Tumor resistance to anti-mesothelin CAR-T cells caused by binding to shed mesothelin is overcome by targeting a juxtamembrane epitope.

Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.

Performance evaluation of two multiplex qualitative RT-PCR assays for detection of respiratory infection in paediatric population.

INTRODUCTION: Acute respiratory infection (ARI) contributes to significant mortality and morbidity worldwide and is usually caused by a wide range of respiratory pathogens. This study aims to describe the performance of QIAstat-Dx® Respiratory Panel V2 (RP) and RespiFinder® 2SMART assays for respiratory pathogens detection. MATERIALS AND METHODS: A total of 110 nasopharyngeal swabs (NPS) were collected from children aged one month to 12 years old who were admitted with ARI in UKMMC during a one-year period. The two qPCR assays were conducted in parallel. RESULTS: Ninety-seven samples (88.2%) were positive by QIAstat-Dx RP and 86 (78.2%) by RespiFinder assay. The overall agreement on both assays was substantial (kappa value: 0.769) with excellent concordance rate of 96.95%. Using both assays, hRV/EV, INF A/H1N1 and RSV were the most common pathogens detected. Influenza A/H1N1 infection was significantly seen higher in older children (age group > 60 months old) (53.3%, p-value < 0.05). Meanwhile, RSV and hRV/EV infection were seen among below one-year-old children. Co-infections by two to four pathogens were detected in 17 (17.5%) samples by QIAstat-Dx RP and 12 (14%) samples by RespiFinder, mainly involving hRV/EV. Bacterial detection was observed only in 5 (4.5%) and 6 (5.4%) samples by QIAstat-Dx RP and RespiFinder, respectively, with Mycoplasma pneumoniae the most common detected. CONCLUSION: The overall performance of the two qPCR assays was comparable and showed excellent agreement. Both detected various clinically important respiratory pathogens in a single test with simultaneous multiple infection detection. The use of qPCR as a routine diagnostic test can improve diagnosis and management.

Pines' demon observed as a 3D acoustic plasmon in Sr2RuO4.

The characteristic excitation of a metal is its plasmon, which is a quantized collective oscillation of its electron density. In 1956, David Pines predicted that a distinct type of plasmon, dubbed a 'demon', could exist in three-dimensional (3D) metals containing more than one species of charge carrier1. Consisting of out-of-phase movement of electrons in different bands, demons are acoustic, electrically neutral and do not couple to light, so have never been detected in an equilibrium, 3D metal. Nevertheless, demons are believed to be critical for diverse phenomena including phase transitions in mixed-valence semimetals2, optical properties of metal nanoparticles3, soundarons in Weyl semimetals4 and high-temperature superconductivity in, for example, metal hydrides3,5-7. Here, we present evidence for a demon in Sr2RuO4 from momentum-resolved electron energy-loss spectroscopy. Formed of electrons in the ß and γ bands, the demon is gapless with critical momentum qc = 0.08 reciprocal lattice units and room-temperature velocity v = (1.065 ± 0.12) × 105 m s-1 that undergoes a 31% renormalization upon cooling to 30 K because of coupling to the particle-hole continuum. The momentum dependence of the intensity of the demon confirms its neutral character. Our study confirms a 67-year old prediction and indicates that demons may be a pervasive feature of multiband metals.

Delocalization and Universality of the Fractional Quantum Hall Plateau-to-Plateau Transitions.

Disorder and electron-electron interaction play essential roles in the physics of electron systems in condensed matter. In two-dimensional, quantum Hall systems, extensive studies of disorder-induced localization have led to the emergence of a scaling picture with a single extended state, characterized by a power-law divergence of the localization length in the zero-temperature limit. Experimentally, scaling has been investigated via measuring the temperature dependence of plateau-to-plateau transitions between the integer quantum Hall states (IQHSs), yielding a critical exponent κ≃0.42. Here we report scaling measurements in the fractional quantum Hall state (FQHS) regime where interaction plays a dominant role. Our Letter is partly motivated by recent calculations, based on the composite fermion theory, that suggest identical critical exponents in both IQHS and FQHS cases to the extent that the interaction between composite fermions is negligible. The samples used in our experiments are two-dimensional electron systems confined to GaAs quantum wells of exceptionally high quality. We find that κ varies for transitions between different FQHSs observed on the flanks of Landau level filling factor ν=1/2 and has a value close to that reported for the IQHS transitions only for a limited number of transitions between high-order FQHSs with intermediate strength. We discuss possible origins of the nonuniversal κ observed in our experiments.

Evidence of high-temperature exciton condensation in a two-dimensional semimetal.

Electrons and holes can spontaneously form excitons and condense in a semimetal or semiconductor, as predicted decades ago. This type of Bose condensation can happen at much higher temperatures in comparison with dilute atomic gases. Two-dimensional (2D) materials with reduced Coulomb screening around the Fermi level are promising for realizing such a system. Here we report a change in the band structure accompanied by a phase transition at about 180 K in single-layer ZrTe2 based on angle-resolved photoemission spectroscopy (ARPES) measurements. Below the transition temperature, gap opening and development of an ultra-flat band top around the zone center are observed. This gap and the phase transition are rapidly suppressed with extra carrier densities introduced by adding more layers or dopants on the surface. The results suggest the formation of an excitonic insulating ground state in single-layer ZrTe2, and the findings are rationalized by first-principles calculations and a self-consistent mean-field theory. Our study provides evidence for exciton condensation in a 2D semimetal and demonstrates strong dimensionality effects on the formation of intrinsic bound electron-hole pairs in solids.

Profiled polyethylene terephthalate filaments that incorporate collagen and calcium phosphate enhance ligamentisation and bone formation.

Polyethylene terephthalate (PET) artificial ligaments offer an unlimited source of ligaments without donor-site-related morbidity and with good mechanical properties for a rapid return to sporting activities. Developing PET artificial ligaments with excellent ligamentisation and ligament-bone healing is still a considerable challenge. This study aimed to investigate the effects of the profiled PET/collagen/calcium phosphate (PET/C/CaP) ligament upon cell growth, ligamentisation and ligament-bone healing in vitro and in vivo. Profiled PET/C/CaP filaments were made by melt-spinning process with 2 % CaP hybrid spinning and collagen coating. Rat mesenchymal stem cells (MSCs) were cultured on the profiled PET/C filaments for cytotoxicity, viability, scanning electron microscopy (SEM) and ligament-related gene expression analysis. MSCs' osteogenic capacity on the profiled PET/CaP filaments was identified by detecting osteogenic gene expression and alizarin red S staining. For in vivo verification, an animal study was performed to evaluate the effect of the profiled PET/C/CaP ligament in a rabbit knee medial collateral ligament reinforcement reconstruction model. The graft ligamentisation and bone formation were investigated by SEM, histology, microcomputed tomography and mechanical tests. The profiled PET/C filaments enhanced MSC proliferation and ligament-related gene expression. Furthermore, they enhanced osteogenic gene expression, alkaline phosphatase activity and mineralisation of MSCs. The in vivo study indicated that the profiled PET/C/CaP ligament enhanced ligamentous matrix remodelling and bone formation. Therefore, their use is an effective strategy for promoting MSCs' ligamentous and osteogenic potential in vitro and enhancing ligamentous matrix remodelling and bone formation in vivo.

Digital intervention increases influenza vaccination rates for people with diabetes in a decentralized randomized trial.

People with diabetes (PWD) have an increased risk of developing influenza-related complications, including pneumonia, abnormal glycemic events, and hospitalization. Annual influenza vaccination is recommended for PWD, but vaccination rates are suboptimal. The study aimed to increase influenza vaccination rate in people with self-reported diabetes. This study was a prospective, 1:1 randomized controlled trial of a 6-month Digital Diabetes Intervention in U.S. adults with diabetes. The intervention group received monthly messages through an online health platform. The control group received no intervention. Difference in self-reported vaccination rates was tested using multivariable logistic regression controlling for demographics and comorbidities. The study was registered at clinicaltrials.gov: NCT03870997. A total of 10,429 participants reported influenza vaccination status (5158 intervention, mean age (±SD) = 46.8 (11.1), 78.5% female; 5271 control, Mean age (±SD) = 46.7 (11.2), 79.4% female). After a 6-month intervention, 64.2% of the intervention arm reported influenza vaccination, vers us 61.1% in the control arm (diff = 3.1, RR = 1.05, 95% CI [1.02, 1.08], p = 0.0013, number needed to treat = 33 to obtain 1 additional vaccination). Completion of one or more intervention messages was associated with up to an 8% increase in vaccination rate (OR 1.27, 95% CI [1.17, 1.38], p < 0.0001). The intervention improved influenza vaccination rates in PWD, suggesting that leveraging new technology to deliver knowledge and information can improve influenza vaccination rates in high-risk populations to reduce public health burden of influenza. Rapid cycle innovation could maximize the effects of these digital interventions in the future with other populations and vaccines.

The influence of diabetes on postoperative complications following colorectal surgery.

BACKGROUND: Diabetes mellitus has been commonly associated with poor surgical outcomes. The aim of this meta-analysis was to assess the impact of diabetes on postoperative complications following colorectal surgery. METHODS: Medline, Embase and China National Knowledge Infrastructure electronic databases were reviewed from inception until May 9th 2020. Meta-analysis of proportions and comparative meta-analysis were conducted. Studies that involved patients with diabetes mellitus having colorectal surgery, with the inclusion of patients without a history of diabetes as a control, were selected. The outcomes measured were postoperative complications. RESULTS: Fifty-five studies with a total of 666,886 patients comprising 93,173 patients with diabetes and 573,713 patients without diabetes were included. Anastomotic leak (OR 2.407; 95% CI 1.837-3.155; p < 0.001), surgical site infections (OR 1.979; 95% CI 1.636-2.394; p < 0.001), urinary complications (OR 1.687; 95% CI 1.210-2.353; p = 0.002), and hospital readmissions (OR 1.406; 95% CI 1.349-1.466; p < 0.001) were found to be significantly higher amongst patients with diabetes following colorectal surgery. The incidence of septicemia, intra-abdominal infections, mechanical failure of wound healing comprising wound dehiscence and disruption, pulmonary complications, reoperation, and 30-day mortality were not significantly increased. CONCLUSIONS: This meta-analysis and systematic review found a higher incidence of postoperative complications including anastomotic leaks and a higher re-admission rate. Risk profiling for diabetes prior to surgery and perioperative optimization for patients with diabetes is critical to improve surgical outcomes.

Development of the Brief Geriatric Assessment for the General Practitioner.

OBJECTIVES: The study aimed to develop a brief geriatric assessment (BGA) tool for the general practitioner to evaluate geriatric syndromes in community-dwelling older adults. DESIGN: A cross-sectional study. SETTING: 58 communities from four aging cities in Taiwan. PARTICIPANTS: 1,258 community-dwelling older adults aged 65 years and above. MEASUREMENTS: The BGA targeted physical function impairment, cognitive impairment, and mood impairment. The cutoff values of physical function tests (handgrip strength and 6-meter walk test [6MWT]) were estimated by receiver operating characteristic analysis. Second, the diagnostic validity of the BGA was calculated in terms of sensitivity, specificity, and predictive values, which were compared to corresponding comprehensive geriatric assessment (CGA) items. Third, the associated risk factors of geriatric syndromes were selected using stepwise logistic regression. Finally, we combined items selected from literature and CGA and then proposed a practical BGA framework. RESULTS: The proposed BGA comprised dominant handgrip strength, 6MWT, self-report personal birthday, address, and telephone number, question 'Do you have depressive mood for the past two weeks?', Rinne tuning-fork tests, Snellen scale, and body mass index. It evaluated multidimensional aspects of geriatrics syndromes including physical, cognitive, mood, and sensory impairment, sarcopenia, and nutrition status. Sensitivities in the Taiwan BGA items ranged from 48% for dominant handgrip strength to 97.6% for 6MWT corresponding to physical impairment; 58.3% for cognitive impairment corresponding to Short Portable Mental Status Questionnaire; 62.7% for mood impairment corresponding to Geriatric Depression Scale. The Taiwan BGA for the general practitioner takes less than 10 minutes and is suitable in the community setting. CONCLUSION: Early management of geriatric syndromes in the community is important. The current study demonstrated a practical BGA tool for the general practitioner to comprehensively assess geriatric syndromes in community-dwelling older adults.

Colorectal resection via natural orifice specimen extraction versus conventional laparoscopic extraction: a meta-analysis with meta-regression.

BACKGROUND: Studies have shown differences in postoperative outcomes between two minimally invasive extraction methods for colorectal lesions-natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic surgery (CLS). The aim of this study was to discover the major differences in NOSES and CLS to refine current practice. METHODS: Electronic databases were searched for articles comparing NOSES and CLS from inception till March 2020. Weighted mean differences (WMD) and odds ratio (OR) were estimated for continuous and dichotomous outcomes, respectively. Summary statistics were calculated using the DerSimonian and Laird random effects. RESULTS: Twenty-one studies (15 on malignant disease, 4 on benign disease, 2 on both) were included in this meta-analysis, totalling 2378 patients (1079 NOSE, 1299 CLS). NOSE was associated with decreased: intraoperative bleeding (WMD: - 10.652 ml; 95% CI: - 18.818 ml to - 2.482 ml; p < 0.001), pain score (WMD: - 1.520; 95% CI - 1.965 to - 1.076; p < 0.001), time to flatus (WMD: - 0.306 days; 95% CI: - 0.526 to - 0.085 days; p < 0.001), length of hospital stay (WMD: - 1.048 days; 95% CI: - 1.488 to - 0.609 days; p < 0.001), and total morbidity (OR: 0.548; 95% CI: 0.387 to 0.777; p = 0.001). Subgroup analyses showed significant differences between malignant and benign lesions for intraoperative bleeding (p = 0.011) and pain score (p = 0.010). Meta-regression analyses showed an association between the American Society of Anaesthesiologists (ASA) physical status classification III with pain (p = 0.03) and ASA III with time to flatus (p = 0.04). CONCLUSIONS: This meta-analysis and meta-regression demonstrated that NOSES had better postoperative outcomes compared to CLS. More comprehensive reviews should be conducted on the long-term outcomes specific to the extraction site to better inform clinical practice.

Severe Group A and Group B Streptococcus Diseases at a Pediatric ICU: Are they Still Sensitive to the Penicillins?

BACKGROUND: Group A ß-hemolytic Streptococcus (GAS) and Group B streptococcus (GBS) are two common pathogens that are associated with many diseases in children. Severe infections as a result of these two streptococci are albeit uncommon but associated with high mortality and morbidity, and often necessitate intensive care support. This paper aims to review the mortality and morbidity of severe infection associated with GAS and GBS isolations at a Pediatric Intensive Care Unit (PICU). METHODS: All children admitted to PICU of a teaching hospital between October 2002 and May 2018 with laboratory-proven GAS and GBS isolations were included. RESULTS: There were 19 patients (0.7% PICU admissions) with streptococcal isolations (GAS, n=11 and GBS, n=8). Comparing to GAS, GBS affected infants were younger (median age 0.13 versus 5.47 years, 95% CI, 1.7-8.5, p=0.0003), and cerebrospinal fluids more likely positive (p = 0.0181). All GAS and GBS were sensitive to penicillin (CLSI: MICs 0.06 - 2.0 µg/mL), with the majority of GAS sensitive to clindamycin and erythromycin, and half of the GBS resistant to clindamycin and erythromycin. Co-infections were prevalent, but viruses were only isolated with GAS (p=0.024). Isolation of GAS and GBS was associated with nearly 40% mortality and high rates of mechanical ventilation and inotropic supports. All non-survivors had high mortality (PIM2) and sepsis scores. CONCLUSIONS: Severe GAS and GBS are rare but associated with high mortality and rates of mechanical ventilation and inotropic supports in PICU. The streptococci are invariably sensitive to penicillin. The high PIM2 and Sepsis scores suggest that prompt recognition of sepsis and the timely judicious institution of antibiotics and intensive care support may be life-saving for these devastating infections.

MART-10, a 1α,25(OH)2D3 Analog, Potently Represses Metastasis of ER+ Breast Cancer Cells with VEGF-A Overexpression.

BACKGROUND: Breast cancer ranks second in the list of cancer-related deaths for women. Even under multidisciplinary treatment, 25-50% of patients with breast cancer still ultimately develop metastasis, leading to poor prognosis. In addition to inducing angiogenesis, vascular endothelial growth factor-A (VEGF-A) is believed to directly increase cancer cell metastatic potential and overexpression of VEGF-A is associated with higher invasiveness of breast cancer. 1α,25(OH)2D3, the active form of vitamin D, and its analogs have been widely applied as anticancer agents in the past. MATERIAL AND METHODS: Western blot, migration and invasion assays, enzyme-linked immunosorbent assay, and immunofluorescent stain were applied in this study. RESULT: VEGF-A increased cell migration and invasion in estrogen receptor-positive (ER+) breast cancer MCF-7 cells. VEGF-A induced an autocrine loop in MCF-7 cells as VEGF-A treatment increased both VEGF-A expression and secretion. The expression of VEGF receptor type 2 (VEGFR2) and neuropilin 1 was also up-regulated by VEGF-A in MCF-7 cells. In addition, F-actin synthesis and LIM domain kinase 1 (LIMK-1) phosphorylation were increased by VEGF-A. VEGF-A also increased ß-catenin expression and nuclear translocation of both ß-catenin and nuclear factor-ĸB (NF-ĸB), indicating increased ß-catenin and NF-ĸB activity. 1α,25(OH)2D3 and MART-10, an analog of 1α,25(OH)2D3, effectively repressed VEGF-A-induced MCF-7 cell migration and invasion and other VEGF-A-induced effects on MCF-7 cells, with MART-10 being more potent than 1α,25(OH)2D3 Conclusion: MART-10 can be deemed as a promising agent for prevention and treatment of metastasis of ER+ breast cancer with VEGF-A overexpression.

Pseudogout - a rare manifestation of hungry bone syndrome after focused parathyroidectomy.

Pseudogout, also known as calcium pyrophosphate deposition disease, is a rheumatological condition arising from accumulation of calcium pyrophosphate dihydrate crystals in connective tissues. We present a case of a 56-year-old Bangladeshi woman who underwent focused right inferior parathyroidectomy for primary hyperparathyroidism from a right inferior parathyroid adenoma. On the first post-operative day, she complained of left elbow painful swelling with redness and warmth. Arthrocentesis of left elbow was done due to suspicion of septic arthritis. Two weeks prior to this surgery, she had sudden bilateral knee swelling was diagnosed in her home country of bilateral knee osteoarthritis with effusion and arthrocentesis showed no crystals. Aspiration of left elbow showed calcium pyrophosphate crystals, associated with post parathyroidectomy hypocalcemia, hypomagnesemia confirming pseudogout. Her uric acid level was normal. Bilateral wrist x-rays showed triangular fibrocartilage complex chondrocalcinosis. The patient's condition improved with colchicine and naproxen, as well as calcium and magnesium replacement. Her left elbow swelling and pain resolved. Pseudogout flare is a rare but known sequelae after parathyroidectomy. Early recognition and expeditious treatment is essential.

Histone deacetylase inhibitor treatment restores memory-related gene expression and learning ability in neonicotinoid-treated Apis mellifera.

Apis mellifera plays crucial roles in maintaining the balance of global ecosystems and stability of agricultural systems by helping pollination of flowering plants, including many crops. In recent years, this balance has been disrupted greatly by some pesticides, which results in great losses of honeybees worldwide. Previous studies have found that pesticide-caused memory loss might be one of the major reasons for colony loss. Histone deacetylase inhibitors (HDACis) are chemical compounds that inhibit the activity of histone deacetylases and are known to cause hyperacetylation of histone cores and influence gene expression. In our study, the HDACi sodium butyrate was applied to honeybees as a dietary supplement. The effect of sodium butyrate on the expression profiles of memory-related genes was analysed by quantitative reverse transcription PCR. The results revealed that this HDACi had up-regulation effects on most of the memory-related genes in bees, even in bees treated with imidacloprid. In addition, using the proboscis extension reflex to evaluate olfactory learning in bees, we found that this HDACi boosted the memory formation of bees after impairment owing to imidacloprid exposure. This study investigated the association between gene expression and memory formation from an epigenetic perspective. Additionally, we further demonstrate the possibility of enhancing bee learning using HDACis and provide initial data for future research.

Risk-benefit perception of pregnancy among breast cancer survivors.

Helping breast cancer patients who desire a pregnancy after cancer treatment is a vital issue. Little is known about the complex context of the decision to become pregnant after breast cancer treatment. The purpose of this study was to understand the risk-benefit perception of choosing conception or contraception after treatment in Taiwan. We applied grounded theory to guide this exploratory qualitative study. Data were collected through in-depth interviews with 16 breast cancer patients. Pregnancy was addressed in the context of cancer as a potentially life-threatening diagnosis and its treatment. The verbatim transcriptions were analysed using constant comparative analysis and methods of open, axial and selective coding. The core theme that described the risk perception of pregnancy among patients with breast cancer after treatment focused on "reaching the balance of life." Seven dimensions of risk-benefit perception of pregnancy, including perceived health status, safety, expected gain, harm, loading, support and time were explored among women treated for breast cancer. We found that women treated for breast cancer applied risk-benefit perceptions to decide whether to become pregnant. Implementing contextual counselling could help to decrease perceived barriers to choose pregnancy and increase the quality of pregnancy care.

Colossal pilomatrixoma.

We describe the largest reported case of pilomatrixoma in the literature. While pilomatrixomas typically present as small soft-tissue nodules of the head, neck and upper extremities, they can also present as much larger masses in atypical locations. When they present in their usual size, pilomatrixomas have typical imaging features and can be correctly diagnosed with imaging studies before histological confirmation. Their clinical and imaging diagnosis become challenging when they are very large, as in our case. A giant pilomatrixoma should also be considered for paediatric patients presenting with a large subcutaneous soft-tissue mass.

Signatures of exciton condensation in a transition metal dichalcogenide.

Bose condensation has shaped our understanding of macroscopic quantum phenomena, having been realized in superconductors, atomic gases, and liquid helium. Excitons are bosons that have been predicted to condense into either a superfluid or an insulating electronic crystal. Using the recently developed technique of momentum-resolved electron energy-loss spectroscopy (M-EELS), we studied electronic collective modes in the transition metal dichalcogenide semimetal 1T-TiSe2 Near the phase-transition temperature (190 kelvin), the energy of the electronic mode fell to zero at nonzero momentum, indicating dynamical slowing of plasma fluctuations and crystallization of the valence electrons into an exciton condensate. Our study provides compelling evidence for exciton condensation in a three-dimensional solid and establishes M-EELS as a versatile technique sensitive to valence band excitations in quantum materials.

1α,25(OH)2D3 Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Metastasis After VEGF-A Stimulation.

AIMS: Pancreatic neuroendocrine tumors (PanNETs) are usually diagnosed in an advanced stage. Most patients with PanNETs die of metastasis. Vascular endothelial growth factor-A (VEGF-A) is a strong stimulator of angiogenesis and tumor metastasis. We aimed to investigate the effect of MART-10 [19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3], a 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3) analog, on PanNET cell metastasis after VEGF-A stimulation. MATERIALS AND METHODS: Migration and invasion assays, western blot, and immunofluorescent staining were applied in this study. RESULTS: VEGF-A increased PanNET cell migration and invasion, which was attenuated by 1α,25(OH)2D3 and MART-10. VEGF-A treatment stimulated epithelial-mesenchymal transition (EMT) of PanNET cells. During this process, expression of snail family transcriptional repressor 1 and 2, and fibronectin was up-regulated. 1α,25(OH)2D3 and MART-10 counteracted VEGF-A-induced EMT. In addition, expression of neuropilin 1, a key protein in VEGF-A signaling, was down-regulated by 1α,25(OH)2D3 and MART-10. Furthermore, synthesis of F-actin was increased by VEGF-A and reduced by 1α,25(OH)2D3 and MART-10. CONCLUSION: Our data indicate that MART-10 could be deemed a promising drug for PanNET treatment.