Treatment of c-kit positive adenoid cystic carcinoma of the tongue: a case report

Adenoid cystic carcinoma (ACC) or ‘cylindroma’ is a malignant tumor that often occurs in the areas of the head and neck, affecting the secretory glands and the major and minor salivary glands. The present study describes a case of a patient who presented with a posterior tongue lesion. The case is of a 71-year-old female with an asymptomatic volume growth of the posterior left tongue perceived 8 months prior, and neoplastic cells positive for c-kit. A computed tomography of the head and neck showed asymmetry of the base of the tongue, which was enlarged in the left portion. A physical examination revealed a nodule on the posterior left tongue of ~3 cm in diameter, while the cervical lymph node chain had a normal size and consistency. Surgical exeresis of the tongue lesion and cervical lymph node dissection were performed. Subsequent to surgical removal of the cancer cells and adjuvant radiotherapy, the patient showed excellent health, although the follow-up remains in progress. ACC, one of the most biologically destructive tumors of the head and neck, is locally aggressive and gives rise to distant metastases. The tongue is the place of origin in 3.4–17.1% of cases. The treatment for ACC consists of primary surgical resection with adjuvant radiotherapy. To prevent the risk for distant metastasis, it is necessary to remove the first echelon nodes and monitor the patient with a long-term follow-up

Sexuality education in Italy 2016-2020: a national survey investigating coverage, content and evaluation of school-based educational activities

Comprehensive sexuality education is an important means of promoting sexual well-being amongst young people and is key to preventing sexually transmitted infections (STIs). However, sexuality education is not currently included in the formal curriculum in Italian schools. The aim of this study was to develop an inventory of schoolbased sexuality education (SBSE) activities carried out by external providers and implemented in Italy from 2016 to 2020. A desk review and survey were carried out. In the desk review online documents on STI prevention were analysed. The survey investigated the providers, objectives, content and methods used to implement SBSE activities in secondary schools. Findings revealed a highly heterogeneous situation in terms of geographical coverage, service providers, objectives and evaluation. Some SBSE activities were classified as adopting a comprehensive approach to sexuality education, while the majority focused on STI prevention, and many were single-session activities. Although most activities were said to have been evaluated no results were available. The data showed that SBSE is not systematically and equally delivered across Italy. Action is needed to provide young people with evidence-based, age-appropriate and accurate education about sexual and reproductive health and wellbeing

Measurement of autophagy by flow cytometry

Autophagy activation is characterized by the accumulation of double-membrane autophagic vesicles (autophagosomes) in the cytoplasm. The mere presence of autophagosomes in the cytoplasm does not necessarily indicate an increased level of autophagy, since the blockade of any step downstream of autophagosome formation increases the number of autophagosomes. Therefore, quantitative methods for the detection of cytoplasmic protein turnover should be employed in addition to autophagosome monitoring, to verify increased levels of autophagy. At the present, multiple methods are available for the quantification of autophagy and the identification of autophagosomes. Here, we detail the in vitro methods currently available to detect autophagic cell death by flow cytometry analysis

Hepatocarcinoma: genetic and epigenetic features

HCC is the third leading cause of cancer-related deaths worldwide, accounting for about 1 million deaths annually. The incidence of HCC is highest in Asia and Africa, where the endemic high prevalence of hepatitis B and hepatitis C strongly predisposes to the development of chronic liver disease and subsequent development of HCC. Patients with HCC generally present at an advanced stage due to compensated cirrhosis defined by the absence of pathognomonic symptoms, resulting in death within 6 to 20 months, suggesting an urgent need in treatment modalities that will dramatically decrease the mortality rate of HCC. The molecular hepatocarcinogenesis is, however, a gradual process during which genetic alterations progressively accumulate and lead to HCC through intermediate preneoplastic stages. With the advent of whole genome sequencing tools, various mutations associated with HCC have been identified, which have advanced our molecular understanding of HCC. However, the frequency of these mutations is rare, and these genetic mutations only partly explain the etiology of the disease. Better understanding and characterization of novel genetic and epigenetic alterations, which are important to hepatocarcinogenesis, may help understand the molecular pathogenesis of HCC, as well as providing novel therapeutic targets for HCC treatment. Further consideration should be given to developing more effective molecular diagnostic markers and targeted drug therapy

Ubiquitination of tissue transglutaminase is modulated by interferon alpha in human lung cancer cells.

The addition of 2500 i.u./ml interferon alpha (IFNalpha) for 48 h induced apoptosis, and caused an approx. 4-fold increase in the activity and expression of tissue transglutaminase (tTG), in human lung cancer H1355 cells. However, the increase in mRNA levels for tTG was just 1.6-fold. On the basis of these data, we investigated whether tTG levels may be regulated through regulation of its degradation via ubiquitination. It was found that 2500 i.u./ml IFNalpha induced a time-dependent decrease in tTG ubiquitination. On the other hand, addition of the proteasome inhibitor lactacystin led to accumulation of the ubiquitinated form of the enzyme and to a consequent increase in its expression. Treatment of the cells with the two agents combined antagonized the accumulation of the ubiquitinated isoforms of tTG induced by lactacystin and caused a potentiation of tTG expression. Moreover, the tTG inducer retinoic acid was also able to cause increased expression and ubiquitination of tTG in H1355 cells. The addition of monodansylcadaverine (a tTG inhibitor) to IFNalpha-treated H1355 cells completely antagonized growth inhibition and apoptosis induced by the cytokine. In conclusion, we demonstrate for the first time that tTG is ubiquitinated and degraded by a proteasome-dependent pathway. Moreover, IFNalpha can, at least in part, induce apoptosis through the modulation of this pathway

Non-coding RNAs as a new dawn in tumor diagnosis

The current knowledge about non-coding RNAs (ncRNAs) as important regulators of gene expression inboth physiological and pathological conditions, has been the main engine for the design of innovativeplatforms to finalize the pharmacological application of ncRNAs as either therapeutic tools or as molecu-lar biomarkers in cancer. Biochemical alterations of cancer cells are, in fact, largely supported by ncRNAdisregulation in the tumor site, which, in turn, reflects the cancer-associated specific modification of cir-culating ncRNA expression pattern. The aim of this review is to describe the state of the art of pre-clinicaland clinical studies that analyze the involvement of miRNAs and lncRNAs in cancer-related processes,such as proliferation, invasion and metastases, giving emphasis to their functional role. A central nodeof our work has been also the examination of advantages and criticisms correlated with the clinical useof ncRNAs, taking into account the pressing need to refine the profiling methods aimed at identify noveldiagnostic and prognostic markers and the request to optimize the delivery of such nucleic acids for atherapeutic use in an imminent future

Future directions and management of liquid biopsy in non-small cell lung cancer

Lung cancer represents the world’s most common cause of cancer death. In recent years, we moved from a generic therapeutic strategy to a personalized approach, based on the molecular characterization of the tumor. In this view, liquid biopsy is becoming an important tool for assessing the progress or onset of lung disease. Liquid biopsy is a non-invasive procedure able to isolate circulating tumor cells, tumor educated platelets, exosomes and free circulating tumor DNA from body fluids. The characterization of these liquid biomarkers can help to choose the therapeutic strategy for each different case. In this review, the authors will analyze the main aspects of lung cancer and the applications currently in use focusing on the benefits associated with this approach for predicting the prognosis and monitoring the clinical conditions of lung cancer disease

The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: from rash mitigation to the increase in anti-tumor activity

The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion