Solving the Dilemma: Van Wyk-Grumbach Syndrome.

The Van Wyk-Grumbach syndrome (VWGS) (hypothyroidism, ovarian mass, and precocious puberty) has been extensively documented in the literature as long-term hypothyroidism manifesting as an ovarian mass. The authors of this study describe this entity in a young girl, aged 10, who presented with abdominal pain with a multiloculated ovarian cyst. She was evaluated, and it was discovered that she had delayed bone age, precocious puberty, and a small height. Following her diagnosis of autoimmune thyroiditis and the initiation of thyroxine replacement therapy, the ovarian cysts spontaneously regressed. To avoid needless assessment and surgical mishaps, this entity should be considered in situations of ovarian mass, particularly those with precocious puberty and thyroid disorders.

Hyperreactio Luteinalis: A Rare Phenomenon Complicating Gestational Trophoblastic Disease Presenting as Acute Abdomen in the Convalescence Period.

The hydatidiform mole is a rare gynaecological condition originating from trophoblastic cells, with an incidence of 1-3 per 1000 pregnancies. Theca lutein cysts (TLCs) and an invasive mole are rarely observed in association with a partial mole. This case describes an unusual case involving a 17-year-old primigravida at 11 weeks of gestation. She presented with abdominal pain and was diagnosed with a molar pregnancy with post-evacuation rupture of TLC, presenting as an acute abdomen, subsequently undergoing laparoscopy. Post-molar pregnancies exhibit a highly variable course, ranging from recurrent pregnancy loss and stillbirths to preterm deliveries and recurrent molar pregnancies. Few studies are available on obstetric outcomes after a molar pregnancy; most available data originate from national databases and monocentric research.

Concept mapping a potential pedagogical strategy to foster meaningful learning in physiology students.

BACKGROUND: Understanding of human physiology is critical for clinical practice and disease management. Escalating the teaching-learning method to improve conceptual knowledge may help the students to apply their knowledge in clinical scenarios. The present study was conducted to teach the use of concept mapping as a learning strategy to foster meaningful learning in physiology, compare its impact as a learning tool with traditional methods on meaningful learning, assess the cognitive gain, and find student's perception regarding concept mapping. MATERIALS AND METHODS: The interventional study was conducted on first-year MBBS students. Depending upon marks obtained in previous internal assessments, the students were classified into "rapid learners" (RL) and "potential learners" (PL). By simple random sampling technique, both groups were divided into interventional (concept mapping) and control groups (question-answer discussion). After a pretest, all students had a lecture on glomerular filtration. The assignment was given to the interventional group to prepare a concept map on glomerular filtration, and question-answer were discussed for control groups. A surprise posttest was conducted after 2-3 days. RESULT: In our study, all four groups showed significant differences in the pretest and posttest scores using a paired t-test (P < 0.05). The mean score of gain in learning, raw gain (G0), absolute learning gain, relative learning gain, and average normalized gain compared between the interventional group and controls group showed statistically significant performance improvement in both RL and PL groups. CONCLUSION: The concept mapping strategy was more efficacious than the question-answer discussion. Concept mapping is an impactful learning tool to improve cognitive gain and potential pedagogical strategy to foster meaningful learning in physiology students.

Empowering Women's Health: Insights Into HPV Vaccination and the Prevention of Invasive Cervical Cancer.

This review article provides a comprehensive analysis of the role of human papillomavirus (HPV) vaccination in empowering women's health by preventing invasive cervical cancer. Cervical cancer remains a significant global health concern, with HPV infection identified as a primary causative factor. The review synthesizes current research findings, epidemiological data, and clinical outcomes to offer a nuanced understanding of the impact of HPV vaccination on cervical cancer prevention. The article explores the biology of HPV, emphasizing its association with cervical carcinogenesis and the development of precancerous lesions. It delves into the epidemiology of HPV infection, highlighting the global prevalence and the burden of cervical cancer, particularly in low-resource settings. The socio-economic factors influencing HPV transmission and cervical cancer incidence are also discussed. The focus of the review is on the efficacy and safety of HPV vaccines, including an examination of vaccine types, dosages, and long-term effectiveness. Insights into the immunological responses triggered by vaccination, as well as the duration of protection against HPV infection and associated cancers, are presented. Special attention is given to addressing myths and misconceptions surrounding HPV vaccination, aiming to enhance public awareness and acceptance. Additionally, the review discusses the impact of vaccination programs on population-wide HPV prevalence and the subsequent reduction in cervical cancer rates. It explores challenges related to vaccine accessibility, affordability, and coverage, especially in underserved populations. Strategies for improving vaccine uptake and ensuring equitable distribution are considered, with a focus on empowering women through education and healthcare access. Furthermore, the article touches upon emerging trends in HPV research, such as the development of next-generation vaccines, therapeutic interventions for existing infections, and the potential for global HPV elimination. The integration of HPV vaccination into comprehensive women's health programs is advocated, emphasizing the importance of a holistic approach to cervical cancer prevention. In conclusion, this review provides a multifaceted exploration of HPV vaccination as a pivotal tool in empowering women's health by preventing invasive cervical cancer. The synthesis of current knowledge underscores the need for continued research, education, and global collaboration to ensure the widespread success of HPV vaccination initiatives, ultimately contributing to the advancement of women's health worldwide.

Interpenetrating polymeric network (IPNs) in ophthalmic drug delivery: Breaking the barriers.

To maintain the therapeutic drug concentration for a prolonged period of time in aqueous and vitreous humor is primary challenge for ophthalmic drug delivery. Majority of the locally administered drug into the eye is lost as to natural reflexes like blinking and lacrimation resulting in the short span of drug residence. Consequently, less than 5% of the applied drug penetrate through the cornea and reaches the intraocular tissues. The major targets for optimal ophthalmic drug delivery are increasing drug residence time in cul-de-sac of the eye, prolonging intraocular exposure, modulating drug release from the delivery system, and minimizing pre-corneal drug loss. Development of in situ gel, contact lens, intraocular lens, inserts, artificial cornea, scaffold, etc., for ophthalmic drug delivery are few approaches to achieve these major targeted objectives for delivering the drug optimally. Interpenetrating polymeric network (IPN) or smart hydrogels or stimuli sensitive hydrogels are the class of polymers that can help to achieve the targets in ophthalmic drug delivery due to their versatility, biocompatibility and biodegradability. These novel ''smart" materials can alter their molecular configuration and result in volume phase transition in response to environmental stimuli, such as temperature, pH, ionic strength, electric and magnetic field. Hydrogel and tissue interaction, mechanical/tensile properties, pore size and surface chemistry of IPNs can also be modulated for tuning the drug release kinetics. Stimuli sensitive IPNs has been widely exploited to prepare in situ gelling formulations for ophthalmic drug delivery. Low refractive index hydrogel biomaterials with high water content, soft tissue-like physical properties, wettability, oxygen, glucose permeability and desired biocompatibility makes IPNs versatile candidate for contact lenses and corneal implants. This review article focuses on the exploration of these smart polymeric networks/IPNs for therapeutically improved ophthalmic drug delivery that has unfastened novel arenas in ophthalmic drug delivery.

Advances on nanoformulation approaches for delivering plant-derived antioxidants: A case of quercetin.

Oxidative stress has been implicated in tumorigenic, cardiovascular, neuro-, and age-related degenerative changes. Antioxidants minimize the oxidative damage through neutralization of reactive oxygen species (ROS) and other causative agents. Ever since the emergence of COVID-19, plant-derived antioxidants have received enormous attention, particularly in the Indian subcontinent. Quercetin (QCT), a bio-flavonoid, exists in the glycosylated form in fruits, berries and vegetables. The antioxidant potential of QCT analogs relates to the number of free hydroxyl groups in their structure. Despite presence of these groups, QCT exhibits substantial hydrophobicity. Formulation scientists have tested nanotechnology-based approaches for its improved solubilization and delivery to the intended site of action. By the virtue of its hydrophobicity, QCT gets encapsulated in nanocarriers carrying hydrophobic domains. Apart from passive accumulation, active uptake of such formulations into the target cells can be facilitated through well-studied functionalization strategies. In this review, we have discussed the approaches of improving solubilization and bioavailability of QCT with the use of nanoformulations.

Immunomodulation and Anticancer Immunity: Reviewing the Potential of Probiotics and Their Delivery with Macromolecular Carriers.

Probiotics colonize in the gastrointestinal tract and regulate the homeostasis in healthy human hosts. These protect the host against putrefactive organisms and secrete soluble factors exhibiting important transductive roles. However, constitutive processes in human host are deregulated following dysbiosis caused during prolonged exposure to cytotoxic agents and pollutants. Apart from restoring the homeostasis, probiotic administration has shown to minimize carcinogenesis and post-surgery complications in cancer patients. Moreover, ability of microbial cells to colonize at tumor foci can be harnessed to deliver genes, therapeutic proteins and antibodies in a selective manner. In this review, we have discussed immunomodulatory roles of probiotics in context to cancer prevention. The article further proposes the use of dietary interventions for boosting anticancer immunity and as an alternative to detrimental chemotherapeutic agents. After summarizing clinical evidences on probiotic efficacy, formulation approaches have been described for effective delivery of the microorganisms. The literature shows that polysaccharide matrices can be employed to achieve the survivability of probiotics. Formulation approaches have been reviewed together with the risks associated with the migration of live microorganisms to systemic circulation and their ability of transmitting antibiotic resistance factors into human pathogens.

Non-ionic Surfactants as a P-Glycoprotein(P-gp) Efflux Inhibitor for Optimal Drug Delivery-A Concise Outlook.

Significant research efforts have been devoted to unraveling the mystery of P-glycoprotein(P-gp) in drug delivery applications. The efflux membrane transporter P-gp is widely distributed in the body and accountable for restricting drug absorption and bioavailability. For these reasons, it is the primary cause of developing multidrug resistance (MDR) in most drug delivery applications. Therefore, P-gp inhibitors must be explored to address MDR and the low bioavailability of therapeutic substrates. Several experimental models in kinetics and dynamic studies identified the sensitivity of drug molecules and excipients as a P-gp inhibitor. In this review, we aimed to emphasize nonionic surface-active agents for effective reversal of P-gp inhibition. As it is inert, non-toxic, noncharged, and quickly reaching the cytosolic lipid membrane (the point of contact with P-gp efflux protein) enables it to be more efficient as P-gp inhibitors. Moreover, nonionic surfactant improves drug absorption and bioavailability through the various mechanism, involving (i) association of drug with surfactant improves solubilization, facilitating its cell penetration and absorption; (ii) weakening the lateral membrane packing density, facilitating the passive drug influx; and (iii) inhibition of the ATP binding cassette of transporter P-glycoprotein. The application of nonionic surfactant as P-gp inhibitors is well established and supported by various experiments. Altogether, herein, we have primarily focused on various nonionic surfactants and their development strategies to conquer the MDR-causing effects of P-gp efflux protein in drug delivery. Graphical Abstract.

The Effect of High Temperature on Cardiovascular Autonomic Function Tests in Steel Plant Furnace Worker.

BACKGROUND: The high temperature in the working environment could be one of the risk factors for cardiovascular diseases in steel plant workers. The excessive high temperature at the working place leads to altered autonomic activity and is related to more cardiovascular risk. AIMS AND OBJECTIVES: The effect of high temperature on cardiovascular autonomic function tests in steel plant furnace worker. MATERIAL AND METHOD: This was a case-control study for which 50 steel plant furnace workers and 50 controls were selected. The cardiovascular sympathetic function status in worker and control were analyzed by three tests: (i) Blood pressure (BP) response to sustained isometric handgrip test, (ii) BP response to the cold pressor test, and (iii) BP response to standing from a supine position (orthostasis). Statistical analysis was done by using an independent t-test. RESULTS: Diastolic BP (DBP) response to sustained isometric handgrip and systolic BP (SBP) and DBP response to the cold pressor test showed that the increase BP in workers were more than controls but the difference was not statistically significant (P > 0.05). SBP response to standing from the supine position showed statistically significant (P < 0.001) greater fall in steel plant workers. CONCLUSION: The sympathetic autonomic dysfunction was seen in steel furnace workers in response to environmental stressor-excessive heat.

Eudragit S-100 Surface Engineered Nanostructured Lipid Carriers for Colon Targeting of 5-Fluorouracil: Optimization and In Vitro and In Vivo Characterization.

5-Fluorouracil (5-FU) is the most preferred chemotherapeutic agent in the management of colon cancer but is associated with poor therapeutic efficacy and lack of site specificity. Hence, it was aimed to employ Eudragit S100 surface engineered 5-FU nanostructured lipid carriers for the spatial and temporal release of the drug for the treatment of colon cancer. Hot high-pressure homogenization (HPH) technique was employed in the preparation of 5-FU-NLCs. The optimization of 5-FU-NLCs was performed using a Quality by Design (QbD) approach. A 32 factorial design was employed wherein the relationship between independent variables [amount of oleic acid (X1) and concentration of Tween®80 (X2)] and dependent variables [particle size (Y1) and % entrapment efficiency (Y2)] was studied. Optimized 5-FU-NLCs were surface treated to obtain Eudragit S100-coated 5-FU-NLCs (EU-5-FU-NLCs). The evaluation parameters for 5-FU-NLCs and EU-5-FU-NLCs included surface morphology, particle size, PDI, and zeta potential. In vitro release from EU-5-FU-NLCs revealed a selective and controlled 5-FU release in the colonic region for 24 h. In vitro cytotoxicity (MTT assay) was performed against Caco-2 cancer cells, wherein EU-5-FU-NLCs exhibited a 2-fold greater cytotoxic potential in comparison to a 5-FU solution (5-FU-DS). Oral administration of EU-5-FU-NLCs in Albino Wistar rats depicted a higher Cmax (2.54 folds) and AUC (11 folds) as well as prolonged Tmax (16 folds) and MRT (4.32 folds) compared to 5-FU-DS confirming higher bioavailability along with the spatial and temporal release in the colonic region. Thus, a multifaceted strategy involving abridgement of nanotechnology along with surface engineering is introduced for effective chemotherapy of colon cancer via oral administration of 5-FU with uncompromised safety and higher efficacy.Graphical abstract.

Nanocarriers based on vitamin E-TPGS: Design principle and molecular insights into improving the efficacy of anticancer drugs.

α-Tocopheryl polyethylene glycol succinate (vitamin E-TPGS or TPGS) is a nonionic amphiphile synthesized by the esterification of vitamin E succinate. It has been categorized as a safe excipient by US-FDA and EMA. Like other polyethylene glycol (PEG) condensates, TPGS spontaneously forms kinetically stable core-shell micelles (diameter 12-15 nm) and exhibits interesting properties as solubilizing agent, emulsifier, dispersant and gelling agent. Its aggregation behavior can be tuned in association with other amphiphiles and organic additives. These properties have been exploited for developing a variety of vesicular, semisolid and multi-particulate drug formulations. It improves the bioavailability of drugs through permeation enhancement and down-regulation of P-glycoproteins. Multimodal therapeutic platforms have been explored following its chemical modification with recognizable and stimuli-responsive groups. Research in the past two decades has revealed its specific role in mediating the re-sensitization of multi-drug resistant cancer cells. This review describes the physicochemical and biological properties of TPGS relevant to drug delivery applications. We have emphasized on the role of TPGS in improving the bioavailability and targetability of anticancer drugs.

Self-Association in EO-BO-EO Triblock Copolymers as a Nanocarrier Template for Sustainable Release of Anticancer Drugs.

Ethylene oxide (EO)-butylene oxide (BO)-ethylene oxide (EO)-based triblock copolymers with varying hydrophilic-hydrophobic ratios in arrangement, generally referred to as EBE, were scrutinized in an aqueous environment. Various self-associative (micellization) physicochemical properties of these EBEs were examined at different temperatures unified with a quantum chemical study. The salting-out effect on 5%w/v EBE was examined by observing their aqueous solution behavior where the clear transparent solution/turbidity suggested the probable presence of spherical or ellipsoidal micelles, which was confirmed from the scattering outline. The hydrodynamic radius (Dh) of the formed micellar geometry as a function of temperature and electrolyte (2 M NaCl) was inspected from dynamic light scattering and further supported by small-angle neutron scattering, where the Q-range prototype and scattering parameters were evaluated by the best fitting of the structure factor. Furthermore, these micelles were employed as potential nanocarriers for anticancer (curcumin and quercetin) drugs, where its release profile at a particular time interval was estimated using UV-vis spectroscopy. Different kinetic models were employed to fit the release profile data that enabled this study to act as an ideal platform for drug delivery. Also, the plausible interactions between EO-BO-EO blocks and the anticancer drugs were inferred from the evaluated computational descriptors.

Evaporation of Inclined Drops: Formation of Asymmetric Ring Patterns.

Evaporation of colloidal drops on horizontal surfaces deposits the contained particles at the drop-edge producing radially symmetric ring-like stains. The symmetry in the particle deposition is broken when the drop is placed on a tilted surface due to the influence of gravity on the suspended particles and the drop itself. Using extremely small drops generated by electrospray, we explore cases where different mechanisms of particle transport dominate. We show that the asymmetric residues are formed as the gravity-induced effects compete with the capillary flow. Our results give a broad insight into the pattern formation of evaporating inclined drops.

A cross-sectional study of epidemiological factors related to road traffic accidents in a metropolitan city.

BACKGROUND: Traffic injuries are one of the major causes of morbidity in India. It involves human sufferings in terms of physical, emotional, and financial losses to the individual, family, and the country. A better insight into the epidemiological determinants will help prevent such injuries. OBJECTIVES: To estimate the proportion of fatal and nonfatal accidents and to determine the epidemiological factors related to nonfatal accidents. METHODS: It was a cross-sectional study carried out in a tertiary care hospital over a period of 6 months. A simple random sampling technique was used for the selection of sample size of 476. Nonfatal accident victims were interviewed. RESULTS: The proportion of nonfatal to fatal accidents was found to be 1.8:1. Around 72.9% of drivers did not use any safety measure while driving. Two-wheelers (39%) and light motor vehicles (28.3%) were mostly involved, 45% of drivers had speed more than 60 km/h. Obstacles in the road (41%), defective roads (36.5%), and poor street lighting (11.4%) were reported as contributing factors of the accident. Lower extremities and head neck and face were involved in 47.2% and 27.1% of cases, respectively. Around 40.4% of cases had a single-site fracture. CONCLUSION: Traffic injuries result from the interaction between agent, host, and environmental factors. Preventing these interactions is very well possible with little extra care given towards road safety and traffic behavior of individuals.

Effect of cosurfactant addition on phase behavior and microstructure of a water dilutable microemulsion.

This study reports a detailed characterization of a nonionic microemulsion (µE) composed of n-butylacetate/α-tocopheryl polyethylene glycol succinate (TPGS)/alcohol/water. Two approaches of expanding the monophasic area were explored; (i) addition of Pluronic® 123 (P123) in aqueous phase, and (ii) use of short chain alcohol (CnHn+1OH; n = 2-4) as cosurfactant. Pseudo-ternary phase diagrams were constructed using water titration method. Characterizations were performed using dynamic light scattering (DLS), differential scanning calorimetry (DSC), small angle neutron scattering (SANS) and electron microscopic techniques. DSC and SANS results showed gradual structural transformation from water-in-oil to oil-in-water system. The optimized formulation (oil/Smix/water - 19/40/41) showed average hydrodynamic diameter of 22 nm, consistent with electron microscopic observations. Ethanol (EtOH), with its high fluidity and smaller headgroup area, offered maximum expansion in the phase boundary. Surfactant unimers, derived from EtOH-driven de-micellization, reinforced the interface and solubilized the incoming oil molecules. Oil incorporation was accompanied with improved loading of carbamazepine, a hydrophobic drug. Except marginal swelling, no significant microstructural changes were noticed during water dilution (≈90%) and salt addition (0.9% NaCl) in the optimized µE formulation. A linear increase in oil incorporation was noticed upon adding propylene glycol as a cosolvent.

Bioadhesive polymeric film-based integrative platform for the unidirectional carbamazepine release from a volatile microemulsion.

Carbamazepine (CBZ) shows inconsistent absorption primarily due to its poor dissolution rate. In this study, we describe a bioadhesive polymeric film, embedded with microemulsion (ME), as a tool to enable improved CBZ dissolution and achieve sustained release. The ME was formulated using pseudo-ternary components; water, oil (n-butyl acetate), surfactant (tocopheryl polyethylene glycol 1000 succinate, TPGS) and cosurfactant (1,4-butanediol). The region at surfactant to co-surfactant ratio of 1:1 was characterized using dynamic light scattering, small angle neutron scattering and differential scanning calorimetry. Scattering studies showed that size distribution did not change upon water addition and temperature. Optimized ME composition containing CBZ was embedded into bioadhesive films composed with a backing layer. We successfully demonstrate the confinement of CBZ-ME into the film matrix and thereupon, the achievement of unidirectional sustained drug release up to 8 h. Our further investigations are directed over testing the system for localized drug delivery applications.

Tumor suppressive miRNA-34a suppresses cell proliferation and tumor growth of glioma stem cells by targeting Akt and Wnt signaling pathways.

MiRNA-34a is considered as a potential prognostic marker for glioma, as studies suggest that its expression negatively correlates with patient survival in grade III and IV glial tumors. Here, we show that expression of miR-34a was decreased in a graded manner in glioma and glioma stem cell-lines as compared to normal brain tissues. Ectopic expression of miR-34a in glioma stem cell-lines HNGC-2 and NSG-K16 decreased the proliferative and migratory potential of these cells, induced cell cycle arrest and caused apoptosis. Notably, the miR-34a glioma cells formed significantly smaller xenografts in immuno-deficient mice as compared with control glioma stem cell-lines. Here, using a bioinformatics approach and various biological assays, we identify Rictor, as a novel target for miR-34a in glioma stem cells. Rictor, a defining component of mTORC2 complex, is involved in cell survival signaling. mTORC2 lays downstream of Akt, and thus is a direct activator of Akt. Our earlier studies have elaborated on role of Rictor in glioma invasion (Das et al., 2011). Here, we demonstrate that miR34a over-expression in glioma stem cells profoundly decreased levels of p-AKT (Ser473), increased GSK-3ß levels and targeted for degradation ß-catenin, an important mediator of Wnt signaling pathway. This led to diminished levels of the Wnt effectors cyclin D1 and c-myc. Collectively, we show that the tumor suppressive function of miR-34a in glioblastoma is mediated via Rictor, which through its effects on AKT/mTOR pathway and Wnt signaling causes pronounced effects on glioma malignancy.

Pulmonary function tests in stone crushers.

A cross-sectional type of observational study was conducted at 7 various stone crusher units on 120 male stone crushers and 120 healthy male controls. Values of FEF25-27% and PEFR were recorded on computerized spirometer and were compared between workers and age matched controls group. The value of FEF25-75% and PEFR was significantly reduced in stone crushers as compared to controls. Also as the duration of exposure increases the values of flow rates goes on decreasing among workers. Stone crushers of Marathwada region of Maharashtra exposed to silica dust were prone to develop lung disorders as indicated by reduced value of FEF25-75% and PEFR.

MiR-145 functions as a tumor-suppressive RNA by targeting Sox9 and adducin 3 in human glioma cells.

BACKGROUND: MicroRNAs (miRNAs) are increasingly being recognized as being involved in cancer development and progression in gliomas. METHODS: Using a model cell system developed in our lab to study glioma progression comprising human neuroglial culture (HNGC)-1 and HNGC-2 cells, we report here that miR-145 is one of the miRNAs significantly downregulated during malignant transformation in glioblastoma multiforme (GBM). In a study using tumor samples derived from various glioma grades, we show that expression of miR-145 is decreased in a graded manner, with GBM patients showing lowest expression relative to lower-grade gliomas (P < .05) and normal brain tissues (P < .0001). Functional studies involving ectopic expression of miR-145 in glioma cells had a negative impact on cell proliferation and tumor development, as well as invasion and induced apoptosis, providing further support to the concept that inactivation of miR-145 is important for glioma disease pathogenesis. More notably, these growth-suppressive effects of miR-145 are mediated through its target proteins Sox9 and the cell adhesion-associated molecule adducin 3 (ADD3). RESULTS: Inhibiting Sox9 and ADD3 rescued effects of miR-145 loss. Interestingly, miR-145 loss in glioma cells led to overexpression of molecules involved in cell proliferation, like cyclin D1, c-myc, and N-myc, as well as enhanced expression of cell adhesion- and invasion-related molecules N-cadherin and E-cadherin, an effect which was again restored upon miR-145 overexpression in glioma cells. The miR-145 promoter was methylated at its cytosine-phosphate-guanine (CpG) islands in the glioma cell lines studied. CONCLUSION: Our study demonstrates that miR-145 has a tumor-suppressive function in glioblastoma in that it reduces proliferation, adhesion, and invasion of glioblastoma cells, apparently by suppressing the activity of oncogenic proteins Sox9 and ADD3. Reduced levels of miR-145 may lead to neoplastic transformation and malignant progression in glioma due to unregulated activity of these proteins.

Wnt3a mediated activation of Wnt/ß-catenin signaling promotes tumor progression in glioblastoma.

Presence of a distinct population of cells that drives tumor progression supports the hierarchical model of tumor development in Glioblastoma (GBM) and substantiates the cancer stem cell hypothesis. Amongst the various developmental signaling pathways that are aberrantly activated, we here show that activated Wnt/ß-catenin signaling pathway plays a critical role in malignant transformation and tumor progression in gliomas. We demonstrate that Wnt ligands - Wnt1 and Wnt3a are expressed in a graded manner in these tumors as well as over-expressed in glioma stem cell-lines. A selective inhibition of Wnt signaling pathway by selective knock-down of its ligands Wnt1 and Wnt3a in glioma-derived stem-like cells led to decreased cell proliferation, cell migration and chemo-resistance. Furthermore, Wnt silencing in glioma cells reduced the capacity to form intra-cranial tumors in vivo. Taken together, our study indicates Wnt/ß-catenin signaling pathway as an essential driver of glioma tumorigenesis, recognizing role of Wnt3a as an oncogene and thereby offering novel therapeutic strategies for management of these tumors.