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This is a case report of a young man who suffered from an anterior inferior angle fracture (teardrop) of the thoracic spine at the dorsal spine third vertebra (D3). It was due to a road traffic accident and led to paraplegia and hypoesthesia below D7 dermatome. The patient was treated with decompression and posterior stabilization using pedicle screw fixation followed by physiotherapy. Teardrop fracture is a type of cervical fracture that is associated with high morbidity and mortality due to its instability, with no reported similar fracture pattern at the thoracic spine level. This is a unique case of a thoracic teardrop fracture that was treated surgically with a posterior approach, a good clinical outcome, and 18 months follow-up.

Background:. This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe®) and the conventional fixed-size ice probe. Materials and methods:. We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe® and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage. Results:. A total of 1124 men were included. Median age, Gleason score, and pretreatment PSA were 70 years (interquartile range [IQR]: 65–74 years), 7 (IQR: 6–7) and 5.9 ng/mL (IQR: 4.6–8.1 ng/mL), respectively. The median follow-up time was 25.0 months (IQR: 11.2–48.6 months). V-Probes® were used in 269 (23.9%) cases and fixed-size ice probes in 858 (76.1%) cases. After adjusting for clinical T stage, PSA, neoadjuvant androgen deprivation therapy and preoperative Gleason score, on the multivariate Cox regression model, we found that there was no significant difference between the type of probe and timing to biochemical recurrence (p = 0.35). On multivariate logistic regression, using the V-Probe® was associated with a 91% increase in postoperative urinary retention compared to the fixed-size ice probe (p = 0.003). Conclusions:. The use of the V-Probe® versus conventional fixed-size ice probe was not associated with a difference in biochemical recurrence in patients undergoing primary cryoablation of the prostate.

Background: Proximal fifth metatarsal fractures are among the most common forefoot injuries in athletes. The management of this injury can be challenging because of delayed union and refractures. Intramedullary (IM) screw fixation rather than nonoperative management has been recommended in the athletic population. Purpose: To provide an updated summary of the return-to-play (RTP) rate and time to RTP after Jones fractures in athletes with regard to their management, whether operative or nonoperative, and to explore the union rate and time to union as well as the rate of complications such as refractures. Study Design: Meta-analysis. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, 2 independent team members searched several databases including PubMed, MEDLINE, Embase, Google Scholar, Web of Science, Cochrane Library, and ClinicalTrials.gov through November 2019 to identify studies reporting on Jones fractures of the fifth metatarsal exclusively in athletes. The primary outcomes were the RTP rate and time to RTP, whereas the secondary outcomes were the number of games missed, time to union, and union rate as well as the rates of nonunion, delayed union, and refractures. Results: Of 168 studies identified, 22 studies were eligible for meta-analysis with a total of 646 Jones fractures. The overall RTP rate was 98.4% (95% CI, 97.3%-99.4%) in 626 of 646 Jones fractures. The RTP rate with IM screw fixation only was 98.8% (95% CI, 97.8%-99.7%), with other surgical fixation methods (plate, Minifix) was 98.4% (95% CI, 95.8%-100.0%), and with nonoperative management was 71.6% (95% CI, 45.6%-97.6%). There were 3 studies directly comparing RTP rates with surgical versus nonoperative management, which showed significant superiority in favor of surgery (odds ratio, 0.033 [95% CI, 0.005-0.215]; P < .001). The RTP rate according to type of sport was 99.0% (95% CI, 97.5%-100.0%) in football, 91.1% (95% CI, 82.2%-99.4%) in basketball, and 96.6% (95% CI, 92.6%-100.0%) in soccer. The overall time to RTP was 9.6 weeks (95% CI, 8.5-10.7 weeks). The time to RTP in the surgical group (IM screw fixation) was 9.6 weeks (95% CI, 8.3-10.9 weeks), which was significantly less than that in the nonoperative group of 13.1 weeks (95% CI, 8.2-18.0 weeks). The pooled union rate in the operative group (excluding refractures) was 97.3% (95% CI, 95.1%-99.4%), whereas the pooled union rate in the nonoperative group was 71.4% (95% CI, 49.1%-93.7%). The overall time to union was 9.1 weeks (95% CI, 7.7-10.4 weeks). The time to union with IM screw fixation (8.2 weeks [95% CI, 7.5-9.0 weeks]) was shorter than that with nonoperative treatment (13.7 weeks [95% CI, 12.7-14.6 weeks]). The rate of delayed union was 2.5% (95% CI, 1.2%-3.7%), and the overall refracture rate was 10.2% (95% CI, 5.9%-14.5%). Conclusion: The RTP rate and time to RTP after the surgical management of Jones fractures in athletes were excellent, regardless of the implant used and type of sport. IM screw fixation was superior to nonoperative management, as it led to a higher rate of RTP, shorter time to RTP, higher rate of union, shorter time to union, and improved functional outcomes. We recommend surgical fixation for all Jones fractures in athletes.

The objective of this report is to present the use and efficacy of ado-trastuzumab as an advanced line of therapy in salivary duct carcinoma (SDC) patient. An 84-year-old gentleman diagnosed with metastatic salivary duct tumor harboring overexpressed human epidermal growth factor receptor-2 has gone through resection surgery. The first line of treatment included initial doublet chemotherapy combined with trastuzumab, which was continued later as maintenance. PET-CT follow-up for 4 years has demonstrated no evidence of disease. However, upon recurrence, use of Ado-trastuzumab emtansine was prompted as second-line of treatment. This targeted patient-tailored therapy has accomplished a complete response. The effectiveness of ado-trastuzumab emtansine was notable within a short time period of two treatment cycles leading to full recovery. Specific agents aimed at altered oncogenes should be considered as a potential drug of choice in neoadjuvant HER2 positive SDC.

Myoepithelial tumor is a rare form of cancer, mainly arising from the salivary glands and extremities. Due to its rarity, no formal treatment guidelines exist. Here we report a case of a male patient diagnosed with metastatic myoepithelial tumor which was successfully treated with an androgen-receptor (AR) antagonist (bicalutamide), based on the results of molecular testing. Six years after the initiation of bicalutamide, patient was diagnosed with metastatic prostate cancer. To our knowledge, this is the first case described in literature that demonstrate the effectiveness of anti-androgens in treating myoepithelial tumor. Vigilance should be maintained when screening these patients for prostate cancer as their 'true' prostate specific antigen levels might be masked by the ongoing endocrine therapy.

The BNT162b2 vaccine was shown to be highly effective in reducing the risk of COVID-19 infection in healthy individuals and patients with chronic disease. However, there are little data regarding its efficacy in patients treated for cancer. We analyzed the humoral response following vaccination with the second dose of BNT162b2 in 140 patients with solid malignancies who were receiving anti-cancer therapy at the time of vaccination and 215 participants who had not been diagnosed with cancer. Multivariate analysis was performed, followed by matching the two groups by age, gender and days from vaccination. The humoral response in the cancer patient group was significantly lower than in the non-cancer group: 20/140 seronegative (14.3%) vs. 3/215 (1.4%), p &lt, 0.001, median IgG levels 2231 AU/mL (IQR 445-8023) vs. 4100 (IQR 2231-6774) p = 0.001 respectively. The odds ratio for negative serology results in cancer patients adjusted by age and gender was 7.35 compared to participants without cancer. This effect was observed only in chemotherapy treated patients: 17/73 seronegative (23.3%) vs. 3/215 (1.4%), p &lt, median IgG 1361 AU/mL vs. 4100, p &lt, 0.001 but not in patients treated with non-chemotherapeutic drugs. Reduced immunogenicity to COVID-19 vaccine among chemotherapy-treated cancer patients, raises the need to continue exercising protective measures after vaccination in these patients.

Background There has been a significant increase in the use of immunotherapy and cannabis recently, two modalities that have immunomodulatory effects and may have possible interaction. We evaluated the influence of cannabis use during immunotherapy treatment on response rate (RR), progression-free survival (PFS), and overall survival (OS). Subjects, Materials, and Methods In this retrospective, observational study, data were collected from the files of patients treated with nivolumab in the years 2015–2016 at our hospital, and cannabis from six cannabis-supplying companies. Included were 140 patients (89 nivolumab alone, 51 nivolumab plus cannabis) with advanced melanoma, non-small cell lung cancer, and renal clear cell carcinoma. The groups were homogenous regarding demographic and disease characteristics. A comparison between the two arms was made. Results In a multivariate model, cannabis was the only significant factor that reduced RR to immunotherapy (37.5% RR in nivolumab alone compared with 15.9% in the nivolumab-cannabis group (p = .016, odds ratio = 3.13, 95% confidence interval 1.24–8.1). Cannabis use was not a significant factor for PFS or OS. Factors affecting PFS and OS were smoking (adjusted hazard ratio [HR] = 2.41 and 2.41, respectively (and brain metastases (adjusted HR = 2.04 and 2.83, respectively). Low performance status (adjusted HR = 2.83) affected OS alone. Tetrahydrocannabinol and cannabidiol percentages did not affect RR in any group (p = .393 and .116, respectively). Conclusion In this retrospective analysis, the use of cannabis during immunotherapy treatment decreased RR, without affecting PFS or OS and without relation to cannabis composition. Considering the limitations of the study, further prospective clinical study is needed to investigate possible interaction. Implications for Practice Although the data are retrospective and a relation to cannabis composition was not detected, this information can be critical for cannabis users and indicates that caution is required when starting immunotherapy.

Lung cancer is a worldwide prevalent malignancy. This disease has a low survival rate due to diagnosis at a late stage challenged by the involvement of metastatic sites. Non-small-cell lung cancer (NSCLC) is presented in 85% of cases. The last decade has experienced substantial advancements in scientific research, leading to a novel targeted therapeutic approach. The newly developed pharmaceutical agents are aimed towards specific mutations, detected in individual patients inflicted by lung cancer. These drugs have longer and improved response rates compared to traditional chemotherapy. Recent studies were able to identify rare mutations found in pulmonary tumors. Among the gene alterations detected were mesenchymal epithelial transition factor (MET), human epidermal growth factor 2 (HER2), B-type Raf kinase (BRAF), c-ROS proto-oncogene (ROS1), rearranged during transfection (RET) and neurotrophic tyrosine kinase (NTRK). Ongoing clinical trials are gaining insight onto possible first and second lines of medical treatment options intended to enable progression-free survival to lung cancer patients.

The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the field of oncology. For many cancer types, treatment paradigms have changed, as immunotherapy is increasingly being integrated into frontline standard-of-care treatments and producing meaningful and prolonged responses. This has inspired an avalanche of clinical trials studying ICIs in all types of malignancies, including gynecological cancers. Ovarian and endometrial cancers are characterized by DNA damage repair defects, either via disruption of the homologous recombination DNA repair mechanism in the former or via defects in the mismatch repair (MMR) pathway in the latter, which lead to a high load of neoantigens in both. Cervical cancer is dependent on the expression of human papillomavirus (HPV) proteins, which induce an immune response. Regardless, clinical trials testing ICIs in gynecological malignancies have initially led to disappointing results. Despite durable responses in some patients, overall response rates have been dismal. Nevertheless, in recent years, with the development of better predictive tumor biomarkers, such as microsatellite instability for endometrial cancer and programmed death ligand 1 for cervical cancer, ICIs have found their way into routine treatments for patients with advanced-stage disease. ICI-based combinations, although adding toxicity, have further improved response rates, and new combinations are currently being tested in clinical trials, as are other immunotherapy modalities, such as adoptive cell transfer and HPV-based vaccines. This review summarizes current clinical evidence supporting the use of immunotherapy in gynecological malignancies and describes studies in progress, with a focus on ICIs and predictive response biomarkers.

Introduction The aim of our study was to evaluate whether a biopsy from the tumor base after transurethral resection of bladder tumor (TURBT) has an impact on subsequent management of patients with bladder tumors. While tumor base biopsy at the completion of TURBT is a common practice, there is no definition of its role within the major international professional guidelines. Material and methods We retrospectively reviewed the records of consecutive patients undergoing TURBT between 2015 and 2019 at our institution. We recorded demographic and tumor characteristics of initial TURBT, tumor base biopsy and restaging TURBT pathology outcomes. The pathologic outcomes were correlated to assess the additional value of a separate tumor base biopsy. Results A total of 532 patients underwent TURBT. A separate tumor base biopsy after completion of TURBT was performed in 154 patients. The mean patient's age was 72.8 ±11.7 years (range 48-94) and 119 (77.2%) were men. In 40 patients (25.9%) muscle was absent in the pathological specimen of the tumor resection. Muscle was present in all but 6 (3.9%) tumor base biopsies. Of the 33 patients who underwent repeated transurethral resection for pT1 tumors, 2 had residual low-grade pTa, 1 had residual high-grade pT1, and 3 patients were upstaged to pT2. Conclusions Although tumor base biopsy at the completion of TURBT is a common practice, our analysis fails to demonstrate any tangible benefit in the staging of bladder tumors. In our experience tumor base biopsy did not change the management in patients with superficial or muscle invasive disease.

Ureteral reconstructions pose a challenge for urologists. We describe a novel reconstructive technique for long upper ureteral obliteration with an intrarenal pelvis. The obliterated ureteral segment was excised and the healthy segment of the ureter was spatulated and anastomosed end-to-side to the intrarenal lower calyx (ureterocalycostomy). The procedure was successfully performed without any complication. To date, the patient's clinical state, renal function and radiographic imaging are stable without any evidence of deterioration. The described technique is a useful surgical option for select patients with long upper ureteral obliteration and intrarenal pelvis.

Approximately one-half of advanced cutaneous melanomas have a V600 mutation in the BRAF gene that activates the mitogen-activated protein kinase pathway. The combination of BRAF plus MEK inhibitors is one of the most effective treatments for these patients. Severe neurological toxicities have been reported in the literature. However, these toxicities are very rare. Here, we present one patient with acute motor and sensory axonal neuropathy, which is a subtype of Guillain-Barre syndrome, secondary to treatment with MEK inhibitors. This side effect had never been described as related to these agents. However, the mitogen-activated protein kinase pathway can be involved in Guillain-Barre syndrome, and awareness of early neurological injury signs is important in patients treated with MEK inhibitors.

Background and Objectives: To determine the efficacy of unilateral transversus abdominis plane (TAP) block versus wound local infiltration for postoperative pain following laparoscopic radical prostatectomy (LRP). Methods: Data of consecutive patients who underwent extraperitoneal LRP and received either wound infiltration or unilateral TAP block for analgesia were retrospectively analyzed. The patients were divided into 2 groups based on the technique used. We compared pain intensity scores and on-demand analgesic use both during the hospital stay and post-discharge between the 2 groups. Results: A total of 48 patients were included, 27 received unilateral TAP blocks (group 1) and 21 were managed with wound infiltration (group 2). The unilateral TAP block group showed lower median pain scores on postoperative days (POD) 1 with pain scores being 0.2 (0–4) and 0.8 (0–4), respectively (p < 0.05). On POD2, the median pain intensity was 0.9 (0–5) and 1.6 (0–6) in groups 1 and 2, respectively (p < 0.05). The median number of on-demand analgesic doses during the POD1 was 0.2 (0–2) and 0.4 (0–2) in groups 1 and 2, respectively (p = 0.19). On POD2, the patients received 0.5 (0–2) and 1.1 (0–3) on-demand doses in groups 1 and 2, respectively (p < 0.05). Conclusion: Unilateral TAP block might improve pain control more pronounced after LRP than wound infiltration.

Angiosarcomas are highly aggressive tumors of endothelial origin, which carry a poor prognosis. Fenofibrate is a hypolipidemic drug, which acts by activating the transcription factor PPARα. It has also been widely reported to have ‘anti-cancer’ activity. The current study investigated its effect in a murine VEGF-dependent angiosarcoma cell-line, MS1 VEGF. The study utilised assays to monitor cell proliferation and viability, apoptosis, cell cycle progression, mitochondrial membrane potential, changes in protein expression, and changes in miRNA expression using microarrays. Fenofibrate showed potent anti-proliferative action in MS1 VEGF angiosarcoma cells, without inducing apoptosis. It enriched cells in G2/M cell cycle phase and hyperpolarised mitochondria. Other PPARα activators failed to mimic fenofibrate action. Inhibitors of PPARα and NFκB failed to reverse the inhibitory effect of fenofibrate and their combination with fenofibrate was cytotoxic. Fenofibrate downregulated the expression of key VEGF-effector proteins, including Akt, ERK, Bcl-2 and survivin, and a chemical inhibitor screen discovered relevance of these proteins to cell proliferation. A miRNA microarray revealed that fenofibrate differentially regulated cellular miRNAs with known roles in cancer and angiogenesis. The data raise the possibility that fenofibrate could be useful in angiosarcoma therapy, especially considering its well-established clinical safety and tolerability profile.

Category: Trauma Introduction/Purpose: INTRODUCTION: Talus fractures are not uncommon and one of the serious fractures in foot and ankle. Peroneal tendon dislocation is one of the commonly missed soft tissue injuries which may have significant impact on the outcomes including persistent pain and swelling. AIM: To report the incidence of peroneal tendon dislocation in talus fracture and the significance of fleck sign in the diagnosis of peroneal tendon dislocation. Methods: We retrospectively reviewed 100 consecutive talus fractures in the period between 1/1/2011 to 1/7/2017. Inclusion criteria were: The patient underwent open reduction and internal fixation, had pre-operative CT scan that is available for review and 3 views ankle plain radiographs. 2 independent authors review the radiographs for peroneal tendon dislocation, fleck sign and fracture classification if any. Any dispute was resolved by the senior author. Patient records were reviewed for laterality, age, sex, mode of injury, associated injuries and operative interventions. 43 ankles met inclusion criteria. 42 were males, mean age was 31 year and the predominant modes of injury were fall from height or unknown. Results: Peroneal tendon dislocation was found in 9 patients out of 43. (20%). All dislocations were found in talar neck fractures, and up to 67% of Hawkins type III and IV Talar neck fractures were associated with peroneal tendon dislocation. Risk of dislocation increased with severity of the fracture. 5 cases of peroneal tendon dislocation out of 9 were associated with lateral or bimalleolar fractures. Most of the dislocations were missed and no additional procedures were done to address such injury. Fleck sign sensitivity was 44.4% while specificity was 88%. The Negative Predictive Value (PPV) was 86%. Conclusion: Peroneal tendons dislocation is associated with 20% of talus fractures. The incidence of dislocation increases with neck fracture and severity of these fractures. Fleck sign is highly specific radiographic sign and hence we recommend intra-operative assessment of peroneal tendons in patients with fleck sign.

Edge devices often have to processdata at low power and would benefit from being adaptable. Given that the data coming into these devices is generally unlabeled, unsupervised training on these devices is beneficial. This paper examines a low power approach to implement the winner takes all algorithm, for self-organizing maps through a memristor crossbar based circuit. A novel neuron circuit is designed for the winning neuron detection and lateral inhibition operations. Our experimental results show that the proposed system can self-organize based on unlabeled training data. The proposed design was around 0.002mm$^{\mathbf{2\, $textbf{{in area and consumed about 0.2mW of power. When compared to a CPU, the design had a higher error rate, but was 100 times faster and consumed much lower area and power. Thus when area or power reduction are crucially important, this approach is quite viable.

Background & objective: The gliptins, dipeptidyl peptidase inhibitors (DPP-4 inhibitors) are a relatively new class of antidiabetic drugs that, via their inhibition of DPP-4, a cell membrane–associated serine-type protease enzyme, promote the effects of the endogenous incretins such as glucagon-like peptide 1 (GLP-1) and enhance glucose disposal. The advantage of the gliptins over GLP-1 analogues is that they are orally effective whereas the clinically used incretins, exenatide and liraglutide, have to be administered via sub-cutaneous injection. The first gliptin, sitagliptin, was approved by the FDA in 2006 and six other gliptins have subsequently been approved – vildagliptin (2007 in Europe); saxagliptin (2009, FDA); linagliptin (2011, FDA); anagliptin (2012, Japan); teneligliptin (2012, Japan); alogliptin (2013, FDA). There is a close association between diabetes and cardiovascular disease (CVD) and vascular complications associated with diabetes are responsible for 75% of the deaths of diabetics. Therefore it is important that for any new class of antidiabetic drugs introduced for clinical use that we determine whether such drugs not only show therapeutic efficacy as antidiabetic drugs, but also that they are vasculoprotective and reduce both cardiovascular morbidity and mortality. Endothelial dysfunction that can be functionally defined as a reduced vasorelaxation response to an endothelium-dependent vasodilator, such as acetylcholine, or, at the molecular level, a reduction in the bioavailability of nitric oxide (NO) and/or reduced activity of the enzyme responsible for the generation of NO, namely, endothelial nitric oxide synthase (eNOS). Endothelial dysfunction is a very early indicator of the onset of vascular disease and thus determining whether the gliptins also reduce endothelial dysfunction is very important. The literature concerning the vasculoprotective effects of the gliptins is contradictory with some of the clinical data suggesting a negative effect of the gliptins on vascular function. Thus, the objective of this study was to determine whether the gliptins possess positive or negative effects on endothelial function. Materials & methods: In the present study we used a cell culture protocol with mouse vascular endothelial endothelial cells (MS1-VEGF; CRL-2460, from ATCC, USA) of micro-vascular endothelial origin. The endothelial cells, MMECs, were either cultured under normoglycaemic (NG) conditions for a mouse, 11 mM, or high glucose 40 mM (HG) – a level that equates to the plasma glucose levels that are seen in mouse models of type 2 diabetes, such as the db/db leptin receptor mutant model of type 2 diabetes. The gliptin, alogliptin was chosen for this study and the protocols were designed to determine whether this gliptin reduced, or prevented, the high glucose induced reduction in eNOS phosphorylation at serine 1177 (p-eNOSser1177) as determined by western immunoblot densitometry quantification. A reduction in p-eNOSser1177 will result in a reduced activity of eNOS and hence a reduction in the generation of NO. Thus, the quantification of p-eNOSser1177 serves as a measure of endothelial function. The band densities of the western blot images for eNOS and p-eNOSser1177 were quantified using the basic Quantity One software (Biorad, Inc. CA, USA). Statistical analysis was performed using one-way analysis of variance (ANOVA) and post-hoc comparisons between groups were performed by Tukey's multiple comparison tests. ‘p’ values less than 0.05 were considered to be statistically significant. Results: Our data indicates that a 24-hour exposure to HG reduced p-eNOSser1177 phosphorylation, but the presence of alogliptin reverses the effects of HG and significantly increased the phosphorylation of eNOS, suggesting that this gliptin does protect the microvascular endothelium against hyperglycaemia-induced endothelial dysfunction. Furthermore, the effects of alogliptin were concentration-dependent and were significant with 50 or 100 μM, but not 10 μM alogliptin. Conclusion: Our findings indicate that, in a concentration-dependent manner, alogliptin protects endothelial cells against the negative effects that hyperglycaemia (high glucose) has on endothelial function as measured by alogliptin-induced changes in the phosphorylation of eNOS at serine 1177. Further studies are underway, using a functional myograph assay, to determine whether alogliptin can also prevent hyperglycaemia-induced endothelial dysfunction in mouse aortic vessels.AcknowledgementThis work was supported by a Summer Student Research Fellowship (SSRF) from Weill Cornell Medicine-Qatar and an Undergraduate Research Experience Program grant, UREP 18-055-3-012 from the Qatar National Research Fund (QNRF). The statements made herein are solely the responsibility of the authors.

Introduction: Angiosarcomas are aggressive and malignant endothelial tumors. Several risk factors have been identified (eg. BRCA1/2 mutations, radiation, toxins and lymphedema), but pathological mechanisms remain unclear and the prognosis is poor. Fenofibrate is a hypolipidemic drug widely prescribed to treat dyslipidemia. It reduces LDL, vLDL, and triglycerides and increases HDL levels. The primary mechanism of fenofibrate action involves activation of the transcription factor PPARα, but other PPARα-independent mechanisms also exist. More recently, its efficacy as an anti-tumor drug has emerged. However, little is known about the endothelial actions of fenofibrate and whether these contribute to its anti-tumor properties. Here, we explore the actions of fenofibrate in endothelial cells that are capable of forming angiosarcomas in vivo. Methods: Mouse endothelial cells (MS1 VEGF; # CRL-2460) capable of inducing angiosarcoma were purchased from ATCC. These are primary mouse pancreatic islet cells that were transformed with temperature-sensitive SV40 large T antigen and screened for resistance with G418. The G418-selected immortalized cells were then retro-virally infected with a vector encoding primate VEGF. These cells have been shown to induce angiosarcomas in vivo in mice and are a good model system for studies of cancers, particularly angiosarcomas. Results: Incubation of MS1 VEGF cells with clinically relevant concentrations of fenofibrate (25-100 μM) strongly reduced their viability, with cell numbers reduced by approximately 10-fold after a 48h incubation with 50 μM fenofibrate {Cells/ml: ~1.8 million (control) versus ~0.2 million (50 μM fenofibrate)}. Morphologically, the cells were characterized by the appearance of perinuclear cytoplasmic vacuoles. In contrast, fenofibrate had a smaller effect on cell viability in primary human endothelial cells {Cells/ml: ~0.6 million (control) versus ~0.4 million (50 μM fenofibrate)}, thereby suggesting a relatively selective effect on MS1 VEGF cells. Hypothesizing that the effect of fenofibrate in these cells occurred through the induction of apoptosis, the effect of fenofibrate on the expression of proteins critical for cell survival and apoptosis was investigated biochemically. The data revealed down-regulation of the anti-apoptotic Bcl family protein Bcl-2 and the inhibitor of apoptosis protein survivin after treatment with fenofibrate. Fenofibrate treatment also decreased the expression of Akt and Erk proteins. In contrast, expression of Bcl-xl was relatively unaffected. Expression of the anti-diabetic hormone FGF-21 was detected in MS1 VEGF cells and this was also decreased after fenofibrate incubation. Conclusions: The data revealed a strong anti-proliferative action of fenofibrate in angiosarcoma-inducing endothelial cells but not primary human endothelial cells. These effects potentially occurred through regulation of proteins critical for cell survival and apoptosis. Future studies: Future investigations will focus on: (a) delineating the mechanisms involved (PPARα-dependent or -independent) (b) direct measurements of apoptosis by flow cytometry (c) the effect of fenofibrate on endothelial migration, invasion, proliferation, wound healing and tubule formation and (d) testing the possibility that fenofibrate acts by triggering changes in cellular calcium handling and (e) testing fenofibrate efficacy in angiosarcomas in vivo in mice. Key words: Apoptosis, Bcl-2, cancer, fenofibrate, FGF-21, survivin. This work was supported by a National Priorities Research Program grant (NPRP 6-428-3-113).