SnO2 nanoparticles/waste masks carbon hybrid materials for DNA biosensor application on voltammetric detection of anti-cancer drug pazopanib.

This present study is the first investigation of pazopanib-dsDNA binding using bare and modified GCE. The interaction was mainly evaluated based on the decrease of voltammetric signal of deoxyadenosine by differential pulse voltammetry using three different ways, including the incubated solutions, dsDNA biosensor, and nanobiosensor. The nanobiosensor was fabricated with the help of SnO2 nanoparticles and carbon hybrid material. The carbon material is derived from the waste mask, the most used personal protective equipment for the ongoing COVID-19 pandemic. Both materials were synthesized via the green synthesis technique and characterized by various techniques, including BET, TEM, SEM-EDX, AFM, XPS, and XRD. Spectrophotometric and molecular docking studies also evaluated the pazopanib-dsDNA binding. All calculations showed that pazopanib (PZB) was active in the minor grove region of DNA.

Metastatic Pulmonary Epithelioid Hemangioendothelioma: A Case Report

Introduction: Pulmonary Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor;with approximately 248 cases of reported in the literature, making diagnosis and management challenging. Case: A 57-year-old female with past history of hypertension, hyperthyroidism and scoliosis was admitted with worsening chronic right flank pain. Initial lab workup was unremarkable. revealed COVID-19 PCR test was negative. CT chest revealed bilateral pleural effusions and CT abdomen showed 2.8 x2.0cm vague hypo-attenuating lesion in the right hepatic lobe. A repeat CT scan following thoracentesis demonstrated multiple bilateral pulmonary nodules, with the largest located in the right lower lobe (RLL) measuring 2.1cm (Image). Flowcytometry on bronchoalveolar lavage fluid was significant for a CD4/CD8 ratio of 5;however, the transbronchial biopsy was unremarkable. Differential diagnosis included sarcoidosis and hence patient was discharged on prednisone with Bactrim prophylaxis. She underwent VATS lung biopsy. RLL and pleural biopsies revealed EHE. Following the prednisone taper, patient was placed on pazopanib 800mg. The dose of medication subsequently reduced to 300-600mg due to adverse events. Repeat CT scans at 3 months demonstrated minimal change in size of the nodules. Patient continues to be followed on regular basis with a stable clinical status. Discussion: EHE is a low-intermediate grade malignancy which affects mostly liver, lungs and bones;although it can be found in any bodily tissue. Up to 50- 76% of patients are asymptomatic at diagnosis, with the most common symptomatic being local pain. Radiologically, Pulmonary EHE consists of bilateral perivascular nodularity. Our case describes the clinical course of a rare and poorly understood disease. Clinicians must be aware of the characteristics of unusual diseases and pursue robust diagnostic approach. In our case, biopsy led to the definitive diagnosis of EHE. Because of its rarity, there is no standard therapy for metastatic disease. Pazopanib has demonstrated prolonged long-term disease control in observational studies. Some other reports have shown response to cytotoxic chemotherapy such as doxorubicin-containing regimens, however, long-term survival is compromised. Lenalidomide, sorafenib and sunitinib have also been used, but the experience is limited. Our patient is currently on her 4th month of treatment with pazopanib, with 3-month follow-up showing no progression of disease. (Figure Presented).

Real-word evidence in patients treated with pazopanib for advanced/metastatic renal cell carcinoma (mRCC): The APOLON study

Background: The efficacy and safety of pazopanib (PZP) have been evaluated in pivotal randomized, clinical trials Real-world evidence (RWE) is required to further assess its use, effectiveness and safety in mRCC in clinical routine practices. Methods: APOLON is a non-interventional, multicentric prospective study with mRCC patients who receive frontline PZP treatment. The study is designed to assess PZP Progression-Free Survival (PFS) (under treatment), Overall Survival (OS), Objective Response Rate (ORR) assessed by investigators, tolerability and subsequent post-pazopanib therapy sequences. Impact of COVID-19 on patient's care was also assessed. Eligible patients were recruited from Nov 2017 to Jan 2019 in 55 participant sites in France. This interim analysis presents results 30 months (mo) after last patient was enrolled in the study. Results: The 217 patients were 71.1% males, with a median age of 69.6 years and had mRCC with a favourable (27.1%), intermediate (52.1%) or poor (20.8%) IMDC risk score according to physician. ECOG-PS was 0, 1 and ≥2 in respectively 43.3%, 39% and 17.6% of patients. Metastases were mainly located in lungs (64.1%), bones (28.6%), mediastinal (18%)/abdominal (17.1%). Patients had an history of partial/total nephrectomy in 54.8% of cases and previous local treatments for metastases in 27.6%. Median PFS, assessed by investigator, was 10.5 mo (95%CI: 9-12.4), similarly in patients < 65-year-old (YO) with 11.3 mo (95%CI: 7-16.3) and in those ≥ 65 YO with 9.9 mo (95%CI: 8.9-12). When assessed according to the IMDC risk score, mPFS was 18.1 mo (95%CI: 9.9-23.3) in favourable, 11.5 mo (95%CI: 8.7-14.4) in intermediate and 6.2 mo (95%CI: 3.5-9.5) in poor mRCC. The median OS was 27.3 mo (95%CI: 24.3 - ND). Investigator-assessed ORR was 48.3% with a CR in 6 patients (3.5%) and a PR in 77 (44.8%). After a median treatment duration of 10.1 mo, 190 patients (87.6%) discontinued PZP and 67.9% received at least one post-PZP line. Second line post-PZP consisted in nivolumab (71.3%), cabozantinib (14.7%), sunitinib (7%) or other (7%). Adverse Event (AE) leading to PZP dose reduction and discontinuation were reported in 42% and 40.9% of patients and treatment-related serious AE in 22.2% of patients. No safety signal was newly identified. The impact of the Covid 19 pandemic was limited on patients' cares and study follow-up. Visits during the pandemic included 84.1% of tumour evaluation. For 29 patients (14.1%), follow-up visits were carried out as a teleconsultation. Few patients (5,7%) had no visits during the pandemic. Conclusions: The APOLON study confirms PZP effectiveness and safety in patients with mRCC in real-life setting. The efficacy of pazopanib remains significant in patients aged 65 years and older. It is highly associated with risk score. The COVID pandemics had limited impact on patients' cares.