Cytotoxic and genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells in vitro

Quercetin is the main flavonoid in diet with a potential in the treatment of cancer, cardiovascular, and neurodegenerative diseases. Due to its specific planar chemical structure, quercetin readily forms chelates with metal ions. Complexes of bioactive compounds and metal ions such as lanthanum often show strong cytotoxic and antitumour properties. The aim of this study was to compare the genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells with compare it to the effects of free ligands, quercetin, and lanthanum alone. The quercetin/lanthanum complex showed considerable cytotoxicity in the concentration range of (100 to 1000) mmol mL-1 and exposure time of three hours. The complex also induced a dose-dependent pro-oxidative effects and the formation of single-strand and double-strand DNA breaks. Although we obtained promising results on the cell level, future experiments should answer whether the quercetin/lanthanum complex is cancer-specific and stable enough in physiological conditions to make a potential new antitumour drug.     

Regressing seborrheic keratosis - clinically and dermoscopically mimicking a regressing melanoma

The diagnosis of seborrheic keratosis is a clinical diagnosis. In a certain percentage of cases, differential diagnosis between seborrheic keratosis and malignant melanoma is difficult. We describe a case of regressing seborrheic keratosis simulating malignant melanoma. Clinical, dermoscopic and histopathologic examinations were performed for the occurrence of an asymmetric, irregularly demarcated, irregularly pigmented lesion measuring 1.3 x 1.5 cm on the right part of the abdomen in a 76-year-old male Caucasian. In order not to miss melanoma, the excision and histopathologic examination of the lesion with peppering is essential.     

25 (OH) D3 levels,incidence and recurrence of different clinical forms of benig paroxysmal positional vertigo

Introduction

Benign paroxysmal positional vertigo is the most common cause of dizziness in the general population. It is a condition with potential impact of reduced levels of vitamin D on its recurrent attacks.

Clinical Outcomes in Stage III Non-small Cell Lung Cancer Patients Treated with Durvalumab After Sequential Or Concurrent Platinum-based Chemoradiotherapy – Single Institute Experience

BackgroundChemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the usage of gemcitabine.Patients and methodsWe retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treatment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients.ResultsEighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during concurrent treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%).ConclusionsOur survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.Key words: non-small cell lung cancer, stage III, chemoradiotherapy, durvalumab     

Adeno-associated Virus–mediated Delivery of a Recombinant Single-chain Antibody Against Misfolded Superoxide Dismutase for Treatment of Amyotrophic Lateral Sclerosis

There is emerging evidence that the misfolding of superoxide dismutase 1 (SOD1) may represent a common pathogenic event in both familial and sporadic amyotrophic lateral sclerosis (ALS). To reduce the burden of misfolded SOD1 species in the nervous system, we have tested a novel therapeutic approach based on adeno-associated virus (AAV)–mediated tonic expression of a DNA construct encoding a secretable single-chain fragment variable (scFv) antibody composed of the variable heavy and light chain regions of a monoclonal antibody (D3H5) binding specifically to misfolded SOD1. A single intrathecal injection of the AAV encoding the single-chain antibody in SOD1^G93A mice at 45 days of age resulted in sustained expression of single-chain antibodies in the spinal cord, and it delayed disease onset and extension of life span by up to 28%, in direct correlation with scFv titers in the spinal cord. The treatment caused attenuation of neuronal stress signals and reduction in levels of misfolded SOD1 in the spinal cord of SOD1^G93A mice. From these results, we propose that an immunotherapy based on intrathecal inoculation of AAV encoding a secretable scFv against misfolded SOD1 should be considered as potential treatment for ALS, especially for individuals carrying SOD1 mutations.     

The influence of varying inspired fractions of O₂ and CO₂ on the development of involuntary breathing movements during maximal apnoea

The growing urge to breathe that occurs during breath-holding results in development of involuntary breathing movements (IBMs). The present study determined whether IBMs are initiated at critical levels of hypercapnia and/or hypoxia during maximal apnoea. Arterial blood gasses at the onset of IBM were monitored during maximal voluntary breath-holds. Eleven healthy men performed breath holds after breathing air, hyperoxic–normocapnia, hypoxic–normocapnia, and normoxic–hypercapnia. Pre-breathing of the gas mixtures facilitated the IBM onset, reducing the time-to-onset for ∼46% (hyperoxic condition) and for ∼80% (hypoxic condition) compared to the normoxic air breathing time. A strong correlation (R = 0.83, P = 0.002) between arterial partial pressure of CO₂ (Pa_CO2${\text{Pa}}_{{\text{CO}}_2}$) at IBM onset after pre-breathing hyperoxic and hypercapnic gas mixtures was observed, suggesting the existence of a possible IBM Pa_CO2${\text{Pa}}_{{\text{CO}}_2}$ threshold level of ∼6.5 ± 0.5 kPa. No clear “threshold” was observed for partial pressure of arterial O₂ (Pa_O2${\text{Pa}}_{{\text{O}}_2}$). However, we observed that IBM onset was influenced, in part, by an interaction between Pa_O2${\text{Pa}}_{{\text{O}}_2}$ and Pa_CO2${\text{Pa}}_{{\text{CO}}_2}$ levels during maximal apnoea. This study demonstrated the complex interaction between arterial blood-gases and the physiological response to maximal breath holding.