group 41 to 60 years (male-female ratio, 1:1.04) had high skin reactivity to brinjal, egg, banana, fish, and Phaseolus mungo. Patients younger than 16 years (male-female ratio, 1:1.33) were sensitized to brinjal, prawn, banana, spinach, and egg. We observed that food hypersensitivity also reflects different genetic factors and variations in cultural and dietary habits of each individual. Keywords: food allergens, Calcutta, India, skin prick test

Background: Misoprostol is the drug of choice for medical abortion worldwide but consensus is yet to be reached regarding its preferred route of administration. Aims: To compare the outcome of sublingual with vaginal administrations of misoprostol for induction of second trimester abortion. Methods: A randomised comparative trial where 300 women at 13–20 weeks gestation, requiring medical abortion, were randomly assigned to sublingual or vaginal route for misoprostol administration with a dose schedule of 400 µg three-hourly, up to a maximum five doses over 24 h. The same doses were repeated for another 24 h in non-responders. Primary outcome measure was complete abortion rate at 24 and 48 h, and the secondary outcome measures were induction–abortion interval, failure rate, side-effects and patients’ preference to the route. Results: No statistically significant differences in the complete abortion rates were observed at 24 h (64.03% vs 61.59%, P = 0.767) and at 48 h (79.14% vs 82.01%, P = 0.651) when sublingual and vaginal groups were compared. Mean induction–abortion intervals in sublingual and vaginal groups were 14.1 and 14.5 h, respectively (P = 0.066). Other outcome measures were also more or less similar in both groups. Differences in the incidence of side-effects were also statistically insignificant when both groups were compared. Sublingual administration of the drug was preferred by most of the women as compared to vaginal administration (P

Cellular auto-fluorescence along with morphological and cytoskeletal features were assessed in lung cancer cells undergoing induced epithelial mesenchymal transition (EMT). During EMT progression, significant increase was observed in cellular aspect ratio (AR), filamentous (F)-actin and green auto-fluorescence intensities while blue intensity decreased. These features were provided to a kernel classification framework. The classification accuracy were impressive, thus these features along with the classification technique can be considered as suitable tools for automated grading of lung cancer cells undergoing EMT progression.

Molecules offering simultaneous detection and killing of cancer cells are advantageous. Hybrid of cancer cell-selective, ROS generator betulinic acid and bis-arylidene oxindole with amino propyl-linker is developed. With intrinsic fluorescence, the molecule exhibited cancer cell-specific residence. Further, it generated ROS, triggered apoptosis, and exhibited potent cytotoxicity in cancer cells selectively. We demonstrate the first example and use of isatins as betulinic acid conjugate for selective detection of cancer and subsequent killing of cancer cells via apoptosis.

Targeting angiogenesis is a strategy to better control tumor growth and metastasis. αvβ3 is an integrin, involved in the regulation of angiogenesis and overexpressed in angiogenic endothelial cells and various cancers including breast, prostate, pancreatic, and brain cancers. cRGDfK peptide has high specificity towards αvβ3 integrin receptors. Docetaxel (DTX) is a broad spectrum anticancer drug, widely used to treat breast, ovarian, prostate, non-small-cell lung, gastric, and neck cancers. Its clinical application is limited owing to its poor aqueous solubility, low oral bioavailability, and nonspecific cytotoxicity. The nanocarriers help to overcome these limitations and further can be surface-modified to conjugate ligand to achieve selective delivery to tumor. d-α-Tocopheryl polyethylene glycol succinate (TPGS) is a water soluble derivative of natural d-α-tocopherol (Vit E). TPGS-based engineered nanocarrier systems have been shown to transport and deliver anticancer drugs more efficiently than the pristine drugs. Herein, we attempt to improve the therapeutic potential of DTX and to target the integrin receptor overexpressing angiogenic tumors, by encapsulating the DTX in nanomicelles and conjugating to cRGDfK peptide for tumor targeting. These nanomicelles are characterized by various analytical techniques and their potential of selective targeting is also evaluated. In the present chapter, we provide the general procedure used in this study: (1) synthesis and characterization of succinoyl-TPGS, (2) preparation and characterization of docetaxel loaded TPSA nanomicelles (DNM), (3) bioconjugation, quantification, and characterization of cRGDfK peptide to DNM (PDNM), (4) in vitro evaluation of cytotoxicity of the nanoparticles, (5) antiangiogenic activity, and (6) stability studies.

BackgroundWe have previously reported that increased glucose levels were associated with higher serum nitric oxide (NO) levels in fructose-fed insulin resistant rats. However, the relationship between hyperglycemia and serum NO level was not clear. Therefore, the present study was designed to find the association between hyperglycemia and serum NO levels in Type 2 diabetic (T2DM) patients and T2DM with cardiovascular complication.MethodsEndothelial cells (HUVEC) were treated with of D-glucose (10-100mM), and NO levels and NOS gene expression was measured. Hyperglycaemia was induced in Sprague-Dawley rats, and serum NO levels were measured after 8 weeks. For clinical evaluation, five groups of patients were recruited: Control (CT, n=48), Type 2 diabetes (T2DM, n=26), T2DM with hypertension (DMHT, n=46), Coronary artery diseases (CAD, n=29) and T2DM with coronary artery diseases (DMCD, n=38). NO (nitrite + nitrate) levels were measured from human serum.ResultsWe found a significant (pConclusionIn conclusion, high NO levels were observed in South Indian diabetic patients. Higher glucose levels in serum might be responsible for activation of endothelial cells to enhance NO levels.

Cancer cells continue to grow and divide, without undergoing apoptosis. p53, a tumor suppressor protein, serves as a checkpoint in prevention of cancer by inducing the abnormal cells to commit apoptosis. p53 can induce both extrinsic and intrinsic pathways of apoptosis and can also induce apoptosis by directly acting on mitochondria. Regulation of p53 concentration in cell is very critical and is regulated by Mdm2 which triggers degradation through ubiquitinylation. Keeping in view, the role of p53 in preventing cancer, many effective strategies can be developed to combat cancer by enhancing either function or stability of p53.