Inducers of epithelial mesenchymal transition and cancer stem cells in malignant pleural effusions

The Epithelial to Mesenchymal Transition (EMT) plays a role not only in tumor metastasis but also in tumor recurrence. This process is believed to be tightly linked to the presence of Cancer Stem Cells (CSCs) however, it is still not clear which factors could induce EMT and how it could be a source for CSCs. It has been demonstrated that Malignant Pleural Effusion (MPEs) may represent an excellent source to identify markers and molecular mechanisms involved in EMT and CSCs development. Growth factors, cell differentiation markers and molecular adhesion are involved in some of the crucial neoplastic cell events such as proliferation, metastasis, resistance to chemotherapy and EMT. In this review, we summarize the current understanding of which molecular markers can orchestrate EMT and CSCs in MPEs

Rapid on-site evaluation (ROSE) in pancreatic cancer diagnosis. doing more with less

Rapid on-site evaluation (ROSE) in pancreatic cancer diagnosis: Doing more with les

Clinical-pathological features of an occult mixed mucinous male breast cancer. a case report

Mucinous carcinoma of the male breast is an uncommon malignant breast neoplasm and its diagnoses remain difficult. It is probably due to such a low rate of breast cancer cases that men tend to be diagnosed at an older age than women and with a later stage of the disease. We describe a case of a 69-year-old male who displayed a palpable lump in his right axilla several years ago, showing signs of cutaneous adnexal mucinous adenocarcinoma after biopsy. After six years and several clinical examination and systemic investigation without results, the patient underwent to fine needle aspiration cytology and subsequently a biopsy of a mass with irregular margins in the retroareolar region of his right breast. The final diagnosis was of a mixed mucinous breast cancer with neuroendocrine differentiation. The tumor cells phenotype showed Synaptophisin (+), CEA (+/-), CK-20 (-), CK-7 (+), TTF-1 (-), estrogen receptor (-), progesterone (-) and HER 2 (++). These results were unusual for a mucinous male breast carcinoma. In the presence of a lesion in the axillary area with no specific primary origin, breast cancer should never be ruled out, even in the absence of clinical evidence and with an immunohistochemical pattern not indicative of mammary origin

Valutazione del percorso di crescita professionale dei laureati nel Corso magistrale in Scienze Tecniche Diagnostiche di Viterbo: analisi statistica pluriennale

La finalità di questa indagine è quella di verificare la posizione lavorativa acquisita dagli studenti che hanno conseguito la Laurea Magistrale in Scienze Tecniche Diagnostiche, descrivere il livello di gradimento del corso e la percezione di quanto le competenze acquisite incidono sul comportamento lavorativo delle quattro classi dei professionisti.Introduction. The research intends to evaluate whether the Bachelor Degree of Diagnostic Technical Sciences of the University “La Sapienza” in Viterbo, helps the change of professional position, and to analyze the students satisfaction. Material and method. Questionnaires have been distributed and telephone interviews have been undertaken with all the students who have attended the course from the beginning of the scholastic year 2007/2008 up 2012/2013. Results. The elaboration of the results has demonstrated that 40% of the students have undergone positive professional changes after the degree course; for example, becoming a university teacher, obtaining a higher leading charge, a managing position or working as researcher. More than 48% among the graduates have declared that the study course has contributed to positive changes in their professional behavior, and that their studies have been useful in the work place. 97% of the students declared their satisfaction with the degree course. Conclusions. Even if the results of the survey have not been compared to the standard level of performance, the analysis of these results has allowed us to underline the students’ approval of the course, and in most cases, a growth in the work contest. Vocational training is a wide topic that deals about different objects, starting from the feedback obtained during the training activity, to the details of the development of students’ abilities, to the impact on the working organization intended as performance. An example is the Kirchpatrick’s traditional model of evaluation. The survey, therefore, allows further considerations for much in-depth analysis

Diagnostic and therapeutic path of breast cancer: Effectiveness, appropriateness, and costs â Results from the DOCMa study

none8noopenGiovagnoli, Maria Rosaria; Bonifacino, Adriana; Neglia, Cosimo; Benvenuto, Marco; Sambati, Francesco Vincenzo; Giolli, Lorenzo; Giovagnoli, Alessandra; Piscitelli, PriscoGiovagnoli, Maria Rosaria; Bonifacino, Adriana; Neglia, Cosimo; Benvenuto, Marco; Sambati, Francesco Vincenzo; Giolli, Lorenzo; Giovagnoli, Alessandra; Piscitelli, Prisc

IMAGE CYTOMETRY FOR DNA ANALYSIS IN ENDOMETRIAL CARCINOMA CORRELATED WITH OTHER PROGNOSTIC PARAMETERS

We evaluated by static cytometry DNA ploidy parameters in 30 stage I-IV endometrial carcinomas and correlated these data with standard clinical-pathological features and disease-free period. We observed a direct correlation between either non-diploid DNA content and deeper myometrial invasion (p<0.02) or D.I.greater than or equal to 1.2 and M2-M3 tumors (p<0.009). The Kaplan Meier survival curves illustrate a more rapid relapse of disease associated with non-diploidy, high 5cExR, high level of proliferation and D.I.greater than or equal to 1.2. while Cox regression model gave relative hazards for disease recurrence of 4, 6, 3.7 and 2.1 for non-diploidy, D.I.greater than or equal to 1.2, high 5cExR and high level of proliferation respectively. This prospective study confirmed the prognostic value of DNA Index, and its usefulness in clinical practice especially in stage I cases, otherwise characterised by favourable standard prognostic factors, is discussed

Breast implant associated anaplastic large cell lymphoma. proposal for a monitoring protocol

BACKGROUND: The authors report four cases of breast implant-associated anaplastic large cell lymphoma (ALCL) from a single institution and propose a multidisciplinary protocol. METHODS: From 2012 to 2014, four breast implant-associated ALCL cases were diagnosed. The authors performed the original operation, and no patients were referred to their practice. Cases 1, 2, and 4 were CD4/CD30/ALK ALCL with previous textured-implant reconstruction, whereas case 3 was CD8/CD30/ALK ALCL with previous polyurethane-implant augmentation. A retrospective study of all patients who underwent breast implant positioning was performed to identify any misdiagnosed cases. RESULTS: Of 483 patients, 226 underwent reconstruction with latissimus dorsi flap and prosthesis, 115 had skin-sparing/nipple-sparing mastectomy and prosthesis, 117 underwent an expander/implant procedure, and 25 underwent breast augmentation. Fifty-eight cases (12 percent) underwent implant replacement for capsular contracture, 15 (3.1 percent) experienced late-onset seroma, and four (0.83 percent) had both capsular contracture and seroma. Seventy-seven symptomatic patients (16 percent) underwent surgical revision (capsulectomy/capsulotomy) and/or seroma evacuation. The second look on histologic specimens did not identify misdiagnosed cases. A multidisciplinary protocol for suspected implant-associated ALCL was established. Ultrasound and cytologic examinations are performed in case of periprosthetic effusion. If implant-associated ALCL is diagnosed, implant removal with capsulectomy is performed. If disseminated disease is detected through positron emission tomography/computed tomography of the total body, the patient is referred to the oncology department. CONCLUSIONS: A multidisciplinary protocol is mandatory for both early diagnosis and patient management. Until definitive data emerge regarding the exact etiopathogenesis of breast implant-associated ALCL, the authors suggest offering only autologous reconstruction if patients desire it

Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity

BACKGROUND: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. METHODS: Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. RESULTS: We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. CONCLUSIONS: Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents

Abnormal "low grade" transformation zone: current diagnostic gold standard

The aim of this work was to examine different methods of investigation in the diagnosis of the abnormal "low grade" transformation zone of the portio. Over a period of one year 41 patients subjected to colposcopic examination underwent exo-endocervical sampling for oncologic evaluation and for detection of viral and bacterial infections (HPV, HSV. adenovirus, mycoplasmas and chlamydia trachomatis), as well as portio biopsy. A 65.8% correlation was found between cytology and the HPV-DNA test results. while histology and the presence of the HPV virus agreed in 51.4% of cases. In those cases in which minimal histological alterations were found (koilocytosis) a high percentage of HPV negativity was found. In discordant negative cytologic tests that were however positive for HPV by PCR. the genotypes identified were always 6 and 11

Spheres Derived from Lung Adenocarcinoma Pleural Effusions: Molecular Characterization and Tumor Engraftment

Malignant pleural effusions (MPEs) could represent an excellent source to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas (AdenoCa) which account for approximately 40% of lung cancer cases. AdenoCa malignant pleural effusions gave rise to in vitro cultures both in adherent and/or in spheroid conditions in almost all cases analyzed. We characterized in greater detail two samples which showed the most efficient propagation in vitro. In these samples we also compared gene profiles of spheroid vs adherent cultures and identified a set of differentially expressed genes. Finally we achieved efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells