RESUMO
Immunotherapy of prostate cancer (CaP) may be a promising novel treatment option for the management of advanced CaP. However, the lack of suitable tumor antigens remains a major obstacle for the rational design of vaccines. To characterize potential CaP antigens, we determined the mRNA expression of the prostate-specific genes C1, C2, C5, PAGE-1, and prostate stem cell antigen (PSCA) in hormone-refractory CaP, benign prostatic hyperplasia, CaP cell lines, and CaP specimens. Among these gene products, only expression of PSCA appears to be retained in the majority of advanced CaP samples, as shown by reverse transcription-PCR analyses. Peptide fragments of PSCA presented in the context of major histocompatibility molecules could serve as recognition targets for CD8 T cells, provided these lymphocytes were not clonally deleted or peripherally tolerized. Our goal was to determine whether the human T-cell repertoire could recognize PSCA-derived peptide epitopes in the context of a common class I allele, HLA-A0201. Of nine peptides that, according to HLA-A0201 binding motifs, were candidate ligands of A0201 class I molecules, three peptides were able to stabilize HLA-A0201 molecules on the cell surface. One of the latter peptides, encompassing amino acid residues 14-22, was capable of generating a PSCA-specific T-cell response in a human lymphocyte culture from a patient with metastatic CaP. PSCA-specific CTLs recognized peptide-pulsed targets as well as three prostate carcinoma lines in cytotoxicity assays, indicating that this peptide could be endogenously processed. In conclusion, our findings establish PSCA as a potential target for antigen-specific, T cell-based immunotherapy of prostate carcinoma.
Assuntos
Antígenos de Neoplasias/imunologia , Imunoterapia Ativa/métodos , Glicoproteínas de Membrana/imunologia , Proteínas de Neoplasias/imunologia , Neoplasias da Próstata/imunologia , Antígenos de Neoplasias/biossíntese , Antígenos de Neoplasias/genética , Vacinas Anticâncer/imunologia , Epitopos de Linfócito T/imunologia , Proteínas Ligadas por GPI , Expressão Gênica , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-A/metabolismo , Humanos , Masculino , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Especificidade de Órgãos , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Hiperplasia Prostática/imunologia , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T Citotóxicos/imunologia , Células Tumorais CultivadasRESUMO
BACKGROUND: We describe a male with functionally impairing radial deviation of the thumb who presented to us at 24 years of age. Two sclerotic skin lesions had been excised 7 years before because of consecutive skin contracture. Latest radiological examination showed a spotted pattern consistent with osteopoikilosis. CASE PRESENTATION: A corrective osteotomy of the thumb was carried out due to the patients discomfort. Facing the simultaneous osteo-cutaneous malformation we postulated a Buschke-Ollendorff syndrome. Buschke-Ollendorff syndrome is a rare autosomal-dominant hereditary disorder of connective tissue with typical osteo-cutaneous manifestations. To explore our hypothesis, biopsies were taken from the affected bone lesions and surrounding skin and soft tissue for histological investigation and genetic testing of the LEMD3 gene was performed on blood of the patient. The histology showed typical changes of the bone architecture and a fibrotic collagenous nodule of the skin. The genetic testing on DNA extracted from peripheral blood leucocytes confirmed a heterozygous loss of function mutation in the LEM domain-containing protein 3 (LEMD3) gene coding for the inner nuclear membrane protein MAN1, which causes osteopoikilosis by antagonizing transforming growth factor ß (TGF-ß) and bone morphogenetic protein (BMP) signalling. CONCLUSIONS: In atypical cases of simultaneous occurrence of fibrotic skin lesions and a spotted pattern in the X-ray we recommend the genetic screening of the LEMD3 gene. A correct diagnosis of Buschke-Ollendorff syndrome is necessary to spare patients from expensive investigations and to provide reassurance about the benign nature of the disease.
Assuntos
Anormalidades Múltiplas/patologia , Osteopecilose/patologia , Anormalidades da Pele , Dermatopatias Genéticas/patologia , Polegar/anormalidades , Anormalidades Múltiplas/genética , Sequência de Bases , Análise Mutacional de DNA/métodos , Proteínas de Ligação a DNA , Humanos , Masculino , Proteínas de Membrana/genética , Mutação , Proteínas Nucleares/genética , Osteopecilose/genética , Homologia de Sequência do Ácido Nucleico , Dermatopatias Genéticas/genética , Polegar/cirurgia , Adulto JovemRESUMO
This article presents a rare case of a primary neuroendocrine tumor (NET) of the kidney. Abdominal magnetic resonance imaging (MRI) was performed in a 56-year-old man during the follow-up of an adrenal adenoma. Incidentally a renal tumor at the upper pole of the left kidney was diagnosed and was suspected of being a renal cell carcinoma. After partial nephrectomy a NET measuring 4.2 cm in diameter could be diagnosed histologically. An extrarenal primary tumor was ruled out by a postoperative gallium 68-tetraazacyclododecane tetraacetic acid-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) scan. A primary NET of the genitourinary tract is rare and less than 100 cases have been reported in the medical literature.
Assuntos
Neoplasias Renais/patologia , Tumores Neuroendócrinos/patologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Raras/patologiaRESUMO
An immunohistochemical study of 15 ovarian formalin-fixed, paraffin-embedded dysgerminomas showed positive staining of tumor cells for vimentin in all cases. Ten dysgerminomas stained for cytokeratin 18. Desmin positivity of single tumor cells was detected in four dysgerminomas. Glial fibrillary acidic protein was present in two tumors. Prominent human beta chorionic gonadotropin staining was seen in one tumor. S-100 protein was found in two and carcinoembryonic antigen in one of the dysgerminomas. Placental alkaline phosphatase was present in 12 of the 15 tumors studied. The heterogeneity of the cytoskeletal profile and of other markers showed some similarities to our previously published results on testicular seminomas. Thus, in contrast to previous concepts, dysgerminoma, as is the case with its testicular counterpart the seminoma, appears to be capable of further differentiation, albeit at a primitive level. Our observations also may help to elucidate the relationship between dysgerminoma and other nondysgerminomatous ovarian germ cell tumors, and may be of help in the differential diagnosis with poorly differentiated carcinoma, ovarian lymphoma, or other germ cell tumors.
Assuntos
Disgerminoma/patologia , Neoplasias Ovarianas/patologia , Biomarcadores Tumorais , Diferenciação Celular , Disgerminoma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/metabolismo , Neoplasias Ovarianas/metabolismoRESUMO
AIMS: To assess the value of homeobox protein CDX-2 expression in the distinction between primary ovarian carcinomas and carcinomas metastatic to the ovary. METHODS: CDX-2 expression was assessed by immunohistochemistry in 120 serous, 68 endometrioid, 24 clear cell, and 16 mucinous carcinomas of the ovary. In addition, CDX-2 immunoreactivity was investigated in 20 metastases from adenocarcinomas to the ovary (15 of colorectal, two of gastric, one of appendiceal, one of pancreatic, and one of cervical origin) and their corresponding primary tumours. RESULTS: Almost all of the primary ovarian carcinomas lacked immunoreactivity for CDX-2. In contrast, 14 of the 16 metastases to the ovary from intestinal primaries showed CDX-2 immunoexpression. CONCLUSION: CDX-2 is a useful marker for differentiating primary ovarian carcinoma from carcinomas metastatic to the ovary.
Assuntos
Biomarcadores Tumorais/análise , Proteínas de Homeodomínio/análise , Proteínas de Neoplasias/análise , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/secundário , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Fator de Transcrição CDX2 , Neoplasias Colorretais/química , Diagnóstico Diferencial , Feminino , Humanos , TransativadoresRESUMO
We analysed 39 prostatic carcinomas for loss of heterozygosity on chromosomal arms 8p, 10q, 16q, 17p and 18q and for mutations in the p53 anti-oncogene. Loss of heterozygosity (LOH) on 8p was detected in one out of 5 informative tumors, LOH on 16q in 3 out of 21 tumors, LOH on 17p in 2 out of 18 tumors, and LOH on 18q in 2 out of 17 tumors. No deletions were observed on 10q in 14 informative tumors. p53 alterations occurred in 3 out of 38 examined tumors, comprising two point mutations and a small deletion. Chromosomal deletions and p53 mutations were confined to locally invasive prostatic carcinomas, suggesting that they are associated with the progression of some prostate cancers rather than with tumor initiation.
Assuntos
Deleção Cromossômica , Cromossomos Humanos , Genes p53 , Mutação Puntual , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 8 , Códon , DNA de Neoplasias/química , DNA de Neoplasias/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo Genético , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
Prostate cancer (PCa) like other tumors expresses antigens that may serve as target for specific immunotherapy. Special antigen-presenting cells (e. g., dendritic cells) are capable of generating tumor-specific immunity. Cytotoxic T-cells (killer cells) are very effective against antigens and, consequently, against the respective tissue or tumor. Cancer testis antigens (CTA) are expressed in various human cancers but, aside from the testicles, not in normal tissue. Therefore, they are suitable for a specific tumor immunotherapy. We looked at different CTA (LAGE-1, PRAME, MAGE-C2, NY-ESO-1, SSX-2 and PAGE4) and their occurrence in prostatic cancer. Expression of CTA in various PCa cell lines and PCa material from patients was very heterogeneous. Only PAGE4 was expressed in primary PCa and in LnCaP cells as well as in hormone-dependent and hormone-refractory PCa probes. We conclude that PAGE4 should be further evaluated as a potential target for immunotherapy of PCa.
Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/uso terapêutico , Células Dendríticas/imunologia , Imunoterapia , Neoplasias da Próstata/terapia , Animais , Antígenos de Superfície , Vacinas Anticâncer/imunologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Imunoterapia/métodos , Masculino , Proteínas de Membrana , Camundongos , Proteínas de Neoplasias , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/terapia , Neoplasias da Próstata/imunologia , Proteínas Repressoras , Linfócitos T Citotóxicos/imunologia , Testículo/imunologia , Células Tumorais CultivadasRESUMO
The case of a 89-year-old women with mammary tuberculosis is reported. The diagnosis was based on histopathological and bacteriological examinations. Chest X-ray showed a lung-pleural tuberculosis, so we considered it a secondary organ manifestation.
Assuntos
Doenças Mamárias/diagnóstico , Tuberculose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Doenças Mamárias/patologia , Doenças Mamárias/cirurgia , Diagnóstico Diferencial , Diagnóstico por Imagem , Feminino , Humanos , Mastectomia Segmentar , Tuberculose/patologia , Tuberculose/cirurgia , Tuberculose Pleural/diagnóstico , Tuberculose Pulmonar/diagnósticoRESUMO
The rare fact of endometrial ossification can be found after abortion or chronic inflammation. We describe a case from our clinic. Despite repeated curettages new ossifications occurred. The resulting secondary infertility is persisting.
Assuntos
Endometrite/diagnóstico por imagem , Endométrio/diagnóstico por imagem , Infertilidade Feminina/diagnóstico por imagem , Ossificação Heterotópica/diagnóstico por imagem , Adulto , Dilatação e Curetagem , Endometrite/patologia , Endométrio/patologia , Feminino , Humanos , Infertilidade Feminina/patologia , Ossificação Heterotópica/patologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Recidiva , UltrassonografiaRESUMO
OBJECTIVE: We analysed the production of soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 at sites of inflammation and measured their plasma concentrations to evaluate them as biological markers of disease activity. METHODS: Plasma samples of 35 patients with Behçet's disease (BD) were collected prospectively at monthly intervals and grouped for inactive disease, active BD without arthritis, and active BD with arthritis. sTNFR1 and sTNFR2 concentrations were measured using immunoassays and compared with other biological disease activity parameters. Plasma sTNFR levels were compared to synovial fluid (SF) levels in seven patients. Sixteen tissue samples of mucocutaneous lesions were stained for TNFR2 expression by immunohistochemistry. RESULTS: sTNFR1 and sTNFR2 were found at increased plasma concentrations in active BD, with the highest concentration in active BD with arthritis (p<0.001). Concentrations of both sTNFRs were at least three times higher in SF of arthritic joints than in the corresponding plasma samples (p = 0.025). A change of more than 1 ng/mL of sTNFR2 plasma concentrations correlated with a concordant change in arthritic activity (96% confidence interval). Sensitivity to change was superior to that of sTNFR1, and other biological disease activity parameters such as erythrocyte sedimentation rate (ESR), immunoglobulin (Ig)G, IgA, and interleukin (IL)-10 plasma concentrations. A strong staining for TNFR2 was found in mucocutaneous lesions, where mast cells were identified as the major source for this receptor. CONCLUSIONS: This longitudinal study demonstrates that sTNFR2 plasma concentrations are closely linked with active BD, and especially with arthritis. Taken together with the expression of TNFR molecules in mast cells of mucocutaneous lesions, our results indicate a fundamental role for the TNF/TNFR pathway in BD.
Assuntos
Artrite/metabolismo , Síndrome de Behçet/metabolismo , Articulações/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Pele/metabolismo , Líquido Sinovial/metabolismo , Adolescente , Adulto , Artrite/etiologia , Artrite/fisiopatologia , Síndrome de Behçet/complicações , Síndrome de Behçet/fisiopatologia , Biomarcadores/metabolismo , Sedimentação Sanguínea , Estudos Transversais , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Interleucina-10/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transdução de Sinais/fisiologiaRESUMO
HISTORY AND CLINICAL FINDINGS: Two years after a first renal transplantation a 53-year-old man suffering from slowly progressing renal failure had developed progressive amyasthenia and myalgia in his legs and arms, but no dyspnea. Clinical examination, especially for neurological and respiratory abnormalities, was unremarkable. INVESTIGATIONS: Laboratory tests revealed a slightly raised calcium level and an extremely high parathormone (PTH) level. The chest x-ray revealed apical infiltrates, which were interpreted as diffuse pulmonary calcifications caused by hyperparathyroidism. TREATMENT AND COURSE: "Tertiary" hyperparathyroidism was diagnosed. After resection of five hyperplastic parathyroid glands the muscular symptoms disappeared, but the lung infiltates persisted. Four years later a second renal transplantation was necessary. Five years thereafter the patient died of congestive heart failure caused by coronary, hypertensive and valvular heart disease. CONCLUSION: In patients with chronic renal failure and pulmonary infiltrates - with or without respiratory symptoms - calcifications in the context of hyperparathyroidism have to be considered. Calcifications in the lung occur with several other diseases and have a variety of clinical presentations. Prognosis is related to the underlying disease.
Assuntos
Calcinose/etiologia , Hiperparatireoidismo/complicações , Transplante de Rim , Pneumopatias/etiologia , Calcinose/diagnóstico , Cálcio/sangue , Evolução Fatal , Insuficiência Cardíaca/complicações , Humanos , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/cirurgia , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Pneumopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Debilidade Muscular , Dor , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Hormônio Paratireóideo/sangueAssuntos
Amiloidose/diagnóstico , Doenças da Bexiga Urinária/diagnóstico , Transtornos Urinários/diagnóstico , Amiloidose/patologia , Calcinose/diagnóstico , Calcinose/patologia , Cistoscopia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Bexiga Urinária/patologia , Doenças da Bexiga Urinária/patologia , Transtornos Urinários/patologiaRESUMO
Appendix carcinoid in children is a rare condition which is found by accident at the histological examination of the appendix. We report on a rare case in which a covered perforation of a diverticulum had occurred. First of all the patient was treated conservatively with antibiotics and 2 months later the appendectomy à froid was performed. The annual follow-up of these patients is certainly indicated.
Assuntos
Abscesso Abdominal/cirurgia , Neoplasias do Apêndice/cirurgia , Apendicite/cirurgia , Tumor Carcinoide/cirurgia , Perfuração Intestinal/cirurgia , Abscesso Abdominal/patologia , Apendicectomia , Neoplasias do Apêndice/patologia , Apendicite/patologia , Apêndice/patologia , Tumor Carcinoide/patologia , Criança , Humanos , Perfuração Intestinal/patologia , Masculino , Ruptura EspontâneaRESUMO
We report on a case of a 67 year old male who had a cyst in the seminal vesicle region on sonography. The computed tomography and magnetic resonance imaging findings included a seminal vesical cyst with an intracystic tumor associated with an ipsilateral renal agenesis and are demonstrated. Postoperatively the diagnosis of an intracystic papillary adenoma in a seminal vesicle cyst was made histologically.
Assuntos
Adenoma/diagnóstico , Cistos/congênito , Doenças dos Genitais Masculinos/congênito , Neoplasias dos Genitais Masculinos/diagnóstico , Rim/anormalidades , Imageamento por Ressonância Magnética , Glândulas Seminais/anormalidades , Tomografia Computadorizada por Raios X , Adenoma/patologia , Idoso , Biomarcadores Tumorais/análise , Cistos/diagnóstico , Cistos/patologia , Diagnóstico Diferencial , Epitélio/patologia , Doenças dos Genitais Masculinos/diagnóstico , Doenças dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/patologia , Humanos , Rim/patologia , Masculino , Glândulas Seminais/patologia , Sensibilidade e EspecificidadeRESUMO
Whipple's disease has been diagnosed more frequently in recent years as a consequence of better awareness and of improved diagnostic tools. The number of case reports of Whipple's disease without gastrointestinal symptoms and without histological lesions of the intestinal mucosa is increasing. Therefore, the traditional perception of this disease as well as the methods for its diagnosis need to be revised. We report on 2 patients with Whipple's disease who had systemic inflammatory reactions but neither gastrointestinal symptoms nor an abnormal duodenal histology. Whipple's disease was diagnosed on the basis of extraintestinal tissue histology (lymph node, vertebral body) and by polymerase chain reaction, and was treated successfully with antibiotics. Recommendations for diagnostic procedure in Whipple's disease with both typical and atypical clinical presentation are discussed.
Assuntos
Doença de Whipple/diagnóstico , Doença de Whipple/patologia , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Duodeno/patologia , Humanos , Mucosa Intestinal/patologia , Linfonodos/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Coluna Vertebral/patologia , Doença de Whipple/tratamento farmacológicoRESUMO
The proteasome is critically involved in the production of MHC class I-restricted T cell epitopes. Proteasome activity and epitope production are altered by IFN-gamma treatment, which leads to a gradual replacement of constitutive proteasomes by immunoproteasomes in vitro. However, a quantitative analysis of changes in the steady state subunit composition of proteasomes during an immune response against viruses or bacteria in vivo has not been reported. Here we show that the infection of mice with lymphocytic choriomeningitis virus or Listeria monocytogenes leads to an almost complete replacement of constitutive proteasomes by immunoproteasomes in the liver within 7 days. Proteasome replacements were markedly reduced in IFN-gamma(-/-) mice, but were only slightly affected in IFN-alphaR(-/-) and perforin(-/-) mice. The proteasome regulator PA28alpha/beta was up-regulated, whereas PA28gamma was reduced in the liver of lymphocytic choriomeningitis virus-infected mice. Proteasome replacements in the liver strongly altered proteasome activity and were unexpected to this extent, since an in vivo half-life of 12 days had been previously assigned to constitutive proteasomes in the liver. Our results suggest that during the peak phase of viral and bacterial elimination the antiviral cytotoxic T lymphocyte response is directed mainly to immunoproteasome-dependent T cell epitopes, which would be a novel parameter for the design of vaccines.
Assuntos
Infecções por Arenaviridae/imunologia , Cisteína Endopeptidases/química , Listeriose/imunologia , Hepatopatias/imunologia , Complexos Multienzimáticos/química , Animais , Infecções por Arenaviridae/enzimologia , Autoantígenos , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/imunologia , Interferon-alfa/fisiologia , Interferon gama/genética , Interferon gama/farmacologia , Interferon gama/fisiologia , Listeriose/enzimologia , Hepatopatias/enzimologia , Vírus da Coriomeningite Linfocítica , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/imunologia , Proteínas Nucleares/metabolismo , Perforina , Proteínas Citotóxicas Formadoras de Poros , Complexo de Endopeptidases do Proteassoma , Biossíntese de Proteínas , Proteínas/genética , RNA Mensageiro/biossíntese , Receptor de Interferon alfa e beta , Receptores de Interferon/genéticaRESUMO
Small cell carcinomas (SCCs) represent a rare histological subtype of urinary bladder cancer. Little is known abut the genetic alterations in these tumours. To identify chromosomal aberrations that are typically present in SCC of the urinary bladder, ten tumours were analysed by comparative genomic hybridization (CGH). CGH allows screening for all relative DNA copy number gains and losses present in a tumour. SCCs of the bladder were characterized by a high number of genomic alterations (mean: 11.3 per tumour). Deletions were most frequent at 10q (7 of 10 tumours deleted), 4q, 5q (5/10 each), and 13q (4/10). These regions may carry tumour suppressor genes with relevance for this particular tumour type. Gains of DNA sequences were most prevalent at 8q (5/10), 5p, 6p, and 20q (4/10 each). High level amplifications were found at 1p22-32, 3q26.3, 8q24, and 12q14-21. These loci may pinpoint the localization of oncogenes with relevance for small cell bladder cancer. The analysis of one tumour having areas of both SCC and transitional cell carcinoma strongly suggests that SCC can develop from TCC through the acquisition of additional genetic alterations.