Impact of root canal preparation using two single-file systems on the intra-radicular microbiome of teeth with primary apical periodontitis.

OBJECTIVES: This study aimed to describe the effects of two single-file systems on the diversity of the endodontic microbiome of teeth with primary asymptomatic apical periodontitis. MATERIALS AND METHODS: The root canals from single-rooted teeth with apical periodontitis were prepared using either the Reciproc Blue (RB) or the XP-endo Shaper (XPS) instrument system. The latter was followed by a supplementary step with the XP-endo Finisher (XPF) instrument. For irrigation, 5.25% sodium hypochlorite was used. Root canal samples were taken at the baseline (S1), after preparation (S2), and after the supplementary step (S3). DNA was extracted and subjected to high-throughput sequencing using the MiSeq Illumina platform. RESULTS: Samples from 10 teeth from the RB and 7 from the XPS group were subjected to DNA sequencing. Initial samples differed significantly from post-preparation samples in bacterial diversity, with no significant difference when comparing the two instrument systems. The most dominant phyla in S2 were Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, and Actinobacteria. The same phyla were found to dominate baseline samples and samples taken after using XPF, but with differences in the ranking of the most dominant ones. At the genus level, the most dominant genera identified after RB instrumentation were Bacteroidaceae [G-1], Fusobacterium, and Staphylococcus, while the most dominant genera after XPS instrumentation were Fusobacterium and Porphyromonas. These genera were also dominant in the initial samples. CONCLUSIONS: Both treatment protocols had measurable effects on the root canal microbial diversity, with no significant differences between them. Most of the dominant taxa involved in the primary infection and probably in the aetiology of apical periodontitis were eliminated or substantially reduced. CLINICAL RELEVANCE: The most dominant taxa that persisted after instrumentation were Fusobacterium, Porphyromonas, Staphylococcus, and Bacteroidaceae [G-1].

How I do it: brainwashing for purulent ventriculitis.

BACKGROUND: The management of ventriculitis remains controversial, with no single management strategy that can provide a good outcome. There are few articles describing the brainwashing technique, and most for neonatal intraventricular hemorrhage. This technical note is important because it describes a practical way to perform brainwashing in case of ventriculitis, and it is more feasible compared to endoscopic lavage in developing countries. METHOD: We describe in a stepwise fashion the surgical technique of ventricular lavage. CONCLUSION: Ventricular lavage is a neglected technique that can help to improve ventricular infection and hemorrhage prognosis.

Use of technology in endodontics by undergraduate dental students in a south-eastern state of Brazil.

INTRODUCTION: This study aimed to determine the level of incorporation of current technologies for endodontic treatment in undergraduate dentistry courses in a south-eastern state of Brazil. METHODS: For data collection, a self-assessment-based online questionnaire was created using the "Google Forms" platform, consisting of 12 multiple-choice and a few open-ended questions. The questions were related to the use of current technologies for diagnosis, imaging, use of ultrasonics in endodontics, instrumentation, use of apex locator, microscopy, photodynamic therapy and thermoplastic techniques during endodontic treatment. The questionnaire was sent to 54 dental schools in Minas Gerais. RESULTS: The results show low technological incorporation during the various stages of endodontic treatment by undergraduate students in dentistry courses in Minas Gerais. CONCLUSION: Despite the availability of several technologies to help perform different stages of endodontic treatment, it was observed that most universities do not teach the use of these technologies. Additional studies are needed to correlate how the lack of incorporation of these technologies could impact on the quality of the endodontic learning for undergraduate students.

Synthesis of Fe2SiO4-Fe7Co3 Nanocomposite Dispersed in the Mesoporous SBA-15: Application as Magnetically Separable Adsorbent.

The mixture containing alloy and oxide with iron-based phases has shown interesting properties compared to the isolated species and the synergy between the phases has shown positive effect on dye adsorption. This paper describes the synthesis of Fe2SiO4-Fe7Co3-based nanocomposite dispersed in Santa Barbara Amorphous (SBA)-15 and its application in dye adsorption followed by magnetic separation. Thus, it was studied the variation of reduction temperature and amount of hydrogen used in synthesis and the effect of these parameters on the physicochemical properties of the iron and cobalt based oxide/alloy mixture, as well as the methylene blue adsorption capacity. The XRD and Mössbauer results, along with the temperature-programmed reduction (TPR) profiles, confirmed the formation of Fe2SiO4-Fe7Co3-based nanocomposites. Low-angle XRD, N2 isotherms, and TEM images show the formation of the SBA-15 based mesoporous support with a high surface area (640 m2/g). Adsorption tests confirmed that the material reduced at 700 °C using 2% of H2 presented the highest adsorption capacity (49 mg/g). The nanocomposites can be easily separated from the dispersion by applying an external magnetic field. The interaction between the dye and the nanocomposite occurs mainly by π-π interactions and the mixture of the Fe2SiO4 and Fe7Co3 leads to a synergistic effect, which favor the adsorption.

Catalytic dehydration of glycerol over Cu-Fe-Al-based oxides: understanding changes in active sites throughout the reaction.

The glycerol conversion into acetol using Fe, Al and Cu-based oxides was investigated. XRD results indicate the formation of nanosized particles with high phase dispersion, however, Raman, Mössbauer, 27Al NMR and XPS spectroscopies suggest the presence of iron(iii) oxide, Al2O3 and CuO phases. The FTIR with pyridine adsorption revealed high Lewis acidity. The TPR profile showed the reduction temperature range for the Fe3+ and Cu2+ sites, indicating the suitable condition for pretreatment. The N2 adsorption-desorption isotherms indicated the presence of micro-mesopores with interesting textural properties and specific area varying between 71 and 220 m2 g-1, while the porous morphology was observed by SEM and TEM images. The optimized catalytic tests showed glycerol conversion of 60% and acetol selectivity of 92% with 17% of coke according to TG profile. The recycling tests confirmed the efficiency of the solid, reaching 28% conversion and 91% acetol selectivity after four reuses and, after reactivation in an oxidizing atmosphere, the catalytic performance obtained results close to the second reuse. The interaction between the different Lewis acid sites involved in the mechanisms for the acetol and coke formation on the catalyst surface is discussed. The charge distribution represented by colors which indicates the acid-base surface was evaluated by a simple theoretical-computational study based on the DFT approach. The synergy between the active sites indicates that the presence of Cu0/Cu+ drastically increases the acetol selectivity which is a more important characteristic than the high Lewis acidity of Fen+ and Al3+.

Limitations and Management of Static-guided Endodontics Failure.

Endodontic treatment in severely calcified canals is always a challenging task because it can result in accidents such as deviations or perforations. Recently, guided endodontics has become an alternative approach for pulp canal calcification, facilitating the location of root canals more predictably through the combined use of cone-beam computed tomographic imaging, oral scanning, and endodontic access guides. Although several reports have shown that guided endodontics is safer, faster and can be performed without an operating microscope and by less experienced operators, the technique has limitations, and iatrogenesis may occur. This article describes the limitations of static-guided endodontics and possible causes of failures. In the present case, not fixing the guide to the bone and inaccuracies generated by manually performing mesh merger software led to root perforation. Endodontic microsurgery was effective in resolving this case and should be considered the treatment of choice when guided endodontics cannot be used safely or when it fails.

Root Canal Microbiome Associated With Asymptomatic Apical Periodontitis as Determined by High-Throughput Sequencing.

INTRODUCTION: Advanced DNA sequencing technology allows more detailed analysis and description of the endodontic microbiome. This study used the MiSeq high-throughput sequencing platform (Illumina, San Diego, CA) to describe the endodontic microbiome of teeth with primary asymptomatic apical periodontitis with no sinus tract. METHODS: Root canal samples from 25 patients were prepared for DNA sequencing analysis. Bacterial diversity of the microbiome was identified and compared between cases and according to the size of the related apical periodontitis lesions. Statistical analyses of the operational taxonomic unit distribution was performed using principal component analysis with the Bray-Curtis distance and a principal coordinate analysis, 2-way permutational multivariate analysis of variance. The chi-square or Fisher exact test was used to evaluate the prevalence of different operational taxonomic units related to small and large apical periodontitis lesions. RESULTS: Although there was a very high bacterial diversity in the microbiome of teeth with asymptomatic apical periodontitis, 4 phyla dominated the microbiome: Firmicutes (27%), Bacteroidetes (21%), Proteobacteria (21%), and Actinobacteria (12%). There was high variability in species composition between root canal samples with no common species pattern for the cases. Large lesions showed a higher number of species but did not significantly differ from small lesions in bacterial diversity indexes. Bacteroidaceae [G-1] bacterium HMT 272, a previously uncultivated but still unnamed and uncharacterized taxon, was the most prevalent and abundant phylotype. CONCLUSIONS: High-throughput sequencing technology confirmed the complexity of the endodontic microbiome and revealed that microbial heterogeneity is a feature between cases. This indicates that various microbial combinations of the endodontic microbiome are able to illicit periapical inflammatory diseases.

Synthesis, Characterization and Photocatalytic Activity of CoFe2O4/Fe2O3 Dispersed in Mesoporous KIT-6.

The present work aimed to synthesize and characterize a solid based on CoFe2O4/Fe2O3-KIT-6 and evaluate its performance in the photocatalytic degradation of the remazol red ultra RGB dye. By analyzing XRD, N2 physisorption, and Mössbauer results, it was possible to identify that the desired CoFe2O4/Fe2O3 phase was achieved, which maintained its structural properties. The FTIR-pyridine indicated the presence of Lewis acid sites, while TPD-CO2 showed a large amount of weak basic sites. The band-gap energy indicated that the compound can be applied in photocatalytic degradation under UV/visible light, with the possibility of magnetic separation at the end of the reaction. The photocatalysis results indicated that there was complete degradation of the remazol red ultra RGB dye within 1 h of reaction. Despite the absence of H2O2, the combination of the proposed photocatalyst with the anatase phase (TiO2) showed significant improvements in the degradation process. The proposed mechanism for complete dye degradation indicated that a sequence of radical reactions is necessary, generating oxidant species such as •OH and the final products were CO2 and H2O.

The use of antimicrobial photodynamic therapy in the successful management of a nonsurgical complex type II Dens Invaginatus.

Because of its complex root canal morphology, dens invaginatus (DI) is a developmental anomaly that represents an endodontic challenge to complete cleaning, shaping, and disinfecting the root canal system. The present case report describes the use of antimicrobial photodynamic therapy as an adjunctive treatment in the successful management of nonsurgical complex type II DI in a left maxillary lateral incisor with thin and fragile dentin walls associated with periradicular lesion.

The use of antimicrobial photodynamic therapy in the successful management of an invasive cervical resorption class 4: A case report with five years follow-up.

A 41-year-old male with a dental history of invasive cervical resorption (ICR) was initially treated with a surgical endodontics approach and secondly with antimicrobial photodynamic therapy (aPDT) along with endodontic retreatment. The use of aPDT was essential to promote bacterial reduction in the resorption defect. Combining these techniques allowed for clinical, radiographic, and tomographic success after five years of follow-up.

Evaluation of the Cyclic and Torsional Fatigue Resistance of Thermally Treated Hyflex CM versus Aurum Blue Nickel-titanium Rotary Instruments.

Introduction: We aim to evaluate the cyclic and torsional fatigue resistance of two rotary instruments, Hyflex CM 25/0.06 (HCM) (Coletene-Whaledent, Allstetten, Switzerland) and Aurum Blue (AB) 25/0.06 (Meta-Biomed, Republic of Korea). Methods and Materials: Forty rotary instruments, HCM 25/0.06 and AB 25/0.06 (n=20 each) were used. The instruments were rotated in an artificial stainless steel canal with a 60° angle and a 5-mm radius of curvature (n=10) at body temperature (35°±1°C). The torsional test evaluated the torque and angle of rotation at failure of new instruments (n=10) in the portion 3 mm from the tip according to ISO 3630-1. The fractured surface of each fragment was observed by scanning electron microscopy. The data were analyzed using unpaired student's t- test, and the level of significance was set at 5%. Results: AB 25/0.06 had significantly greater number of cycles to failure than HCM 25/0.06 (P<0.05). The torsional test showed there were no significant differences in the torsional strength and angular rotation to fracture between the groups (P>0.05). Conclusion: Based on this in vitro study, AB 25/0.06 instrument was more resistant to cyclic fatigue than the HCM 25/0.06 instrument, suggested that these instruments are safer than HCM 25/0.06 for the preparation of severely curved canals. However; there was no significant difference in the torsional properties of the two instruments then appear to have similar performance during constricted canal preparation.

The impact of the use of magnifying dental loupes on the performance of undergraduate dental students undertaking simulated dental procedures.

OBJECTIVES: This study aimed to evaluate the impact of the use of magnification (2.5x dental loupes) for third-year dental students in simulated endodontics and fixed prosthodontics assessments compared to those using no magnification. METHODS: Upon institutional review board exemption, third-year dental students were assessed during endodontics and fixed prosthodontics exams in the simulation laboratory. The endodontic group (n = 93) consisted of students who made an endodontic access preparation on a plastic lower left first molar (Nissan). The prosthodontic group (n = 86) consisted of students who made porcelain fused to metal preparation (PFM) on a plastic lower right first molar mounted on an acrylic lower jaw model (Columbia Dentoform). The impact of the use of dental loupes was evaluated. Assessment of the tasks was undertaken by experts-calibrated, blinded examiners-using a standardized marking rubric for each task. The statistical analysis included Chi-square test, one-way ANOVA, and Logistic regression. The level of significance adopted was 5%. RESULTS: Students' preparations using magnification were better compared with those without magnification. Students using magnification had a significantly higher pass rate than those not using magnification in both endodontic and prosthodontic groups (P < 0.05). CONCLUSIONS: In conclusion, third-year dental students who used loupes in the endodontics and prosthodontics simulation laboratory had significantly higher scores at the assessments.

Photocatalytic degradation of ibuprofen using titanium oxide: insights into the mechanism and preferential attack of radicals.

The present work studied ibuprofen degradation using titanium dioxide as a photocatalyst. Mechanistic aspects were presented and the preferred attack sites by the OH˙ radical on the ibuprofen molecule were detailed, based on experimental and simple theoretical-computational results. Although some previous studies show mechanistic proposals, some aspects still need to be investigated, such as the participation of 4-isobutylacetophenone in the ibuprofen degradation and the preferred regions of attack by OH˙ radicals. The photodegradation was satisfactory using 0.03 g of TiO2 and pH = 5.0, reaching 100% decontamination in 5 min. The zeta potential curve showed the regions of attraction and repulsion between TiO2 and ibuprofen, depending on the pH range and charge of the species, influencing the amount of by-products formed. Different by-products have been identified by GC-MS, such as 4-isobutylacetophenone. Ibuprofen conversion to 4-isobutylacetophenone takes place through decarboxylation reaction followed by oxidation. The proposed mechanism indicates that the degradation of ibuprofen undergoes a series of elementary reactions in solution and on the surface. Three different radicals (OH˙, O2 -˙ and OOH˙) are produced in the reaction sequence and contribute strongly to the oxidation and mineralization of ibuprofen and by-products, but the hydroxyl radical has a greater oxidation capacity. The simple study using the DFT approach demonstrated that the OH˙ radical attacks preferentially in the region of the ibuprofen molecule with high electronic density, which is located close to the aromatic ring (C[double bond, length as m-dash]C bond). The presence of the OH˙ radical was confirmed through a model reaction using salicylic acid as a probe molecule.

Tracing the toxic ions of an endodontic tricalcium silicate-based sealer in local tissues and body organs.

BACKGROUND: This study aimed to track the toxic ions released by MTA Fillapex, BioRoot RCS, and an experimental tricalcium silicate-based sealer (CEO) into local and distant tissues as well as to investigate their potential adverse effects. In addition, the chemical constituents of the sealers were also evaluated. The main components of the dry powders, pastes, and mixed sealers were characterized. MATERIAL AND METHODS: Dry powder and sealer discs were each set for 72 h and their main components were characterized by energy dispersive X-ray spectroscopy. Polyethylene tubes filled with sealers were used to measure silicon and calcium ions. Polyethylene tubes filled with sealers or empty tubes were implanted into the dorsal connective tissue of Wistar rats. On days 7, 15, 30, and 45, the animals were euthanized and their brains, livers, kidneys, and subcutaneous tissues were removed and processed to determine the concentrations of chromium, cobalt, copper, lead, iron, magnesium and nickel using an inductively coupled plasma optical emission spectrometer. RESULTS: The main compounds in all sealers were carbon, oxygen, silicon, and calcium. MTA Fillapex release more Si while highest levels of Si were found in presence of BioRoot. The release of Si and Ca ions promoted by MTA Fillapex raise by time. No traces of cobalt, chromium, or magnesium were detected in any tissue. Irrespective of the sealer, no traces of copper and lead were found in the subcutaneous tissue; however, they were observed in the organs. The highest concentration of iron was identified in the liver. All sealers exhibited similar nickel traces in the brain, kidney, and liver except for MTA Fillapex, which demonstrated levels higher than CEO in the subcutaneous tissue on day 7. Tracing nickel ions over time revealed that lowest concentrations were found in subcutaneous tissue. CONCLUSION: Taken together, our data demonstrate that CEOs have chemical compositions similar to those of other commercial sealers. Furthermore, none of them exhibited a threat to systemic health. Moreover, the minimal amounts of iron and nickel detected were not related to the sealers.

Reduction with dithiothreitol causes serglycin-specific defects in secretory granule integrity of bone marrow derived mast cells.

Mast cell granule maturation and storage of granule components has previously been shown to be critically dependent on serglycin (SG), a proteoglycan abundantly stored in mast cell secretory granules. The N-terminal portion of serglycin contains a conserved disulfide motif that is similar to motifs found in secretory granule compounds of neuroendocrine cells. Interference with such motifs of neuroendocrine cells with dithiothreitol (DTT) has previously been shown to cause cellular missorting. To investigate the implication for serglycin, serglycin(+/+) and serglycin(-/-) bone marrow derived mast cells (BMMCs) were treated with DTT followed by assessment of proteoglycan synthesis and secretory granule integrity. Treatment of serglycin(+/+) BMMCs with DTT almost completely abolished biosynthetic incorporation of (35)S-sulfate into proteoglycans, caused a dramatic reduction of granular staining with May Grünwald/Giemsa as well as disruption of granule dense core formation as shown by transmission electron microscopy. In addition, the storage of carboxypeptidase A, a major secretory granule compound, was markedly reduced following DTT treatment. In contrast, none of these effects were seen after treatment of SG(-/-) BMMCs with DTT, indicating that they were serglycin-specific. Notably, DTT treated serglycin(+/+) BMMCs showed similar morphology as did the serglycin(-/-) BMMCs. DTT treatment affected neither the viability of the BMMCs nor the mRNA levels for serglycin or carboxypeptidase A. Together, these data indicate that DTT causes dramatic, serglycin-specific effects on mast cell granule. These findings are thus in accordance with a role for the N-terminal disulfide motif in serglycin for regulation of mast cell secretory granule integrity.

Antimicrobial photodynamic therapy and guided endodontics: A case report.

A 35-year-old woman with a history of pulp canal obliteration (PCO) and apical periodontitis was treated with guided endodontics combined with antimicrobial photodynamic therapy (aPDT). The use of aPDT was paramount to the approach performed, and its application should be encouraged in cases of severely calcified canals when apical patency is unachievable. The combination of these techniques ensured successful clinical, radiographic, and tomographic outcomes at the 1-year follow-up. Key Words: Antimicrobial PDT, guided endodonics, periodontitis, pulp canal obliteration.

Quantitative Assessment of the Efficacy of Two Different Single-file Systems in Reducing the Bacterial load in Oval-Shaped Canals: A Clinical Study.

INTRODUCTION: This randomized clinical study compared the in vivo antibacterial efficacy of Reciproc Blue (RB), XP-endo Shaper (XP-S), and XP-endo Shaper associated with XP-endo Finisher (XP-F) systems in infected oval-shaped root canals with primary apical periodontitis. METHODS: In this study, 28 human teeth with a single root and a single canal were randomly assigned to 2 groups according to the instrumentation technique: group 1, RB (n = 14) and group 2, XP-endo (XP-S and XP-F, n = 14). The single-rooted teeth were prepared by reciprocating and rotary nickel-titanium instruments with 5.25% sodium hypochlorite irrigation. Samples were collected from the canal at the baseline (S1), after chemomechanical preparation (S2), and after XP-F instrumentation (S3). The DNA extracts were subjected to quantitative analysis for total bacterial counts by quantitative real-time polymerase chain reaction. The data were analyzed using the analysis of variance test, and the level of significance was set at 5%. RESULTS: All samples tested positive for the presence of bacteria at baseline, and the bacterial counts substantially reduced after treatment procedures (P < .01). The results showed no statistical difference between RB and XP-S instrumentation with respect to the bacterial reduction (P > .05). A marked bacterial reduction was observed after the use of the XP-F instrument (P < .01). CONCLUSIONS: The XP-S and RB systems sharply reduced the bacterial load in oval-shaped root canals with primary apical periodontitis. XP-F used as a supplementary instrument to chemomechanical preparation promoted a significantly higher bacterial reduction.

Serglycin proteoglycan is required for secretory granule integrity in mucosal mast cells.

SG (serglycin) PGs (proteoglycans) are strongly implicated in the assembly of MC (mast cell) granules. However, this notion has mainly been on the basis of studies of MCs of the connective tissue subtype, whereas the role of SG PG in mucosal MCs has not been explored. In the present study, we have addressed the latter issue by using mice with an inactivated SG gene. Bone marrow cells were differentiated in vitro into the mucosal MC phenotype, expressing the markers mMCP (mouse MC protease) -1 and -2. Biosynthetic labelling experiments performed on these cells revealed an approximately 80% reduction of 35SO4(2-) incorporation into PGs recovered from SG-/- cells as compared with SG+/+ counterparts, indicating that SG is the dominating cell-associated PG of mucosal MCs. Moreover, the absence of SG led to defective metachromatic staining of mucosal MCs, both in vivo and in the in vitro-derived mucosal MCs. Ultrastructural analysis showed that granules were present in similar numbers in SG+/+ and SG-/- cells, but that their morphology was markedly affected by the absence of SG, e.g. with electron-dense core formation only seen in SG+/+ granules. Analysis of the MC-specific proteases showed that mMCP-1 and mMCP-7 were completely independent of SG for storage, whereas mMCP-2 showed a partial dependence. In contrast, mMCP-4 and -6, and carboxypeptidase A were strongly dependent on SG for storage. Together, our data indicate that SG PG is of crucial importance for assembly of mature mucosal MC granules, but that the specific dependence on SG for storage varies between individual granule constituents.

X-linked spinal and bulbar muscular atrophy (Kennedy's disease): the first case described in the Brazilian Amazon.

The X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is a rare X-linked, recessive, lower motor neuron disease, characterized by weakness, atrophy, and fasciculations of the appendicular and bulbar muscle. The disease is caused by an expansion of the CAG repetition in the androgen receptor gene. Patients with Kennedy's disease have more than 39 CAG repetitions. We report a case of 57-year-old man, resident of Monte Dourado (PA, Brazil) who complained of brachiocrural paresis evolving for 3 years along with fasciculations and tremors of extremities. In addition, he also developed dysarthria, dysphagia, and sexual dysfunction. The patient clinical picture included gait impairment, global hyporeflexia, proximal muscle atrophy of upper limbs, deviation of the uvula to right during phonation and tongue atrophy with fasciculations. The patient reported that about 30 years ago he had undergone gynecomastia surgery. His electroneuromyography suggested spinal muscular atrophy, and nuclear magnetic resonance imaging showed tapering of the cervical and thoracic spinal cord. Patient's creatine kinase level was elevated. In view of the findings, an exam was requested to investigate Kennedy's disease. The exam identified 46 CAG repetitions in the androgen receptor gene, which confirmed the diagnostic suspicion. This was the first case of Kennedy's disease diagnosed and described in the Brazilian Amazon. To our knowledge only other four papers were published on this disease in Brazilian patients. A brief review is also provided on etiopathogenic, clinical and diagnostic aspects.

Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to Sunitinib.

Resistance to chemotherapy is a challenging problem for treatment of cancer patients and autophagy has been shown to mediate development of resistance. In this study we systematically screened a library of 306 known anti-cancer drugs for their ability to induce autophagy using a cell-based assay. 114 of the drugs were classified as autophagy inducers; for 16 drugs, the cytotoxicity was potentiated by siRNA-mediated knock-down of Atg7 and Vps34. These drugs were further evaluated in breast cancer cell lines for autophagy induction, and two tyrosine kinase inhibitors, Sunitinib and Erlotinib, were selected for further studies. For the pharmacological inhibition of autophagy, we have characterized here a novel highly potent selective inhibitor of Vps34, SB02024. SB02024 blocked autophagy in vitro and reduced xenograft growth of two breast cancer cell lines, MDA-MB-231 and MCF-7, in vivo. Vps34 inhibitor significantly potentiated cytotoxicity of Sunitinib and Erlotinib in MCF-7 and MDA-MB-231 in vitro in monolayer cultures and when grown as multicellular spheroids. Our data suggests that inhibition of autophagy significantly improves sensitivity to Sunitinib and Erlotinib and that Vps34 is a promising therapeutic target for combination strategies in breast cancer.