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1.
Ann Hematol ; 93(1): 57-64, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24241126

RESUMEN

In a retrospective study, 43 patients with dysplastic neoplasms of the bone marrow (myelodysplastic syndromes and myelodysplastic/myeloproliferative-overlap neoplasms) associated with marked (grades 2-3) fibrosis were examined. Histopathologic and morphologic findings as well as cytogenetic and molecular results were correlated with clinical endpoints. Multilineage dysplasia (34 of 43 patients, 79 %) and hypercellular bone marrow (64 %) were found in most patients. In ten of 35 patients, poor risk karyotypes according to the International Prognostic Scoring System (IPSS) were recorded. The JAK2 V617F mutation was detected in four of 30 patients (13 %), and the KIT D816V mutation was found in two of 30 patients (6 %). Patients were mainly treated with palliative drugs and best supportive care. After an observation time of 1-41 (median 21) months, ten of 43 patients (23 %) had developed a secondary acute leukemia. The median survival of all 43 patients was 21.4 months (range 1.8-88.2 months). Of all prognostic parameters examined, the blast cell count at diagnosis was found to be a most reliable and most predictive marker concerning survival and leukemia progression. This confirms previous studies in dysplastic bone marrow neoplasms without fibrosis.


Asunto(s)
Médula Ósea/patología , Células Madre Hematopoyéticas/patología , Síndromes Mielodisplásicos/patología , Trastornos Mieloproliferativos/patología , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células , Linaje de la Célula , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Janus Quinasa 2/genética , Estimación de Kaplan-Meier , Cariotipificación , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Mutación Missense , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/mortalidad , Cuidados Paliativos , Mutación Puntual , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/patología , Pronóstico , Proteínas Proto-Oncogénicas c-kit/genética , Estudios Retrospectivos
2.
Leukemia ; 27(10): 1988-95, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23787396

RESUMEN

Monosomal karyotype (MK) is associated with an adverse prognosis in patients in acute myeloid leukemia (AML). This study analyzes the prognostic impact of MK in a cohort of primary, untreated patients with myelodysplastic syndromes (MDS). A total of 431 patients were extracted from an international database. To analyze whether MK is an independent prognostic marker in MDS, cytogenetic and clinical data were explored in uni- and multivariate models regarding overall survival (OS) as well as AML-free survival. In all, 204/431 (47.3%) patients with MK were identified. Regarding OS, MK was prognostically significant in patients with ≤ 4 abnormalities only. In highly complex karyotypes (≥ 5 abnormalities), MK did not separate prognostic subgroups (median OS 4.9 months in MK+ vs 5.6 months in patients without MK, P=0.832). Based on the number of abnormalities, MK-positive karyotypes (MK+) split into different prognostic subgroups (MK+ and 2 abnormalities: OS 13.4 months, MK+ and 3 abnormalities: 8.0 months, MK+ and 4 abnormalities: 7.9 months and MK+ and ≥ 5 abnormalities: 4.9 months; P<0.01). In multivariate analyses, MK was not an independent prognostic factor. Our data support the hypothesis that a high number of complex abnormalities, associated with an instable clone, define the subgroup with the worst prognosis in MDS, independent of MK.


Asunto(s)
Aberraciones Cromosómicas , Monosomía/genética , Síndromes Mielodisplásicos/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndromes Mielodisplásicos/clasificación , Síndromes Mielodisplásicos/genética , Pronóstico , Tasa de Supervivencia , Adulto Joven
3.
Bone Marrow Transplant ; 47(2): 172-80, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21460872

RESUMEN

Between 1988 and 2007, international searches for matched unrelated donors (MUDs) were performed for 1586 Austrian patients. Between 2004 and 2007, a MUD was identified for 76.7% of the patients. Between 1996 and 2003, a donor was identified for 71.3% of the patients, and between 1988 and 1995, only for 53.4% of the patients. Search times of successful searches decreased from 7.7 months in the first period to 1.7 months in the period from 2004 to 2007. However, transplants were not performed in all cases in which a donor was found: only in 61.6% of the patients between 2004 and 2007, in 53.4% between 1996 and 2003 and in 29.6% between 1988 and 1995. Multivariate analysis determined that having a common HLA type was the most important variable impacting on finding a MUD for a patient. Factors that most strongly influence a patient's access to transplant were the patient's European origin and a short time between diagnosis and start of donor search. The strongest factor for both finding a donor and being transplanted was a search being performed during more recent years: patients' chances increased from year to year.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Donadores Vivos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Donante no Emparentado/provisión & distribución , Adulto , Austria , Niño , Femenino , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Donadores Vivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Fenotipo , Donante no Emparentado/estadística & datos numéricos
4.
Ann Oncol ; 21(1): 120-5, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19605511

RESUMEN

BACKGROUND: The International Prognostic Scoring System (IPSS) is the golden standard to assess prognosis in myelodysplastic syndromes (MDS). The aim of this analysis was to study age and gender as interacting variables for individualized prognostication. PATIENTS AND METHODS: In all, 897 patients with primary MDS treated with supportive care only were examined in a retrospective multicenter study. A Cox model was developed to determine the prognostic impact of age and gender on survival and to examine their modulating influence on IPSS results. Based on main effects and interactions of these variables, we established an individualized age- and gender-adapted scoring system to improve prognostication in MDS. RESULTS: While the risk of a patient in the IPSS is best represented by the values 0 (low), +1 (intermediate-1), +2 (intermediate-2), and +3 (high), these values were found to vary between -1.9 and +3.5 in the same patients when including age and gender. Whereas in low-risk MDS, male patients were found to have a less favorable survival, a particularly high risk (+3.5) was found in younger (< or = 66 years) high-risk female patients. CONCLUSION: The inclusion of age and gender and their respective interactions contribute to improved and individualized prognostication in MDS.


Asunto(s)
Síndromes Mielodisplásicos/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores Sexuales , Adulto Joven
5.
Blood ; 98(10): 2935-41, 2001 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-11698274

RESUMEN

In 1999 a working group of the World Health Organization (WHO) published a revised classification for myelodysplastic syndromes (MDS): RA, RARS, refractory cytopenia with multilineage dysplasia (RC+Dys), RAEB I and II, del (5q) syndrome, and MDS unclassifiable. Chronic myelomonocytic leukemia (CMML) and RAEB-t were excluded. Standard French-American-British (FAB) and new WHO classifications have been compared in a series of patients (n = 431) from a single center, analyzing morphologic, clinical, and cytogenetic data. According to the WHO findings, dysgranulocytopoiesis or dysmegakaryocytopoiesis only were found in 26% of patients with less than 5% medullary blasts. These patients are thus unclassified and should remain in the subgroups RA and RARS. Splitting of heterogeneous RAEB into 2 subgroups according to blast count was supported by a trend to a statistically significant difference in the single-center study population. Patients with CMML whose white blood cell counts are above 13 000/microL may be excluded from the MDS classification, as warranted by WHO, but a redistribution of patients with dysplastic CMML according to medullary blast count leads to more heterogeneity in other WHO subgroups. Although the natural courses of RAEB-T and acute myeloid leukemia (AML) with dysplasia are different, comparable median survival durations after treatment in patients with RAEB-T and AML were in favor of the proposed 20% medullary blast threshold for AML. The homogeneity of subgroups was studied by evaluating prognostic scores. A significant shift into lower IPSS risk groups was evident in the new classification. These data cannot provide evidence for the new WHO proposal, which should not be adopted for routine clinical use at present. Some of its aspects can provide a starting point for further studies involving refined cytogenetics and clinical results.


Asunto(s)
Síndromes Mielodisplásicos/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Recuento de Células , Femenino , Humanos , Leucemia Mielomonocítica Crónica/sangre , Leucemia Mielomonocítica Crónica/clasificación , Leucemia Mielomonocítica Crónica/mortalidad , Leucemia Mielomonocítica Crónica/patología , Recuento de Leucocitos , Tablas de Vida , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Estudios Retrospectivos , Análisis de Supervivencia , Organización Mundial de la Salud
6.
Leuk Res ; 25(9): 741-7, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11489467

RESUMEN

In chronic myelomonocytic leukemia (CMML) segregation of two subtypes has been suggested depending on WBC count-myelodysplastic (MD-CMML) and myeloproliferative (MP-CMML). In a retrospective analysis of 91 (60/31) previously untreated CMML patients, we compared the presenting clinical, haematological, laboratory and bone marrow features and examined the clinical impact of this reclassification. LDH values and bone marrow cellularity were significantly increased in MP-CMML. Median survival was significantly longer for patients with MD-CMML, progression rate was higher for MP-CMML. Patients with MD-CMML had longer median preleukemic duration; after transition to AML, MP-CMML patients had longer median survival. In MDS phase anemia was more common in MP-CMML and thrombocytopenia more common in MD-CMML whereas transfusion rates showed no difference. Evaluation of prognostic scoring systems for both groups confirmed that patients' characteristics and outcome could be well compared. Our data suggest that segregation into MD-CMML and MP-CMML is justified.


Asunto(s)
Leucemia Mielomonocítica Crónica/complicaciones , Trastornos Mieloproliferativos/etiología , Defectos del Tubo Neural/etiología , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Leucemia Mielomonocítica Crónica/mortalidad , Leucemia Mielomonocítica Crónica/patología , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/mortalidad , Trastornos Mieloproliferativos/patología , Defectos del Tubo Neural/mortalidad , Defectos del Tubo Neural/patología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo
7.
Br J Haematol ; 106(2): 455-63, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10460606

RESUMEN

In myelodysplastic syndromes (MDS) different prognostic risk analysis systems based on clinical and morphological data are used for predicting survival. Data on diagnostic and prognostic relevance of karyotype aberrations have prompted the development of scores including cytogenetics. The aim of this study was to assess and compare the explanatory power of different scoring systems and to assess the additional explanatory power of cytogenetics by evaluating the clinical and laboratory data of MDS patients from a single institution. Data of 386 MDS patients was available, with cytogenetic analysis at time of diagnosis in 256. Clinical/morphological scores: Bournemouth, modified Bournemouth and Düsseldorf; and scores including cytogenetics: Lausanne-Bournemouth, Lille and the International Prognostic Scoring System (IPSS), were calculated and their predictive power was compared for both overall survival and preleukaemic duration. Each of the scores had significant correlation on both endpoints. Calculating the prognostic value of different cytogenetic aberrations we found that differentiating between evidence for no aberration, single aberrations excluding chromosomes 7 and 8, aberrations on chromosomes 5, 7 or 8 and complex aberrations was important. These data were incorporated in a 'prognostic index cytogenetics' (pi score). Cytogenetic scores significantly improved the prognostic value of the best clinical/morphological score in regard to both overall survival and preleukaemic duration. In conclusion, our data further stress the importance of cytogenetics for predicting prognosis in MDS.


Asunto(s)
Síndromes Mielodisplásicos/genética , Adulto , Anciano , Anciano de 80 o más Años , Citogenética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
8.
Dis Colon Rectum ; 42(1): 50-5, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10211520

RESUMEN

PURPOSE: This retrospective study was undertaken to evaluate immunohistochemically the expression of CD44 standard protein and CD44v5 and CD44v6 isoforms in colorectal adenomas and early invasive cancers developing within adenomas as possible markers characterizing colorectal polyps with a more aggressive biologic potential. METHODS: Archival tissues of 81 consecutive locally resected colorectal polyps, comprising 57 colorectal adenomas and 24 carcinomas-in-adenomas, were stained immunohistochemically with the use of commercially available mouse monoclonal antibodies: SFF-2 for CD44 standard protein, VFF-8 for CD44v5, and VFF-7 for CD44v6. RESULTS: Sixty-three percent of the colorectal polyps were positive for CD44 standard protein, 59 percent were positive for CD44v5, and 27 percent were positive for CD44v6. Ninety-three percent of the low-grade adenomas were CD44 standard protein-positive, in contrast to 50 percent of the high-grade adenomas and only 42 percent of the carcinomas-in-adenomas (Kendall's Tau = -0.42; P < 0.0001). CD44v6 expression was more frequently found in early invasive cancers (54 percent) than in high-grade adenomas (25 percent) and low-grade adenomas (7 percent). This difference also was statistically significant (Kendall's Tau-b = 0.39; P = 0.00003). Surprisingly, a downregulation of CD44 standard protein expression was observed in the adenoma tissue adjacent to carcinomas (62 percent) and areas with high-grade atypia (71 percent), compared with low-grade adenomas (93 percent; Kendall's Tau-b = -0.28; P = 0.004). CONCLUSIONS: Our data suggest that CD44 standard protein and CD44 isoform v6 expression differs considerably in benign and malignant colorectal polyps. Clinical studies with larger patient groups could clarify the prognostic potential of CD44 further.


Asunto(s)
Adenoma/química , Pólipos del Colon/química , Neoplasias Colorrectales/química , Receptores de Hialuranos/análisis , Adenoma/patología , Animales , Biomarcadores de Tumor/análisis , Carcinoma/química , Carcinoma/patología , Pólipos del Colon/patología , Neoplasias Colorrectales/patología , Humanos , Inmunohistoquímica , Ratones , Estadificación de Neoplasias , Estudios Retrospectivos
9.
J Med Virol ; 57(4): 361-6, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10089047

RESUMEN

Among risk groups for GB virus C (GBV-C)/HGV infection, patients with haematological diseases are particularly exposed due to the combination of transfusional support and immunodeficiency status. To examine any association between GBV-C/HGV positivity and different malignancy potential of hematological diseases, we investigated two groups of patients, one with clonal stem cell disease with long latency period (myelodysplasia, myeloproliferative disease) and one with malignant haematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia, multiple myeloma). Virus positivity was compared with the data from cytogenetic analysis at first diagnosis. The frequency of GBV-C/HGV infection in these patients was studied using reverse transcription-polymerase chain reaction (RT-PCR) and E2 antibody assay. Serum GBV-C RNA was found in 29/47 (62%) patients. The prevalence of GBV-C RNA in the group of oncological cases (72%) was significantly higher (P= .02) than in the patients with clonal stem cell diseases (28%). Among the GBV-C negative cases, only 25% had malignant haematological diseases. The data from GBV-C/ HGV tested cases for which cytogenetic analysis was carried out indicated an association of GBV-C/HGV positivity with genomic destabilization in general. Of the cases with numerical and structural aberrations, 64% were GBV-C positive. A correlation could not be confirmed between GBV-C/HGV and liver enzyme levels, blood transfusions, chemotherapy treatment, or viral coinfection. These findings suggest a high risk of GBV-C/HGV infection in patients with haematological disorders especially in the group of malignant diseases. These observations may indicate that the persistence of GBV-C/HGV in these patients could be associated with susceptibility to genomic destabilisation.


Asunto(s)
Flaviviridae/aislamiento & purificación , Neoplasias Hematológicas/virología , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/virología , Flaviviridae/genética , Anticuerpos Antihepatitis/sangre , Humanos , Síndromes Mielodisplásicos/virología , Trastornos Mieloproliferativos/virología , ARN Viral/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
10.
Breast Cancer Res Treat ; 50(2): 125-34, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9822217

RESUMEN

Tumor samples of 240 patients with primary breast cancer were biochemically and immunohistochemically investigated for estrogen receptors (ER) and, in 130 of the samples, for progesterone-receptors (PgR) in order to examine reasons for discordant findings. The biochemical (DCCA) and immunohistochemical assays (ICA) yielded positivity in 71% for ER, and in 44% for PgR. Concordant ER-DCCA and ER-ICA results were obtained in 84%; two thirds of the discordant ER-findings manifested as DCCA-neg/ICA-pos. Concordance in the case of PgR amounted to 72%, and of the discordances 60% were DCCA-neg/ICA-pos. Significant association with postmenopausal status existed only for ER positivity in ICA (p = 0.01), whereas ER-DCCA, PgR-DCCA and PgR-ICA were all more or less independent of the menopausal status. The frequency of discordances was independent of menopausal status. Discordance for ER-assays increased significantly near the respective cut-off point; this was not unequivocally true for PgR-assays. The correlation of tumor types of sparse cellularity, as well as prominent stroma content ('scirrhous carcinoma') with increased frequency of the constellation DCCA-neg/ICA-pos was of borderline significance for PgR (p = 0.06), but not for ER. The percentage of discordant ER-findings, figuring as DCCA-neg/ICA-pos, was statistically significantly increased in locally advanced breast cancer (p = 0.03). Fibrocystic disease in peritumoral breast tissue had no impact on receptor-assay discordance. In any case, the models derived from theoretical thought, laboratory data and singular observations can only in part explain the discordance in steroid receptor values measured with different methods.


Asunto(s)
Neoplasias de la Mama/química , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Factores de Confusión Epidemiológicos , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad
11.
Ann Thorac Surg ; 65(4): 909-12, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9564899

RESUMEN

BACKGROUND: Although surgical resection is accepted widely as first-line therapy for pulmonary metastases, few data exist on the surgical treatment of recurrent pulmonary metastatic disease. In a retrospective study, we analyzed patients who were operated on repeatedly for recurrent metastatic disease of the lung with curative intent over a 20-year period. METHODS: From 1973 to 1993, 396 metastasectomies were performed in 330 patients. The study population included patients with any histologic tumor type who had undergone at least two (range, 2 to 4) complete surgical procedures because of recurrent metastatic disease. Surgical and functional resectability of the recurrent lung metastases and control of the primary lesion served as objective criteria for reoperation. A subgroup of 35 patients that included patients with histologic findings such as epithelial cancer and osteosarcoma then was analyzed retrospectively to calculate prognosis and define selection criteria for repeated pulmonary metastasectomy. RESULTS: The 5- and 10-year survival rates after the first metastasectomy were 48% and 28%, respectively. The overall median survival was 60 months. A mean disease-free interval (calculated for all intervals, with a minimum of two) of greater than 1 year was significantly associated with a survival advantage beyond the last operation. Univariate analysis failed to show size, number, increase or decrease in number or size, or distribution of metastases as factors related significantly to survival. CONCLUSIONS: Although patients with different histologic tumor types were included, the study population appeared to be homogeneous in terms of survival benefit and prognostic factors, and it probably represented the selection of biologically favorable tumors in which histology, size, number, and laterality are of minor importance. We conclude that patients who are persistently free of disease at the primary location but who have recurrent, resectable metastatic disease of the lung are likely to benefit from operation a second, third, or even fourth time.


Asunto(s)
Neoplasias Pulmonares/secundario , Neumonectomía , Adolescente , Adulto , Anciano , Análisis de Varianza , Neoplasias de la Mama/patología , Carcinoma/patología , Carcinoma/secundario , Carcinoma/cirugía , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Pulmón/fisiopatología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Osteosarcoma/patología , Osteosarcoma/secundario , Osteosarcoma/cirugía , Selección de Paciente , Neumonectomía/métodos , Pronóstico , Reoperación , Estudios Retrospectivos , Sarcoma/patología , Sarcoma/secundario , Sarcoma/cirugía , Tasa de Supervivencia , Resultado del Tratamiento
12.
Leukemia ; 11 Suppl 2: S52-4, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9178841

RESUMEN

We evaluated 1179 consecutive patients with low-grade B-NHL diagnosed according to criteria of the Kiel classification and presenting with initial bone marrow involvement. Therapeutic approaches were not changed during the observation period 1975-1995. CLL (n=895) and IC (n=169) were treated palliatively with chlorambucil/prednisone or prednimustine. In CBCC (n=65) and CC (n=50) remission was induced with COP or CHOP. The overall response rate was 67%, but only 35% of CBCC and 23% of CC patients achieved complete remission. Median survival was 64 months in CBCC and 28 months in CC. As the median age of our patient population was 68 years (range: 23-93) it seems doubtful whether overall prognosis can be improved by aggressive therapeutic measures. One exception might be CBCC patients who were younger (median age 56 years) and who were usually in good general condition so that they might qualify for high dosage chemotherapy and stem cell support. Whether the prognosis of IC and CLL (median survival 74 months and 107 months, respectively) can be improved by treatment with drugs such as purine analogs will depend on the long-term outcome of clinical studies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Clorambucilo/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Humanos , Linfoma de Células B/mortalidad , Cuidados Paliativos , Prednimustina/administración & dosificación , Prednisona/administración & dosificación , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , Vincristina/administración & dosificación
13.
Leukemia ; 10(7): 1117-21, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8683989

RESUMEN

G-proteins are essential in signal transduction pathways. A G-protein alpha subunit termed G alpha 16 was found to be exclusively expressed in hematopoietic cell lines. In cells derived from patients, G alpha 16 expression has been detected in progenitor- and pre-B ALL cells and also in peripheral blood stem cells (PBSC). In this study, we analyzed G alpha 16 expression using a RT-PCR technique by testing elutriated blood cells from normal donors, PBSC from breast cancer patients and bone marrow or peripheral blood cells from acute leukemia patients. Both of two ALL patients and 15/16 AML patients expressed G alpha 16. In elutriation experiments, G alpha 16 expression was found in fractions containing the highest number of precursor cells but was absent in mature T and B cell fractions. In addition, CD34-enriched PBSC were positive for G alpha 16 expression. Further in vitro experiments using the cell line KG1 showed that G alpha 16 expression was not affected by the growth inhibiting hemoregulatory peptide pEEDCK which has a sequence homology present within G alpha 16. Taken together, these data demonstrate that G alpha 16 is expressed in various normal and malignant hematopietic progenitors but not in their differentiated counterparts. G alpha 16 could play a vital role in signal transduction pathways controlling proliferation in early normal and malignant hematopoiesis.


Asunto(s)
Proteínas de Unión al GTP/metabolismo , Hematopoyesis , Leucemia/metabolismo , Enfermedad Aguda , Antígenos CD34/metabolismo , Secuencia de Bases , Inhibidores de Crecimiento/farmacología , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/metabolismo , Humanos , Leucemia/genética , Leucemia/inmunología , Leucemia Mieloide Aguda/metabolismo , Datos de Secuencia Molecular , Oligopéptidos/farmacología , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Ácido Pirrolidona Carboxílico/análogos & derivados , Transducción de Señal
14.
Breast Cancer Res Treat ; 41(2): 171-6, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8944335

RESUMEN

It has been previously shown that p43- a breast cancer associated antigen-has immunosuppressive properties. The present study was carried out in order to elucidate the pathomechanisms of immunosuppression in breast cancer patients influenced by the expression of p43. Lymphocytes were cultured from blood of 29 women with benign lesions in the breast as well as from 41 female patients with breast cancer. Lymphocyte stimulation was performed by addition of Concanavalin (Con A) in cultures with lymphocytes alone (CONLYM) or in lymphocytes incubated with p43 (CONAg). In other series immunomodulation was tried by addition of indomethacin (INDLYM, INDAg), levamisole (LEVLYM, LEVAg), or interleukin-2 (ILLYM, ILAG). In breast cancer patients, addition of p43 significantly inhibited the activation of lymphocyte proliferation by Con A compared to women with benign tumors. The addition of indomethacin or levamisole did not influence this inhibitory effect of p43 in breast cancer patients. Contrary to these observations, addition of IL-2 resulted in increased proliferation of lymphocytes from patients with benign as well as malignant tumors, which was inhibited after addition of p43. Analysis of the correlation of the immunosuppressive properties of p43 in correlation with prognostic factors for breast cancer showed evidence for a stronger activity of p43 in early stage tumors (i.e. smaller than 2 cm, lymph node negative, histologic grading GI), confirming previous observations of a higher expression of p43 in early stages of breast cancer.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Antígenos de Neoplasias/inmunología , Neoplasias de la Mama/inmunología , Tolerancia Inmunológica/inmunología , Activación de Linfocitos/inmunología , Factor Tu de Elongación Peptídica/inmunología , Antígenos de Neoplasias/farmacología , Concanavalina A/farmacología , Femenino , Humanos , Activación de Linfocitos/efectos de los fármacos , Proteínas Mitocondriales , Factor Tu de Elongación Peptídica/farmacología , Estimulación Química
15.
Breast Cancer Res Treat ; 36(1): 11-21, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7579502

RESUMEN

The immunohistochemically determined receptor status, as well as first-generation risk factors (tumor size, lymph node status, histologic grading including subfactors, tumor histology, and biochemically determined receptor status) were prospectively analyzed in 288 cases of primary breast cancer for their impact on recurrence-free survival (RFS) and overall survival (OS) after a median observation period of 41 months. Immunohistochemically (ER-ICA) and biochemically determined estrogen receptors (ER-DCC), as well as tumor size, lymph node status, histologic grading, mitotic rate, and nuclear polymorphism, were of prognostic value for recurrence-free survival and/or overall survival. In multivariate analysis, lymph node status, tumor size, and mitotic rate proved to be independent prognosticators; ER-ICA showed significance in the univariate analysis which dropped, however, when multivariate analysis was applied. The prognostic power of histologic grading in our series seemed to depend mainly on the subfactors which relate to nuclear features.


Asunto(s)
Neoplasias de la Mama/química , Recurrencia Local de Neoplasia/diagnóstico , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Estudios de Casos y Controles , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo
16.
Cancer Lett ; 82(1): 105-11, 1994 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-8033063

RESUMEN

Placental isoferritin-associated p43 has proven to induce immune suppression during pregnancy in order to avoid rejection of the fetus' alloantigens by maternal lymphocytes. It has been demonstrated previously that p43 is also synthesized by breast cancer cells and can also be found on the surface of a subpopulation of T cells in women with this disease. Therefore, it was the aim of the present study to investigate if breast cancer-associated p43 has immunosuppressive properties. In 40 women undergoing surgical excision of a suspicious lump in their breast, blood was withdrawn and lymphocytes were isolated. Lymphocyte cultures were incubated with p43 antigen and anti-p43 antibody (CM-H-9). In a second series, lymphocyte mitogenesis was activated by addition of concanavalin A (Con A), Con A + p43 and Con A + anti-p43, respectively. While lymphocytes of breast cancer patients (n = 21) and women with benign breast disease (n = 19) incubated with p43 as well as with anti-p43 antibody did not show any difference in terms of incorporation of [3H]thymidine, activation of lymphocytes by addition of Con A was significantly inhibited after addition of p43 antigen in breast cancer patients compared to women with benign breast disease (P = 0.0178). Analysis of prognostic factors for breast cancer showed that inhibition of lymphocyte mitogenesis was dependent on the degree of tumor differentiation and was significantly higher in well differentiated tumors (GI) compared with more dedifferentiated tumors (GIII). The present study shows that breast cancer-associated antigen p43 is able to induce immune suppression in breast cancer patients but not in women with benign breast disease.


Asunto(s)
Neoplasias de la Mama/metabolismo , Activación de Linfocitos , Proteínas de Neoplasias/farmacología , Adulto , Anciano , Neoplasias de la Mama/inmunología , Femenino , Humanos , Persona de Mediana Edad , Linfocitos T/inmunología , Linfocitos T/metabolismo , Timidina/metabolismo
17.
Ann Surg ; 218(1): 13-21, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8328824

RESUMEN

OBJECTIVE: The authors investigated correlations of estrogen-receptor and progesterone-receptor with conventional risk factors as well as histopathology in patients with primary breast cancer. SUMMARY BACKGROUND DATA: Immunohistochemically determined hormone receptors have gained importance as prognosticators in primary breast cancer, but their definitive role has not yet been evaluated. METHODS: Tumor samples from 299 patients were examined for estrogen and progesterone receptors by biochemical and immunohistochemical assay. Correlations with established risk factors (tumor size, lymph node status, menopausal status, grading including subfactors) and histopathology were analyzed. RESULTS: The estrogen receptor, determined by immunohistochemical method revealed positivity in 80.6% of patients; biochemical measurement yielded 76.2% positive results. The progesterone receptor measured by immunohistochemistry yielded 61.3% positivity versus 55.8% detected by biochemical analysis. Invasive lobular, tubular, and ductal invasive carcinoma with prominent stroma content ("scirrhous carcinoma") rather than ductal invasive carcinoma was more frequently estrogen-receptor positive with immunohistochemistry than with biochemical assay. For progesterone receptor, the same pattern of positivity was seen with immunohistochemical assay. With progesterone receptor determined biochemically, "scirrhous" and lobular carcinoma showed positive results in a lower proportion than invasive ductal and tubular carcinoma. Significant correlations were observed between the estrogen-receptor status, the histologic grade of malignancy, nuclear polymorphism, and the rate of mitosis with both methods (p < 0.001 respectively). Different correlations were found between tumor size, menopausal status and estrogen receptor status with both assays respectively. For the progesterone receptor status, immunohistochemistry yielded significant correlations with the histologic grade of malignancy, nuclear polymorphism, rate of mitosis (p < 0.001 respectively) as well as growth pattern (p < 0.01), while biochemical analysis revealed a correlation with nuclear polymorphism (p < 0.05). The correlation analysis of both components of the immunoreactive score revealed a more significant impact of percentage of positive cells than of staining intensity. CONCLUSIONS: Immunohistochemistry detected a closer correlation between prognostic factors and receptor data than biochemical analysis.


Asunto(s)
Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Menopausia , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo
18.
Med Pediatr Oncol ; 21(5): 340-6, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8492748

RESUMEN

The prognostic significance of expression of myeloid-associated antigens in childhood acute lymphoblastic leukemia (myA+ALL) was evaluated. From 1984 to 1990, 251 children with immunologically verified ALL were treated in two prospective consecutive Austrian studies. Complete immunophenotyping was performed in 206 cases (82%). Out of these 175 cases were classified as B-cell precursor ALL, 31 cases as T-ALL. Expression of myeloid-associated antigens was demonstrated in 23 cases (13.1%) of childhood B-cell precursor ALL, particularly in immature (CD10 negative) forms (P < .0001), and in 1 case (3.2%) of T-ALL. CDw65 was expressed most frequently (12 cases), followed by CD13 and CD15 (5 cases each), CD33 (4 cases), and blood-group H (3 cases). Compared to myA- ALL prognosis of children with myA+ B-cell precursor ALL was poor, despite intensive multiagent chemotherapy according to BFM protocols. Remission rates were not impaired, but pEFS was 74.6% for myA- ALL, and only 37.8% for myA+ ALL (P = .0001). As demonstrated by multivariate analysis the expression of myeloid-associated antigens was the most important prognostic variable for EFS in B-cell precursor ALL, whether or not CD10 was expressed.


Asunto(s)
Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Leucemia-Linfoma de Células T del Adulto/inmunología , Antígeno Lewis X/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Irradiación Craneana , Hemoglobinas/análisis , Humanos , Inmunofenotipificación , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/terapia , Leucocitos , Análisis Multivariante , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Resultado del Tratamiento
19.
Wien Klin Wochenschr ; 105(10): 277-83, 1993.
Artículo en Alemán | MEDLINE | ID: mdl-8517057

RESUMEN

In the evaluation of therapeutic measures it is important to consider the consequences of the proposed treatment on the subjective quality of health and the subjective quality of life. Since no adequate instrument existed to provide such assessments, a short, theoretically based questionnaire was developed and psychometrically tested. The construction phase was based on data of 104 adults with haemato-oncological diseases, leading to the design of a questionnaire which was tested using data of a further 292 patients. The validity of the "questionnaire for attitudes towards quality of health and quality of life" was assessed by comparing it with physicians' ratings and by correlation with the results of an extensive questionnaire. The reliability was satisfactory; the questionnaire met with high acceptance by patients, physicians and health care personnel. It complies with the requirements of clinical trials where the objective is to measure quality of health and quality of life.


Asunto(s)
Costo de Enfermedad , Indicadores de Salud , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicos/terapia , Calidad de Vida , Encuestas y Cuestionarios , Adaptación Psicológica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia/psicología , Linfoma/psicología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/psicología , Aceptación de la Atención de Salud , Rol del Enfermo
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