3,6-dimethoxyxanthone from 2,2’,4,4’- tetrahydroxy-benzophenone via Microwave-Assisted Annulation

Xanthones are tricyclic aromatic compounds that have multiple pharmacological uses due to their anti-tumor, antioxidant, anti-inflammatory, anti-bacterial, and potentially chemopreventive properties. The target of this research was to optimize a two-step synthesis of 3,6-dimethoxyxanthone (3) from 2,2’,4,4’-tetrahydroxy-benzophenone (1) via microwave-assisted (200 °C, 30-40 min., 150 W) sodium acetate-catalyzed annulation. The product, 3,6-dihydroxyxanthone (2), was then methylated to (3) using dimethyl sulfate (DMS) and sodium carbonate in acetone at reflux. The product yields were 93% (\u3e99% purity) for (2) and 94% (\u3e99% purity) for (3). Characterization was accomplished using 1H NMR, FTIR, melting point, TLC, HPLC, and GCMS. The product (3) was made available for additional screening and research, such as synthesizing dyes like fluorescein and its derivatives

Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

<p>Abstract</p> <p>Background</p> <p>BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP). BSEP disease is associated with an increased risk of hepatobiliary cancer.</p> <p>Case Presentation</p> <p>A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat.</p> <p>Conclusions</p> <p>Clinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.</p

Patterns of patient-reported symptoms and association with sociodemographic and systemic sclerosis disease characteristics: a scleroderma Patient-centered Intervention Network (SPIN) Cohort cross-sectional study

Background: Systemic sclerosis is a heterogenous disease in which little is known about patterns of patient-reported symptom clusters. We aimed to identify classes of individuals with similar anxiety, depression, fatigue, sleep disturbance, and pain symptoms and to evaluate associated sociodemographic and disease-related characteristics. Methods: This multi-centre cross-sectional study used baseline data from Scleroderma Patient-centered Intervention Network Cohort participants enrolled from 2014 to 2020. Eligible participants completed the PROMIS-29 v2.0 measure. Latent profile analysis was used to identify homogeneous classes of participants based on patterns of anxiety, depression, fatigue, sleep disturbance, and pain scores. Sociodemographic and disease-related characteristics were compared across classes. Findings: Among 2212 participants, we identified five classes, including four classes with “Low” (565 participants, 26%), “Normal” (651 participants, 29%), “High” (569 participants, 26%), or “Very High” (193 participants, 9%) symptom levels across all symptoms. Participants in a fifth class, “High Fatigue/Sleep/Pain and Low Anxiety/Depression” (234 participants, 11%) had similar levels of fatigue, sleep disturbance, and pain as in the “High” class but low anxiety and depression symptoms. There were significant and substantive trends in sociodemographic characteristics (age, education, race or ethnicity, marital or partner status) and increasing disease severity (diffuse disease, tendon friction rubs, joint contractures, gastrointestinal symptoms) across severity-based classes. Disease severity and sociodemographic characteristics of “High Fatigue/Sleep/Pain and Low Anxiety/Depression” class participants were similar to the “High” severity class. Interpretation: Most people with systemic sclerosis can be classified by levels of patient-reported symptoms, which are consistent across symptoms and highly associated with sociodemographic and disease-related variables, except for one group which reports low mental health symptoms despite high levels of other symptoms and substantial disease burden. Studies are needed to better understand resilience in systemic sclerosis and to identify and facilitate implementation of cognitive and behavioural strategies to improve coping and overall quality of life. Funding: National Institute of Nursing Research (F31NR019007), Canadian Institutes of Health Research, Arthritis Society Canada, the Lady Davis Institute for Medical Research, the Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland

Protein tyrosine phosphatases in glioma biology

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas

Human parvovirus B19 infection and hydrops fetalis in Rio de Janeiro, Brazil

Formalin-fixed paraffin embedded lung and liver tissue from 23 cases of non immune hydrops fetalis and five control cases, in which hydrops were due to syphilis (3) and genetic causes (2), were examined for the presence of human parvovirus B19 by DNA hybridisation. Using in situ hybridisation with a biotynilated probe one positive case was detected. Using 32P-labelled probes in a dot blot assay format, five further positives were obtained. These were all confirmed as positive by a nested polymerase chain reaction assay. Electron microscopy revealed virus in all these five positive cases. The six B19 DNA positive cases of hydrops fetalis were from 1974, 1980, 1982, 1987 and 1988, four of which occurred during the second half of the year, confirming the seasonality of the disease

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt

BACKGROUND: Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. METHODS: In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. RESULTS: Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. CONCLUSIONS: The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area