Gt75 aptamer against eukaryotic elongation factor 1a as potential anticancer drug For castrate-resistant prostate cancer (crpc)

Prostate cancer diagnosis is increasing, being the second most frequently cancer in men worldwide. The treatment of castrate-resistant prostate cancer is often unsuccessfully and new therapeutic interventions are searching for. Nucleic acid aptamers targeting eEF1A proteins are emerging molecular tools for the control of cancer growth. We found that an aptamer named GT75 was able to bind to eEF1A proteins of human prostate cancer cell lines and to significantly and specifically reduce their growth with respect to the control oligomer CT75. The highest anti-proliferation effect was found in the androgen-independent PC-3 cells. Interestingly, GT75 was able to specifically inhibit the migration of PC-3 cells but not that of the nontumorigenic PZHPV-7 cells. The overall results suggest that the GT75 aptamer targeting eEF1A proteins is a promising molecular drug to develop for the control of the castrate-resistant prostate cancer

Medicine, Biology and Mathematics

Although mathematics finds large application in physical sciences, its use in the medical and biological field is less usual. Nevertheless, mathematical models can help in understanding many medical and biological phenomena and they can be a powerful tool in the designing process of many technological devices connected to the above mentioned phenomena. Of course, fundamental pre-requisite for building up a reliable mathematical model is the deep cooperation of different competences such as those of medical doctors, biologists, pharmacists and engineers. This paper deals with four different examples of mathematical models developed by our group and dealing with restenosis, enzyme action on two dimensional DNA brushes, oral delivery of drug in amorphous or nano-crystalline form and tumour cell behaviour

Plasma Circular RNAs as Biomarkers for Breast Cancer

Breast cancer (BC) is currently the most common neoplasm, the second leading cause of cancer death in women worldwide, and is a major health problem. The discovery of new biomarkers is crucial to improve our knowledge of breast cancer and strengthen our clinical approaches to diagnosis, prognosis, and follow-up. In recent decades, there has been increasing interest in circulating RNA (circRNA) as modulators of gene expression involved in tumor development and progression. The study of circulating circRNAs (ccircRNAs) in plasma may provide new non-invasive diagnostic, prognostic, and predictive biomarkers for BC. This review describes the latest findings on BCassociated ccircRNAs in plasma and their clinical utility. Several ccircRNAs in plasma have shown great potential as BC biomarkers, especially from a diagnostic point of view. Mechanistically, most of the reported BC-associated ccircRNAs are involved in the regulation of cell survival, proliferation, and invasion, mainly via MAPK/AKT signaling pathways. However, the study of circRNAs is a relatively new area of research, and a larger number of studies will be crucial to confirm their potential as plasma biomarkers and to understand their involvement in BC

Breastfeeding: a reproductive factor able to reduce the risk of luminal B breast cancer in premenopausal White women

In the medical literature, the role of breastfeeding and reproductive factors in the risk of breast carcinoma is still an open debate in premenopausal women. We highlight the role of breastfeeding and reproductive factors in luminal A and luminal B, the most frequent breast cancers. This case-control study analyzes a White premenopausal population of 286 breast cancer patients, divided into molecular subtypes, and 578 controls matched by age. Multivariate logistic regression models were used to assess the relationships of breastfeeding and other reproductive factors (age at menarche, parity, age at first pregnancy, number of children) with the risk of breast cancers. Among the variables examined, reproductive factors did not alter the risk of cancer, whereas breastfeeding up to 12 months was a significant protective factor against luminal B breast cancer (multivariate odds ratio: 0.22, 95% confidence interval: 0.09-0.59, P=0.002). In contrast, luminal A cases did not significantly correlate with breastfeeding or other reproductive factors. Breastfeeding up to 12 months is strongly protective against the more aggressive luminal B, but not against the less aggressive luminal A breast cancer in premenopausal White women

GT75 aptamer against eukaryotic elongation factor 1A as potential anticancer drug for castrate-resistant prostate cancer (CRPC).

Prostate cancer diagnosis is increasing, being the second most frequently cancer in men worldwide. The treatment of castrate-resistant prostate cancer is often unsuccessfully and new therapeutic interventions are searching for. Nucleic acid aptamers targeting eEF1A proteins are emerging molecular tools for the control of cancer growth. We found that an aptamer named GT75 was able to bind to eEF1A proteins of human prostate cancer cell lines and to significantly and specifically reduce their growth with respect to the control oligomer CT75. The highest anti-proliferation effect was found in the androgen-independent PC-3 cells. Interestingly, GT75 was able to specifically inhibit the migration of PC-3 cells but not that of the nontumorigenic PZHPV-7 cells. The overall results suggest that the GT75 aptamer targeting eEF1A proteins is a promising molecular drug to develop for the control of the castrate-resistant prostate cance

Impact of psychosocial, behavioral and lifestyle factors on subjective cognitive complaints and perceived quality of life in a large cohort of Italian breast cancer patients

The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study’s purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive complaints in breast cancer patients (37%) compared to a representative sample of women in the same age group without an oncological diagnosis (p < 0.001). Moreover, breast cancer patients showed significantly lower levels of cognitive reserve (p < 0.05) and worse sleep quality (p < 0.01) compared to age-matched controls. Further analysis revealed that breast cancer patients reporting subjective cognitive complaints differed significantly from breast cancer patients without subjective cognitive complaints on measures of perceived cognitive abilities (p < 0.001) and on the impact of cognitive difficulties on perceived quality of life (p < 0.01). Future studies are needed to examine behavioral directed interventions to prevent subjective cognitive deficits in breast cancer patients

Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications

The poor survival of triple-negative breast cancer (TNBC) is due to its aggressive behavior, large heterogeneity, and high risk of recurrence. A comprehensive molecular investigation of this type of breast cancer using high-throughput next-generation sequencing (NGS) methods may help to elucidate its potential progression and discover biomarkers related to patient survival. In this review, the NGS applications in TNBC research are described. Many NGS studies point to TP53 mutations, immunocheckpoint response genes, and aberrations in the PIK3CA and DNA repair pathways as recurrent pathogenic alterations in TNBC. Beyond their diagnostic and predictive/prognostic value, these findings suggest potential personalized treatments in PD -L1-positive TNBC or in TNBC with a homologous recombination deficit. Moreover, the comprehensive sequencing of large genomes with NGS has enabled the identification of novel markers with clinical value in TNBC, such as AURKA, MYC, and JARID2 mutations. In addition, NGS investigations to explore ethnicity-specific alterations have pointed to EZH2 overexpression, BRCA1 alterations, and a BRCA2-delaAAGA mutation as possible molecular signatures of African and African American TNBC. Finally, the development of long-read sequencing methods and their combination with optimized short-read techniques promise to improve the efficiency of NGS approaches for future massive clinical use

Aptamer targeting of the elongation factor 1A impairs hepatocarcinoma cells viability and potentiates bortezomib and idarubicin effects

8noThe high morbidity and mortality of hepatocellular carcinoma (HCC) is mostly due to the limited efficacy of the available therapeutic approaches. Here we explore the anti-HCC potential of an aptamer targeting the elongation factor 1A (eEF1A), a protein implicated in the promotion of HCC. As delivery methods, we have compared the effectiveness of cationic liposome and cholesterol-mediated approaches. A75 nucleotide long aptamer containing GT repetition (GT75) was tested in three HCC cell lines, HepG2, HuH7 and JHH6. When delivered by liposomes, GT75 was able to effectively reducing HCC cells viability in a dose and time dependent fashion. Particular sensitive were JHH6 where increased apoptosis with no effects on cell cycle were observed. GT75 effect was likely due to the interference with eEF1A activity as neither the mRNA nor the protein levels were significantly affected. Notably, cholesterol-mediated delivery of GT75 abrogated its efficacy due to cellular mis-localization as proven by fluorescence and confocal microscopic analysis. Finally, liposome-mediated delivery of GT75 improved the therapeutic index of the anticancer drugs bortezomib and idarubicin. In conclusion, liposome but not cholesterol-mediated delivery of GT75 resulted in an effective delivery of GT75, causing the impairment of the vitality of a panel of HCC derived cells.partially_openopenScaggiante, Bruna; Farra, Rossella; Dapas, Barbara; Baj, Gabriele; Pozzato, Gabriele; Grassi, Mario; Zanconati, Fabrizio; Grassi, GabrieleScaggiante, Bruna; Farra, Rossella; Dapas, Barbara; Baj, Gabriele; Pozzato, Gabriele; Grassi, Mario; Zanconati, Fabrizio; Grassi, Gabriel

Cancer management during the COVID-19 world pandemic

Since 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients; this has been caused by multiorgan failure, which might be due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors-functional receptors of SARS-CoV-2-in multiple organs. Patients with cancer may be particularly susceptible to COVID-19 because cancer treatments (e.g., chemotherapy, immunotherapy) suppress the immune system. Thus, patients with cancer and COVID-19 may have a poor prognosis. Knowing how to manage the treatment of patients with cancer who may be infected with SARS-CoV-2 is essential. Treatment decisions must be made on a case-by-case basis, and patient stratification is necessary during COVID-19 outbreaks. Here, we review the management of COVID-19 in patients with cancer and focus on the measures that should be adopted for these patients on the basis of the organs or tissues affected by cancer and by the tumor stage

Cell-free DNA integrity for the monitoring of breast cancer: Future perspectives?

Breast cancer (BC) is the most common cancer and the second cause of death in women worldwide. Therapeutic options are increasing, but the response to treatments is not always efficient and the risk of recurrence covers decades. In this perspective, the need to have a proper follow-up for the therapeutic responses and for anticipating recurrence it is urgent in the clinical setting. Liquid biopsy provides the basic principle for a non-invasive method for the routinely monitoring of BC. However, due to the heterogeneity of tumors during onset and progression, the search for tumor DNA mutations of targeted genes in plasma/serum is a limiting factor. A possible approach overtaking this problem comes from the measurement of cell-free DNA integrity, which is an independent factor from the mutational status and theoretically is representative of all tumors. This review summarizes the state-of-the-art of cell-free DNA integrity researches in BC, the controversies and the future perspective