Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection.

BACKGROUND: The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH. METHODS: We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS). DISCUSSION: The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented. TRIAL REGISTRATION: ClinicalTrials.gov NCT04735445. Registered on 25 June 2019.

Computational Study of the Binding Modes of Diverse DPN Analogues on Estrogen Receptors (ER) and the Biological Evaluation of a New Potential Antiestrogenic Ligand.

Estrogen (17ß-estradiol) is essential for normal growth and differentiation in the mammary gland. In the last three decades, previous investigations have revealed that Estrogen Receptor Alpha (ERα) plays a critical role in breast cancer. More recently, observations regarding the widespread expression of ERß-like proteins in normal and neoplastic mammary tissues have suggested that ERß is also involved in the mentioned pathology. Design of new drugs both steroidal and nonsteroidal that target any of these receptors represents a promise to treat breast cancer although it remains a challenge due to the sequence similarity between their catalytic domains. In this work, we propose a new set of compounds that could effectively target the estrogen receptors ERα and ERß. These ligands were designed based on the chemical structure of the ERß-selective agonist Diarylpropionitrile (DPN). The designed ligands were submitted to in silico ADMET studies, yielding in a filtered list of ligands that showed better drug-like properties. Molecular dynamics simulations of both estrogen receptors and docking analysis were carried-out employing the designed compounds, from which two were chosen due to their promising characteristics retrieved from theoretical results (docking analysis or targeting receptor predictions). They were chemically synthetized and during the process, two precursor ligands were also obtained. These four ligands were subjected to biological studies from which it could be detected that compound mol60b dislplayed inhibitory activity and its ability to activate the transcription via an estrogenic mechanism of action was also determined. Interestinly, this observation can be related to theoretical binding free energy calculations, where the complex: ERß-mol60b showed the highest energy ΔGbind value in comparison to others.

Assessment of cell death mechanisms triggered by 177Lu-anti-CD20 in lymphoma cells.

The aim of this research was to evaluate the cell cycle redistribution and activation of early and late apoptotic pathways in lymphoma cells after treatment with 177Lu-anti-CD20. Experimental and computer models were used to calculate the radiation absorbed dose to cancer cell nuclei. The computer model (Monte Carlo, PENELOPE) consisted of twenty spheres representing cells with an inner sphere (cell nucleus) embedded in culture media. Radiation emissions of the radiopharmaceutical located in cell membranes and in culture media were considered for nuclei dose calculations. Flow cytometric analyses demonstrated that doses as low as 4.8Gy are enough to induce cell cycle arrest and activate late apoptotic pathways.

Click chemistry for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin.

(99m)Tc-HYNIC labeled Lys(3)-bombesin has shown specific binding to gastrin-releasing peptide receptors (GRP-r) over-expressed in cancer cells. Click chemistry offers an innovative functionalization strategy for biomolecules such as bombesin. The aim of this research was to apply a click chemistry approach for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin and to compare the in vitro MCF7 breast cancer cell uptake and biodistribution profile in mice with that of (99m)Tc-EDDA/HYNIC-Lys(3)-bombesin. The results suggest a higher lipophilicity for (99m)Tc(CO)(3)-triazole-Lys(3)-bombesin which explains its higher in vivo hepatobiliary elimination. Pancreas-to-blood ratio for (99m)Tc(CO)(3)-triazole-Lys(3)-bombesin was 4.46 at 3 h and both bombesin radiopharmaceuticals showed specific recognition for GRP receptors in MCF7 cancer cells. Click chemistry is a reliable approach for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin.

[Chagas' disease among blood donors in Bolivia].

A questionnaire survey of blood donors at Santa Cruz General Hospital, Bolivia, showed that while there were no seropositive cases of syphilis, HBsAg, and HIV, the prevalence of Chagas' disease was very high (23%) among the 225 blood donors who responded to this questionnaire. Actual cases of Chagasic seropositive blood being used for blood transfusion were seen, including the urgent need for a program for Chagas' disease in Bolivia. From the results of this study, it is recommended that for blood donors from South American countries, the presence/absence of Chagas' disease should be confirmed.