Primary prophylaxis of neutropenia in women affected by breast cancer undergoing adjuvant chemotherapy with fec 100+/- docetaxel. Comparison of efficacy and tolerability between lenograstim and pegfilgrastim

Objectives: evaluate safety and toxicity of a single injection of pegfilgrastim compared to daily administration of lenograstim in breast cancer patient undergoing adjuvant chemotherapy

Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC)

Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach

Background: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development. Methods: A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was performed. The results were then correlated with irAEs onset. The IP was studied by means of multiplex assay, evaluating circulating concentration of 12 cytokines, 5 chemokines, 13 soluble immune checkpoints and 3 adhesion molecules. Indoleamine 2, 3-dioxygenase (IDO) activity was measured through a modified liquid chromatography-tandem mass spectrometry using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. A connectivity heatmap was obtained by calculating Spearman correlation coefficients. Two different networks of connectivity were constructed, based on the toxicity profile. Results: Toxicity was predominantly of low/moderate grade. High-grade irAEs were relatively rare, while cumulative toxicity was high (35%). Positive and statistically significant correlations between the cumulative toxicity and IP10 and IL8, sLAG3, sPD-L2, sHVEM, sCD137, sCD27 and sICAM-1 serum concentration were found. Moreover, patients who experienced irAEs had a markedly different connectivity pattern, characterized by disruption of most of the paired connections between cytokines, chemokines and connections of sCD137, sCD27 and sCD28, while sPDL-2 pair-wise connectivity values seemed to be intensified. Network connectivity analysis identified a total of 187 statistically significant interactions in patients without toxicity and a total of 126 statistically significant interactions in patients with toxicity. Ninety-eight interactions were common to both networks, while 29 were specifically observed in patients who experienced toxicity. Conclusions: A particular, common pattern of immune dysregulation was defined in patients developing irAEs. This immune serological profile, if confirmed in a larger patient population, could lead to the design of a personalized therapeutic strategy in order to prevent, monitor and treat irAEs at an early stage

Vaginal atrophy in breast cancer survivors: role of vaginal estrogen therapy

Early menopause and related vaginal atrophy is a well known side-effect of hormone adjuvant treatment in breast cancer patients, particularly during aromatase-inhibitors therapy. Due to estrogens contra-indication, proper therapy for such symptom remains often an inadequately addressed clinical problem. After an accurate assessment of the risk/benefit ratio, vaginal low-dose estrogen treatment (better with estriol) may have a role in controlling vaginal atrophy in selected and informed breast cancer women

Subjective visual vertical in erect/supine subjects and under microgravity: effects of lower body negative pressure

Perception of the subjective visual vertical (SVV) is mainly based on the contributions from the visual, vestibular, and proprioceptive systems, and participates to the process of spatial orientation in relation to the surrounding environment and to the gravito-inertial force. The SVV can be significantly influenced by the presence of a displaced visual field, as in the case of the rod and frame test (RFT). A series of studies showed the effects of haematic mass shifts to and from the lower limbs on SVV, due to visceral mechanoreceptors (VM) located at the level of the kidneys and of the thorax. These sensors may be artificially activated with a lower body negative pressure (LBNP) device. In this study, the role of visual and VM cues to orientation perception have been evaluated using the RFT and the LBNP devices under a microgravity environment. A preliminary investigation was conducted in a sample of military pilots to develop a RFT protocol to be used in microgravity environments. This protocol was adopted to evaluate the contribution of VM to the SVV in a cosmonaut before, during and after a 10 day space flight, with and without concurrent activation of LBNP. The same test sequence, including LBNP exposure, was repeated a few months later on Earth on the same subject. As expected, the influence of the frame on rod positioning was statistically significant in all test conditions. During the in-flight experimental step, a substantial lack of significant changes compared to the pre-flight condition was observed. Moreover, substantially no effects due to LBNP were observed. A mild rod displacement from the body axis was detected under microgravity compared to the pre-flight recording. Such a finding was in part reduced during LBNP. The same findings were observed during the post-flight repetition of the experiment. Our results showed an absence in this subject of significant effects on the RFT due to microgravity. In conclusion, no effects from his VM on the RFT and minor changes in the SVV could be detected

Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis

Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs

Immunologic treatments for precancerous lesions and uterine cervical cancer

Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether. After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem

Gender effects on mental rotation in pilots vs. nonpilots.

Introduction: Mental rotation ability has an important role in human navigation and, together with other cognitive abilities such as processing speed, working memory, and attention, is crucial for aircraft navigation. In the human performance literature, mental rotation tasks have consistently yielded reports of gender differences favoring men. The aim of this study was to compare the gender difference measured in a specialized population of aviators vs. a matched population of nonpilots. Methods: Studied were 41 pilots (20 men and 21 women) and 38 nonpilots (20 men and 18 women) matched for age and education. Pilots were stratified for fl ying hours. Participants performed a mental rotation task (MRT) in which accuracy and response time were recorded, and also completed sense-of-direction (SOD) and spatial cognitive styles selfevaluation scales. Results: Men had significantly smaller response time in the MRT (men 279.6 ± 147.0 s, women 401.6 ± 361.3) and greater SOD (men ' s score 49.1 ± 8.6, women ' s score 46.6 ± 7.8), but these differences were absent among pilots. A positive relationship was also identified between pilots ' response times and their fl ight hours. Conclusion: These data suggest that the effect of gender on the speed of cognitive spatial processing is absent in a population with aviation experience. Gender effects may be associated with a low spatial cognitive style, whereas in groups such as aviators, who are expected to have high spatial cognitive style, other factors such as experience may come into play. © by the Aerospace Medical Association, Alexandria, VA