RESUMEN
Immunoglobulin G4 (IgG4)-related disease is a recently coined systemic disease characterized by specific histopathologic findings of an intense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis in the presence of predominant IgG4-positive plasma cells. Although IgG4-related disease has been described in many organs, involvement of the esophagus is very rare. In this study, we describe the clinicopathologic characteristics of eight patients with IgG4-related esophagitis. We evaluated chronic esophagitis specimens with lymphoplasmacytic infiltrate obtained over the past 6 years (from January 2011 to February 2017) using a chart review, pathologic examination, and IgG4 immunohistochemical staining. The diagnoses of the specimens were either confirmed as IgG4-related esophagitis (IgG4-RE) or chronic esophagitis, not otherwise specified (CENOS), and the clinicopathologic data from each group were compared. Eight patients were diagnosed with IgG4-RE and 10 controls were identified and diagnosed with CENOS. In the IgG4-RE group, esophageal strictures were identified in three patients, two patients had postmyotomy treated achalasia, one patient had erosive esophagitis and another presented with an esophageal nodule. Only one patient had an unremarkable mucosa on endoscopy. In the CENOS group, four patients had esophageal strictures, six had erosive esophagitis, one patient had mild esophagitis. The IgG4-RE group had significantly higher numbers of IgG4-positive plasma cells (66.9 ± 21.9 vs. 4.7 ± 2.4 per high power field; P< 0.001) and a greater IgG4: IgG ratio 0.76 ± 0.13 vs. 0.06 ± 0.05; P< 0.001) when compared to CENOS patients. Two of the patients with recurrent esophageal strictures in the IgG4-RE group showed initial response to steroid therapy and are currently on immunosuppressive therapy which has significantly reduced the need for multiple esophageal dilatations. The presentation of IgG4-related esophageal disease can vary and the key to diagnosis is dependent on histopathology. These observations highlight the need for IgG4 immunohistochemical staining of esophageal biopsies especially in patients with mucosal ulceration, chronic inflammation, and plasmacytosis on biopsy. This will prevent unwarranted esophagectomies and failed medical treatment due to lack of recognition of this entity.
Asunto(s)
Esofagitis/inmunología , Esofagitis/patología , Inmunoglobulina G/metabolismo , Células Plasmáticas/metabolismo , Adolescente , Anciano , Enfermedad Crónica , Trastornos de Deglución/etiología , Dilatación , Estenosis Esofágica/etiología , Esofagitis/diagnóstico , Esofagitis/terapia , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
Posttransplantation lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities ranging from benign lymphocytic proliferations to high-grade malignant lymphomas. The majority of PTLDs are associated with reactivation of Epstein-Barr virus (EBV), which induces B-cell proliferation and occurs in the setting of severe immune suppression after solid organ or bone marrow transplantation. T-cell/natural killer cell PTLDs are relatively rare, constituting â¼15% of all cases. T-cell PTLDs are usually aggressive, and outcomes are poor. This article describes an unusual case of T-cell PTLD with a favorable outcome. The patient is a 57-year-old man who underwent a liver transplantation due to hepatitis C cirrhosis. He developed graft-versus-host disease with skin and gastrointestinal involvement and generalized lymphadenopathy 4 months after transplantation. Histologic sections of an excised axillary lymph node showed atypical medium and larger T-lymphocytes that were positive for CD3, CD5, CD43, and CD8 but were negative for B-cell antigens, CD56, and in situ hybridization for EBV-encoded RNA. Polymerase chain reaction analysis revealed monoclonal T-cell receptor gamma chain gene rearrangement. A diagnosis of high-grade T-cell PTLD was made. The patient was treated with 4 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone and is currently in remission, 4 years after therapy. The rapid presentation of an EBV-negative T-cell PTLD with a nonaggressive course and complete response to treatment is an unusual presentation of posttransplantation T-cell lymphoma, which is usually associated with a high mortality rate.
Asunto(s)
Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Hígado/efectos adversos , Linfoma de Células T/inmunología , Células T Asesinas Naturales/inmunología , Complicaciones Posoperatorias/inmunología , Antineoplásicos/uso terapéutico , Humanos , Linfoma de Células T/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológicoRESUMEN
Few studies examined the clinicopathologic features of PTLD arising in pediatric SBT patients. Particularly, the association between ATG and PTLD in this population has not been described. Retrospective review of 81 pediatric patient charts with SBT--isolated or in combination with other organs--showed a PTLD incidence of 11%, occurring more frequently in females (median age of four yr) and with clinically advanced disease. Monomorphic PTLD was the most common histological subtype. There was a significant difference in the use of ATG between patients who developed PTLD and those who did not (p < 0.01); a similar difference was seen with the use of sirolimus (p < 0.001). These results suggested a link between the combination of ATG and sirolimus and development of more clinically and histologically advanced PTLD; however, the risk of ATG by itself was not clear. EBV viral loads were higher in patients with PTLD, and median time between detection of EBV to PTLD diagnosis was three months. However, viral loads at the time of PTLD diagnosis were most often lower than at EBV detection, thereby raising questions on the correlation between decreasing viral genomes and risk of PTLD.
Asunto(s)
Enfermedades Intestinales/terapia , Intestino Delgado/trasplante , Trastornos Linfoproliferativos/etiología , Complicaciones Posoperatorias , Adolescente , Suero Antilinfocítico/uso terapéutico , Niño , Preescolar , Femenino , Reordenamiento Génico , Genoma Viral , Humanos , Inmunosupresores/uso terapéutico , Hibridación in Situ , Lactante , Enfermedades Intestinales/complicaciones , Linfoma/complicaciones , Linfoma/etiología , Trastornos Linfoproliferativos/complicaciones , Masculino , Estudios Retrospectivos , Riesgo , Sirolimus/uso terapéutico , VDJ Recombinasas/genética , Carga Viral , Adulto JovenAsunto(s)
Cistitis/etiología , Cistitis/virología , Citomegalovirus/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Benzamidas , Biopsia , Médula Ósea/patología , Hemoglobinas/metabolismo , Humanos , Mesilato de Imatinib , Inmunohistoquímica , Leucocitosis , Masculino , Persona de Mediana Edad , Piperazinas/farmacología , Piperazinas/uso terapéutico , Recuento de Plaquetas , Neumonía/etiología , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Factores de Tiempo , Acondicionamiento PretrasplanteRESUMEN
We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing's sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma. Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases. Cases were retrieved from the files of the Department of Pathology at Georgetown University and from the Soft Tissue Registry of the Armed Forces Institute of Pathology. The cases were studied by light microscopy, immunohistochemistry, and PCR for IgH-R and T cell receptor gamma chain gene rearrangement (Tgamma-R). There were 17 females and 16 males; the mean age was 29.3 years. Locations included the extremities (n = 17) and trunk (n = 16). All cases fit the ES spectrum by light microscopy and immunohistochemistry, as previously determined, and were negative for lymphoid markers (LCA, CD3, CD20, CD43, CD79a, and TdT), CD10 and CD34. CD99 was positive in 31/33 and bcl-2 was weakly positive in 13/33 cases. All 21 cases studied for gene rearrangements by PCR were negative for IgH-R and Tgamma-R. Distinction of intraosseous lymphoblastic lymphoma from ES may be difficult because lymphomas may occasionally exhibit unexpected morphologic and immunophenotypic properties including LCA, CD3 and CD20 negativity and cytokeratin positivity. Additional analysis using CD79a, CD43, TdT, and PCR should be performed to avoid misdiagnosis. True ES is negative for lymphoid markers including CD79a, CD43, and TdT, as well as for IgH-R and Tgamma-R.
Asunto(s)
Neoplasias Óseas/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Sarcoma de Ewing/patología , Antígeno 12E7 , Adolescente , Adulto , Antígenos CD/análisis , Biomarcadores/análisis , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Moléculas de Adhesión Celular/análisis , Niño , ADN de Neoplasias/genética , Diagnóstico Diferencial , Femenino , Reordenamiento Génico , Humanos , Región Variable de Inmunoglobulina/genética , Inmunohistoquímica , Linfocitos/química , Linfocitos/patología , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Vimentina/análisisAsunto(s)
Aspergilosis/diagnóstico , Aspergillus niger/aislamiento & purificación , Endocarditis Bacteriana/diagnóstico , Prótesis Valvulares Cardíacas/microbiología , Complicaciones Posoperatorias/microbiología , Anticuerpos Antibacterianos/sangre , Válvula Aórtica/cirugía , Aspergilosis/microbiología , Aspergilosis/patología , Aspergillus niger/inmunología , Diagnóstico Diferencial , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/patología , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , ReoperaciónRESUMEN
Tumor suppressor genes p53 and Rb are important in cell cycle control. Necessity of wild type p53 is implicated in irradiation-induced apoptosis. Numerous tumor cells carry p53 mutations and yet are sensitive to irradiation or chemotherapeutic agents. Therefore p53-and Rb-independent pathways must exist to account for irradiation-induced apoptosis. We evaluated the apoptotic response of a p53- and Rb-mutated, Human Papilloma Virus (HPV) negative cervical cancer cell line (C33a), and C33a cell lines infected with HPV 18 oncoproteins E6, E7, and E6&7 using recombinant retrovirus to various apoptosis-inducing agents including gamma irradiation, mitomycin C (MMC), and staurosporine (SSP). Apoptosis was measured by avidinebiotin tunnel staining method. Our results showed significant apoptosis in C33a cell lines in response to gamma-irradiation, MMC, and SSP. Moreover, apoptosis was enhanced when HPV 18 E6, and E6&7 infected C33a cell lines were treated with irradiation, MMC, and SSP. HPV 18 E7 infected C33a cell lines enhanced the apoptotic response to irradiation and to MMC, but not to SSP. In conclusion, our results imply the presence of a p53- and Rb-independent pathway in irradiation-induced apoptosis in cervical cancer cell lines: this effect is even more evident in HPV oncoprotein infected cell lines. The radiosensitizing effects of HPV oncoproteins may lead to new perspectives in the treatment of cervical cancer.
Asunto(s)
Apoptosis , Proteínas de Unión al ADN , Genes de Retinoblastoma , Genes p53 , Proteínas Oncogénicas Virales/fisiología , Neoplasias del Cuello Uterino/terapia , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Femenino , Humanos , Mitomicina/farmacología , Estaurosporina/farmacología , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patologíaRESUMEN
Fas (CD95) and Fas ligand (FasL) are a receptor/ligand pair critically involved in lymphocyte homeostasis and peripheral tolerance such that genetic defect in either Fas or FasL results in an autoimmune lymphoproliferative syndrome. Fas is a type I transmembrane protein and a member of the tumor necrosis factor receptor (TNFR) family whereas FasL is a type II transmembrane protein and a member of TNF family. Binding of Fas by FasL induces apoptosis of the Fas-expressing cells. In the past few years, Fas/FasL interaction has been connected to a series of important phenomena previously viewed as independent immune processes. The activation-induced T cell death (AICD) and the FasL-mediated cytotoxicity by activated T cells are two critical mechanisms that can account for most of these phenomena. It is in the context of the two mechanisms that we discuss in this review the molecular and cellular events that occur during T/T and T/B interactions that account for the down-regulation of the immune response. We have also discussed recent advances in the areas of FasL gene regulation, lymphokine regulation of AICD, and regulation of B cell susceptibility to FasL. Investigation in these areas should help elucidate the role of Fas/FasL in the complex network of regulatory mechanisms that control immune response and autoimmunity.
Asunto(s)
Apoptosis/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Glicoproteínas de Membrana/inmunología , Linfocitos T/inmunología , Linfocitos T/patología , Receptor fas/inmunología , Animales , Autoinmunidad , Proteína Ligando Fas , Humanos , InmunidadRESUMEN
Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.
Asunto(s)
Neoplasias Óseas/diagnóstico , Linfoma de Células B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Sarcoma de Ewing/diagnóstico , Adulto , Antígenos CD/metabolismo , Niño , Preescolar , ADN Nucleotidilexotransferasa/metabolismo , Diagnóstico Diferencial , Resultado Fatal , Femenino , Reordenamiento Génico de Cadena Pesada de Linfocito B/genética , Humanos , Inmunohistoquímica , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismoRESUMEN
The effect of Fas ligand (FasL) cytotoxicity on T/B collaboration was examined in vitro using cloned T helper 1 cells and antigen-pulsed, activated B cells. We compared antigen-pulsed B cells that had been activated through different membrane receptors (IgM, CD14 and CD40) for their ability to induce T cell proliferation and to respond to T cell help. We also used a Fas-Ig fusion protein, an inhibitor of FasL-mediated cytotoxicity, to determine the effect of FasL cytotoxicity on the T and B cell proliferative responses. The data show that the extent of both T and B cell proliferative responses correlate with the relative resistance of activated B cell populations to FasL cytotoxicity. Moreover, both T and B cell proliferation could be enhanced by Fas-Ig. Our results demonstrate that FasL cytotoxicity is a negative regulatory mechanism for both T and B cell proliferative responses and that Fas-Ig can be an immunopotentiating agent for both T and B cell immunity.
Asunto(s)
Linfocitos B/inmunología , Epítopos/inmunología , Activación de Linfocitos , Cooperación Linfocítica , Complejo Mayor de Histocompatibilidad/inmunología , Glicoproteínas de Membrana/farmacología , Células TH1/inmunología , Receptor fas/farmacología , Animales , Células Presentadoras de Antígenos/inmunología , Comunicación Celular/inmunología , Células Cultivadas , Regulación hacia Abajo/inmunología , Epítopos/efectos de los fármacos , Proteína Ligando Fas , Inmunoglobulinas/metabolismo , Ligandos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/genética , Cooperación Linfocítica/genética , Complejo Mayor de Histocompatibilidad/efectos de los fármacos , Complejo Mayor de Histocompatibilidad/genética , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes de Fusión/inmunologíaRESUMEN
BACKGROUND: Hodgkin's disease (HD) rarely presents as a solitary bone tumor. Fewer than 20 such cases have been reported in the English literature; many of these were reported prior to the development of immunohistologic markers for HD and T- and B-cell lymphomas. In this report, we describe four cases of HD that presented as a localized solitary mass in bone; the diagnosis was confirmed by immunohistochemical studies in all cases. METHODS: The biopsy specimens of four cases identified in our files were studied by conventional histopathology and immunohistochemistry. Clinical data and follow-up information were obtained for all patients. RESULTS: Three cases presented as a localized, solitary mass in the ilium and one case in the vertebra (T12). Three patients were female and one male. The average age was 43 years. Three of the patients presented with lower back pain without constitutional symptoms. All had solitary osteoblastic lesions. All four cases were diagnostic problems, and the diagnosis was confirmed in each case only after finding lymph node involvement. Bone biopsies showed fibrosis and a mixed inflammatory infiltrate with rare atypical cells. All four patients were subsequently found to have nodal involvement by HD. The histology of the associated nodal disease was mixed cellularity in two cases and nodular sclerosis in two. On immunohistochemical staining, the neoplastic cells in all cases expressed CD15 and CD30 and lacked CD45 and other B- and T-cell antigens. Three patients who were treated for HD are alive and well, 1, 6, and 14 years later. CONCLUSIONS: Although rare, HD should be considered in the differential diagnosis of solitary bone lesions. Most patients who present with apparently solitary HD of bone prove to have nodal involvement. Long-term survival is possible with aggressive treatment.
Asunto(s)
Neoplasias Óseas/diagnóstico , Enfermedad de Hodgkin/diagnóstico , Adulto , Anciano , Biopsia con Aguja , Neoplasias Óseas/patología , Diagnóstico Diferencial , Femenino , Enfermedad de Hodgkin/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
Previous studies have demonstrated that murine CD4 Th1 cells lack perforin and use a pathway distinctive from CD8 CTL to express cytotoxicity. Whether the cytotoxic process of Th1 cells can be separated into identifiable stages and how these differences affect this process were determined in this study. We have resolved the cytotoxic process of Th1 clones into three stages identical with those of CD8 CTL, namely, conjugate formation/activation, lethal hit, and effector-independent programming for target DNA fragmentation. By comparing the cytotoxic processes between Th1 clones on Ag-pulsed targets and (PMA+A23187)-activated Th1 clones on unpulsed targets, we have also demonstrated that 1) the requirement of CD4 Th1 cells for de novo synthesis of cytotoxic machinery was partly responsible for the lag time in the induction of target DNA fragmentation by Th1 clones; 2) lethal hit was delivered rapidly; 3) lethal hit under forced contact by centrifugation did not need extracellular Ca2+ and Mg2+; 4) without centrifugation, lethal hit required extracellular Mg2+, but not Ca2+; 5) the average functional half life of the cytotoxic machinery was 54 +/- 24 (n = 4) min. The data demonstrate that the cytotoxic process of Th1 clones uses an activation-dependent cytotoxic machinery to deliver a short-lived, short-ranged, and quick-acting lethal hit to target, which induces a program in target for DNA fragmentation.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Citotoxicidad Inmunológica , Subgrupos de Linfocitos T/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Calcimicina/farmacología , Cationes Bivalentes , Cicloheximida/farmacología , Citotoxicidad Inmunológica/efectos de los fármacos , Daño del ADN , Dactinomicina/farmacología , Ratones , Acetato de Tetradecanoilforbol/farmacología , Factores de TiempoRESUMEN
A novel cytotoxicity, which is normally hidden but unveiled upon interacting with heat-shocked tumor target, has been identified in CD4+ Th1 cells. When TNF-resistant, Ag-presenting tumor targets were heat shocked, the cytotoxicity by specific Th1 clones was significantly enhanced. Interestingly, the DNA of heat-shocked, unpulsed targets including Ia- tumor cells were also fragmented by Th1 clones. In contrast to the Ag-dependent, MHC-restricted cytotoxicity, the heat-shock-induced sensitivity to Th1 clones was a) Ag independent and MHC unrestricted, b) insensitive to CD4-mAb, c) resistant to actinomycin D and cycloheximide, and d) greatly enhanced by cholera toxin, PGE1, PGE2, and dibutyryl cAMP. This novel cytotoxicity was inhibited by mAb specific to lymphocyte function-associated Ag-1 and intercellular adhesion molecule-1. Upon culturing at 37 degrees C, mildly heat-shocked target cells gradually recovered, indicating that the heat-shock-induced sensitivity was transient and reversible. The implication of this study for a signal-induced internal disintegration mechanism for target death is discussed. The novel cytotoxicity of CD4+ Th1 cells may be an important mechanism of immune regulation under febrile conditions and an underlying mechanism for the hyperthermia treatment of cancers.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Citotoxicidad Inmunológica , Calor , Linfocitos T Colaboradores-Inductores/inmunología , Células Tumorales Cultivadas/inmunología , Animales , Antígenos de Neoplasias/inmunología , Antígenos CD8/inmunología , Células Clonales , AMP Cíclico/fisiología , Daño del ADN , Metabolismo Energético , Inmunidad Celular , Ratones , Receptores de Antígenos de Linfocitos T/fisiología , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Cathepsin B mRNA levels and banding patterns were characterized in human colorectal mucosa and carcinoma tissues from patients with tumors of different Dukes' stages. Quantitation of mRNA content using slot blot hybridization demonstrated an increase in cathepsin B message in seven of eight tumor tissues with an average increase of 3.5-fold over patient-matched control mucosa samples. This tumor-specific increase in cathepsin B mRNA confirms and extends our previous observation that cathepsin B enzyme specific activity levels are significantly elevated in colorectal carcinomas. In fact, the increase in mRNA levels is greater and more consistent than the observed increase in enzyme activity, suggesting that posttranscriptional or posttranslational regulation of cathepsin B expression occurs in colorectal tumors. The mRNA data also support our earlier observation that cathepsin B enzyme activity levels are inversely correlated with Dukes' stage. The tumor-specific increase in cathepsin B mRNA content is almost 4 times greater in earlier stage (Dukes' A and B) tumors than in later stage (Dukes' C and D) tumors. Thus, increased cathepsin B gene expression is particularly characteristic of tumors which are in the process of invading the bowel wall or local tissues compared with tumors which have already spread to more distant sites. Northern blot data on cancer/normal pairs indicate that the increase in cathepsin B mRNA in colorectal carcinoma is due primarily to changes in the amount of the 2.2- and 4.0-kilobase transcripts which are seen in control tissue. However, low levels of two additional cathepsin B mRNA transcripts (1.5 and 3 kilobases in size) were also observed in tumor tissue.
Asunto(s)
Catepsina B/biosíntesis , Neoplasias Colorrectales/metabolismo , ARN Mensajero/biosíntesis , Biomarcadores de Tumor , Northern Blotting , Bandeo Cromosómico , Sondas de ADN , Glucuronidasa/farmacología , Humanos , Estadificación de Neoplasias , Biosíntesis de Proteínas , Tubulina (Proteína)/biosíntesisRESUMEN
A cellular ADP-ribosyltransferase, specific for elongation factor 2 (EF-2), is found in extracts from rat liver. Co-migrating with EF-2 throughout purification, this activity is, moreover, located in the protein bands corresponding to EF-2 after native or sodium dodecyl sulfate polyacrylamide gel electrophoresis. The observed activity is thus implicated to be an inherent property of EF-2. Preincubation of EF-2 with GuoPPCH2Pox inhibits endogenous, but not diphtheria toxin catalyzed ADP-ribosylation.