30 results on '"Antonello Domenico Cabras"'
Search Results
2. Peritoneal Mesothelioma: Disease Biology and Patterns of Peritoneal Dissemination
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Matteo Montenovo, Federica Perrone, Marcello Guaglio, Antonello Domenico Cabras, Dario Baratti, M. Deraco, S. Kusamura, and Nadia Zaffaroni
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Pathology ,medicine.medical_specialty ,Tunica vaginalis ,respiratory system ,Biology ,medicine.disease ,respiratory tract diseases ,medicine.anatomical_structure ,Peritoneum ,Malignant Peritoneal Mesothelioma ,cardiovascular system ,medicine ,Peritoneal mesothelioma ,Neoplasm ,Pericardium ,Mesothelioma ,neoplasms ,Mesothelial Cell - Abstract
Mesothelioma is a rare neoplasm arising from the mesothelial cells lining the pleura, peritoneum, pericardium, and tunica vaginalis layer of testis [1]. Diffuse malignant peritoneal mesothelioma (DMPM) represents about one-fifth to one-third of all forms of mesothelioma.
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- 2020
3. Peritoneal Mesothelioma: Diagnosis and Management
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S. Kusamura, Dario Baratti, Marcello Guaglio, Eran Nizri, Antonello Domenico Cabras, and M. Deraco
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Oncology ,medicine.medical_specialty ,Systemic chemotherapy ,business.industry ,Disease ,medicine.disease ,Debulking ,Internal medicine ,medicine ,Peritoneal mesothelioma ,Fatal disease ,Hyperthermic intraperitoneal chemotherapy ,Cytoreductive surgery ,business ,Pathological - Abstract
Peritoneal mesothelioma (PM) is an uncommon and locally aggressive tumor encompassing a wide spectrum of biological behaviors, from clinically indolent to rapidly fatal disease. PM has been historically treated with debulking (DBK) surgery and/or palliative systemic chemotherapy (sCT), resulting in a median survival of only 1 year in the malignant variants. The biology of this disease has been poorly understood until recent years when mechanisms of resistance to therapy and new potential molecular therapeutic targets have been thoroughly investigated. Pathological and histological classifications of PM are still evolving. The clinical management of these conditions has improved during the last 30 years with the advent of a comprehensive treatment approach involving cytoreductive surgery (CRS) and intraperitoneal drug administration, such as hyperthermic intraperitoneal chemotherapy (HIPEC), resulting in increased patient survival. This review addresses relevant clinical and biological issues of PM, including molecular features, diagnosis, pathology, role of modern systemic and targeted therapies, patient selection for combined surgical treatment, surgical technique, and prognostic factors.
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- 2019
4. Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression
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Antonello Domenico Cabras, Paola Deho, Chiara Camisaschi, Monica Rodolfo, Barbara Vergani, Federica Crippa, Niccolò Bassani, Antonino Carbone, Roberto Patuzzo, Silvana Canevari, Paola Frati, Flavio Arienti, Mario Santinami, Loris De Cecco, Licia Rivoltini, Viviana Vallacchi, Elia Biganzoli, Federico Ambrogi, Chiara Castelli, Antonello Villa, Marialuisa Sensi, Elisabetta Vergani, Vallacchi, V, Vergani, E, Camisaschi, C, Deho, P, Cabras, A, Sensi, M, De Cecco, L, Bassani, N, Ambrogi, F, Carbone, A, Crippa, F, Vergani, B, Frati, P, Arienti, F, Patuzzo, R, Villa, A, Biganzoli, E, Canevari, S, Santinami, M, Castelli, C, Rivoltini, L, and Rodolfo, M
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Cancer Research ,Pathology ,medicine.medical_specialty ,CD30 ,T-Lymphocytes ,Population ,Ki-1 Antigen ,Antigens, CD30 ,Immune system ,Biopsy ,medicine ,Humans ,education ,Melanoma ,education.field_of_study ,medicine.diagnostic_test ,Sentinel Lymph Node Biopsy ,business.industry ,Computational Biology ,FOXP3 ,Sentinel node ,medicine.disease ,Immunohistochemistry ,Treatment Outcome ,T-Lymphocyte ,Oncology ,Disease Progression ,Transcriptome ,business ,CD8 ,Human - Abstract
Sentinel lymph nodes set the stance of the immune system to a localized tumor and are often the first site to be colonized by neoplastic cells that metastasize. To investigate how the presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, we analyzed the transcriptional profiles of archival sentinel node biopsy specimens obtained from melanoma patients. Biopsies from positive nodes were selected for comparable tumor infiltration, presence or absence of further regional node metastases, and relapse at 5-year follow-up. Unsupervised analysis of gene expression profiles revealed immune response to be a major gene ontogeny represented. Among genes upregulated in patients with progressing disease, the TNF receptor family member CD30/TNFRSF8 was confirmed in biopsy specimens from an independent group of patients. Immunohistochemical analysis revealed higher numbers of CD30+ lymphocytes in nodes from progressing patients compared with nonprogressing patients. Phenotypic profiling demonstrated that CD30+ lymphocytes comprised a broad population of suppressive or exhausted immune cells, such as CD4+Foxp3+ or PD1+ subpopulations and CD4−CD8− T cells. CD30+ T lymphocytes were increased in peripheral blood lymphocytes of melanoma patients at advanced disease stages. Our findings reinforce the concept that sentinel nodes act as pivotal sites for determining progression patterns, revealing that the presence of CD30+ lymphocytes at those sites associate positively with melanoma progression. Cancer Res; 74(1); 130–40. ©2014 AACR.
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- 2014
5. Lymph Node Metastases in Diffuse Malignant Peritoneal Mesothelioma
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Barbara Laterza, Dario Baratti, Maria Rosaria Balestra, Marcello Deraco, Shigeki Kusamura, and Antonello Domenico Cabras
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Hyperthermia ,Oncology ,Chemotherapy ,medicine.medical_specialty ,Pathology ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,medicine.anatomical_structure ,Surgical oncology ,Internal medicine ,medicine ,Peritoneal Cancer Index ,Surgery ,Hyperthermic intraperitoneal chemotherapy ,business ,Lymph node ,Survival rate - Abstract
Background Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The significance of lymph node involvement in this disease is still poorly understood.
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- 2009
6. Pseudomyxoma Peritonei
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Antonello Domenico Cabras, Dario Baratti, Marcello Deraco, Barbara Laterza, Daisuke Nonaka, and Shigeki Kusamura
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Mitomycin ,Treatment outcome ,Young Adult ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Pseudomyxoma peritonei ,Infusions, Parenteral ,In patient ,Aged ,business.industry ,Hyperthermia, Induced ,Middle Aged ,Prognosis ,Pseudomyxoma Peritonei ,medicine.disease ,Immunohistochemistry ,Treatment Outcome ,Female ,Surgery ,Hyperthermic intraperitoneal chemotherapy ,Cisplatin ,business - Abstract
To investigate outcome and prognostic factors in patients with pesudomyxoma peritonei (PMP) treated by complete cytoreduction and hyperthermic intraperitoneal chemotherapy.After comprehensive treatment, prognosis of PMP is predominantly dependent on the completeness of cytoreduction. Once complete cytoreduction is achieved, additional factors predicting long-term outcome are still poorly understood.From a prospective database, we selected 102 patients undergoing complete cytoreduction (residual tumor nodulesor =2.5 mm) and closed-abdomen hyperthermic intraperitoneal chemotherapy with mitomycin-C and cisplatin. Previously, 22 patients had systemic chemotherapy. PMP was histologically classified into disseminated peritoneal adenomucinosis, peritoneal mucinous carcinomatosis (PMCA), and intermediate/discordant group. Twenty-one patient-, tumor-, and treatment-related variables were assessed by multivariate analysis with respect to overall (OS) and progression-free (PFS) survival. The following immunohistochemical markers were tested: cytokeratin (CK)-7, CK-20, CDX-2, MUC-2, and MUC-5AC.Operative mortality was 1%. Seventy-eight patients were diagnosed with disseminated peritoneal adenomucinosis, 24 with PMCA, none with intermediate/discordant group. For the overall series, median follow-up, 5-year OS, and PFS were 45 months (range 1-110), 84.4%, and 48.3%, respectively. In most cases, CK20, CDX-2, and MUC-2 were diffusely positive, whereas CK-7 and MUC-5AC were variably expressed. At multivariate analysis, previous systemic chemotherapy and PMCA correlated to both worse OS and PFS, elevated serum CA125 only to worse PFS. CK20, CDX-2, and MUC-2 expression correlated to prognosis at univariate analysis.After complete cytoreduction and hyperthermic intraperitoneal chemotherapy, prognosis of PMP is primarily dependent on pathologic and biologic features. MUC-2, CK-20, and CDX-2 may be related to the disease biology. Understanding PMP molecular basis may facilitate personalized treatment.
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- 2009
7. Diffuse Malignant Peritoneal Mesothelioma: Failure Analysis Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
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S. Kusamura, Barbara Laterza, Marcello Deraco, P. Dileo, D. Baratti, and Antonello Domenico Cabras
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Adult ,Male ,Mesothelioma ,medicine.medical_specialty ,Neoplasm, Residual ,Mitomycin ,Antineoplastic Agents ,Gastroenterology ,Jejunum ,Young Adult ,Surgical oncology ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Treatment Failure ,Risk factor ,Peritoneal Neoplasms ,Aged ,business.industry ,Hyperthermia, Induced ,Middle Aged ,Prognosis ,medicine.disease ,Debulking ,Combined Modality Therapy ,Minimal residual disease ,Confidence interval ,Surgery ,Survival Rate ,medicine.anatomical_structure ,Oncology ,Doxorubicin ,Chemotherapy, Cancer, Regional Perfusion ,Disease Progression ,Female ,Hyperthermic intraperitoneal chemotherapy ,Cisplatin ,Neoplasm Recurrence, Local ,business ,Progressive disease - Abstract
Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The issue of treatment failure has never been extensively addressed. The present study assessed the failure pattern, management, and outcome of progressive DMPM following comprehensive treatment. Clinical data on 70 patients with DMPM undergoing cytoreduction and HIPEC were prospectively collected; after a median follow-up of 43 months, disease progression occurred in 38 patients. Progressive disease distribution in 13 abdominopelvic regions was analyzed. In 28 patients undergoing adequate cytoreduction (residual tumoror =2.5 mm), clinicopathological factors correlating to disease progression in each region were investigated. Median time to progression was 9 months [95% confidence interval (CI) 1.6-35.9]. Median survival from progression was 8 months (95% CI 4-16.2). The failure pattern was categorized as peritoneal progression (n = 31), liver metastases (n = 1), abdominal lymph-node involvement (n = 2), pleural seeding (n = 4). Small bowel was the single site most commonly involved (n = 27). Residual tumoror =2.5 mm (versus no visible) was the only independent risk factor for disease progression in epigastric region (P = 0.047), upper ileum (P = 0.029), upper jejunum (P = 0.034), and lower jejunum (P = 0.002). Progressive disease was treated with second HIPEC in 3 patients, debulking in 4, systemic chemotherapy in 16, and supportive care in 15. At multivariate analysis, time to progression9 months (P = 0.009), poor performance status (P = 0.005), and supportive care (P = 0.003) correlated to reduced survival from progression. We conclude that minimal residual disease, compared with macroscopically complete cytoreduction, correlated to failure in critical anatomical areas, suggesting the need for maximal cytoreductive surgical efforts. In selected patients, aggressive management of progressive disease seems worthwhile.
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- 2008
8. The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
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Pilar Adriana Torres Mesa, Dario Baratti, Marcello Deraco, Shigeki Kusamura, and Antonello Domenico Cabras
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Oncology ,Adult ,Male ,Mesothelioma ,medicine.medical_specialty ,Lung Neoplasms ,Risk Assessment ,Immunoenzyme Techniques ,03 medical and health sciences ,Peritoneal Neoplasm ,Young Adult ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Medicine ,Humans ,Prospective Studies ,Survival rate ,Peritoneal Neoplasms ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,business.industry ,Proportional hazards model ,Mesothelioma, Malignant ,Cytoreduction Surgical Procedures ,Hyperthermia, Induced ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Survival Rate ,Pemetrexed ,Ki-67 Antigen ,030220 oncology & carcinogenesis ,Chemotherapy, Cancer, Regional Perfusion ,Conventional PCI ,Peritoneal Cancer Index ,030211 gastroenterology & hepatology ,Surgery ,Hyperthermic intraperitoneal chemotherapy ,Female ,business ,medicine.drug ,Follow-Up Studies - Abstract
We conducted a prognostic analysis of preoperative parameters and Ki-67 determination to develop selection criteria for cytoreductive surgery (CRS) and HIPEC in patients with diffuse malignant peritoneal mesothelioma (DMPM). DMPM patients treated with CRS and HIPEC at NCI of Milan participated in this study. Multivariate analysis was conducted using Cox proportional hazard model and conditional inference tree method to select independent predictors of overall survival (OS) from the followings pre-cytoreduction parameters: age, sex, ECOG performance status, Charlson comorbidity index, previous systemic chemotherapy, CA-125, histological subtype (epithelioid vs. biphasic/sarcomatoid), Ki-67 (determined with immunohistochemistry), and peritoneal cancer index (PCI). A total of 117 patients (male/female: 67/50) with median age of 60.5 (range 22–75) years were included. Eighty-three patients had ECOG performance status = 0, median Charlson comorbidity index was 4 (range 2–9), and 102 cases had epithelioid subtype. Median Ki-67 was 5 % (range 1–60). Ninety-four (80.3 %) cases were optimally cytoreduced. The Cox analysis identified Ki-67, PCI, and histological subtype as independent prognosticators of OS. Conditional inference tree method identified three prognostic subsets: (I) Ki-67 ≤ 9 %; (II) Ki-67 > 9 % and PCI ≤ 17; and (III) Ki-67 > 9 % and PCI > 17. The median OS for subsets I, II, and III were, 86.6, 63.2, and 10.3 months, respectively. Ki-67 is a powerful prognosticator that allows, along with PCI, and histological subtype, a good prediction of OS in patients with DMPM. Patients with Ki-67 > 9 % and PCI > 17 are unlikely to benefit from the procedure and should be considered for other treatment protocols.
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- 2015
9. Species identification of mycobacteria in paraffin-embedded tissues: frequent detection of nontuberculous mycobacteria
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Hans Bösmüller, Heinz Höfler, Stephan Schulz, Martin Werner, Marcus Kremer, Gregor Weirich, Falko Fend, Antonello Domenico Cabras, and Thomas Miethke
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DNA, Bacterial ,Pathology ,medicine.medical_specialty ,Microbiological culture ,Molecular Sequence Data ,Mycobacterium gordonae ,Polymerase Chain Reaction ,Mycobacterium ,Pathology and Forensic Medicine ,Microbiology ,Mycobacterium tuberculosis ,Species Specificity ,Sequence Homology, Nucleic Acid ,medicine ,Gene ,Mycobacterium Infections ,Paraffin Embedding ,Base Sequence ,biology ,Sequence Analysis, DNA ,biology.organism_classification ,Mycobacterium fortuitum Complex ,Nontuberculous mycobacteria ,Sequence Alignment ,Nested polymerase chain reaction ,Polymorphism, Restriction Fragment Length - Abstract
Diagnosis of infections caused by mycobacteria, especially nontuberculous mycobacteria still represents a difficult task both in microbiology and pathology. The aim of this study was to determine the frequency of mycobacterial DNA detectable by PCR in formalin-fixed paraffin-embedded tissues showing suspicious granulomatous lesions. A total of 190 archival specimens were analyzed, using a nested PCR protocol, which amplifies a fragment of the mycobacterial 65-kDa heat-shock protein gene. Restriction fragment-length polymorphisms and sequencing were utilized to further analyze the obtained PCR products. Corresponding microbiological culture results were available for 41 cases. We detected mycobacterial DNA in 119 cases (63%), of which 71 (60%) were positive for Mycobacterium tuberculosis complex DNA and 41 (34%) for DNA of nontuberculous mycobacteria. Seven cases (6%) could not be subtyped for technical reasons. The largest group of nontuberculous mycobacteria comprised 29 cases (25% of the 119 positive cases), which were assigned to Mycobacterium fortuitum complex. Mycobacterium avium-intracellulare complex was detected in eight (7%) cases, Mycobacterium gordonae in three (2.5%) and Mycobacterium rhodesiae in a single case (0.8%). All cases of Mycobacterium tuberculosis were unequivocally identified by restriction fragment-length polymorphism analysis. In contrast, sequencing provided a gain of information over restriction fragment-length polymorphism analysis in 37% of the nontuberculous mycobacteria cases (15 of 41). Alignment studies on DNA of nontuberculous mycobacteria showed frequent sequence variations, supporting the existence of sequevars. Comparison of molecular data to available results of microbiological culture assays showed a good concordance of 83%. In conclusion, amplification and sequencing of the mycobacterial 65-kDa heat-shock protein gene is an excellent tool for species identification of mycobacteria, especially nontuberculous mycobacteria, in formalin-fixed paraffin-embedded tissues.
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- 2005
10. Herpesvirus 8-Associated Penile Kaposiʼs Sarcoma in an HIV-Negative Patient
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Heinz Höfler, Antonello Domenico Cabras, Teresa Pusiol, Luca Morelli, Gregor Weirich, Martin Werner, and Francesco Piscioli
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Male ,Pathology ,medicine.medical_specialty ,viruses ,Penile Neoplasm ,HIV Infections ,Dermatology ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Virus ,Herpesviridae ,Pathology and Forensic Medicine ,Immunophenotyping ,medicine ,Humans ,Penile Neoplasms ,Sarcoma, Kaposi ,Kaposi's sarcoma ,virus diseases ,DNA, Neoplasm ,General Medicine ,Middle Aged ,medicine.disease ,Epstein–Barr virus ,medicine.anatomical_structure ,DNA, Viral ,Herpesvirus 8, Human ,Sarcoma ,Penis - Abstract
Kaposi's sarcoma is a neoplastic vascular lesion. Its form of onset is frequently disseminated, especially in HIV-positive patients. Its association with the infection caused by a virus of the Epstein-Barr family, human herpesvirus 8 (HHV-8), has been recently demonstrated. In this article we discuss the unusual presentation of a solitary manifestation of Kaposi's sarcoma on the penis of a 53-year-old HIV-negative patient. Polymerase chain reaction analysis of the tumor tissue was positive for HHV-8 in the tumor cells but not in the reactive stroma cells surrounding the tumor. The case is interesting for its unusual site of presentation, the young age of onset, the association with HHV-8 infection, the HIV-negative serology, and the benign course of the disease.
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- 2003
11. Rapid Identification of Wilson's Disease Carriers by Denaturing High-Performance Liquid Chromatography
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Pier P Coni, Stefano Serra, Anna Maria Nurchi, Gavino Faa, Gregor Weirich, Heinz Höfler, and Antonello Domenico Cabras
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Male ,Epidemiology ,Compound heterozygosity ,medicine.disease_cause ,Polymerase Chain Reaction ,Sensitivity and Specificity ,law.invention ,Denaturing high performance liquid chromatography ,Exon ,Hepatolenticular Degeneration ,law ,medicine ,Humans ,Cation Transport Proteins ,Chromatography, High Pressure Liquid ,Polymerase chain reaction ,Adenosine Triphosphatases ,Mutation ,business.industry ,Haplotype ,Public Health, Environmental and Occupational Health ,Exons ,medicine.disease ,Molecular biology ,Wilson's disease ,genomic DNA ,Italy ,Copper-Transporting ATPases ,Carrier State ,Female ,business ,Copper - Abstract
Background. Wilson's disease is an autosomal recessive disorder characterized by decreased biliary copper excretion and reduced copper incorporation into ceruloplasmin. The disease gene ATP7B maps to chromosome 13q14.3, contains 21 exons, and encodes a copper-transporting P-type ATPase. ATP7B mutations are scattered over the entire gene, and scanning methods to detect mutation carriers are in demand. We have tested the usefulness of denaturing high-performance liquid chromatography for mutation detection in Wilson's disease. Methods. Genomic DNA from five Sardinian Wilson's disease families (32 individuals, 8 patients) was subjected to polymerase chain reactions for ATP7B exons 2–21 and the 5′ untranslated region. PCR products were analyzed by chromatography and by direct sequencing. Results. Three disease-causing mutations and seven sequence variants were detected by chromatography. Five patients were homozygotes for −441/−427del, and three were compound heterozygotes for V1146M plus 1512-13insT (N505X) and for −441/−427del plus V1146M, respectively. Eighteen unaffected individuals were mutation carriers. Sequence variants comprised V290V, A406S, L456V, R832K, A1140V, the novel K952R, and T991T. The novel intronic IVS18+6c>t change escaped detection by chromatography. Conclusions. Denaturing high-performance liquid chromatography is a dependable tool for ATP7B screening that is superior to traditional haplotyping. This method allows for fast, sensitive, and specific mutation detection and identification of carriers in Wilson's disease families.
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- 2002
12. Molekularpathologische Diagnostik solider Tumoren Was ist klinisch relevant?
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Martin Werner, Antonello Domenico Cabras, and Heinz Höfler
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Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,business ,Pathology and Forensic Medicine - Abstract
Nur wenige der zahlreichen potenziellen Anwendungen molekularpathologischer Untersuchungen sind fur solide Tumoren derzeit klinisch relevant. Befunde, die eine Therapieentscheidung beeinflussen konnen, sind Amplifikationen des Her-2/neu-Gens beim Mammakarzinom und spezifische Translokationen bei Sarkomen. Wenige sehr spezielle Anwendungen ergeben sich fur Mutationsanalysen von p53, etwa zur Unterstutzung einer hochgradigen Dysplasie im oberen Gastrointestinaltrakt, oder fur die Diagnose eines malignen Weichgewebs- oder Knochentumors in Einzelfallen. Durch die Mikrosatellitenanalyse kann der Pathologe zur Abklarung eines HNPCC-Syndroms beitragen oder Verwechslungen von Geweben aufklaren. Weitere molekularpathologische Testverfahren, wie z. B. Nachweise einer “Minimal Residual Disease” bzw. Tumorzelldissemination oder FISH-Untersuchungen in der Urin- und Ergusszytologie, werden moglicherweise in Zukunft starker angewandt.
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- 2002
13. Epstein-Barr Virus–Negative Hodgkin's Lymphoma After Mycosis Fungoides: Molecular Evidence for Distinct Clonal Origin
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Marcus Kremer, Birgit Geist, Heinz Höfler, Antonello Domenico Cabras, Michael Sandherr, and Falko Fend
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Male ,Herpesvirus 4, Human ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,CD30 ,Bone Marrow Cells ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,Mycosis Fungoides ,hemic and lymphatic diseases ,Biopsy ,Biomarkers, Tumor ,medicine ,Humans ,Reed-Sternberg Cells ,In Situ Hybridization ,DNA Primers ,Mycosis fungoides ,medicine.diagnostic_test ,Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ,Receptors, Antigen, T-Cell, gamma-delta ,DNA, Neoplasm ,Gene rearrangement ,Middle Aged ,medicine.disease ,Hodgkin's lymphoma ,Hodgkin Disease ,Immunohistochemistry ,Epstein–Barr virus ,Clone Cells ,Lymphoma ,Skin biopsy ,Immunoglobulin Heavy Chains - Abstract
The association of mycosis fungoides (MF) and Hodgkin's lymphoma is a relatively frequent occurrence, but the potential clonal relationship of the two neoplasms is still controversial. We report a case of a patient with a history of MF in Clinical Stage 1A who developed retroperitoneal lymphadenopathy 9 years after the initial diagnosis of MF. A bone marrow biopsy obtained at this time showed nodular involvement by a mixed cellular infiltrate with large, atypical cells consistent with Hodgkin and Reed-Sternberg (RS) cells. These atypical cells were positive for CD30 and CD15 and did not express B- or T-cell markers. In addition, they lacked evidence of infection by Epstein-Barr virus, both by immunohistochemical staining for latent membrane protein 1 and by in situ hybridization for EBER1/2. The background population consisted mainly of small T cells without morphological or phenotypical signs of malignancy. Review of the skin biopsy obtained 9 years before showed the typical features of MF. Polymerase chain reaction analysis of the T-cell receptor T-gene confirmed the presence of a clonal T-cell rearrangement in the skin specimen. The bone marrow biopsy, however, showed a polyclonal pattern both for the T-cell receptor gamma-gene, as well as for immunoglobulin heavy chain genes. Isolation of RS cells stained for CD30 was performed by laser capture microdissection. Polymerase chain reaction analysis of several groups of RS cells showed a reproducible biallelic rearrangement of IgH genes, which was confirmed by cloning and sequencing of polymerase chain reaction products. To our knowledge, this is the first case in which a distinct clonal origin of MF and Hodgkin's lymphoma arising in the same patient is clearly demonstrated, based on molecular analysis of microdissected RS cells.
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- 2001
14. Is Tumour Angiogenesis a Prognostic Factor in Patients with Colorectal Cancer and No Involved Nodes?
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Peracchia A, Pietro Caruana, Renato Costi, Antonello Domenico Cabras, Nicola Pietra, Sara Gobbi, Leopoldo Sarli, and Cesare Bordi
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Male ,Prognostic variable ,medicine.medical_specialty ,Multivariate analysis ,Colorectal cancer ,Angiogenesis ,Recurrence ,Carcinoma ,Humans ,Medicine ,Microvessel ,Survival analysis ,Aged ,Neoplasm Staging ,Retrospective Studies ,Analysis of Variance ,Neovascularization, Pathologic ,business.industry ,Microcirculation ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Surgery ,Female ,Colorectal Neoplasms ,business - Abstract
To examine a possible association between tumour angiogenesis and conventional prognostic variables and to assess the prognostic value of the variables examined in patients with colorectal cancer, with no involved nodes.Retrospective study.University hospital, Italy.119 patients who had had colorectal cancers resected for cure with no involved nodes between 1985-1990.The three microscopic fields with the most microvessels were identified by immunohistochemical techniques. 10 high-power fields in each area were used for the microvessel count and the mean values indicated the microvessel density.Correlation of microvessel density with conventional prognostic factors, recurrence rates, and survival.There was a significant correlation between microvessel density and sex, women having a higher density than men (p0.05), but no significant correlations between density and recurrence rates or survival. Multivariate analysis did not indicate that microvessel density had a prognostic role.Microvessel density in colorectal cancer without involved nodes does not correlate with conventional prognostic factors and provides no prognostic information.
- Published
- 2000
15. Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC)
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Ionut Hutanu, Shigeki Kusamura, Marcello Deraco, Rossella Bertulli, Antonello Domenico Cabras, and Dario Baratti
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Oncology ,Adult ,Male ,Mesothelioma ,Cancer Research ,medicine.medical_specialty ,Proliferative index ,Mitomycin ,Cytokeratin ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Doxorubicin ,Prospective Studies ,Survivors ,Survival analysis ,Peritoneal Neoplasms ,Aged ,Cisplatin ,Intraoperative Care ,business.industry ,Hyperthermia, Induced ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Survival Analysis ,Treatment Outcome ,Podoplanin ,Multivariate Analysis ,Immunohistochemistry ,Hyperthermic intraperitoneal chemotherapy ,Female ,business ,medicine.drug - Abstract
Background Prognosis of diffuse malignant peritoneal mesothelioma (DMPM) has been recently improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). As with other peritoneal surface malignancies, the survival benefit is maximal when a complete surgical cytoreduction is achieved, but additional factors predicting long-term outcome are still poorly understood. We sought to investigate outcome and prognostic factors in patients with DMPM treated by complete cytoreduction and HIPEC. Methods From a prospective database, we selected 108 patients with DMPM undergoing complete cytoreduction (residual tumour nodules ⩽2.5 mm) and closed-abdomen HIPEC with cisplatin and doxorubicin or mitomycin-C. Twenty-seven patient-, tumour- and treatment-related variables were assessed by multivariate analysis with respect to overall (OS) and progression-free (PFS) survival. A panel of immunohistochemical markers was tested. Results Operative mortality was 1.9% and major morbidity 38.9%. Median follow-up was 48.8 months (95% confidence interval (CI) 37.1–60.6). Median OS and PFS were 63.2 months (95%CI 29.6–96.7) and 25.1 months (95%CI 5.1–45.1). The survival curve reached a plateau after 7 years, representing 19 actual survivors of 39 patients (43.6%) with potential follow-up ⩾7 years. Cytokeratin 5/6, calretinin, Wilms tumour-1 (WT-1), podoplanin and epithelial growth factor receptor (EGFR) were mostly positive. At multivariate analysis, epithelial histological subtype, negative lymph-nodes, ⩽10% Ki67-positive cells correlated with both increased OS and PFS. Positive podoplanin correlated to increased PFS. Conclusions After complete cytoreduction and HIPEC, prognosis of DMPM is primarily dependent on pathologic and biologic features. Patients with DMPM surviving ⩾7 years appeared to be cured. Cure rate was 43.6%. Proliferative index and podoplanin may be used for prognostic stratification.
- Published
- 2012
16. Cytoreductive surgery with selective versus complete parietal peritonectomy followed by hyperthermic intraperitoneal chemotherapy in patients with diffuse malignant peritoneal mesothelioma: a controlled study
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Dario Baratti, Antonello Domenico Cabras, Shigeki Kusamura, and Marcello Deraco
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Hyperthermia ,Adult ,Male ,Mesothelioma ,medicine.medical_specialty ,Surgical oncology ,Peritonectomy ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Combined Modality Therapy ,Humans ,Survival rate ,Peritoneal Neoplasms ,Aged ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Hyperthermia, Induced ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Treatment Outcome ,Oncology ,Malignant Peritoneal Mesothelioma ,Case-Control Studies ,Hyperthermic intraperitoneal chemotherapy ,Female ,Peritoneum ,business ,Omentum ,Follow-Up Studies - Abstract
Combined treatment involving peritonectomy procedures, multivisceral resections, and hyperthermic intraperitoneal chemotherapy (HIPEC) has reportedly resulted in survival benefit for peritoneal surface malignancies, including diffuse malignant peritoneal mesothelioma (DMPM). Many unanswered questions remain regarding the surgical options in the management of DMPM. The aim of this case–control study was to assess the impact of the type and extent of parietal peritonectomy on survival and operative outcomes.Thirty patients with DMPM undergoing selective parietal peritonectomy (SPP) of macroscopically involved regions, and 30 matched patients undergoing routine complete parietal peritonectomy (CPP), regardless of disease distribution, were retrospectively identified from a prospective database.Groups were comparable for all characteristics, except for a higher proportion of patients treated before July 2003 and undergoing preoperative systemic chemotherapy in the SPP group. Median follow-up was 86.2 months in the SPP group and 50.3 months in the CPP group. Median overall survival was 29.6 months in the SPP group and not reached in the CPP group; 5-year overall survival was 40.0% and 63.9%, respectively (P = 0.0269). At multivariate analysis, CPP versus SPP was recognized as an independent predictor of better prognosis, along with complete cytoreduction, negative lymph nodes, epithelial histology, and lower MIB-1 labelling index. Morbidity and reoperation rates were not different between groups. No operative mortality occurred. In 12 of 24 patients undergoing CPP, pathologic examination detected disease involvement on parietal surfaces with no evident tumor at surgical exploration.CPP improved survival in patients with DMPM undergoing combined treatment. This information may contribute to standardize surgical options for DMPM and other peritoneal malignancies.
- Published
- 2011
17. Receptor tyrosine kinase and downstream signalling analysis in diffuse malignant peritoneal mesothelioma
- Author
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Marcello Deraco, Marta Orsenigo, Rossella Bertulli, Eva Tarantino, Claudia Bertan, Nadia Zaffaroni, Genny Jocollè, Antonello Domenico Cabras, Silvia Brich, Cinzia De Marco, Dario Baratti, Silvana Pilotti, Marco A. Pierotti, Federica Perrone, Marzia Pennati, Perrone, Federica, Jocoll, Genny, Pennati, Marzia, Deraco, Marcello, Baratti, Dario, Brich, Silvia, Orsenigo, Marta, Tarantino, Eva, De Marco, Cinzia, Bertan, Claudia, Cabras, Antonello, Bertulli, Rossella, Pierotti, Marco Alessandro, Zaffaroni, Nadia, and Pilotti, Silvana
- Subjects
Male ,Mesothelioma ,Cancer Research ,Receptor, Platelet-Derived Growth Factor alpha ,Diffuse malignant peritoneal mesothelioma ,DNA Mutational Analysis ,p16 ,Apoptosis ,medicine.disease_cause ,Receptor tyrosine kinase ,Platelet-Derived Growth Factor Receptor Beta ,Pleural Neoplasm ,biology ,Middle Aged ,Immunohistochemistry ,Platelet-Derived Growth Factor beta ,Receptor Protein-Tyrosine Kinase ,ErbB Receptors ,EGFR ,mTOR ,PDGFRB ,Adult ,Aged ,Female ,Genes, p16 ,Humans ,Mutation ,Pleural Neoplasms ,Receptor Protein-Tyrosine Kinases ,Receptor, Epidermal Growth Factor ,Receptor, Platelet-Derived Growth Factor beta ,Oncology ,KRAS ,Human ,medicine.drug ,Receptor ,PDGFRA ,DNA Mutational Analysi ,Gefitinib ,medicine ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Epidermal Growth Factor ,Platelet-Derived Growth Factor alpha ,Apoptosi ,Genes ,Cancer research ,biology.protein - Abstract
Our aim was to assess the activation profile of EGFR, PDGFRB and PDGFRA receptor tyrosine kinases (RTK) and their downstream effectors in a series of cryopreserved diffuse malignant peritoneal mesothelioma (DMPM) surgical specimens to discover the targets for drug inhibition. We also made a complementary analysis of the cytotoxic effects of some kinase inhibitors on the proliferation of the human peritoneal mesothelioma STO cell line. We found the expression/phosphorylation of EGFR and PDGFRB in most of the tumours, and PDGFRA activation in half. The expression of the cognate ligands TGF-α, PDGFB and PDGFA in the absence of RTK mutation and amplification suggested the presence of an autocrine/paracrine loop. There was also evidence of EGFR and PDGFRB co-activation. RTK downstream signalling analysis demonstrated the activation/expression of ERK1/2, AKT and mTOR, together with S6 and 4EBP1, in almost all the DMPMs. No KRAS/BRAF mutations, PI3KCA mutations/amplifications or PTEN inactivation were observed. Real-time polymerase chain reaction revealed the decreased expression of TSC1 c-DNA in half of the tumours. In vitro cytotoxicity studies showed the STO cell line to be resistant to gefitinib and sensitive to sequential treatment with RAD001 and sorafenib; these findings were consistent with the presence of the KRAS mutation G12D in these cells although it was not detectable in the original tumour. Our results highlight the ligand-dependent activation and co-activation of EGFR and PDGFRB, as well as a connection between these activated RTKs and the downstream mTOR pathway, thus supporting the role of combined treatment with RTK and mTOR inhibitors in DMPM.
- Published
- 2010
18. Using Q-RT-PCR to measure cyclin D1, TS, TP, DPD, and Her-2/neu as predictors for response, survival, and recurrence in patients with esophageal squamous cell carcinoma following radiochemotherapy
- Author
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Antonello Domenico Cabras, Martin Werner, Gisela Keller, Katja Specht, Raymonde Busch, Björn L.D.M. Brücher, Silke Lassmann, Michael Molls, Heinz Höfler, J. Rüdiger Siewert, Hans Dieter Allescher, Hubert J. Stein, Falko Fend, and Ulrike Müller
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Esophageal Neoplasms ,Receptor, ErbB-2 ,medicine.medical_treatment ,Gene Expression ,Cyclin D1 ,Internal medicine ,Gene expression ,medicine ,Humans ,Microdissection ,Neoadjuvant therapy ,Dihydrouracil Dehydrogenase (NADP) ,Aged ,Thymidine Phosphorylase ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Gastroenterology ,Thymidylate Synthase ,Hepatology ,Middle Aged ,Prognosis ,Neoadjuvant Therapy ,Esophagectomy ,Cohort ,Carcinoma, Squamous Cell ,Female ,RNA extraction ,Neoplasm Recurrence, Local ,business - Abstract
The purpose of this study was to evaluate the use of thymidilate synthetase (TS), thymidilate phosphorylase (TP), dihydropyrimidin dehydrogenase (DPD), Her-2/neu, and cyclin D1 as predictors of therapy response, survival, and recurrence in patients with esophageal squamous cell carcinoma (ESCC) following radiochemotherapy. Twenty-six patients with histologically proven intrathoracic, locally advanced ESCC (cT3, cN0/+, cM0) underwent preoperative, combined simultaneous radiochemotherapy followed by R0-transthoracic esophagectomy. Because R0 resection is the strongest known independent prognostic factor in this tumor entity, only R0-resected patients were included in this study. Pre-therapeutically taken, formalin-fixed, and paraffin-embedded tumor biopsies were used for laser-assisted microdissection of tumor cells and RNA extraction and subjected to real-time (TaqMan) quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR). No significant correlation between clinical or histopathological parameters and the relative gene expression of TS, TP, DPD, or Her-2/neu was observed. However, patients with relative cyclin D1 levels below the median gene expression did not reach median survival compared to the 19.9 months seen in patients with relative cyclin D1 gene expression above the median (P = 0.02). Patients with low cyclin D1 levels experienced significantly less frequent recurrence of the tumor (20% versus 63%; P = 0.006), and there was a significant difference in the recurrence-free interval (P = 0.003). Despite the small number of investigated patients, our data seem to show that high levels of cyclin D1 measured by real-time Q-RT-PCR before neoadjuvant radiochemotherapy correlate significantly with patient survival, tumor recurrence, and recurrence-free-interval. Cyclin D1 might be useful in identifying patients at high risk of poor prognosis and suffering from recurrence after neoadjuvant radiochemotherapy treatment and R0 resection. Further investigations with a larger cohort are warranted.
- Published
- 2008
19. Advances in clinical research and management of diffuse peritoneal mesothelioma
- Author
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Marcello, Deraco, Dario, Baratti, Nadia, Zaffaroni, Antonello Domenico, Cabras, and Shigeki, Kusamura
- Subjects
Mesothelioma ,Humans ,Peritoneal Neoplasms - Published
- 2007
20. Advances in Clinical Research and Management of Diffuse Peritoneal Mesothelioma
- Author
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Marcello Deraco, Shigeki Kusamura, Nadia Zaffaroni, Antonello Domenico Cabras, and Dario Baratti
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,respiratory system ,medicine.disease ,medicine.disease_cause ,Asbestos ,respiratory tract diseases ,medicine.anatomical_structure ,Clinical research ,Peritoneum ,medicine ,Peritoneal mesothelioma ,Peritoneal Cancer Index ,Pericardium ,Mesothelioma ,business ,Carcinogen - Abstract
Diffuse malignant mesothelioma is a tumor arising from the serosal surfaces of the pleura, peritoneum, pericardium, or tunica vaginalis testis. Although the tumor is exceedingly uncommon, there is a substantial interest in this disease, as either biological or occupational and medical-legal issues are concerned: asbestos is the principal carcinogen associated with malignant mesothelioma, and up to 8 million living persons in the USA have been occupationally exposed to asbestos over the last five decades (Robinson and Lake 2005).
- Published
- 2007
21. Oligoclonality of a 'composite' gastric diffuse large B-cell lymphoma with areas of marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type
- Author
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Gregor Weirich, Falko Fend, Antonello Domenico Cabras, Jörg Nährig, Cesare Bordi, Martin Werner, and Heinz Höfler
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Molecular Sequence Data ,Gene Rearrangement, B-Lymphocyte, Heavy Chain ,Biology ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,Immunophenotyping ,Micromanipulation ,immune system diseases ,Stomach Neoplasms ,hemic and lymphatic diseases ,medicine ,Humans ,Amino Acid Sequence ,Molecular Biology ,Base Sequence ,Dissection ,Large-cell lymphoma ,MALT lymphoma ,Neoplasms, Second Primary ,Cell Biology ,General Medicine ,Gene rearrangement ,DNA, Neoplasm ,Lymphoma, B-Cell, Marginal Zone ,Gastric Diffuse Large B-Cell Lymphoma ,Middle Aged ,medicine.disease ,Marginal zone ,Clone Cells ,Mantle cell lymphoma ,Marginal zone B-cell lymphoma ,Lymphoma, Large B-Cell, Diffuse ,Mucosa-associated lymphoid tissue - Abstract
We analyzed a case of oligoclonal Helicobacter pylori-associated, primary gastric diffuse large B-cell lymphoma (DLBCL) with areas of extranodal marginal zone B-cell lymphoma (MZBL) of mucosa-associated lymphoid tissue (MALT) type in a 61-year-old male patient. The patient had two separate tumors, in the corpus and in the antrum, each showing two morphologically distinct components (DLBCL and MZBL of MALT type). To determine the clonal relationship between the large- and small-cell components, we microdissected four samples from morphologically distinct tumor components at both tumor sites. PCR analysis revealed rearranged immunoglobulin heavy chain (IgH) genes of different sizes in three of the four microdissected samples. Cloning and sequencing of the PCR products displayed different IgH gene rearrangements in the two small cell components of the antrum and the corpus. A third genuinely differently rearranged IgH gene was found in the large-cell components of both antrum and corpus. Our results suggest that in primary gastric DLBCL with areas of MZBL of MALT type, the small-cell component may comprise more than one tumor clone. Furthermore, the large-cell component may evolve independently from coexisting MZBL.
- Published
- 2002
22. Biclonality of gastric lymphomas
- Author
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Martin Werner, Gregor Weirich, Cesare Bordi, Heinz Höfler, Sonja Candidus, Stephan Schulz, Falko Fend, Antonello Domenico Cabras, and Marcus Kremer
- Subjects
Pathology ,medicine.medical_specialty ,Lymphoma, B-Cell ,Molecular Sequence Data ,Clone (cell biology) ,Biology ,Somatic evolution in cancer ,Pathology and Forensic Medicine ,immune system diseases ,Stomach Neoplasms ,hemic and lymphatic diseases ,Sequence Homology, Nucleic Acid ,medicine ,Humans ,Molecular Biology ,Laser capture microdissection ,Electrophoresis, Agar Gel ,Base Sequence ,Large-cell lymphoma ,MALT lymphoma ,Cell Biology ,DNA, Neoplasm ,medicine.disease ,Marginal zone ,Lymphoma ,Cancer research ,Immunoglobulin heavy chain ,Lymphoma, Large B-Cell, Diffuse - Abstract
The pathogenesis and clonal evolution of gastric diffuse large B-cell lymphoma (DLBCL) and its relationship to extranodal marginal zone B-cell lymphoma (MZBL), mucosa-associated lymphoid tissue (MALT) type, are still controversial. The aim of this study was to establish the clonality of morphologically distinct areas of gastric lymphomas as well as their genetic relationship to each other. Six gastric lymphomas, consisting of two MZBL, MALT type, two DLBCL, and two “composite” lymphomas were subjected to laser capture microdissection and subsequent PCR-based amplification of the immunoglobulin heavy chain gene. One DLBCL showed a biclonal pattern of rearranged immunoglobulin heavy chain (IgH) genes of two different areas without evidence of a common origin. Two composite DLBCL with areas of extranodal MZBL, MALT type, were also biclonal and displayed different IgH gene rearrangements in the small-cell and in the large-cell components, respectively. Sequencing of the CDR3 region revealed unique VH-N-D and D-N-JH junctions, thus corroborating the presence of two genuinely distinct tumor clones in each of these three cases. In contrast, the remaining three gastric lymphomas (one DLBCL and two MZBL, MALT type) showed IgH gene rearrangements in which CDR3 regions were identical in the different tumor areas. Our results suggest that gastric DLBCL may be composed of more than one tumor cell clone. Further, DLBCL may not necessarily evolve by transformation of a low-grade lymphoma, but may also originate de novo. An ongoing emergence of new tumor clones may considerably hamper molecular diagnosis and follow-up of gastric DLBCL.
- Published
- 2001
23. Molecular diagnosis of a Mycobacterium chelonae infection
- Author
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Heinz Höfler, Andreas Lügering, Markus Kremer, Martin Werner, Stephan Schulz, Matthias Seidel, and Antonello Domenico Cabras
- Subjects
Adult ,DNA, Bacterial ,Mycobacterium chelonae ,Mycobacterium Infections, Nontuberculous ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,Microbiology ,law.invention ,law ,Clarithromycin ,medicine ,Humans ,Reactive arthritis ,Amikacin ,Polymerase chain reaction ,biology ,Cell Biology ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,Imipenem ,Immunology ,Nontuberculous mycobacteria ,Female ,Lymph ,Lymph Nodes ,medicine.drug ,Mycobacterium - Abstract
Summary A 23-year-old female presented with enlarged cervical lymph nodes, and a diagnosis of nonspecific lymphadenitis with formation of pyogranulomas was rendered. Despite an initial oral antibiosis and subsequent long-term intravenous and oral antibiosis under hospitalized conditions, the symptoms progressed. The lymph nodes became larger and then affected the cervical region bilaterally. Her general condition worsened, and an exanthema of the extremities accompanied by a reactive arthritis occurred. Serological assays of various viral and bacterial markers and blood cultures were negative. Application of a polymerase chain reaction (PCR) protocol allowing specific amplification of mycobacterial DNA revealed DNA of Mycobacterium chelonea in formalin-fixed, paraffin-embedded lymph node tissue. Sequencing of the PCR product showed a 97% homology with the known Mycobacterium chelonae sequence. Modification of the antibiotic therapy with clarithromycin, imipenem and amikacin resulted in a rapid regression of the symptoms. The clinical course, in combination with the difficulties in detecting the infectious agent, supports the usefulness of molecular pathological analyses specific for nontuberculous mycobacteria (NTM).
- Published
- 2001
24. In Reply: Five Reasons Why Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy Must Be Regarded as the New Standard of Care for Diffuse Malignant Peritoneal Mesothelioma
- Author
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S. Kusamura, Barbara Laterza, Marcello Deraco, Dario Baratti, Maria Rosaria Balestra, and Antonello Domenico Cabras
- Subjects
medicine.medical_specialty ,Standard of care ,Oncology ,Surgical oncology ,business.industry ,Malignant Peritoneal Mesothelioma ,General surgery ,medicine ,Surgery ,Hyperthermic intraperitoneal chemotherapy ,business ,Cytoreductive surgery - Published
- 2010
25. 30 INVITED Peritoneal Mesothelioma
- Author
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F. Parrone, Shigeki Kusamura, Antonello Domenico Cabras, Silvana Pilotti, M. Deraco, Nadia Zaffaroni, and Dario Baratti
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Oncology ,business.industry ,Peritoneal mesothelioma ,medicine ,medicine.disease ,business - Published
- 2011
26. 112 Diffuse malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Experience of NCI of Milan
- Author
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Daisuke Nonaka, S. Kusamura, D. Baratti, Nadia Zaffaroni, Antonello Domenico Cabras, M. Deraco, and P. Casali
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Oncology ,Malignant Peritoneal Mesothelioma ,business.industry ,Medicine ,Hyperthermic intraperitoneal chemotherapy ,Cytoreductive surgery ,business ,Surgery - Published
- 2006
27. Advances in clinical research and management of diffuse peritoneal mesothelioma
- Author
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Deraco, M., Baratti, D., Zaffaroni, N., Antonello Domenico Cabras, and Kusamura, S.
28. Quality assessment in diagnostic molecular pathology: Experience from a German-Austrian-Swiss multicenter trial
- Author
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Michael Hummel, Martin Werner, Marcus Kremer, Heinz Höfler, Paul Komminoth, Gerald Höfler, Stephan Schulz, and Antonello Domenico Cabras
- Subjects
DNA, Bacterial ,Quality Control ,medicine.medical_specialty ,Lymphoma, B-Cell ,Tuberculosis ,Sarcoidosis ,Lymphoma, T-Cell ,Mycobacterium ,Pathology and Forensic Medicine ,Lymphadenitis ,Germany ,Internal medicine ,Multicenter trial ,medicine ,Humans ,Molecular Biology ,Gene Rearrangement ,Pathology, Clinical ,Tissue Embedding ,Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ,Quality assessment ,business.industry ,Molecular pathology ,Cell Biology ,General Medicine ,medicine.disease ,Molecular analysis ,Internal quality ,Genetic Techniques ,Multicenter study ,Austria ,Immunology ,Gene Rearrangement Analysis ,Immunoglobulin Heavy Chains ,Laboratories ,business ,Switzerland - Abstract
In order to assess the current technical standard of diagnostic molecular pathology, we have conducted a multicenter trial with 34 participating pathology laboratories in Germany, Austria and Switzerland. Formalin-fixed, paraffin-embedded tissue blocks were selected from 15 cases, comprising 4 B-cell non-Hodgkin's lymphomas, 4 T-cell non-Hodgkin lymphomas, 4 cases with lymphadenitis, 2 cases with confirmed tuberculosis and 1 case of sarcoidosis. All participating laboratories received one 10-microm section from each of the 15 cases to detect clonality using immunoglobulin heavy chain (IgH) gene or T-cell receptor (TCR)-gamma gene rearrangement analysis in 12 and mycobacterial DNA in 3 cases. In addition, participants had to answer technical questions about the application of internal quality controls and performance of fragment length or sequence analysis. Correct results were reported in 80% and 90% for IgH and TCR-gammagene rearrangement analysis, respectively, and in 83% for mycobacterial DNA analysis. No significant differences in the quality of results were obvious when the individual techniques used for molecular analysis were compared. However, when two independent techniques were used by the same laboratory, a higher rate of correct results was obtained for IgH and TCR rearrangement analysis. In conclusion, this study demonstrates a high technical standard of molecular diagnostic adjuncts among the participating laboratories. Regular multicenter trials with a greater number of participating laboratories working in this field will be indispensable to ensure a continuing or increasing standard in diagnostic molecular pathology.
29. Survivin is highly expressed and promotes cell survival in malignant peritoneal mesothelioma
- Author
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Roberta Erdas, Maria Grazia Daidone, Emanuela Affini, Cinzia De Marco, Dario Baratti, Marzia Pennati, Nadia Zaffaroni, Marcello Deraco, Aurora Costa, Antonello Domenico Cabras, Shigeki Kusamura, and Maria Madeo
- Subjects
Male ,Mesothelioma ,Cancer Research ,Survivin ,Inhibitor of Apoptosis Proteins ,caspase-9 ,RNA, Small Interfering ,Peritoneal Neoplasms ,Gene knockdown ,lcsh:Cytology ,Reverse Transcriptase Polymerase Chain Reaction ,apoptosis ,General Medicine ,Transfection ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunohistochemistry ,Caspase 9 ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,IAPs ,Molecular Medicine ,Female ,Microtubule-Associated Proteins ,medicine.drug ,Adult ,Cell Survival ,Biology ,lcsh:RC254-282 ,Pathology and Forensic Medicine ,Cell Line, Tumor ,peritoneal mesothelioma ,medicine ,Humans ,lcsh:QH573-671 ,neoplasms ,Aged ,Cell Proliferation ,Cisplatin ,Cell growth ,Cell Biology ,Molecular biology ,Cell culture ,Apoptosis ,siRNA ,Cancer research ,Other ,Apoptosis Regulatory Proteins - Abstract
Background: The biology of malignant peritoneal mesothelioma (MPM) is largely unknown. In the present study, we assessed the expression of survivin and other members of the inhibitors of apoptosis proteins (IAP) family (IAP-1, IAP-2 and X-IAP) in a series of 32 MPM surgical specimens and investigated the effects of survivin knockdown in an established MPM cell line. Methods: Expression of different IAPs was measured by immunohistochemistry. MPM cells were transfected with a small-interfering RNA (siRNA) targeting survivin mRNA and analyzed for survivin expression, growth rate, and ability to undergo spontaneous and drug (cisplatin, doxorubicin)-induced apoptosis. Results: Survivin expression was observed in 29 (91%) surgical MPM specimens, whereas the positivity rate for the other IAPs ranged from 69% to 100%. Transfection of MPM cells with the survivin siRNA induced a marked inhibition of survivin protein expression, a time-dependent decline in cell growth and an enhanced rate of spontaneous and drug-induced apoptosis, with a concomitant increase in the catalytic activity of caspase-9. Conclusion: Our results show for the first time that survivin, as well as other IAPs, is largely expressed in clinical MPMs and suggest that strategies aimed at down-regulating survivin may provide a novel approach for the treatment of the malignancy.
30. HIV-associated Hodgkin's lymphoma. Antiapoptotic pathways and mechanisms for immune escape by tumor cells in the setting of improved immunity
- Author
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Antonino Carbone, Antonello Domenico Cabras, and Annunziata Gloghini
- Subjects
0301 basic medicine ,Cancer Research ,T-Lymphocytes ,Clinical Biochemistry ,Apoptosis ,HIV Infections ,Biology ,Virus ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Antigens, CD ,Immunity ,Immunopathology ,medicine ,Humans ,medicine.disease ,biology.organism_classification ,Hodgkin Disease ,Lymphoma ,Antiapoptotic Agent ,030104 developmental biology ,Oncology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,CD4 Antigens ,Immunology ,Lentivirus ,Lymph Nodes
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