Metformin delivery using chitosan-capped gold nanoparticles in glioblastoma cell lines

Introduction: Metformin (MET), an old anti-diabetic drug, has proven unexpected anti-glioblastoma effects, by impacting cell proliferation, migration and invasion. However, its remarkable anti-cancer efficacy is mainly limited to the use of high millimolar concentrations in in vitro studies, which are hard to be attained in the clinical setting. Aim: The aim of this paper was to synthetize gold nanoparticles loaded with MET and to test if an enhanced drug delivery via nanotechnology could overcome the limitations of small drug concentrations. Materials and Methods: Gold nanoparticles were functionalized with chitosan (GNPc) and loaded with 80 µM of MET. Their size, zeta potential and stability were characterized and their internalization within tumor cells was assayed through dark field microscopy. Three primary glioblastoma stem cell lines were treated with 5, 10 and 20 µg/mL concentrations of nanoparticles and irradiated. The anti-tumoral effect was evaluated through the MTT cell viability assay. Results: MET-GNPc are easily synthetized and have a positive zeta potential, spherical shape and a median size of 26 nm. MET-GNPc have an increased cell internalization and affect the viability of all three glioblastoma cell lines used compared to control and free MET. However, their anti-cancer effect is not statistically different when compared to GNPc, although a slight tendency to a better response may be observed. Conclusion:Despite an increased cell internalization, the small micromolar concentrations of metformin does not bring an additional benefit to chitosan-based GNPs. Novel delivery methods being able to carry a higher drug concentration of metformin should be tested

Real-World Patterns and Decision Drivers of Radiotherapy for Lung Cancer Patients in Romania: RADIO-NET Study Results

Radiotherapy (RT) plays a crucial role in all stages of lung cancer. Data on recent real-world RT patterns and main drivers of RT decisions in lung cancer in Romania is scarce; we aimed to address these knowledge gaps through this physician-led medical chart review in 16 RT centers across the country. Consecutive patients with lung cancer receiving RT as part of their disease management between May–October 2019 (pre-COVID-19 pandemic) were included. Descriptive statistics were generated for all variables. This cohort included 422 patients: median age 63 years, males 76%, stages I–II 6%, III 43%, IV 50%, mostly adeno- and squamous cell carcinoma (76%), ECOG 0-1 50% at the time of RT. Curative intent RT was used in 36% of cases, palliative RT in 64%. Delays were reported in 13% of patients, mostly due to machine breakdown (67%). Most acute reported RT toxicity was esophagitis (19%). Multiple disease-, patient-, physician- and context-related drivers counted in the decision-making process. This is the first detailed analysis of RT use in lung cancer in Romania. Palliative RT still dominates the landscape. Earlier diagnosis, coordinated multidisciplinary strategies, and the true impact of the multimodal treatments on survival are strongly needed to improve lung cancer outcomes

Contrast enhanced ultrasound of renal masses. A reappraisal of EFSUMB recommendations and possible emerging applications

Abstract The main imagistic method for characterization of renal lesions is contrast enhanced computed tomography (CECT). Disadvantages of CECT are a contrast-induced nephropathy in patients with renal impairment, allergic reactions and high costs. Contrast-enhanced ultrasound (CEUS) evaluation of hepatic and non-hepatic lesions is a relatively new, but increasingly utilised, diagnostic method. In 2011 the European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) updated the Guidelines and Recommendations on the Clinical Practice of CEUS and included in the recommendation the renal pathology. However, there are several possible new indications that have not been discussed (pyelocaliceal masses and renal vein thrombosis) and several issues that remain controversial such as the differentiation of benign and malignant tumours or the differentiation of lymphoma and metastasis. This study aims to review literature data, as well as reveal the latest findings in the field of renal CEUS

Microwave ablation in the treatment of liver tumors. A better tool or simply more power?

It has been a long time since tumor ablation was first tested in patients with liver cancer, especially hepatocellular carcinoma. Since than it has become a first line treatment modality for hepatocellular carcinoma. Over the years, the indications of thermal ablation have expanded to colorectal cancer liver metastases and intrahepatic cholangiocarcinoma as well. Together with the new indication for ablation, new ablation devices have been developed as well. Among them microwave ablation shows potential in replacing radiofrequency ablation as the preferred method of thermal ablation in liver cancer. The debate whether radiofrequency or microwave ablation should be the preferred method of treatment in patients with liver cancer remains open. The main purpose of this review is to offer some answers to the question: Microwave ablation in liver tumors: a better tool or simply more power? Various clinical scenarios will be analyzed including small, medium, and intermediate size hepatocellular carcinoma, colorectal cancer liver metastases and intrahepatic cholangiocarcinoma. Furthermore, the advantages, limitations, and technical considerations of MWA treatment will be provided also

Arsenic trioxide plus cisplatin/interferon α-2b/doxorubicin/capecitabine combination chemotherapy for unresectable hepatocellular carcinoma

BACKGROUND AND OBJECTIVES: The failure of existing treatments for liver cancer has recently been attributed to the existence of cancer stem cells, which are difficult to kill using current drugs due to their chemoresistant properties as well as their ability to stimulate neoangiogenesis. The aim of the current study was to evaluate in vitro the antitumor efficacy of arsenic trioxide in combination with conventional chemotherapy, as proposed by the concept of “differentiation therapy” in anticancer research. MATERIALS AND METHODS: Cancer stem cells showed enhanced chemoresistance to cancer drugs (carboplatin and doxorubicin) and had the ability to exclude rhodamine 123 dye, proving the existence of the multidrug resistance efflux pump. Arsenic trioxide was added prior to a tyrosine kinase inhibitor or to a slightly modified Piaf regimen with capecitabine replacing 5-fluorouracil. We also compared both cancer and normal stem cell lines with the hepG2 non-stem liver cancer cell line to investigate the differences between differentiated and more anaplastic cells. Molecular characterization (immunocytochemistry and rt-PCr analysis) of all the cell lines was carried out. RESULTS: Initially, the cells had a high proliferative potential, even when cultured in a medium supplemented with cytostatics, eliminated rhodamine 123 immediately in culture and also formed spheroids in suspension. The molecular characterization showed the expression of albumin, α1-antitrypsin, α-fetoprotein, citokeratin-18, telomerase, CD90 and CD133. Low concentrations of arsenic trioxide lead to morphologic differentiation and differentiation-associated cytochemical features, like increased sensitivity to cytostatic drugs. CONCLUSION: Our study suggests that arsenic trioxide sensitizes liver stem-like cancer cells to conventional chemotherapy. Still, further studies on animal models will be needed before we implement this idea in human clinical trials

Management of bone metastases in patients with castration-resistant prostate cancer

Bone metastases are a very common problem in prostate cancer. They are associated with considerable morbidity, adversely affect quality of life and frequently lead to advanced bone events (so-called skeletal-related events, SREs); SREs include fractures, spinal cord compression and the requirement for bone surgery or bone radiation. The aim of this paper was to evaluate currently available treatment options in the prevention and management of SREs and bone metastases in men with castration-resistant prostate cancer and to outline the importance of interdisciplinary management strategies. It also discusses the diagnostic workup of osseous metastases and practical considerations for the utilization of bone-targeted therapies in accordance with current guidelines to provide a consensus for special and/or difficult clinical situations.</jats:p