Amalia Luce

Nanoparticle albumin bound Paclitaxel in the treatment of human cancer: nanodelivery reaches prime-time?

Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms.

Urotensin II receptor determines prognosis of bladder cancer regulating cell motility/invasion

BackgroundNon Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs.MethodsWe have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples.ResultsUTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells.ConclusionsThe evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.

Endocrine disruptors and female cancer: Informing the patients (Review)

Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk of female cancers. The carcinogenic effect of ED on humans has been confirmed by experimental studies for various substances including pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as heavy metals, but it is difficult to quantify precisely for several reasons hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that manifests itself over a long period of time, making difficult the detection of the specific contribution of the pollutants, whose absorbed dose is often unknown. The combined effect of various substances leads to complex interactions whose outcome is difficult to predict. These substances may accumulate and carry out their harmful effect on critical periods of life, probably also at doses considered harmless to an adult. ED can also have epigenetic adverse effects on the health of future generations. In conclusion, the carcinogenic effects of endocrine disruptors on female cancer types is plausible although additional studies are needed to clarify their mechanisms and entities. In the last part of the review we suggest ways to reduce ED exposure as it is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as the embryonic period and puberty.

Anaplastic lymphoma kinase: a glimmer of hope in lung cancer treatment?

Anaplastic lymphoma kinase (ALK) rearrangements (ALK-Rs) have been identified in 3–7% of all non-small-cell lung cancers (NSCLCs) and represent an important molecular target for NSCLC treatment. The authors discuss the role of ALK-Rs in the prediction of clinical–pathological features of NSCLCs and the technical problems related to their determination in specimens. The authors also describe the preclinical and clinical results derived from the use of ALK inhibitors. ALK-R is generally detected in patients with specific clinical–pathological features: never-smokers, young males, adenocarcinoma histotype and EGF receptor/KRAS wild-type. The diagnosis of ALK-R remains a challenge, implicating the need of a careful filtering of patients. NSCLC patients harboring ALK-R have shown sensitivity to ALK inhibitors even if their activity is limited at the time by the occurrence of mechanisms of resistance. The authors summarize the strategies that in the future could overcome these mechanisms of escape.

Chemotherapy in the management of brain metastases: the emerging role of fotemustine for patients with melanoma and NSCLC

Introduction: An estimated 20 – 40% of cancer patients will develop brain metastases that are the most common intracranial tumors in adults. Patients with cerebral metastases represent a variegate group where selection of the most appropriate treatment depends on many patient- and disease-related factors. The impact of therapeutic option on overall survival is lacking and it is important to consider quality of life (QOL) when treating patients with brain metastases. Areas covered: A considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. The role of chemotherapy was limited in the past. Recently, several chemotherapeutic agents have been identified as potentially useful. This article examines the pharmacokinetics, efficacy and safety and tolerability of fotemustine (FTM) for the management of patients with cerebral metastasis from melanoma and non-small cell lung cancer (NSCLC). Expert opinion: FTM is a third-generation nitrosourea that has proved its efficacy on brain metastases of melanoma and showed promising results for the treatment of brain metastasis of NSCLC because of its ability to pass the blood–brain barrier.

Carcinogenetic mechanisms of endocrine disruptors in female cancers (Review)

Endocrine disruptors (EDs) are pollutants that alter the endocrine system and are involved in carcinogenesis. EDs have multiple and complex levels of action. They can affect the synthesis, release and transport of natural hormones. In target tissues, EDs can reduce or increase the effects of natural hormones on their receptors and change signaling cascades. When ED exposure happens at critical periods of life, from embryo to puberty, they can act at doses considered safe for an adult. Furthermore, their epigenetic effects can also influence the cancer risk of future generations. The cancer mechanisms of known EDs are hereby reviewed, There are thousands of newly introduced substances whose potential endocrine-disrupting and cancer effects are completely unknown. Although there are still gaps in our knowledge, these data support the urgent need for health and environmental policies aimed at protecting the public and in particular, the developing fetus and women of reproductive age.

Keratin 5 expression in squamocellular carcinoma of the head and neck

Keratin 5 (K5) is present in the basal layer of a stratified squamous keratinized and non-keratinized epithelium. K5 and K14 have been demonstrated in the mucosa and tumors of the oral cavity, oropharynx, hypopharynx and larynx, and in the mitotic active basal cells of a stratified squamous epithelium. The aim of the present study was to assess K5 expression in squamocellular carcinoma with various localizations in the head and neck. A total of 13 biopsy fragments were included from patients diagnosed with squamocellular carcinoma of the larynx area (n=2), pharynx (n=2), hard palate (n=1), tongue (n=2), submandibular (n=1), lip (n=1), gingival sulcus (n=1), nasal pyramid (n=1), maxilla (n=1) and zygomatic (n=1). The immunohistochemical staining for K5 was evaluated according to the following score criteria: 0 (0% positive cells); 1 (<10% positive cells); 2 (10–30% positive cells); and 3 (>30% positive cells). K5 expression was observed in all squamocellular carcinomas included in the present study with scores between 1 and 3. For well- and moderately-differentiated histopathological types, a maximum score of 3 was recorded for all of the cases, not including the laryngeal area, which presented a score of 2. The following scores were identified in the regions of the poorly differentiated carcinomas: Jaw, 3; gingival sulcus, 2; and tongue and submandibular area, 1. These observations may aid with an improved stratification of head and neck squamocellular carcinoma, thus improving the diagnosis and treatment strategies for this type of cancer.

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.

Peptide Functionalization of Silicon for Detection and Classification of Prostatic Cells

The development of simple, rapid, and low cost methods for early detection, identification, and measurement of multiple biomarkers remains a challenge to improve diagnosis, treatment monitoring, and prognosis of cancer. Biosensing technology, combining the properties of biological systems with functional advanced materials, guarantees rapid, reproducible, and highly sensitive cell detection. In this study, we developed silicon-based biochips for prostate cancer PC3 cells detection by using cytokeratin 8/18 and Urotensin Receptor (UTR) as markers in order to obtain a biochip-based diagnostic system. Spectroscopic ellipsometry and fluorescence microscopy were used to characterize surface homogeneity and chemical properties. Cell detection was investigated by optical microscopy. Moreover, synthetic fluorescently labeled peptides were prepared and used for developing faster and lower-cost identification assay compared with classic ELISA immunoassay. Results showed an effective immobilization of PC3 cells on silicon surface and the specific recognition of these cells by fluorescent Urotensin II (4–11). In conclusion, this strategy could be really useful as diagnostic system for prostate cancer.

Basal Cell Carcinoma: Molecular and Pathological Features

Basal cell carcinoma is the most common malignant tumour of humans, recording a progressive increase in incidence during the last decades. Basal cell carcinomas are locally destructive malignancies, mainly involving sun-exposed areas, such as head and neck skin. Basal cell carcinoma derives from basaloid epithelia located in the follicular bulges, and its development seems to be related to the deregulation of Hedgehog signalling pathway, primarily studied in the Gorlin-Goltz syndrome, characterised by a wide range of developmental abnormalities and predisposition to neoplasm, such as basal cell carcinomas. Basal cell carcinoma shows a clinical favourable behaviour, but some pathological features could suggest a more aggressive clinical course. In addition, the high incidence is responsible of a significant increasing workload for the health service, in relation to their treatment. Thus, novel therapy approaches have been developed in order to improve the treatment.