The role of Autophagy in Hepatocellular Carcinoma

Autophagy is a cellular catabolic process in which cytoplasmic material is delivered to lysosomes for degradation. The autophagy process is regulated by highly conserved autophagy-related genes (ATGs) via different signalling pathways. Among the various biological functions of autophagy, the link between autophagy and cancer has been extensively studied, demonstrating its dual role, of tumor suppressor or promoter in cancer development. Hepatocellular carcinoma (HCC) is one of the most lethal cancers that affects most of the world's population and it is caused by different etiological factors: HBV and HCV viral infections, heavy alcohol consumption, NAFLD (non-alcoholic fatty liver disease), aflatoxin B1 contaminated food. In recent years, the involvement of autophagy in both prevention and promotion of liver cancer has been increasingly studied. Here, we summarize molecular mechanisms and physiological function of liver autophagy, its dual role and its therapeutic potential in HCC

Ultrasonic decontamination in smoked salmon experimentally contaminated with Listeria monocytogenes: Preliminary results

The purpose of this work was to evaluate the effects of ultrasound (sonication) and their combination with temperature (thermosonication) on the inactivation of Listeria monocytogenes (LM) in smoked salmon. The trial was conducted on smoked salmon samples experimentally contaminated with a cocktail of 4 strains of Listeria monocytogenes (LM ATCC 19114, LM ATCC 15313, LM ATCC 19111 and LM ATCC 7644) at a final concentration of 8 log cfu/g and kept at 4°C until its use. Thermosonication treatments between 40°C and 50°C for 5, 10 and 15 minutes proved to be more effective without altering the sensory characteristics of the food

Pheochromocytoma mimicking a non-ST elevation acute myocardial infarction

We report a 57 year-old male patient admitted with a diagnosis of non-ST elevation acute myocardial infarction. He had suffered from chest pain, diaphoresis and intense asthenia for three days. The electrocardiogram on admission showed a high frequency sinus tachycardia. Troponin T levels were elevated. An echocardiogram suggested an antero-lateral myocardial infarction. Eventually, a left adrenal pheochromocytoma was discovered. Left ventricular function, severely depressed, returned to normal after medical and surgical therapy

An Outlook on Ovarian Cancer and Borderline Ovarian Tumors: Focus on Genomic and Proteomic Findings

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers. Ovarian tumors can be classified on the basis of the cells of origin in epithelial, stromal and germ cell tumors. Epithelial ovarian tumors display great histological heterogeneity and can be further subdivided into benign, intermediate or borderline, and invasive tumors. Several studies on ovarian tumors, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomolecular study and genomic discovery; unfortunately, validity of these should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management. Therefore, considerable interest lies in identifying molecular and protein biomarkers and indicators to guide treatment decisions and clinical follow up. In this review, the current state of knowledge about the genoproteomic and potential clinical value of gene expression profiling in ovarian cancer and ovarian borderline tumors is discussed, focusing on three main areas: distinguishing normal ovarian tissue from ovarian cancers and borderline tumors, identifying different genotypes of ovarian tissue and identifying proteins linked to cancer or tumor development. By these targets, authors focus on the use of novel molecules, developed on the proteomics and genomics researches, as potential protein biomarkers in the management of ovarian cancer or borderline tumor, overlooking on current state of the art and on future perspectives of researches

Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury

COVID-19; Angiotensin-converting enzyme 2; MetabolomicsCOVID-19; Enzim convertidor d'angiotensina 2; MetabolòmicaCOVID-19; Enzima convertidora de angiotensina 2; MetabolómicaBackground Angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the kidneys. Beyond serving as a crucial endogenous regulator of the renin–angiotensin system, ACE2 also possess a unique function to facilitate amino acid absorption. Our observational study sought to explore the relationship between urine ACE2 (uACE2) and renal outcomes in coronavirus disease 2019 (COVID-19). Methods In a cohort of 104 patients with COVID-19 without acute kidney injury (AKI), 43 patients with COVID-19-mediated AKI and 36 non-COVID-19 controls, we measured uACE2, urine tumour necrosis factor receptors I and II (uTNF-RI and uTNF-RII) and neutrophil gelatinase-associated lipocalin (uNGAL). We also assessed ACE2 staining in autopsy kidney samples and generated a propensity score–matched subgroup of patients to perform a targeted urine metabolomic study to describe the characteristic signature of COVID-19. Results uACE2 is increased in patients with COVID-19 and further increased in those that developed AKI. After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with a >3-fold higher risk of developing AKI [odds ratio 3.05 (95% confidence interval 1.23‒7.58), P = .017]. Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in patients with COVID-19, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2. Conclusions Elevated uACE2 is related to AKI in patients with COVID-19. The loss of tubular ACE2 during SARS-CoV-2 infection demonstrates a potential link between aminoaciduria and proximal tubular injury.This work was supported by the Heart and Stroke Foundation (grant 855632 to G.Y.O.) and the Canada Foundation for Innovation (grant 35456). A.V. is a current recipient of a Fundacion Alfonso Martin Escudero–2020 Research Grant

Ovarian Cancer Biomarkers: A Focus on Genomic and Proteomic Findings

Among the gynaecological malignancies, ovarian cancer is one of the neoplastic forms with the poorest prognosis and with the bad overall and disease-free survival rates than other gynaecological cancers; several studies, analyzing clinical data and pathological features on ovarian cancers, have focused on the identification of both diagnostic and prognostic markers for applications in clinical practice. High-throughput technologies have accelerated the process of biomarker discovery, but their validity should be still demonstrated by extensive researches on sensibility and sensitivity of ovarian cancer novel biomarkers, determining whether gene profiling and proteomics could help differentiate between patients with metastatic ovarian cancer and primary ovarian carcinomas, and their potential impact on management

An Outlook on Uterine Neoplasms: From Hormonal and DNA Damaging to Cervical and Endometrial Cancer Development and Minimally Invasive Management.

Uterine neoplasms are common tumors, formed by endometrial and cervical cancers; endometrial cancer is the fourth most frequently diagnosed cancer in developed countries and the eighth leading cause of cancer death in women, and cervical cancer is the second most common cancer in women worldwide and is a leading cause of cancer-related death in women in underdeveloped countries. Cervical cancer arises by HPV DNA damaging; in fact cervical cancer starts in the cells on the surface of the cervix, exposed to viral infective agents, as HPV, founded in 80% of patients affected by cervical cancer. Thus, more than 99% of cervical uterine cancer cases show HPV presence. Nevertheless, Endometrial cancer involves cancerous growth of the endometrium, and increasing evidence indicates that different biological and genetic factors play relevant roles its onset so as carcinogenesis generally develops by hormonal modifications. Both tumors can be safely and feasibly managed from minimally invasive surgical techniques till to endoscopic radical operations, such as hysterectomy, bilateral salpingo- oophorectomy, pelvic and para-aortic lymphadenectomy for surgical treatment. The authors reviewed several excellent reviews and studies in the area of hormonal, viral and genetical risk factors associated with endometrial and cervical cancer risk and development, analyzing the area of biologic markers, all papers dealing with serum and plasma markers involved in uterine cancer detection, development, progression and minimally invasive treatment

Alternative proteins are functional regulators in cell reprogramming by PKA activation

Abstract It has been recently shown that many proteins are lacking from reference databases used in mass spectrometry analysis, due to their translation templated on alternative open reading frames. This questions our current understanding of gene annotation and drastically expands the theoretical proteome complexity. The functions of these alternative proteins (AltProts) still remain largely unknown. We have developed a large-scale and unsupervised approach based on cross-linking mass spectrometry (XL-MS) followed by shotgun proteomics to gather information on the functional role of AltProts by mapping them back into known signalling pathways through the identification of their reference protein (RefProt) interactors. We have identified and profiled AltProts in a cancer cell reprogramming system: NCH82 human glioma cells after 0, 16, 24 and 48 h Forskolin stimulation. Forskolin is a protein kinase A activator inducing cell differentiation and epithelial–mesenchymal transition. Our data show that AltMAP2, AltTRNAU1AP and AltEPHA5 interactions with tropomyosin 4 are downregulated under Forskolin treatment. In a wider perspective, Gene Ontology and pathway enrichment analysis (STRING) revealed that RefProts associated with AltProts are enriched in cellular mobility and transfer RNA regulation. This study strongly suggests novel roles of AltProts in multiple essential cellular functions and supports the importance of considering them in future biological studies

Androgen receptor in breast cancer: The "5W" questions

Androgen receptor (AR) is expressed in 60-70% of breast cancers (BCs) and the availability of anti-AR compounds, currently used for treating prostate cancer, paves the way to tackle specifically AR-positive BC patients. The prognostic and predictive role of AR in BC is a matter of debate, since the results from clinical trials are not striking, probably due to both technical and biological reasons. In this review, we aimed to highlight WHAT is AR, describing its structure and functions, WHAT to test and HOW to detect AR, WHERE AR should be tested (on primary tumor or metastasis) and WHY studying this fascinating hormone receptor, exploring and debating on its prognostic and predictive role. We considered AR and its ratio with other hormone receptors, analyzing also studies including patients with ductal carcinoma in situ and with early and advanced BC, as well. We also emphasized the effects that both other hormone receptors and the newly emerging androgen-inducible non coding RNAs may have on AR function in BC pathology and the putative implementation in the clinical setting. Moreover, we pointed out the latest results by clinical trials and we speculated about the use of anti-AR therapies in BC clinical practice