Role of Adhesion Molecules in the Mechanism of Non-MHC (Major Histocompatibility Complex) Restricted Cell-Mediated Cytotoxicity

Adhesion molecules involved in the interaction between immune system effector cells and tumor targets are surface molecules which contribute to the formation of cell-to-cell contacts and belong to the integrin family. In this paper, the role played by the adhesion molecules in the process of cell-mediated cytotoxicity is reviewed. Furthermore, the contact area between effector and target cells has been analyzed by scanning electron microscopy. This region, termed closed chamber , seems to contribute to killing efficiency by creating an intimate contact region in which cytotoxic factors can easily induce lethal hit in target cell. Thus, the extension of the closed chamber seems to be positively related to effector cell killing potential as well as to target cell sensitivity and, in this context, the adhesion molecules prove to play a pivotal role. In fact, a receptor-ligand interaction occurs between CD11a/CD18 (LFA-1) and CD2 molecules, expressed on the effector cells, and the respective counterparts on target cells, i.e., ICAM-1, ICAM-2, or LFA-3. Treatment with antibodies against such molecules strongly modifies closed chamber formation without inhibiting cell-to-cell binding. Nevertheless, in these conditions, the killing ability of different effector cells toward tumor targets appears to be strongly impaired. Hence, the adhesion molecules seem to be strongly involved in the formation of the closed chamber as well as in the activation of effector cell killing machinery

Ultrastructural imaging reveals vascular remodeling in migraine patients

Migraine is a neurological disorder and one of the most common pain conditions worldwide. Despite its prevalence, the basic biology and underlying mechanisms contributing to the development of migraine are still poorly understood. It is still unclear, for instance, whether the vasculature, both extra and intracranial, plays a significant role in the generation of migraine pain. Neuroimaging data, indeed, have reported conflicting results on blood vessels abnormalities like vasodilation, while functional studies suggest that vessels dysfunction may extend beyond vasodilation. Here we combined light and electron microscopy imaging to investigate the fine structure of superficial temporal (STA) and occipital arteries (OA) from patients that underwent minimally invasive surgery for migraine. Using optical microscopy, we observed that both STA and OA vessels showed marked endothelial thickening and internal elastic lamina fragmentation. In the muscular layer, we found profound shape changes of vascular smooth muscle cells (VSMCs), abundant extracellular matrix, and the presence of clear extracellular vacuoles. The electron microscopy analysis confirmed putative VSMCs infiltrated within the intima layer and revealed a consistent shifting of VSMCs from contractile to a synthetically active phenotype. We also report the presence of (i) abundant extracellular vacuoles filled with fine granular material and membranes, (ii) multilamellar structures, (iii) endosome-like organelles, and (iv) bona fide extracellular vesicles in the matrix space surrounding synthetically active cells. As both the endothelial layer and VSMCs coordinate a variety of vascular functions, these results suggest that a significant vascular remodeling is occurring in STA and OA of migraine patients. Thus, this phenomenon may represent an important target for future investigation designed toward the development of new therapeutic approaches

A Scanning Electron Microscopy Analysis of Human Cytotoxic Cell Subsets and of Their Mode of Conjugation with Tumor Cell Targets

In this study we describe the surface features of non-MHC (Major Histocompatibility Complex)-restricted cytotoxic cells isolated from human peripheral blood. Purified populations of CD3-, natural killer (NK) cells were allowed to interact with NK-sensitive (K562) and NK-resistant (THP-1-0) tumor cell targets. The type of effector to target cell binding was investigated by scanning electron microscope (SEM) analysis. A different interaction with the effectors is described for NK-resistant targets in comparison with NK-susceptible tumor cells. SEM was also used to investigate the relationship between interleukin 2 (IL2)-activated cytotoxic cells (lymphokine-activated killer, LAK, cells) and the tumor targets. We also describe the unique growth features of certain clones of cytotoxic T cells expressing γδ antigen receptors which support the contention that these cells may have a special ability of homing into tissues. We conclude that non-specific cytotoxic cells constitute a diverse population of effectors which differ not only for the expression of surface antigens, but also for their ability to interact with tumor cell targets and to home into the peripheral tissues where they may exert their lytic functions

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Teaching histology and anatomy online during the Covid-19 pandemic

The aim of this study is to analyze differences in participation, and in the results obtained in the anatomy and histology exams, over two academic years of the Sport Sciences degree course. During the first semester of the academic year 2019/2020 both the lectures and the exam took place face-to-face, while during the academic year 2020/2021 everything was done online. Statistical analysis revealed that the online modality was especially advantageous for the anatomy exam. Students' opinions were also assessed through a short questionnaire. The results showed that teachers involved themselves in both groups. Students needed to interact socially with teachers and colleagues and to ask them questions. Even if the differences were not significant, the difference was greater for face-to-face students in most comparisons. Finally, the most common methods of peer communication were by social media

Anatomia umana e movimento. Anatomia umana generale e anatomia funzionale dell'apparato locomotore

VII Edizione Italiana di Anatomia umana e movimento di Soames & Palastanga, anatomia umana generale e anatomia funzionale dell' apparato locomotore

Final Report of the Oceanographic Survey NextData201. Project NEXTDATA WP-1.5 : Paleoclimatic Data from Marine Sediments

The retrieval of series of proxy data on the past climate will serve to acquire a deeper understanding of the climate system and a more accurate prediction of its future development, as a priority task for the scientific community. In particular, the analysis of climate data of the past is an essential tool for studying the dynamics of the earth's climatic system in conditions different from present ones, and irreplaceable for testing the validity of medium- and long-term forecasting models. The determination of the influence of anthropogenic impacts on the planet’s environment is predicated on a clear understanding of the natural ways in which the earth's climate responds to the complex set of external forcings. Therefore, in recent decades, many national and international research groups have focused attention on the study of the climate evolution in late-Quaternary sediments from the Mediterranean area. By virtue of its close relationship with continental masses subject to different climatic processes, the Mediterranean basin permits the documentation of climate evolution both globally and in the Northern Hemisphere. Finally, it is worth noting that shallow sea (continental shelf) areas are natural repositories for the monitoring of short-term climate change and anthropogenic impacts on the marine system. To make available information on climate history and environment yielded by marine sediments, this WP will be dedicated to analyzing and, where possible, collecting cores of marine sediments, especially those drilled in shallow sea environments, and focusing on climate dynamics in the Mediterranean over past centuries. During its course, the project will analyse and, where possible, sample marine sediment cores in continental shelf environments and in different sectors of the Mediterranean basin. Previous studies have indicated them as key sites for the identification of major short-term climate fluctuations, due to global and local forces active during the Quaternary and particularly in the past thousand years. In fact, the possibility of enriching the databases referring to this time interval (to date, still limited to the Mediterranean) will provide new working hypotheses for the implementation of numerical models that attempt simulate how the Mediterranean, in particular the marine-coastal sector, has responded to past climate dynamics (Medieval Warm Period / Little Ice Age transition, Little Ice Age, the Industrial Age, and Modern Warming). The cores obtained will be the focus of multidisciplinary studies involving national and international research groups

Morphological features of cloned lymphocytes expressing gamma/delta T cell receptors.

We have analyzed the morphological characteristics of human T lymphocytes bearing CD3-associated T cell receptor (TcR) gamma and delta chains. BB3 and delta-TCS1 monoclonal antibodies (mAb) were used to identify two distinct, nonoverlapping populations of TcR gamma/delta + cells which express the products of V delta 2 and V delta 1 gene segments, respectively. In the peripheral blood, most V delta 1+ (delta TCS-1+) lymphocytes express the non-disulfide-linked form of receptor whereas V delta 2+ (BB3+) cells express the disulfide-linked form. The majority of cloned TcR gamma/delta + cells exhibit a growth pattern different from that of conventional TcR alpha/beta + cells as they adhere promptly to surfaces and undergo morphological changes which can be summarized as follows: cells spread on the surface, form a distinct uropod and, in the final phase of adherence, emit long filopodia ending with adhesion plaques. Immunofluorescence studies of TcR gamma/delta + clones demonstrated the presence of submembraneous actin microfilaments and actin-binding protein confirming that these cells are capable of active motility which is related to the propensity of TcR gamma/delta + cells to home to epithelia. Scanning electron microscope analyses of effector/target cell conjugates showed that in TcR gamma/delta + cells the region of the uropodia next to the cell body is responsible for the binding to tumor target cells. Interestingly, immunofluorescence analyses revealed that LFA-1 molecules are predominantly distributed in the uropodium whereas they are virtually absent in the cell bodies. These morphological characteristics of TcR gamma/delta + cells may pertain to defensive mechanisms the mucosal level