Carcinoma sieroso papillare del peritoneo in paziente già operata di carcinoma mammario. Caso clinico

Il carcinoma sieroso papillare del peritoneo (PPSC) è un tumore raro che si riscontra più frequentemente nel sesso femminile. L?età media al momento della diagnosi è di 56 anni. Si diffonde coinvolgendo il peritoneo, la superficie delle ovaie e la pelvi. L?istologia è indistinguibile dall?analogo tumore ovarico, cioè il carcinoma sieroso papillare (PSCO). L?istogenesi del PPSC è probabilmente correlata all?epitelio celomatico embrionale. Sintomi e segni clinici tipici sono distensione addominale, costipazione, nausea, vomito, riduzione dell?appetito, malessere generale e perdita di peso. La chirurgia citoriduttiva, in aggiunta alla chemioterapia con cisplatino e ad altre terapie come l?immunoterapia e la radioterapia, aumenta la sopravvivenza dei pazienti affetti da PPSC. Viene descritto il caso di una paziente di 51 anni, già operata di carcinoma mammario, nella quale si manifestavano alcuni dei segni e sintomi descritti. L?intervento chirurgico dimostrò le localizzazioni sierose caratteristiche. Si fece una larga exeresi ma la malata morì 14 mesi dopo per la fatale progressione della malattia. English version The peritoneal papillary serous carcinoma (PPSC) is a rare tumor more frequently revealed in female. The onset mean age is 56 years. It implicate peritoneum, ovary?s surface and pelvis. The histology of this disease is similar to papillary serous carcinoma ovary (PSCO). The PPSC histogenesis is probably correlated to coelomatic embryonal epithelium. Clinical characteristics are abdominal swelling, constipation, nausea, emesis, inappetence, feel unwell, lose weight. The cytoreductive surgery and the cisplatinum chemotherapy, and other treatments like immunotherapy and radiotherapy, increase the PSCP patient survival. A case of a 51 years old patient with previous surgery for breast cancer is here described. She show some of the yet described clinical findings. At the surgery we found the typically serous peritoneal localizations. We performed a debulking, and the patient died 14 months after the operation due to the disease progression

Different biological and prognostic breast cancer populations identified by FDG-PET in sentinel node-positive patients: Results and clinical implications after eight-years follow-up

Abstract Background Sentinel node (SN) biopsy is the standard method to evaluate axillary node involvement in breast cancer (BC). Positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG-PET) provides a non-invasive tool to evaluate regional nodes in BC in a metabolic-dependent, biomolecular-related way. In 1999, we initiated a prospective non-randomized study to compare these two methods and to test the hypothesis that FDG-PET results reflect biomolecular characteristics of the primary tumor, thereby yielding valuable prognostic information. Patients and methods A total of 145 cT1N0 BC patients, aged 24–70 years, underwent FDG-PET and lymphoscintigraphy before surgery. SN biopsy was followed in all cases by complete axillary dissection. Pathologic evaluation in tissue sections for involvement of the SN and other non-SN nodes served as the basis of the comparison between FDG-PET imaging and SN biopsy. Results FDG-PET and SN biopsy sensitivity was 72.6% and 88.7%, respectively, and negative predictive values were 80.5% and 92.2%, respectively. A subgroup of more aggressive tumors (ER-GIII, Her2+) was found mainly in the FDG-PET true-positive (FDG-PET+) patients, whereas LuminalA, Mib1 low-rate BCs were significantly undetected ( p = 0.009) in FDG-PET false-negative (FDG-PET−) patients. Kaplan–Meier survival estimates after a median follow-up of more than 8 years showed significantly worse overall survival for FDG-PET+ patients in node-positive (N+) patients ( p = 0.035) as compared to N+/FDG-PET− patients, which overlapped with survival curves of N− and FDG-PET+ or − patients. Conclusions Our findings suggest that FDG-PET results reflect intrinsic biologic features of primary BC tumors and have prognostic value with respect to nodal metastases. FDG-PET false negative cases appear to identify less aggressive indolent metastases. The possibility to identify a subgroup of N+ BC patients with an outcome comparable with N− BC patients could reduce the surgical and adjuvant therapeutic intervention

Radiolabeling and Characterization of 111In-FGF-2 for In Vivo Imaging

Fibroblast growth factor-2 (FGF-2) is a regeneration potent modulator of cell growth and regulation, with improper FGF2-signaling being involved in impaired responses to injury or even cancer. Therefore, the exploitation of FGF2 as a therapeutic drives the prerequisite for effective insight into drug disposition kinetics. In this article, we present an 111In-radiolabeled FGF-2 derivative for non-invasive imaging in small animals deploying Single Photon Emission Tomography (SPECT). 111In-FGF-2 is equally well suitable for in vitro and ex vivo investigations as 125I-FGF-2. Furthermore, 111In-FGF-2 permits to perform in vivo imaging, for example for the analysis of FGF-2 containing pharmaceutical formulations in developmental or pre-clinical stages. Radiolabeled FGF-2 had the same affinity for the low molecular weight heparin enoxaparin (Kd: 0.6 ± 0.07 µM resp. 0.33 ± 0.03 µM) and heparan sulfate proteoglycan (HPSG) binding as assessed by a saturation binding assay (Kd value in the nanomolar range of 104 ± 8 nM) as compared to natIn-FGF-2 and unlabeled FGF-2. FGF-2 and natIn-FGF-2 had similar proliferative effects on fibroblasts (EC50 = 12 ± 2 pM resp. 25 ± 6 pM). In vivo biodistribution in healthy nude mice indicated a predominant accumulation of 111In-FGF-2 in filtering organs and minor uptake in the retina, salivary, and pituitary glands, respectively, which was confirmed by SPECT imaging. Therefore, 111In-FGF-2 is a valid tracer for future non-invasive animal imaging of FGF-2 in pharmaceutical development

Splenic abscess due to Streptococcus anginosus. Case report

Splenic abscess is a rare condition. Haematogenous seeding to the spleen from an infection at a distant site, most often endocarditis, is been the most common predisposing condition but an increase has been observed in immuno-compromised patients too. Fever, leukocytosis and left upper quadrant pain are suggestive, but the signs and symptoms of splenic abscesses are often non-specific. Rare is the onset with diarrhoea as in our case. Ultrasound and computed tomography are reliable diagnostic tools. Splenectomy and antibiotics are the treatments of choice. We describe a case of splenic abscess with gas level and peritonitis from dissemination of Streptococcus anginosus (of Streptococcus millerii group) from duodenal ulcer contamined. It was diagnosed with CT, ultrasound, and abdomen X-ray with contrast then treated with splenectomy and peritoneal lavag

Fibronectin fibers are highly tensed in healthy organs in contrast to tumors and virus-infected lymph nodes

The extracellular matrix (ECM) acts as reservoir for a plethora of growth factors and cytokines some of which are hypothesized to be regulated by ECM fiber tension. Yet, ECM fiber tension has never been mapped in healthy versus diseased organs. Using our recently developed tension nanoprobe derived from the bacterial adhesin FnBPA5, which preferentially binds to structurally relaxed fibronectin fibers, we discovered here that fibronectin fibers are kept under high tension in selected healthy mouse organs. In contrast, tumor tissues and virus-infected lymph nodes exhibited a significantly higher content of relaxed or proteolytically cleaved fibronectin fibers. This demonstrates for the first time that the tension of ECM fibers is significantly reduced upon pathological tissue transformations. This has wide implications, as the active stretching of fibronectin fibers adjusts critical cellular niche parameters and thereby tunes the reciprocal cell-ECM crosstalk. Mapping the tensional state of fibronectin fibers opens novel and unexpected diagnostic opportunities.ISSN:2590-028

Novel peptide probes to assess the tensional state of fibronectin fibers in cancer

Transformations of extracellular matrix (ECM) accompany pathological tissue changes, yet how cell-ECM crosstalk drives these processes remains unknown as adequate tools to probe forces or mechanical strains in tissues are lacking. Here, we introduce a new nanoprobe to assess the mechanical strain of fibronectin (Fn) fibers in tissue, based on the bacterial Fn-binding peptide FnBPA5. FnBPA5 exhibits nM binding affinity to relaxed, but not stretched Fn fibers and is shown to exhibit strain-sensitive ECM binding in cell culture in a comparison with an established Fn-FRET probe. Staining of tumor tissue cryosections shows large regions of relaxed Fn fibers and injection of radiolabeled 111In-FnBPA5 in a prostate cancer mouse model reveals specific accumulation of 111In-FnBPA5 in tumor with prolonged retention compared to other organs. The herein presented approach enables to investigate how Fn fiber strain at the tissue level impacts cell signaling and pathological progression in different diseases.ISSN:2041-172

Radiolabeled ¹¹¹In-FGF‑2 Is Suitable for <i>In Vitro</i>/<i>Ex Vivo</i> Evaluations and <i>In Vivo</i> Imaging

Fibroblast growth factor-2 (FGF-2) is a potent modulator of cell growth and regulation, with improper FGF-2 signaling being involved in impaired responses to injury or even cancer. Therefore, the exploitation of FGF-2 as a therapeutic drives the prerequisite for effective insight into drug disposition kinetics. In this article, we present an ¹¹¹In-radiolabeled FGF-2 derivative for noninvasive imaging in small animals deploying single photon emission tomography (SPECT). ¹¹¹In-FGF-2 is equally well suitable for <i>in vitro</i> and <i>ex vivo</i> investigations as ¹²⁵I-FGF-2. Furthermore, ¹¹¹In-FGF-2 permits the performance of <i>in vivo</i> imaging, for example for the analysis of FGF-2 containing pharmaceutical formulations in developmental or preclinical stages. ¹¹¹In-FGF-2 had affinity for the low-molecular-weight heparin enoxaparin identical to that of unlabeled FGF-2 (<i>K</i>_d: 0.6 ± 0.07 μM and 0.33 ± 0.03 μM, respectively) as assessed by isothermal titration calorimetry. The binding of ¹¹¹In-FGF-2 to heparan sulfate proteoglycans (HPSGs) and the biological activity were comparable to those of unlabeled FGF-2, with EC₅₀ values of 12 ± 2 pM and 25 ± 6 pM, respectively. <i>In vivo</i> biodistribution in healthy nude mice indicated a predominant accumulation of ¹¹¹In-FGF-2 in filtering organs and minor uptake in the retina and the salivary and pituitary glands, which was confirmed by SPECT imaging. Therefore, ¹¹¹In-FGF-2 is a valid tracer for future noninvasive animal imaging of FGF-2 in pharmaceutical development