University of Kerala

New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive "smart" MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

More than 2.5 billion people on the globe rely on groundwater for drinking and providing high-quality drinking water has become one of the major challenges of human society. Although groundwater is considered as safe, high concentrations of heavy metals like arsenic (As) can pose potential human health concerns and hazards. In this paper, we present an overview of the current scenario of arsenic contamination of groundwater in various countries across the globe with an emphasis on the Indian Peninsula. With several newly affected regions reported during the last decade, a significant increase has been observed in the global scenario of arsenic contamination. It is estimated that nearly 108 countries are affected by arsenic contamination in groundwater (with concentration beyond maximum permissible limit of 10 ppb recommended by the World Health Organization. The highest among these are from Asia (32) and Europe (31), followed by regions like Africa (20), North America (11), South America (9) and Australia (4). More than 230 million people worldwide, which include 180 million from Asia, are at risk of arsenic poisoning. Southeast Asian countries, Bangladesh, India, Pakistan, China, Nepal, Vietnam, Burma, Thailand and Cambodia, are the most affected. In India, 20 states and 4 Union Territories have so far been affected by arsenic contamination in groundwater. An attempt to evaluate the correlation between arsenic poisoning and aquifer type shows that the groundwater extracted from unconsolidated sedimentary aquifers, particularly those which are located within the younger orogenic belts of the world, are the worst affected. More than 90% of arsenic pollution is inferred to be geogenic. We infer that alluvial sediments are the major source for arsenic contamination in groundwater and we postulate a strong relation with plate tectonic processes, mountain building, erosion and sedimentation. Prolonged consumption of arsenic-contaminated groundwater results in severe health issues like skin, lung, kidney and bladder cancer; coronary heart disease; bronchiectasis; hyperkeratosis and arsenicosis. Since the major source of arsenic in groundwater is of geogenic origin, the extend of pollution is complexly linked with aquifer geometry and aquifer properties of a region. Therefore, remedial measures are to be designed based on the source mineral, climatological and hydrogeological scenario of the affected region. The corrective measures available include removing arsenic from groundwater using filters, exploring deeper or alternative aquifers, treatment of the aquifer itself, dilution method by artificial recharge to groundwater, conjunctive use, and installation of nano-filter, among other procedures. The vast majority of people affected by arsenic contamination in the Asian countries are the poor who live in rural areas and are not aware of the arsenic poisoning and treatment protocols. Therefore, creating awareness and providing proper medical care to these people remain as a great challenge. Very few policy actions have been taken at international level over the past decade to reduce arsenic contamination in drinking water, with the goal of preventing toxic impacts on human health. We recommend that that United Nations Environment Programme (UNEP) and WHO should take stock of the global arsenic poisoning situation and launch a global drive to create awareness among people/medical professionals/health workers/administrators on this global concern.

A comprehensive methodology that integrates Revised Universal Soil Loss Equation (RUSLE) model and Geographic Information System (GIS) techniques was adopted to determine the soil erosion vulnerability of a forested mountainous sub-watershed in Kerala, India. The spatial pattern of annual soil erosion rate was obtained by integrating geo-environmental variables in a raster based GIS method. GIS data layers including, rainfall erosivity (R), soil erodability (K), slope length and steepness (LS), cover management (C) and conservation practice (P) factors were computed to determine their effects on average annual soil loss in the area. The resultant map of annual soil erosion shows a maximum soil loss of 17.73 t h-1 y-1 with a close relation to grass land areas, degraded forests and deciduous forests on the steep side-slopes (with high LS). The spatial erosion maps generated with RUSLE method and GIS can serve as effective inputs in deriving strategies for land planning and management in the environmentally sensitive mountainous areas.

Vascular endothelial growth factor-A (VEGF-A) is essential for endothelial cell functions associated with angiogenesis. Signal transduction networks initiated by VEGFA/VEGFR2, the most prominent ligand-receptor complex in the VEGF system, leads to endothelial cell proliferation, migration, survival and new vessel formation involved in angiogenesis. Considering its biomedical importance, we have developed the first comprehensive map of endothelial cell-specific signaling events of VEGFA/VEGFR2 system pertaining to angiogenesis. Screening over 20,000 published research articles and following the post-translational modification (PTM) and site specificity of VEGFR2, we have documented 240 proteins and their diverse PTM-dependent reactions involved in VEGFA/VEGFR2 signal transduction. From the ligand-receptor complex, this map has been extended to the level of major transcriptionally regulated genes for which the signaling cascades leading to their transcription factors are reported. We believe that this map would serve as a novel platform for reference, integration, and representation and more significantly, the progressive analysis of dynamic features of VEGF signaling in endothelial cells including their cross-talks with other ligand-receptor systems involved in angiogenesis.

The synthesis of Zinc oxide nanoparticles using a plant-mediated approach is presented in this paper. The nanoparticles were successfully synthesized using the Nitrate derivative of Zinc and plant extract of the indigenous medicinal plant Cayratia pedata. 0.1 mM of Zn (NO3)2.6H2O was made to react with the plant extract at different concentrations, and the reaction temperature was maintained at 55 °C, 65 °C, and 75 °C. The yellow coloured paste obtained was wholly dried, collected, and packed for further analysis. In the UV visible spectrometer (UV–Vis) absorption peak was observed at 320 nm, which is specific for Zinc oxide nanoparticles. The characterization carried out using Field Emission Scanning Electron Microscope (FESEM) reveals the presence of Zinc oxide nanoparticles in its agglomerated form. From the X-ray diffraction (XRD) pattern, the average size of the nanoparticles was estimated to be 52.24 nm. Energy Dispersive Spectrum (EDX) results show the composition of Zinc and Oxygen, giving strong energy signals of 78.32% and 12.78% for Zinc and Oxygen, respectively. Fourier Transform - Infra-Red (FT-IR) spectroscopic analysis shows absorption peak of Zn–O bonding between 400 and 600 cm−1. The various characterization methods carried out confirm the formation of nano Zinc oxide. The synthesized nanoparticles were used in the immobilization of the enzyme Glucose oxidase. Relative activity of 60% was obtained when Glucose oxidase was immobilized with the green synthesized ZnO nanoparticles. A comparative study of the green synthesized with native ZnO was also carried out. This green method of synthesis was found to be cost-effective and eco-friendly.

UNLABELLED: It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and impaired delivery/efficacy of chemotherapeutics through reduced perfusion. Genetic and pharmacologic inhibition of angiotensin-II type-1 receptor reverses obesity-augmented desmoplasia and tumor growth and improves response to chemotherapy. Augmented activation of pancreatic stellate cells (PSC) in obesity is induced by tumor-associated neutrophils (TAN) recruited by adipocyte-secreted IL1β. PSCs further secrete IL1β, and inactivation of PSCs reduces IL1β expression and TAN recruitment. Furthermore, depletion of TANs, IL1β inhibition, or inactivation of PSCs prevents obesity-accelerated tumor growth. In patients with pancreatic cancer, we confirmed that obesity is associated with increased desmoplasia and reduced response to chemotherapy. We conclude that cross-talk between adipocytes, TANs, and PSCs exacerbates desmoplasia and promotes tumor progression in obesity. SIGNIFICANCE: Considering the current obesity pandemic, unraveling the mechanisms underlying obesity-induced cancer progression is an urgent need. We found that the aggravation of desmoplasia is a key mechanism of obesity-promoted PDAC progression. Importantly, we discovered that clinically available antifibrotic/inflammatory agents can improve the treatment response of PDAC in obese hosts. Cancer Discov; 6(8); 852-69. ©2016 AACR.See related commentary by Bronte and Tortora, p. 821This article is highlighted in the In This Issue feature, p. 803.

Groundwater is an essential and vital component of any life support system. It is not only the basic need for human existence but also a vital input for all development activities. The present hydro-geochemical study was confined to the coastal belt of Alappuzha district, which lies in the coastal lowland division of Kerala. Groundwater quality and its suitability for irrigation and domestic purpose were examined by various physico-chemical parameters such as pH, electrical conductivity, total dissolved solids, total hardness, calcium, magnesium, sodium, potassium, bicarbonate, sulfate, and chloride. These parameters were used to assess the suitability of groundwater for domestic purpose by comparing with the WHO and Indian standards. TDS, sodium adsorption ratio (SAR), and permeability index were used for irrigation suitability assessment. The sample analysis reveals that the groundwater is not entirely fit for drinking with respect to pH, EC, Ca2+, Mg2+, Na+, and Cl−. In some of the collected samples, the concentrations of these parameters exceed the permissible limits of WHO and ISI standards. Based on TDS and SAR almost all samples are suitable for irrigation purpose except a few locations, which show values beyond the permissible limits. Ca–Mg–HCO3 is the dominant water type in the study area. The sequence of the abundance of the major cations and anions is Ca > Na > Mg > K = HCO3 > Cl > SO4. Based on the total hardness and TDS, 96 % of groundwater samples are found suitable for drinking purpose.

Motivation drives most human activities, including foreign language learning, and it is affected by several intrinsic and extrinsic factors. This study investigated how ChatGPT impacts learning English. A quantitative research design was used to collect data from 80 teachers and students who had access to the ChatGPT in its very beginning phase in early 2023. The sample, selected in a non-probability sampling technique, responded to an online questionnaire. Findings showed that ChatGPT generally motivates learners to develop reading and writing skills. The respondents had neutral attitudes towards the effect of ChatGPT on developing listening and speaking skills. The findings suggest that ChatGPT-based teaching is motivational. ChatGPT should be used as a learning tool instead of fearing its negative impacts, which require further detailed investigations. Further research is required to explore more advantages of ChatGPT for other aspects of the language and illuminate its negative effects to help educators reduce them in English programs.

S-allyl cysteine sulphoxide (SACS), a sulphur containing amino acid of garlic which is the precursor of allicin and garlic oil, has been found to show significant antidiabetic effects in alloxan diabetic rats. Administration of it at a dose of 200 mg/kg body weight decreased significantly the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase and liver glucose-6-phosphatase. It increased significantly liver and intestinal HMG CoA reductase activity and liver hexokinase activity.

Road accident hot spots are evaluated and delineated in a South Indian city where inadequate development of land transport network often leads to traffic congestion and accidents. The patterns of localization and distribution of hotspots are examined with the help of geo-information technology to bring out the influence of spatial and/or temporal factors in their formation. Assessment of spatial clustering of accidents and hotspots spatial densities was carried out following Moran's I method of spatial autocorrelation, Getis-Ord Gi* statistics and point Kernel density functions. The accidents as a whole show a clustered nature while the comparison of spatio-temporal break ups indicates random distribution in certain classes. The Kernel density surface, estimated from the results of hotspot analysis delineates the road stretches as well as isolated zones where the hotspots are concentrated. The results can be effectively used by various agencies for adopting better planning and management strategies for improved traffic conditions as well as accident reduction.

Groundwater pollution by fluoride is one of the prime concerns of the world population due to its toxicity, which results in adverse health impacts. In this paper, we review the current scenario of the fluoride contamination of groundwater in various countries across the globe and its impact on human health. During the last decade, several newly affected regions have been reported all over the world, with more than 100 countries affected by fluoride contamination in groundwater (concentration exceeding the acceptable limit of 1.5 mg/L defined by the World Health Organization). Fluoride poisoning is mainly due to the unsupervised ingestion of products for dental and oral hygiene and over-fluoridated drinking water. It is estimated that more than 200 million people from different countries are affected by fluoride-related groundwater issues and health problems. The highest among these are from the countries in Africa (38), Asia (28), and Europe (24), followed by countries like South America (5), North America (3), and Australia (2). The source of fluoride in drinking water is primarily geogenic, together with forage, grasses and grains, tea, and anthropogenic sources. These countries affected were correlated with climatic zones and geological factors to gain insights into geospatial relations. Our analyses show that most of the fluoride pollution-prone zones are located in high-grade metamorphic terranes with granitoid or alkaline intrusions, geothermal hot springs, and volcanic regions with arid or semi-arid climatic conditions. This study also finds that children across the globe are more vulnerable than adults to fluoride contamination. The review finds that, although there are efficient fluoride removal techniques, including filters with next-generation nanomaterials, to date, there has not been a single technique developed that can claim to be a practically robust solution for fluoride removal from drinking water. Therefore, we suggest developing next-generation filters that can retain essential minerals in water and remove only harmful ones and selecting purification technologies according to need, climate, geology, and geographic location. The findings from our review would help policymakers take effective and sustainable measures for safe water supply in the affected areas. Within the framework of the Sustainable Development Goals (SDGs), particularly SDG 3 (Good Health and Well-being) and SDG 6 (Clean Water and Sanitation), this study emphasizes the critical role of fluoride as a key indicator. It underscores the imperative of addressing elevated fluoride levels in drinking water, particularly in African and Asian countries, to achieve the overarching objective of universal and equitable access to safe, affordable, and uncontaminated drinking water for global society by the targeted year of 2030.

Onion and garlic contain many sulfur containing active principles mainly in the form of cysteine derivatives, viz. S-alkyl cysteine sulfoxides which decompose into a variety of thiosulfinates and polysulfides by the action of an enzyme allinase on extraction. Decomposed products are volatile and present in the oils of onion and garlic. They possess antidiabetic, antibiotic, hypocholesterolaemic, fibrinolytic and various other biological actions. In addition to free sulfoxides in alliums, there are nonvolatile sulfur-containing peptides and proteins which possess various activities and thus make these vegetables as an important source of therapeutic agents. As allyl and related sulfoxides are inhibiting thiol group enzymes, alliums are to be used only in limited quantities.

It is well-known that on an inverse semigroup S the relation ≦ defined by a ≦ b if and only if aa −1 = ab −1 is a partial order (called the natural partial order) on S and that this relation is closely related to the global structure of S (cf. ( 1 , §7.1), ( 10 )). Our purpose here is to study a partial order on regular semigroups that coincides with the relation defined above on inverse semigroups. It is found that this relation has properties very similar to the properties of the natural partial order on inverse semigroups. However, this relation is not, in general, compatible with the multiplication in the semigroup. We show that this is true if and only if the semigroup is pseudo-inverse (cf. ( 8 )). We also show how this relation may be used to obtain a simple description of the finest primitive congruence and the finest completely simple congruence on a regular semigroup.

Removal of cadmium(II) from aqueous solutions was studied using steam activated sulphurised carbon (SA-S-C) prepared from bagasse pith (a sugar-cane industry waste). Batch adsorption experiments were performed as a function of solute concentration, contact time, adsorbent dose, pH, temperature and ionic strength. The maximum removal took place in the pH range of 5.0 to 9.0. The maximum adsorption of 98.8 % (24.70 mg/g) took place by SA-S-C with 8.9 % sulphur content at pH 6.0 from an initial Cd(II) concentration of 50 mg/dm3. The sorption process follows pseudo-second-order kinetics. Kinetic parameters as a function of initial concentration and temperature were determined to predict the adsorption behaviour of Cd(II) onto SA-S-C. Decrease in ionic strength of the solution was found to improve the adsorption capacity of the adsorbent. The equilibrium data could be best fitted by the Langmuir adsorption isotherm equation over the entire concentration range (50 to 1 000 mg/dm3). The effectiveness of the SA-S-C for Cd(II) removal was examined and compared with other adsorbents reported in the literature. At solution pH of 6.0, the maximum adsorption capacity of SA-S-C calculated by the Langmuir isotherm is 149.93 mg/g at 30°C. Acid regeneration was tried for several cycles with a view to recover the sorbed metal ions and also to restore the sorbent to its original state. Keywords: Adsorption dynamics , Langmuir equation, Cd(II) removal, Sulphurised carbon, Desorption (WaterSA: 2003 29(2): 147-156)

Nanostructured nickel oxide thin films were prepared by the pulsed laser ablation technique. The effects of annealing on the structural, morphological, electrical and optical properties are discussed. Phase imaging was used to examine the surface contaminants, adhesion and hardness and height imaging to evaluate the height profile of the films. Morphological investigations using atomic force microscopy and scanning electron microscopy indicate a strong influence of the annealing process on the surface roughness and particle size. A self-assembly of nanocrystals agglomerating together to form an island-like structure is observed in films annealed at 773 K. X-ray diffraction and x-ray photoelectron spectroscopy investigations indicate the presence of Ni2O3 in the as-deposited films. A transformation to cubic NiO with growth along (111) and (200) planes with increase of annealing temperature is also observed.

In this paper, a revision for the existing method of locating exons by genomic signal processing technique employing four binary indicator sequences is presented. The existing method relies on the pronounced period three peaks observed in the Fourier power spectrum of the exon regions which are absent in non-coding regions. The authors have abandoned the four sequences all together and adopted a single 'EIIP indicator sequence' which is formed by substituting the electron-ion interaction pseudopotentials (EIIP) of the nucleotides A, G, C and T in the DNA sequence, reducing the computational overhead by 75%. The power spectrum of this sequence reveals period three peaks for exon regions. Also a number of exons have been identified which exhibit period three peaks when mapped to 'EIIP indicator sequence' and which do not show the same when the binary indicator sequences are employed. We could get better discrimination between exon areas and non-coding areas of a number of genomes when the sequences are mapped to EIIP indicator sequences and the power spectra of the same are taken in a sliding Kaiser window, compared to the existing method using a rectangular window which utilizes binary indicator sequences.

A physical mechanism of the positive ionospheric storms at low latitudes and midlatitudes is presented through multi‐instrument observations, theoretical modeling, and basic principles. According to the mechanism, an equatorward neutral wind is required to produce positive ionospheric storms. The mechanical effects of the wind (1) reduce (or stop) the downward diffusion of plasma along the geomagnetic field lines, (2) raise the ionosphere to high altitudes of reduced chemical loss, and hence (3) accumulate the plasma at altitudes near and above the ionospheric peak centered at around ±30° magnetic latitudes. Daytime eastward prompt penetration electric field (PPEF), if it occurs, also shifts the equatorial ionization anomaly crests to higher than normal latitudes, up to approximately ±30° latitudes. The positive ionospheric storms are most likely in the longitudes where the onset of the geomagnetic storms falls in the ionization production dominated morning‐noon local time sector when the plasma accumulation due to the mechanical effects of the wind largely exceeds the plasma loss due to the chemical effect of the wind. The mechanism agrees with the multi‐instrument observations made during the supergeomagnetic storm of 7–8 November 2004, with 18 h long initial phase (IP) and 10 h long main phase (MP). The observations, which are mainly in the Japanese‐Australian longitudes where the MP onset was in the morning (0600 LT, 2100 UT), show (1) strong positive ionospheric storms (in Ne, Nmax, hmax, Global Positioning System–total electron content (GPS‐TEC), and 630 nm airglow intensity) in both Northern and Southern hemispheres started at the morning (0600 LT) MP onset and lasted for a day, (2) repeated occurrence of strong eastward PPEF events penetrated after the MP onset and superposed with westward electric field started before the MP onset, and (3) storm time equatorward neutral winds (inferred from 1 and 2). Repeated occurrence of an unusually strong F 3 layer with large density depletions around the equator was also observed during the morning‐noon MP.

Revised Universal Soil Loss Equation (RUSLE) model coupled with transport limited sediment delivery (TLSD) function was used to predict the longtime average annual soil loss, and to identify the critical erosion-/deposition-prone areas in a tropical mountain river basin, viz., Muthirapuzha River Basin (MRB; area = 271.75 km2), in the southern Western Ghats, India. Mean gross soil erosion in MRB is 14.36 t ha−1 yr−1, whereas mean net soil erosion (i.e., gross erosion–deposition) is only 3.60 t ha−1 yr−1 (i.e., roughly 25% of the gross erosion). Majority of the basin area (∼86%) experiences only slight erosion (<5 t ha−1 yr−1), and nearly 3% of the area functions as depositional environment for the eroded sediments (e.g., the terraces of stream reaches, the gentle plains as well as the foot slopes of the plateau scarps and the terrain with concordant summits). Although mean gross soil erosion rates in the natural vegetation belts are relatively higher, compared to agriculture, settlement/built-up areas and tea plantation, the sediment transport efficiency in agricultural areas and tea plantation is significantly high, reflecting the role of human activities on accelerated soil erosion. In MRB, on a mean basis, 0.42 t of soil organic carbon (SOC) content is being eroded per hectare annually, and SOC loss from the 4th order sub-basins shows considerable differences, mainly due to the spatial variability in the gross soil erosion rates among the sub-basins. The quantitative results, on soil erosion and deposition, modelled using RUSLE and TLSD, are expected to be beneficial while formulating comprehensive land management strategies for reducing the extent of soil degradation in tropical mountain river basins.

Single crystalline nickel ferrite (NiFe2O4) which has an inverse spinel structure is reported to exhibit a mixed spinel structure when its grain size is reduced to nanometer range. It is known that structural transformations in the nanosize regime are not akin to those of bulk crystals. Additionally, magnetic properties like superparamagnetism and contribution to it by surface layers are critically influenced by the synthesis route of the samples. In this article, we present an investigation on the structural transformation of nanostructured NiFe2O4 using x-ray diffraction (XRD), Mössbauer and magnetization measurements, and Fourier transform infrared (FTIR) and micro-Raman spectroscopy. Nanostructured NiFe2O4 samples were synthesized by a coprecipitation technique followed by thermal processing. Four samples having average grain sizes 13, 20, 26, and 51 nm were synthesized. XRD results confirmed the samples to be nanostructured NiFe2O4 and gave evidence for the mixed spinel structure of the samples of lower grain sizes. Mössbauer study of the smallest and largest grain-sized samples revealed surface spin canting and change in coordination of the iron ions at tetrahedral and octahedral sites with reduction in grain size. The spin canting angle and the coordination factor were determined from the Mössbauer spectra. Vibrating sample magnetometer measurements gave a lower value of magnetization for the samples of lowest grain size and this observation could be explained on the basis of a structural transformation of the sample from inverse to mixed spinel. FTIR and micro-Raman spectroscopic studies also yielded convincing evidence for a transformation of the structure. The results of the present study lead to the inference that the properties of nanosized NiFe2O4 particle emerged from a transformation of their structure from inverse spinel structure to mixed spinel.

Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment. Mouse models revealed that obesity impairs the effects of anti-VEGF on angiogenesis, tumor growth, and metastasis. In one murine BC model, obesity was associated with increased IL-6 production from adipocytes and myeloid cells within tumors. IL-6 blockade abrogated the obesity-induced resistance to anti-VEGF therapy in primary and metastatic sites by directly affecting tumor cell proliferation, normalizing tumor vasculature, alleviating hypoxia, and reducing immunosuppression. Similarly, in a second mouse model, where obesity was associated with increased FGF-2, normalization of FGF-2 expression by metformin or specific FGF receptor inhibition decreased vessel density and restored tumor sensitivity to anti-VEGF therapy in obese mice. Collectively, our data indicate that obesity fuels BC resistance to anti-VEGF therapy via the production of inflammatory and angiogenic factors.