Cancer progression: a single cell perspective

Tumor tissues are constituted by a dynamic diversity of malignant and non-malignant cells, which shape a puzzling biological ecosystem affecting cancer biology and response to treatments. Over the course of the tumoral disease, cancer cells acquire genotypic and phenotypic changes, allowing them to improve cellular fitness and overcome environmental and treatment constraints. This progression is depicted by an evolutionary process in which single cells expand as a result of an interaction between single-cell changes and the lovelopments have made it possible to depict the development of cancer at the single-cell level, offering a novel method for understanding the biology of this complex disease. Here, we review those complex interactions from the perspective of single cells and introduce the concept of omics for single-cell studies. This review emphasizes the evolutionary dynamics that control cancer progression and the capacity of single cells to escape the local environment and colonize distant sites. We are assisting a rapid progression of studies carried out at the single-cell level, and we survey relevant single-cell technologies looking at multi-omics studies. These path for precision medicine in cancer

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

Cholinergic innervation of human mesenteric lymphatic vessels

Background: The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity.Materials and methods: Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data.Results: The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods.Conclusions: The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

Neuroprotective role of phosphoserine in primary open-angle glaucoma patients

OBJECTIVE: To evaluate the neuroprotective role of phosphoserine (P-Ser) in primary open-angle glaucoma (POAG) patients and to compare its therapeutic effectiveness to placebo treatment. PATIENTS AND METHODS: Fifty-one patients (24 males and 27 females) between 35 and 61 years (average 46 years ± 3.8 SD) affected by POAG were enrolled in this study. Patients were divided in two groups: group A included 28 subjects that received an oral P-Ser treatment for 12 months; and group B included 23 subjects that received an oral placebo treatment for 12 months. Complete ophthalmological examination, standard automated perimetric examination, analysis of ON fibers via scanning laser polarimetry and glaucoma staging was performed in all patients at enrolment and 1, 3, 6, and 12 months after. Statistical analysis was performed using STATA 14.0 (Collage Station, TX, USA). RESULTS: Mean deviation (MD) and pattern standard deviation (PSD) analysis by means of 30-2 full threshold of the visual fields (VFs), retinal nerve fiber layer (RNFL) thickness by means of GDx, and IOP were considered to evaluate P-Ser therapy effectiveness in both groups. A statistically significant improvement (p<0.05) in VF, RNFL thickness and IOP compared to pre-treatment was found in patients in group A. CONCLUSIONS: Our study shows a significant improvement in several variables in patients with glaucoma treated with P-Ser compared to placebo and suggests a potential neuroprotective effect of P-Ser in treating glaucoma patients in association with the traditional hypotonic topical therapy

Arthrogenic human synovial cysts: immunohistochemical profile of interleukin-1beta, interleukin-6, tumour necrosis factor-alpha

Background: Synovial cysts are currently classified as degenerative lesions affectingthe joint capsule or adjacent structures. Materials and methods: In our study we describe the results obtained in an immunohistochemicalstudy comprising 18 patients with synovial cysts, performedto evaluate the pathophysiological role of some inflammatory cytokines such as:interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α). Results: Results showed an over-expression of TNF-α, IL-1β and IL-6 which appearsto be involved in the onset and progression of the disease. At the presenttime it is not possible to affirm that these molecules play a direct role also dueto the absence of further and more specific investigations. The authors thereforehypothesize that inhibition of inflammation may have a significant role in thepathogenesis and regression of synovial cysts. Conclusions: Hence, these inflammatory cytokines may be considered potentialtherapeutic targets. The development of synthetic inhibitors of these inflammatoryfactors could lead to a reduction in the intensity of inflammation, thus inhibitingthe onset and development of the disease

Inflammatory profile of neurotrophins, IL-6, IL1-β, TNF-α, VEGF, ICAM-1 and TGF-β in the Human Waldeyer’s ring

The palatine tonsils, nasopharyngeal tonsil (adenoid) and lingual tonsil constitute the major part of Waldeyer’s ring, with the tubal tonsils and lateral pharyngeal bands as less prominent components. The lymphoid tissue of Waldeyer’s ring is located at the gateway of the respiratory and alimentary tract and belongs to the mucosa-associated lymphoid tissue (MALT). The lymphatic tissue is known to interact with the nervous system and several organs implicated in the host response to a wide range of stressors (Otten et al., 1995; Kaneko et al., 2012; Ogasawara et al., 2011). This study focusses on the expression of some neurotrophins (NTs), their high- and low-affinity receptors in human adenoid tissues, lingual and palatine tonsils via immunohistochemical analysis, as well as on the expression of some inflammatory cytokines and other tissue growth factors (IL-6, IL1-β, TNF-α, VEGF, ICAM-1 and TGF-β)). Light microscopy immunohistochemistry performed on human samples showed to be generally positive for all the NTs investigated (NGF, BDNF, NT-3) and their receptors (TrKA, TrKB and TrKC) as well as the other cytokines and growth factors studied with some different expression levels. Real time PCR analysis is in progress to quantitate these data. Our data corroborate previous studies, suggesting that neurotrophins and inflammatory cytokines may mediate functional signals in lymphoid aggregates (Yusuf-Makagiansar et al., 2002; Ruoco et al., 1990)

Vascularized head and neck tumors and growth factors: immunohistochemical and rt-pcr profile in pediatric age

Brain tumors account approximately for 20% of all childhood cancers and are characterized by a large diversity of morphological entities. The formation of abnormal, dysfunctional tumor vasculature and glioblastoma stem-like cells (GSCs) are believed to be the major components of the difficulty to treat these tumors effectively. Massive formation of blood vessels is one of the most important histological elements to determine the progression and histological grading of tumors. We hypothesized that an increased expression of TGF-β1 in tumor cells stimulates tumor neo-vascularization by mediating the secretion of relevant angiogenic factors via an autocrine mechanism. Expression of TGF-β in relation to VEGF and VEGF-receptors involved in angiogenesis and inflammation pathways was evaluated in pediatric patients with brain tumors and compared with normal tissues. Our results demonstrated that TGF-β1, VEGF-A and VEGF-RII were significantly related to the development and to the growth of glioblastoma. We can speculate that TGF-β1 and VEGF are involved in the cascade of the malignant progression of glioblastoma. These factors promote tumorigenesis and malignant progression of glioblastoma by a mechanism determining anti-apoptotic, angiogenetic and invasive behaviour of the tumor cells. Basing on our experimental data, we propose that VEGF may be the double promoter responsible not only for the tumor vessels, but also for the tumor stem cells [1]. Our data demonstrate that GSCs in association with high levels of VEGF-A and TGF-β play a key role in the development of the tumor vascularization acting on endothelial cells differentiation

Rapid clinical management of leishmaniasis in emergency department: A case report with clinical review of recent literature

Systemic or localized lympho-adenomegaly is a common cause of access to the emergency department (ED), and differential diagnosis is often complicated. The combination of anamnesis, physical examination, laboratory tests, and instrumental diagnosis are extremely important to orientate toward a rapid and correct therapy, even if a prompt discrimination of the etiology of this lymphadenomegaly is not often possible. Our aim with this review is to improve the management of a differential diagnosis between hematological and infective diseases as leishmaniasis in ED and suggest quick diagnostic techniques that might be useful for early identification. Together in the review, we describe a case report of a young man affected from visceral leishmaniasis who presented to our ED and was incorrectly addressed to the wrong ward for the study of his condition. Subsequently, we focus on the clinical presentation of visceral leishmaniasis and compare it to the most common differential diagnoses that are usually taken into account in the management of such patients

Anteriorly placed tumors to the conus: removal by interradicular window

Tumors anteriorly situated to the medullary conus are rarely encountered and represent a true surgical challenge. We examined the literature on this topic, concluding that there are no previous reports on alternative surgical techniques different to the traditional one. We report two cases of intradural extramedullary tumor operated on by a technique performed through a window opened between the spinal roots, which allows an easy, effective and useful resection. We describe a new operative technique which ensures a complete removal of these tumors and discuss clinical implications in the light of the available literature on this topic

Francesco Durante and the first intracranial tumor successfully operated on with long survival (1884)

Francesco Durante was born in Sicily, precisely Letojanni Gallodoro. He contributed to the history of neurosurgery in not only Italy but the whole world. In June 1884, he removed a left frontal meningioma, describing a personal technique of craniotomy with a discontinuous osteotangential section flap. It was the first such operation to be performed in any country after which the patient had a long survival. The important and pioneering contribution made by Durante to the history of neurosurgery is testified by his Treaty on Pathology and Surgical Therapy. Durante's procedure for craniotomy remained the best for several years. His contributions are still valid in medicine today, within not only the neurosurgical community but also other surgical disciplines, because he also developed innovative practices in the fields of oncology, general surgery, and orthopedics in addition to designing special surgical instruments