RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms.

RAS proteins are important direct activators of p110α, p110γ, and p110δ type I phosphoinositide 3-kinases (PI3Ks), interacting via an amino-terminal RAS-binding domain (RBD). Here, we investigate the regulation of the ubiquitous p110ß isoform of PI3K, implicated in G-protein-coupled receptor (GPCR) signaling, PTEN-loss-driven cancers, and thrombocyte function. Unexpectedly, RAS is unable to interact with p110ß, but instead RAC1 and CDC42 from the RHO subfamily of small GTPases bind and activate p110ß via its RBD. In fibroblasts, GPCRs couple to PI3K through Dock180/Elmo1-mediated RAC activation and subsequent interaction with p110ß. Cells from mice carrying mutations in the p110ß RBD show reduced PI3K activity and defective chemotaxis, and these mice are resistant to experimental lung fibrosis. These findings revise our understanding of the regulation of type I PI3K by showing that both RAS and RHO family GTPases directly regulate distinct ubiquitous PI3K isoforms and that RAC activates p110ß downstream of GPCRs.

The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer deaths worldwide; nearly half contain mutations in the receptor tyrosine kinase/RAS pathway. Here we show that RAS-pathway mutant NSCLC cells depend on the transcription factor GATA2. Loss of GATA2 reduced the viability of NSCLC cells with RAS-pathway mutations, whereas wild-type cells were unaffected. Integrated gene expression and genome occupancy analyses revealed GATA2 regulation of the proteasome, and IL-1-signaling, and Rho-signaling pathways. These pathways were functionally significant, as reactivation rescued viability after GATA2 depletion. In a Kras-driven NSCLC mouse model, Gata2 loss dramatically reduced tumor development. Furthermore, Gata2 deletion in established Kras mutant tumors induced striking regression. Although GATA2 itself is likely undruggable, combined suppression of GATA2-regulated pathways with clinically approved inhibitors caused marked tumor clearance. Discovery of the nononcogene addiction of KRAS mutant lung cancers to GATA2 presents a network of druggable pathways for therapeutic exploitation.

Neuroprotective role of chloroquine via modulation of autophagy and neuroinflammation in MPTP-induced Parkinson's disease.

Parkinson's disease (PD) is a neuro-motor ailment that strikes adults in their older life and results in both motor and non-motor impairments. In neuronal and glial cells, PD has recently been linked to a dysregulated autophagic system and cerebral inflammation. Chloroquine (CQ), an anti-malarial drug, has been demonstrated to suppress autophagy in a variety of diseases, including cerebral ischemia, Alzheimer's disease (AD), and Traumatic brain injury (TBI), while its involvement in PD is still unclear. BALB/c mice were randomly allocated to one of four groups: 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), CQ treatment with or without MPTP, or control. The CQ treatment group received CQ (intraperitoneally, 8 mg/kg body weight) after 1 h of MPTP induction on day 1, and it lasted for 7 days. CQ therapy preserves dopamine levels stable, inhibits tyrosine hydroxylase (TH) positive dopaminergic cell death, and lowers oxidative stress. CQ reduces the behavioural, motor, and cognitive deficits caused by MPTP after injury. Furthermore, CQ therapy slowed aberrant neuronal autophagy (microtubule-associated protein-1 light chain 3B; LC3B & Beclin1) and lowered expression levels of the inflammatory cytokines interleukin 1 (IL-1ß) and tumour necrosis factor (TNF-α) in the mice brain. In addition, CQ's antioxidant and anti-inflammatory effects were also tested in MPTP-mediated cell death in PC12 cells, demonstrating that CQ has a neurorestorative impact by successfully rescuing MPTP-induced ROS generation and cell loss. Our findings show that CQ's can help to prevent dopaminergic degeneration and improve neurological function after MPTP intoxication by lowering the harmful effects of neuronal autophagy and cerebral inflammation.

Substituent Effect on the Photophysics and ESIPT Mechanism of N,N'-Bis(salicylidene)-p-phenylenediamine: A DFT/TD-DFT Analysis.

Excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) processes are widely exploited in the designing of organic materials for multifarious applications. This work explores the aftereffects of combining both ESIPT and ICT events in a single molecule, namely, N,N'-bis(salicylidene)-p-phenylenediamine (BSP) exploiting DFT and TD-DFT formalisms. The PBE0 functional employed in the present study is found to yield results with better accuracy for excited-state calculations. The results reveal that introduction of electron donor (-NH2) and electron acceptor (-NO2) substituents on BSP produces a strikingly red-shifted emission with respect to the corresponding emission from the unsubstituted analogue in polar solvents. This red-shifted emission originated due to the coupled effect of ESIPT and planar-ICT (PICT) processes from the coplanar geometry adopted by the substituted molecule (s-BSP). Based on the computed potential energy curves, the ground-state intramolecular proton transfer (GSIPT) was found to take place more favorably in s-BSP than in BSP under all solvent conditions. In the case of ESIPT, the barrier and relative energies of the phototautomers of s-BSP were slightly higher than BSP, which shows that simultaneous substitution of -NH2 and -NO2 groups causes slight perturbation to the ESIPT process. Overall, the computed results show that simultaneous substitution of suitable electron donor and acceptor substituents provides profitable changes in the photophysical properties of ESIPT molecules like BSP. These molecular-level insights will pave way for designing better materials for diverse applications.

The keto-enol tautomerization of ethyl acetoacetate in choline ionic liquids: the role of cation and anion in switching the tautomeric equilibrium.

In this work, density functional theory (DFT) calculations were carried out to study the role of the explicit treatment of four different choline-based ionic liquids (CS, CP, NS, and NP) by utilizing two different cations and anions in the tautomeric equilibrium of ethyl acetoacetate (EAA). The involvement of the acidic N-H proton from the cationic part of NS and NP ionic liquid offers the possibility to have two more additional transition states for the tautomeric equilibrium of EAA. The computed results demonstrated that a high activation free energy barrier (ΔG = 49.4 kcal mol-1) is associated with the direct enol to keto (E → K) interconversion via a 4-membered ring transition state. Upon explicit involvement of the cationic part of ionic liquids in the tautomeric equilibrium via a 6-membered ring transition state (CAT), ΔG is substantially reduced to 21.88 kcal mol-1. Further, ΔG is drastically reduced to 10.57 kcal mol-1 upon the involvement of the anionic part of the ionic liquid explicitly via an 8-membered ring transition state (AAT). The W-shaped TS in the CAT pathway causes steric hindrance and increases the energy penalty, while the sickle-shaped TS in AAT facilitates easy proton transfer without the influence of the steric factor. In addition, the RDG scatter graphs predict large negative values of ρ*, which indicate that the hydrogen bonding network in AAT is stronger, enhancing the delocalization of the electron density. The QTAIM analysis substantiated the role of intermolecular hydrogen bonding interactions between the ionic liquid and EAA and within the anion-cation pair in stabilizing the keto group of EAA. Besides, the involvement of the acidic N-H proton in the transition state is the key factor in influencing the energetics of the keto-enol tautomerization reaction. The present study illustrates molecular-level insights into the role of individual ions of ionic liquids and also provides adequate ideas for designing novel ionic liquid-based catalysts for industrially relevant chemical reactions.

HMGA2 functions as a competing endogenous RNA to promote lung cancer progression.

Non-small-cell lung cancer (NSCLC) is the most prevalent histological cancer subtype worldwide. As the majority of patients present with invasive, metastatic disease, it is vital to understand the basis for lung cancer progression. Hmga2 is highly expressed in metastatic lung adenocarcinoma, in which it contributes to cancer progression and metastasis. Here we show that Hmga2 promotes lung cancer progression in mouse and human cells by operating as a competing endogenous RNA (ceRNA) for the let-7 microRNA (miRNA) family. Hmga2 can promote the transformation of lung cancer cells independent of protein-coding function but dependent upon the presence of let-7 sites; this occurs without changes in the levels of let-7 isoforms, suggesting that Hmga2 affects let-7 activity by altering miRNA targeting. These effects are also observed in vivo, where Hmga2 ceRNA activity drives lung cancer growth, invasion and dissemination. Integrated analysis of miRNA target prediction algorithms and metastatic lung cancer gene expression data reveals the TGF-ß co-receptor Tgfbr3 (ref. 12) as a putative target of Hmga2 ceRNA function. Tgfbr3 expression is regulated by the Hmga2 ceRNA through differential recruitment to Argonaute 2 (Ago2), and TGF-ß signalling driven by Tgfbr3 is important for Hmga2 to promote lung cancer progression. Finally, analysis of NSCLC-patient gene-expression data reveals that HMGA2 and TGFBR3 are coordinately regulated in NSCLC-patient material, a vital corollary to ceRNA function. Taken together, these results suggest that Hmga2 promotes lung carcinogenesis both as a protein-coding gene and as a non-coding RNA; such dual-function regulation of gene-expression networks reflects a novel means by which oncogenes promote disease progression.

A Self-Organizing Fuzzy Logic Classifier for Benchmarking Robot-Aided Blasting of Ship Hulls.

Regular dry dock maintenance work on ship hulls is essential for maintaining the efficiency and sustainability of the shipping industry. Hydro blasting is one of the major processes of dry dock maintenance work, where human labor is extensively used. The conventional methods of maintenance work suffer from many shortcomings, and hence robotized solutions have been developed. This paper proposes a novel robotic system that can synthesize a benchmarking map for a previously blasted ship hull. A Self-Organizing Fuzzy logic (SOF) classifier has been developed to benchmark the blasting quality of a ship hull similar to blasting quality categorization done by human experts. Hornbill, a multipurpose inspection and maintenance robot intended for hydro blasting, benchmarking, and painting, has been developed by integrating the proposed SOF classifier. Moreover, an integrated system solution has been developed to improve dry dock maintenance of ship hulls. The proposed SOF classifier can achieve a mean accuracy of 0.9942 with an execution time of 8.42 µ s. Realtime experimenting with the proposed robotic system has been conducted on a ship hull. This experiment confirms the ability of the proposed robotic system in synthesizing a benchmarking map that reveals the benchmarking quality of different areas of a previously blasted ship hull. This sort of a benchmarking map would be useful for ensuring the blasting quality as well as performing efficient spot wise reblasting before the painting. Therefore, the proposed robotic system could be utilized for improving the efficiency and quality of hydro blasting work on the ship hull maintenance industry.

Pyrene-Based Chemosensor for Picric Acid-Fundamentals to Smartphone Device Design.

Developing a fluorescent probe for the selective and sensitive detection of explosives is a topic of continuous research interest. Additionally, underlying the principles behind the detection mechanism is indeed providing substantial information about the design of an efficient fluorescence probe. In this context, a pyrene-tethered 1-(pyridin-2-yl)imidazo[1,5-a]pyridine-based fluorescent probe (TL18) was developed and employed as a fluorescent chemosensor for nitro explosives. The molecular structure of TL18 was well-characterized by NMR and EI-MS spectrometric techniques. UV-visible absorption, steady-state, and time-resolved fluorescence spectroscopic techniques have been employed to explicate the photophysical properties of TL18. The fluorescent nature of the TL18 probe was explored for detection of nitro explosives. Intriguingly, the TL18 probe was selectively responsive to picric acid over other explosives. The quantitative analysis of the fluorescence titration studies of TL18 with picric acid proved that the probe achieved a detection limit of 63 nM. Further, DFT and QTAIM studies were used to establish the nature of the sensing mechanism of TL18. The hydrogen-bonding interactions are the reason for the imperative sensing property of TL18 for picric acid. Thus, our experimental and theoretical studies provide an adequate and appropriate prerequisite for an efficient fluorescent probe. Furthermore, a smartphone-interfaced portable fluorimeter module is developed to facilitate sensitive and real-time sensing of picric acid. This portable module was capable of detecting picric acid down to 99 nM. Eventually, these studies will have a significant impact on development and application of a new class of chemosensors for detection of explosives.

Theoretical Investigation of Steric Effect Influence on Reactivity of Substituted Butadienes with Bromocyclobutenone.

The Diels-Alder reaction (DA) between various mono- and disubstituted 1,3-butadiene (Dn-1 to Dn-10) and 2-bromocyclobutenone (DPh) was carried out in gas phase using density functional theory (DFT) at the M06-2X/6-31+g** level. The reaction was found to proceed through a concerted asynchronous transition state. Further, the asynchronous and early nature of the transition state was clearly pinpointed with the frontier molecular orbital (FMO) and bond order index (BOI) analyses. The intermolecular hydrogen bonding interaction along with steric encumbrance in the transition state were found to be the predominant factors in controlling the reactivity of the dienes. Among the investigated dienes, Dn-6 was found to be the most reactive diene which is attributed to its low activation barrier due to the presence of strong intermolecular H-bonding interactions. These factors were further supported by quantum mechanical calculations using global descriptor indexes, natural bond orbital analysis, and quantum theory of atoms in molecules analysis. These theoretical results were found to be in good agreement with the previous experimental findings.

Genetic diversity & drug sensitivity profiles of Mycobacterium tuberculosis isolates from two slums of Jaipur city, Rajasthan, India.

BACKGROUND & OBJECTIVES: Slums are considered as hotspots of tuberculosis (TB). The study of genetic diversity and drug susceptibility profile of Mycobacterium tuberculosis (MTB) will help understand the transmission dynamics and can be used for better prevention and control of the disease. The aim of this study was to determine the drug susceptibility profiles and genetic diversity using the random amplified polymorphic DNA (RAPD) and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU VNTR) of MTB isolates from sputum samples of pulmonary TB patients residing in the two slums of Jaipur city in Rajasthan, India. METHODS: Sputum samples collected from pulmonary TB patients, their contacts and suspects during 2010-2012 were processed for microscopy and mycobacterial culture. Drug susceptibility testing was done by one per cent indirect proportion method on Lowenstein-Jensen medium for first-line anti-TB drugs rifampicin, isoniazid, ethambutol and streptomycin. MTB DNA was extracted by physicochemical method, and DNA fingerprinting was done by RAPD and MIRU VNTR analysis. RESULTS: Among 175 sputum samples collected, 75 were positive (43.8%) for acid-fast bacilli, 83 for MTB culture and four were contaminated. Fifty two isolates (62.7%) were fully sensitive to four drugs, and five (6%) were multidrug resistant (MDR). RAPD analysis of 81 isolates revealed six clusters containing 23 (28.4%) isolates, and 58 (71.6%) were unique. MIRU VNTR analysis clustered 20 (24.7%) isolates, and 61 (75.3%) were unique. INTERPRETATION & CONCLUSIONS: About 62.7 per cent isolates from the sputum samples from slum areas were sensitive to four drugs; six per cent of isolates were MDR. Poly-resistance other than MDR was high (16%). About one-fourth isolates were clustered by either method. RAPD was rapid, less expensive but had low reproducibility. MIRU VNTR analysis could identify to greater extent the epidemiological link in the population studied.

Dicer1 functions as a haploinsufficient tumor suppressor.

While the global down-regulation of microRNAs (miRNAs) is a common feature of human tumors, its genetic basis is largely undefined. To explore this question, we analyzed the consequences of conditional Dicer1 mutation (Dicer1 "floxed" or Dicer1(fl)) on several mouse models of cancer. Here we show Dicer1 functions as a haploinsufficient tumor suppressor gene. Deletion of a single copy of Dicer1 in tumors from Dicer1(fl/+) animals led to reduced survival compared with controls. These tumors exhibited impaired miRNA processing but failed to lose the wild-type Dicer1 allele. Moreover, tumors from Dicer1(fl/fl) animals always maintained one functional Dicer1 allele. Consistent with selection against full loss of Dicer1 expression, enforced Dicer1 deletion caused inhibition of tumorigenesis. Analysis of human cancer genome copy number data reveals frequent deletion of DICER1. Importantly, however, the gene has not been reported to undergo homozygous deletion, suggesting that DICER1 is haploinsufficient in human cancer. These findings suggest Dicer1 may be an important haploinsufficient tumor suppressor gene and, furthermore, that other factors controlling miRNA biogenesis may also function in this manner.

Impaired microRNA processing enhances cellular transformation and tumorigenesis.

MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate the expression of target mRNA transcripts. Many of these target mRNA transcripts are involved in proliferation, differentiation and apoptosis, processes commonly altered during tumorigenesis. Recent work has shown a global decrease of mature miRNA expression in human cancers. However, it is unclear whether this global repression of miRNAs reflects the undifferentiated state of tumors or causally contributes to the transformed phenotype. Here we show that global repression of miRNA maturation promotes cellular transformation and tumorigenesis. Cancer cells expressing short hairpin RNAs (shRNAs) targeting three different components of the miRNA processing machinery showed a substantial decrease in steady-state miRNA levels and a more pronounced transformed phenotype. In animals, miRNA processing-impaired cells formed tumors with accelerated kinetics. These tumors were more invasive than control tumors, suggesting that global miRNA loss enhances tumorigenesis. Furthermore, conditional deletion of Dicer1 enhanced tumor development in a K-Ras-induced mouse model of lung cancer. Overall, these studies indicate that abrogation of global miRNA processing promotes tumorigenesis.

Molecular response to imatinib & its correlation with mRNA expression levels of imatinib influx & efflux transporters in patients with chronic myeloid leukaemia in chronic phase.

BACKGROUND & OBJECTIVES: Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML) patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2) in CML patients and to correlate these levels with molecular response. METHODS: Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non-responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined. RESULTS: No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05) while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene. INTERPRETATION & CONCLUSIONS: Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings.

Co-existence of Carcinoma Tongue with Pulmonary Tuberculosis.

We present the case of a 45-year-old male diagnosed to have carcinoma base of tongue, whose chest radiograph showed bilateral lung infiltrates and was referred for evaluation of suspected pulmonary metastases. Diagnostic evaluation confirmed the diagnosis of smear-positive pulmonary tuberculosis.

Silicone oil tamponade induced vasculitis- a rare manifestation of toxic posterior segment syndrome.

AIM: To report silicone oil tamponade induced vasculitis in the early post operative period - a rare manifestation of 'Toxic Posterior Segment Syndrome' after pars plana vitrectomy for rhegmatogenous retinal detachment. CASE DESCRIPTION: A 50-year-old gentleman presented with vasculitis after a pars plana vitrectomy with silicone oil tamponade on the first post-operative day. He was started on oral steroids (1 mg/ kg) tapered sequentially every week. All signs of vasculitis resolved over a period of one month after which the silicone oil was removed. The patient maintained a visual acuity of 20/90 even after 3 months. There was no recurrence of vasculitis observed thereafter. CONCLUSION: Silicone oil induced vasculitis is a rarely described entity, especially as a manifestation of toxic posterior segment syndrome. This differential must be kept in mind even on the first post-operative day in cases where silicone oil has been used for tamponade.

Unilateral solitary choroidal tuberculoma as the presenting sign in disseminated tuberculosis in an immunocompetent patient.

INTRODUCTION: Tuberculosis can involve any organ in the body including ocular tissue of which the uveal tissue is most commonly infected. Choroidal involvement ranges from choroidal tubercles to granulomas. This is one of the few cases of a solitary choroidal granuloma with no other systemic symptoms in an immunocompetent child. METHOD: A case report. RESULTS: A 12-year-old female, presented with diminution of vision in the left eye for a month. The anterior segment of her left eye was normal. A fundus examination revealed an isolated orangish-yellow choroidal mass, 4 DD in size, involving the posterior pole with overlying subretinal exudation. CT scan of the thorax showed large pulmonary, cervical and pancreatic lymph nodes, along with lytic lesions of the thoracic vertebrae. Excision biopsy of the cervical lymph nodes showed caseating granulomas with no e/o malignancies on histopathology. The patient was started on anti-tubercular therapy. Six months after the treatment, the lesion had reduced in size and her vision had improved. CONCLUSION: Isolated choroidal tuberculomas can be present in eyes with little associated ocular inflammation and no other symptoms of systemic tuberculosis. High suspicion, early diagnosis and rapid initiation of medication are important for the treatment of ocular and systemic tuberculosis.

Coordinate loss of a microRNA and protein-coding gene cooperate in the pathogenesis of 5q- syndrome.

Large chromosomal deletions are among the most common molecular abnormalities in cancer, yet the identification of relevant genes has proven difficult. The 5q- syndrome, a subtype of myelodysplastic syndrome (MDS), is a chromosomal deletion syndrome characterized by anemia and thrombocytosis. Although we have previously shown that hemizygous loss of RPS14 recapitulates the failed erythroid differentiation seen in 5q- syndrome, it does not affect thrombocytosis. Here we show that a microRNA located in the common deletion region of 5q- syndrome, miR-145, affects megakaryocyte and erythroid differentiation. We find that miR-145 functions through repression of Fli-1, a megakaryocyte and erythroid regulatory transcription factor. Patients with del(5q) MDS have decreased expression of miR-145 and increased expression of Fli-1. Overexpression of miR-145 or inhibition of Fli-1 decreases the production of megakaryocytic cells relative to erythroid cells, whereas inhibition of miR-145 or overexpression of Fli-1 has a reciprocal effect. Moreover, combined loss of miR-145 and RPS14 cooperates to alter erythroid-megakaryocytic differentiation in a manner similar to the 5q- syndrome. Taken together, these findings demonstrate that coordinate deletion of a miRNA and a protein-coding gene contributes to the phenotype of a human malignancy, the 5q- syndrome.

Armchair silicon carbide nanoribbon for potential anode material in lithium-ion batteries (LIBs).

In this work, we have investigated the electrochemical characteristics of armchair silicon carbide nanoribbon (ASiCNR) for its potential deployment as 2D lithium-ion battery anode material. Density functional theory approach is used to calculate the adsorption energy, storage capacity, and open circuit voltage of ASiCNR for LIB. Adsorption of Li atoms introduces the new energy bands which cross the Fermi level; this results in semiconductor to metallic transition of ASiCNR. It indicates the strong interaction of Li atoms towards the ASiCNR. When adsorption of Li atoms increases one by one, the adsorption energy (E[Formula: see text]) per Li atoms increases gradually. When all favourable sites are adsorbed by Li atoms E[Formula: see text] reached its maximum value and it results in maximum storage capacity of 818 mAhg[Formula: see text] and open circuit voltage of 1.15 V. Diffusion barrier of Li atoms for the substrate is 0.42 eV. Our computational results suggest that ASiCNR can be used as an anode material for Li-ion batteries, and it provides the theoretical background for the future study on ASiCNR and other Li storage structures.

A malignant transformation of borderline phyllodes tumor to fibrosarcoma breast: A rare case report.

ABSTRACT: Phyllodes tumor of the breast with malignant transformation to fibrosarcoma of the breast is a rare entity. Breast fibrosarcoma is uncommon, accounting for less than 1% of all breast tumors. Prognosis of fibrosarcoma of the breast is poor. Due to its rarity, survival rates are not defined. A 23-year-old woman presented with a mass in the left breast, and another 48-year-old woman presented with right breast mass. Both patients underwent for surgery. The histological & immunohistochemical examination confirms the diagnosis of a malignant transformation from borderline phyllodes tumor to fibrosarcoma. We concluded that the phyllodes tumor is mostly benign but local recurrence is common. As the tumor progresses toward malignancy, due to the difficulty in the diagnosis of borderline phyllodes tumors, total mastectomy with axillary resection must be recommended.

Barriers related to Oral Cancer Screening, Diagnosis and Treatment in Karnataka, India.

BACKGROUND: The most predominant cancer in India is Oral cancer. Annually 130,000 people yield to oral cancer in India, which translates into about 14 deaths per hour and 60-80% of patients present with advanced disease as compared to 40% in developed countries. AIM: To decide factors associated with primary, secondary and tertiary delays and identify reasons for a lack of follow-up. MATERIALS AND METHODS: This study was conducted at the Kidwai Memorial Institute of Oncology, Bengaluru. A hospitalbased cross-sectional study using the direct personal interview method was done. A total of 200 oral cancer patients were included in the study. RESULTS: 34.5% were men and 65.5% were women. About 97.5% of patients were engaged with either one of the habits like smoking, chewing or alcohol consumption. 84% of patients were not aware of the risk of getting oral cancer. 29% of people agreed that tobacco and alcohol are risk factors for oral cancer and they know about the signs of oral cancer. If detected early, cure rates were higher compared to illiterate people and this difference is statistically significant p< 0.05. 83.5% of patients did not know that oral cancer can be diagnosed early by regular screening of the oral cavity. The cost of staying near a Regional cancer centre, job security, and the social and economic burden on relatives were significant barriers to incomplete treatment and a decreased follow-up rate. CONCLUSION: Low awareness is the main barrier to oral cancer detection. Conducting cancer awareness and screening camps frequently will detect oral cancers at an early stage. KEY WORDS: Oral Cancer, Barriers, Cancer awareness, Oral Screening.