Diagnostic Delay in Oncology: A Case Report of Metastatic Seminoma

Germ cell tumours are the most common malignancy among young men; cryptorchidism is a possible risk factor for the development of testicular cancer. Psycho-oncology studies indicate that diagnostic delay can often be explained by different social conditions and that symptoms worsened under lack of appropriate treatment can lead to an urgent admission to the hospital. Nevertheless, germ cell tumours are considered curable malignancies even in advanced stages since the introduction of a chemotherapy regimen based on bleomycin, etoposide and cisplatin. Cell lines derived from germ cell tumours are sensitive to cisplatin-based treatment more than other solid cancers, which is reflected in the good clinical response. We report an unusual manifestation of malignancy in an adult man presenting with a metastatic seminoma of the left testicle. The large ulcerate and necrotic mass suggested a secondary infection from a tumour site. The patient reported surgical orchiopexy for left cryptorchidism in his childhood. Despite worsening of physical features, he had not sought help at the hospital for social reasons. The patient achieved complete clinical remission after receiving standard chemotherapy, and a good objective response of the primitive mass was clearly visible. Complete response was persistent at the 30-month clinical follow-up. The chemotherapy administration was later complicated by acute haemorrage in the site of the primitive tumour that needed urgent surgical management; in addition to this, the artificial graft material was rejected and the arterial prosthesis had to be removed

Brown globules in lentigo maligna (LM): A useful dermoscopic clue

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Comparison of the Aptima HIV-1 Quant Dx Assay with the COBAS\uae AmpliPrep/COBAS\uae TaqMan\uae HIV-1 v2.0 Test for HIV-1 Viral Load Quantification in Plasma Samples from HIV-1-Infected Patients.

Background and aims: HIV\u20101 RNA viral load (VL) in plasma samples of HIV\u20101\u2013positive patients is used to assess the level of viral replication, the risk of disease progression, and the response and efficacy to antiretroviral treatment. Knowing the performance of different tests for HIV\u20101 RNA detection is, therefore, important for clinical care. This study compared the performance of the recently introduced Aptima HIV\u20101 Quant Dx assay (Hologic, Inc) and the standard COBAS AmpliPrep/COBAS TaqMan HIV\u20101 v2.0 Test (CAP/CTM2) (Roche Molecular System, Inc) for HIV\u20101 RNA quantitation. Methods: Assay performance was assessed using 335 clinical samples, a standard HIV\u20101 low VL panel, and 2 diluted samples from well\u2010characterized patients infected with different HIV\u20101 subtypes tested in 5 replicates over 3 days. All samples were tested on both assays to evaluate inter\u2010assay agreement, both qualitatively and quantitively. Altogether, we evaluated assay sensitivity, linearity, accuracy, precision, repeatability, and reproducibility. Results: Assay agreement for qualitative results in 335 clinical samples was fair (80.6%). Correlation of quantitative assay results (n = 164) was excellent (R2 = 0.97), with 96.3% of the results within the 95% limit of assay agreement ( 120.42 to +0.86 log), and 98.8% within 1 log of each other. Aptima\u2010HIV\u20101 yielded results, on average, 0.22 log higher than CAP/CTM2. Both assays accurately quantitated the HIV\u20101 standard at low VL (R2 65 0.94), with all samples within 0.5 log of the target. Conclusion: Aptima\u2010HIV\u20101 assay demonstrated sensitivity, accuracy, reproducibility, and precision for the detection and quantitation of HIV\u20101 RNA across a wide dynamic range of VLs. Its performance, together with full automation and high throughput, suggests that Aptima\u2010HIV\u20101 could be a suitable assay for reliable monitoring of HIV\u20101 VL in patients undergoing treatment

Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhighand ALDHlowderived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma

COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a member of the Coronavirus family which caused the worldwide pandemic of human respiratory illness coronavirus disease 2019 (COVID-19). Presumably emerging at the end of 2019, it poses a severe threat to public health and safety, with a high incidence of transmission, predominately through aerosols and/or direct contact with infected surfaces. In 2020, the search for vaccines began, leading to the obtaining of, to date, about twenty COVID-19 vaccines approved for use in at least one country. However, COVID-19 continues to spread and new genetic mutations and variants have been discovered, requiring pharmacological treatments. The most common therapies for COVID-19 are represented by antiviral and antimalarial agents, antibiotics, immunomodulators, angiotensin II receptor blockers, bradykinin B2 receptor antagonists and corticosteroids. In addition, nutraceuticals, vitamins D and C, omega-3 fatty acids and probiotics are under study. Finally, drug repositioning, which concerns the investigation of existing drugs for new therapeutic target indications, has been widely proposed in the literature for COVID-19 therapies. Considering the importance of this ongoing global public health emergency, this review aims to offer a synthetic up-to-date overview regarding diagnoses, variants and vaccines for COVID-19, with particular attention paid to the adopted treatments

Diarylureas: New Promising Small Molecules against Streptococcus mutans for the Treatment of Dental Caries

Dental caries is a biofilm-mediated disease that represents a worldwide oral health issue. Streptococcus mutans has been ascertained as the main cariogenic pathogen responsible for human dental caries, with a high ability to form biofilms, regulated by the quorum sensing. Diarylureas represent a class of organic compounds that show numerous biological activities, including the antimicrobial one. Two small molecules belonging to this class, specifically to diphenylureas, BPU (1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea) and DMTU (1,3-di-m-tolyl-urea), showed interesting results in studies regarding the antimicrobial activity against the cariogenic bacterium S. mutans. Since there are not many antimicrobials used for the prevention and treatment of caries, further studies on these two interesting compounds and other diarylureas against S. mutans may be useful to design new effective agents for the treatment of caries with generally low cytotoxicit

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

Over the past decade, metal complexes based on N-heterocyclic carbenes (NHCs) have attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In particular, the gold-based complexes are the focus of research efforts for the development of new anticancer compounds. Literature data and recent results, obtained by our research group, reported the design, the synthesis and the good anticancer activity of some silver and gold complexes with NHC ligands. In particular, some of these complexes were active towards some breast cancer cell lines. Considering this evidence, here we report some new Au-NHC complexes prepared in order to improve solubility and biological activity. Among them, the compounds 1 and 6 showed an interesting anticancer activity towards the breast cancer MDA-MB-231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the activity of the human topoisomerases I and II and the actin polymerization reaction. Moreover, a downregulation of vimentin expression and a reduced translocation of NF-kB into the nucleus was observed. The interference with these vital cell structures induced breast cancer cells’ death by triggering the extrinsic apoptotic pathway

Triclosan: A Small Molecule with Controversial Roles

Abstract: Triclosan (TCS), a broad-spectrum antimicrobial agent, has been widely used in personal care products, medical products, plastic cutting boards, and food storage containers. Colgate Total® toothpaste, containing 10 mM TCS, is effective in controlling biofilm formation and maintaining gingival health. Given its broad usage, TCS is present ubiquitously in the environment. Given its strong lipophilicity and accumulation ability in organisms, it is potentially harmful to biohealth. Several reports suggest the toxicity of this compound, which is inserted in the class of endocrine disrupting chemicals (EDCs). In September 2016, TCS was banned by the U.S. Food and Drug Administration (FDA) and the European Union in soap products. Despite these problems, its application in personal care products within certain limits is still allowed. Today, it is still unclear whether TCS is truly toxic to mammals and the adverse effects of continuous, long-term, and low concentration exposure remain unknown. Indeed, some recent reports suggest the use of TCS as a repositioned drug for cancer treatment and cutaneous leishmaniasis. In this scenario it is necessary to investigate the advantages and disadvantages of TCS, to understand whether its use is advisable or not. This review intends to highlight the pros and cons that are associated with the use of TCS in humans

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

Over the past decade, metal complexes based on N-heterocyclic carbenes (NHCs) have attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In particular, the gold-based complexes are the focus of research efforts for the development of new anticancer compounds. Literature data and recent results, obtained by our research group, reported the design, the synthesis and the good anticancer activity of some silver and gold complexes with NHC ligands. In particular, some of these complexes were active towards some breast cancer cell lines. Considering this evidence, here we report some new Au-NHC complexes prepared in order to improve solubility and biological activity. Among them, the compounds 1 and 6 showed an interesting anticancer activity towards the breast cancer MDA-MB- 231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the activity of the human topoisomerases I and II and the actin polymerization reaction. Moreover, a downregulation of vimentin expression and a reduced translocation of NF-kB into the nucleus was observed. The interference with these vital cell structures induced breast cancer cells’ death by triggering the extrinsic apoptotic pathway