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1.
Educ Treat Children ; 45(3): 277-291, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35854976

RESUMO

Adolescents are often burdened with academic, home, and peer stressors. With adolescent mental health issues and suicide on the rise, administrators have worked with nonprofit organizations and the community to address stress and internalized behavior problems. School-based wellness centers are tranquil rooms with various sensory activities, calming nature scenes, and sounds for relaxation purposes. School-based wellness centers may have behavioral effects by reducing exposure to aversive events and increasing access to positive and negative reinforcers. There has not yet been a formal study of school-based wellness centers published in the literature. In the present study, we used questionnaires to examine the perceptions of 752 students, 124 parents, and 69 school staff of their high school wellness center. Results indicated that stakeholders had positive perceptions of the wellness center. In particular, results implied that stakeholders believed the wellness center contributed to students' academic success, elevation of mood, confidence, and coping skills. Results also suggested that attendance at the wellness center was associated with a decrease in student stress and anxiety, though recommendations for improvements were noted. Implications and limitations of this study are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s43494-022-00079-1.

2.
Am J Community Psychol ; 63(3-4): 286-297, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30653277

RESUMO

Teachers' stress is a dynamic combination of the individual teacher's characteristics and characteristics of the classroom and school environment. To date, there are limited studies on teachers' stress in the context of lower-middle-income countries (LMICs), where working conditions as well as general political and economic circumstances might pose a considerable threat for teachers' well-being. This study explores whether certain combinations of individual and environmental experiences of teachers in LMICs may result in stress, assessed as patterns of diurnal cortisol rhythm. Participants were kindergarten teachers in Kosovo and Ukraine, two LMICs in Europe. Latent Profile Analysis identified three subgroups of teachers that significantly differed on teachers' education and experience. Preliminary results of Latent Growth Modeling suggested differences between profiles in baseline waking cortisol and patterns of diurnal decline. Teachers in the profile that was characterized by the longest experience working in the field but the lowest level of education showed blunted cortisol in the morning and a flatter slope; a pattern that could indicate a maladaptive cortisol response. Future directions for studying stress processes among teachers in LMICs and implications for policy and practice on how to support teacher well-being in low-resource contexts are discussed.


Assuntos
Ritmo Circadiano , Hidrocortisona/metabolismo , Professores Escolares/psicologia , Estresse Psicológico/metabolismo , Adulto , Países Desenvolvidos , Escolaridade , Feminino , Humanos , Kosovo/epidemiologia , Análise de Classes Latentes , Pessoa de Meia-Idade , Pobreza/estatística & dados numéricos , Saliva/química , Estresse Psicológico/psicologia , Fatores de Tempo , Uso de Tabaco/epidemiologia , Ucrânia/epidemiologia
3.
Br J Educ Psychol ; 85(4): 533-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26255789

RESUMO

BACKGROUND: Educational processes and outcomes are influenced by a multitude of factors, including individual and contextual characteristics. Recently, studies have demonstrated that student and context characteristics may produce unique and cumulative effects on educational outcomes. AIMS: The study aimed to investigate (1) the relative contribution of student, classroom, and school characteristics to reading fluency and orthographic spelling, (2) the relative contribution of specific predictors to reading fluency and orthographic spelling within the sets of student, classroom, and school characteristics, and (3) whether the contribution of student, classroom, and school characteristics differs for reading fluency and orthographic spelling. SAMPLE: Participants were 789 German third-grade students from 56 classrooms in 34 schools. METHOD: Students completed an intelligence test and a questionnaire assessing self-control. Reading fluency and orthographic spelling performance were assessed using standardized achievement tests. Multilevel structural equation modelling was used to control for the hierarchical structure of educational data. RESULTS AND CONCLUSION: Variances in students' reading and spelling skills were in large part explained by student characteristics (>90%). Classroom and school characteristics yielded little variance. Student-level intelligence and self-control were significantly related to reading fluency. For orthographic spelling, student-level intelligence and self-control, class-average intelligence, and, at the school level, the socio-economic status of the school's neighbourhood were significant predictors. Future research needs to investigate relevant classroom and school factors that may directly and indirectly relate to academic outcomes.


Assuntos
Leitura , Estudantes/estatística & dados numéricos , Redação , Logro , Adolescente , Feminino , Humanos , Masculino , Instituições Acadêmicas/estatística & dados numéricos , Fatores Socioeconômicos
4.
Am J Health Behav ; 34(3): 328-39, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20001190

RESUMO

OBJECTIVES: To explore the factor structure and psychometric properties of data collected with the Adolescent Health Risk Behavior Survey (AHRBS) instrument. METHODS: Measures of the AHRBS instrument were tested using statistical analyses to assess validity and reliability of data collected from a sample of 1992 Indiana adolescents. RESULTS: Factor analyses yielded a 13-factor solution with acceptable model fit statistics. Tests of internal consistency reliability for data in instrument scales ranged from 0.455 to 0.916. Measures were consistent across adolescent subdemographic categories. CONCLUSION: The AHRBS instrument is a valuable tool for investigating adolescent drug use.


Assuntos
Comportamento do Adolescente , Comportamentos Relacionados com a Saúde , Psicologia/instrumentação , Psicometria/instrumentação , Assunção de Riscos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Análise Fatorial , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Reprodutibilidade dos Testes
5.
J Clin Oncol ; 18(13): 2567-75, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10893288

RESUMO

PURPOSE: Advances in chemotherapy and supportive care have slowly improved survival rates for patients with high-risk neuroblastoma. The focus of many of these chemotherapeutic advances has been dose intensification. In this phase II trial involving children with advanced neuroblastoma, we used a program of induction chemotherapy followed by tandem high-dose, myeloablative treatments (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence. PATIENTS AND METHODS: Patients underwent induction chemotherapy during which peripheral-blood stem and progenitor cells were collected and local control measures undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart. Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of HDT/SCR were completed. RESULTS: Pheresis was possible in the case of all patients, despite their young ages, with an average of 7.2 x 10(6) CD34(+) cells/kg available to support each cycle. Engraftment was rapid; median time to neutrophil engraftment was 11 days. Four patients who completed the first HDT course did not complete the second, and there were three deaths due to toxicity. With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained event-free. The 3-year event-free survival rate for these patients was 58%. CONCLUSION: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible treatment strategy for children and may improve disease-free survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Neuroblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Remoção de Componentes Sanguíneos , Criança , Pré-Escolar , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Masculino
6.
Cytotherapy ; 1(5): 367-76, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-20426538

RESUMO

BACKGROUND: Contaminating tumor cells present in the BM or apheresis peripheral blood (APB) autologous transplant products have been shown to contribute to relapse following high-dose chemotherapy and stem-cell rescue (HDC/ASCR). Enhanced methods for tumor detection in BM or APB products for breast-cancer patients are required. METHODS: We evaluated a laboratory-scale tumor-cell enrichment column (TEC) as an enhanced method of detecting tumor cells in APB or BM of breast-cancer patients. Seventeen women with breast cancer (14 Stage IV and three Stage III) were evaluated using the TEC for residual tumor cells present in 20 samples of APB or BM biopsies following HDC/ASCR. RESULTS: Using conventional histological staining methods (without TEC), only one patient had evidence of tumor cells present in the BM biopsy, while 16 patients had negative biopsies. Using the TEC for tumor cell capture and immunocytochemical (ICC) staining with anti-cytokeratin MAb (CAM 5.2) for tumor detection, we were able to positively identify tumor cells in 20 samples (14 BM aspirates and six APB products). In 15 samples (nine BM and six APB), we used CAM 5.2 to positively identify cytokeratin(+) cells prior to using the TEC. However, positive cells were detected only after using the TEC in the remaining five samples. The level of sensitivity was significantly enhanced (p < or = 0.05) by 100-400 fold in the post-TEC (absorbed) fraction compared with the pre-TEC (post-Ficoll) fraction. DISCUSSION: We conclude from this study that the use of TEC improves our ability to detect residual breast-cancer cells in the APB or BM and could be potentially utilized to purge contaminating tumor cells from the stem-cell transplant.


Assuntos
Transplante de Medula Óssea/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Transplante de Células/métodos , Neoplasia Residual/sangue , Neoplasias/imunologia , Adulto , Biópsia , Remoção de Componentes Sanguíneos , Transfusão de Sangue/métodos , Neoplasias da Mama/tratamento farmacológico , Terapia Combinada/métodos , Feminino , Citometria de Fluxo/métodos , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Neoplasias/patologia , Células-Tronco/citologia
7.
J Clin Oncol ; 16(11): 3509-17, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9817268

RESUMO

PURPOSE: To determine whether occult tumor contamination of autologous bone marrow or peripheral-blood progenitor cells (PBPC) influences clinical outcome after high-dose chemotherapy in patients with stage IV breast cancer. PATIENTS AND METHODS: We used an immunocytochemical assay capable of detecting one tumor cell in 5 x 10(5) hematopoietic cells to analyze bone marrow and/or PBPC collections obtained from 57 consecutive women with chemotherapy-sensitive metastatic breast cancer who received high-dose chemotherapy. The influence of occult tumor on time to progression, overall survival, and first site of recurrence (old or new) was studied. RESULTS: Twenty-three of 57 (40%) patients received bone marrow (n=6) or peripheral-blood progenitor collections (n=17) that contained microscopic cancer. Median time to progression and overall survival were 9 and 22 months in patients who did not receive infused tumor cells, compared with 10 and 24 months, respectively, in those who received occult tumor (P=not significant [NS]). Worse survival, but not time to progression, was observed in six patients who received > or = 2/100,000 tumor cells. Regardless of whether occult tumor was infused, the majority of relapses occurred in prior, rather than new sites of disease. Three patients who received stem-cell products contaminated by microscopic breast cancer remain free from progression at 21+, 47+, and 52+ months. CONCLUSION: Microscopic tumor was frequently detected by immunocytochemistry in hematopoietic stem-cell products, but did not predict for inferior treatment outcome in this cohort of patients with metastatic breast cancer. Quantitative information regarding infused tumor burden may have prognostic significance.


Assuntos
Neoplasias da Medula Óssea/secundário , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias da Medula Óssea/complicações , Transplante de Medula Óssea/efeitos adversos , Neoplasias da Mama/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Neoplasia Residual , Recidiva , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento
8.
J Hematother ; 7(1): 9-18, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9507377

RESUMO

The increase in the number of patients treated with high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) for solid tumor malignancies has generated concern about the infusion of tumor cell contamination in the graft. In an effort to study so-called minimal residual disease (MRD) in the HDC/ASCT setting, a variety of assay methods have been used. Although these assays vary in terms of sensitivity and specificity of tumor detection, they are in agreement as to the presence and viability of tumor cells in ASCT grafts. A growing body of evidence indicates that MRD is present in ASCT grafts from neuroblastoma, breast cancer, and ovarian cancer patients. More importantly, several retrospective studies have determined that the infusion of tumor cells with the ASCT graft is strongly associated with post-ASCT relapse. Gene-marking studies have directly demonstrated that infused tumor cells are present at sites of disease relapse. Thus, the issue of tumor contamination of autologous grafts is an area of growing concern. This review article details the current status of MRD in solid tumor malignancies, with emphasis on assay methodology, clinical utility, and clinical relevance in transplantation medicine.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasia Residual/diagnóstico , Neuroblastoma/diagnóstico , Antineoplásicos/uso terapêutico , Feminino , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Humanos , Neoplasia Residual/terapia , Transplante Autólogo
9.
Clin Cancer Res ; 3(2): 249-56, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9815680

RESUMO

Because a significant number of patients with pathologically organ-confined carcinoma of the prostate subsequently develop recurrent disease, metastasis may occur much earlier than previously believed. We have used a reverse transcription-PCR assay for prostate-specific antigen mRNA and an immunocytochemical staining method for cytokeratins to test this hypothesis in paired peripheral blood (PB) and bone marrow (BM) specimens from 71 patients with clinically localized disease before radical prostatectomy, 14 patients with advanced-stage carcinoma of the prostate, and 30 controls (young healthy volunteers, patients without prostate disease, and patients with benign prostatic hyperplasia). Controls were negative in BM and PB. Fifty-six% of patients with organ-confined tumors (pT2) and 73% of those with extracapsular extension (pT3) were positive in the BM versus 16% of those with pT2 tumors and 27% of those with pT3 tumors in the PB. Patients with advanced-stage disease were positive in 86% of BM versus 71% of PB. The sensitivity of the immunocytochemistry assay to detect tumor cells was lower as compared with the reverse transcription-PCR assay. The results suggest that tumor cell dissemination occurs early during disease progression. Prostate cells seem to preferentially concentrate in the BM rather than the PB, which may be due to sequestration there by homing mechanisms. As the rate of detection in the BM exceeds the proportion of patients with subsequently progressing disease, we hypothesize that only a subset of these cells can survive in the BM and evolve to clinically apparent disease.


Assuntos
Medula Óssea/patologia , Antígeno Prostático Específico/análise , Neoplasias da Próstata/patologia , Adulto , Idoso , Biópsia , Contagem de Células , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Antígeno Prostático Específico/genética , Neoplasias da Próstata/química , Neoplasias da Próstata/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
10.
Biol Blood Marrow Transplant ; 3(6): 316-23, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9502299

RESUMO

In this retrospective study, we assessed the impact of each of three consecutive cycles of conventional-dose chemotherapy on CD34+ cells, colony-forming units granulocyte-macrophage (CFU-GM), and contaminating breast cancer cells collected in the leukapheresis products of patients with metastatic breast cancer. The patients subsequently underwent high-dose chemotherapy followed by autologous blood progenitor cell transplantation. We analyzed 172 leukapheresis products from 17 patients and have correlated the long-term clinical outcome with tumor cell contamination. The induction chemotherapy regimen consisted of three cycles of cyclophosphamide 750 mg/m2 i.v., epirubicin 100 mg/m2, and 5-fluorouracil (5-FU) 750 mg/m2 i.v., followed by 5 microg/kg body weight of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) daily until leukapheresis was completed. An average of 10 leukapheresis products (three to four collections after each cycle of chemotherapy) were obtained from each patient. Numbers of CD34+ cells, CFU-GM, and mononuclear cells (MNCs) in the leukapheresis products were determined at the time of collection. Aliquots from the same products were frozen and breast cancer cells were detected by immunocytochemistry with a cocktail of anti-cytokeratin antibodies (AE-1, AE-3, CAM 5.2, Keratin 8+18+19) using a standardized immunoalkaline phosphatase method. A minimum of 10(6) cells were examined by light microscopy and by at least two blinded observers. Cells were considered positive when immunostaining was detected in the cytoplasm and on the cell membrane, and cellular morphology was consistent with a malignant phenotype. Of the 172 samples analyzed, 13 of 57 (23%) leukapheresis products collected after cycle I were positive for tumor cells; 3 of 60 (5%) after cycle II; and 4 of 55 (7%) after cycle III. The likelihood of contamination by breast cancer cells after cycle I was significantly higher than after subsequent cycles of chemotherapy (p = 0.0052). Simultaneously, there was a significant decrease in quantity of CD34+ cells and CFU-GM (p < 0.0001 for both comparisons). Our study indicated that leukapheresis products collected after the second or third cycles of induction chemotherapy carry a significantly lower likelihood of tumor cell contamination, albeit the quantity of CD34+ cells or CFU-GM collected was also significantly reduced.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Leucaférese/métodos , Células-Tronco/citologia , Adulto , Antígenos CD34/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Células , Ensaio de Unidades Formadoras de Colônias , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Pessoa de Meia-Idade , Neoplasia Residual , Proteínas Recombinantes , Estudos Retrospectivos , Células-Tronco/patologia , Resultado do Tratamento
11.
J Hematother ; 5(6): 617-24, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9117250

RESUMO

Patients undergoing high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) may have tumor cells inadvertently infused if their stem cell product is tumor contaminated. We used an immunocytochemical (ICC) method to analyze 31 histologically negative bone marrow (BM) specimens taken from women with advanced-stage breast cancer at the time of BM harvest before HDC. All 31 patients were treated on one of three consecutive HDC protocols and received BM or BM and peripheral stem cells (PSC) as ASCR. Six of 26 evaluable patients had ICC-detectable contaminating tumor cells in their BM harvests. These 6 patients had a trend toward decreased overall survival compared with those patients without ICC-detectable tumor cells (17 months median versus 25+ months, p = 0.11, log rank test for those patients achieving complete response, CR, from HDC). The sites of relapse in the ICC-positive and ICC-negative groups were not notably different when analyzed for new sites versus previous sites of disease. Therefore, our retrospective analysis of a small cohort of patients suggests that the infusion of tumor cells in breast cancer patients undergoing HDC may confer a poor prognosis. Relapse patterns however suggest failure both in new sites and in sites of previous disease. Additional studies in expanded patient populations are needed to explore further the role of tumor cell infusion in ASCR and the possible clinical benefits of tumor cell removal procedures.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Neoplasias da Mama/patologia , Transplante de Células-Tronco Hematopoéticas , Neoplasias da Mama/terapia , Separação Celular , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva , Transplante Autólogo/efeitos adversos
13.
J Clin Oncol ; 14(9): 2569-75, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8823337

RESUMO

PURPOSE: To evaluate tumor-cell contamination of peripheral-blood progenitor-cell (PBPC) collections obtained after priming with granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Immunocytochemical (ICC) and tumor clonogenic (TCA) assays were used to analyze tumor-cell contamination of pretreatment peripheral-blood (PB) and bone marrow (BM) samples, and of PBPC collection samples obtained after priming with G-CSF 5 micrograms/kg/d for 5 or 7 days in 38 women with advanced breast cancer undergoing high-dose chemotherapy (HDC). Results were compared with 37 historical control patients who underwent PBPC mobilization with cyclophosphamide (4 g/m2) followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 micrograms/kg/d for 14 days. RESULTS: Before PBPC priming with G-CSF, only one of 37 (3%) PB and four of 36 (11%) BM samples had tumor cells detected by ICC. Tumor-cell contamination of PBPC collections obtained after 5 or 7 days of G-CSF priming was observed in only three of 38 patients (8%). All patients with tumor cells detected in the PBPC collection had stage IV disease. Cells with in vitro clonogenic potential were detected only in the pretreatment BM sample in one patient, and another two patients had ICC- and TCA-positive PBPC samples despite tumor-negative PB and BM before priming. These results are similar to those previously reported for PBPC primed with cyclophosphamide and GM-CSF. CONCLUSION: In patients with advanced breast cancer responsive to cytotoxic chemotherapy, tumor-cell contamination is not increased in PBPC collected after 5 or 7 days priming with G-CSF and appears similar to that seen when PBPC are primed with cyclophosphamide followed by GM-CSF.


Assuntos
Transplante de Medula Óssea , Neoplasias da Mama/terapia , Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucaférese , Condicionamento Pré-Transplante , Adulto , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Ensaio Tumoral de Célula-Tronco
14.
Exp Hematol ; 23(14): 1478-83, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8542934

RESUMO

We examined peripheral blood progenitor cell (PBPC) collections and CD(34+)-selected fractions cultured in PIXY321, a fusion protein comprising analog interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) domains, for the presence of contaminating tumor cells from 14 patients with advanced-stage breast cancer. Five of the 14 (36%) pre-culture PBPC specimens contained immunocyto-chemically (ICC)-detectable tumor cells using two different cocktails of monoclonal antibodies (mAbs). After 10 days in culture with PIXY321, the CD(34+)-selected fractions showed a median 23.6-fold expansion of hematopoietic cells. No ICC-positive tumor cells were detected in any post-culture specimens. We conclude that in vitro expansion of CD(34+)-selected PBPCs with PIXY321 can expand hematopoietic cell populations apparently without risk of expanding contaminating breast cancer cell populations.


Assuntos
Neoplasias da Mama/patologia , Células-Tronco Hematopoéticas/patologia , Imuno-Histoquímica , Anticorpos Monoclonais , Antígenos CD34/análise , Separação Celular , Sobrevivência Celular , Meios de Cultura , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-3/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Células Tumorais Cultivadas
15.
Bone Marrow Transplant ; 15(6): 929-33, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7581093

RESUMO

High-dose chemotherapy (HDC) followed by autologous hematopoietic reconstitution is an experimental treatment option for patients with epithelial ovarian cancer. However, the incidence of occult ovarian tumor cell involvement in autologous bone marrow (BM) or peripheral blood stem cell (PBSC) autografts has not been widely investigated. We used a highly sensitive immunocytochemical (ICC) procedure that detects occult blood-borne tumor micrometastases. We analyzed 24 BM specimens (15 obtained during therapy and 9 harvest samples) and seven PBSC specimens from 22 patients with ovarian cancer. Overall, ICC analysis detected immunostained tumor cells in 10 of 23 evaluable BM specimens (43%) from 9 of 19 patients (47%). One of 9 (11%) harvest samples contained tumor cells. Only one of the 10 ICC-positive BM specimens had tumor cells detected by routine histopathological analysis. ICC-detectable tumor cells were cleared from the marrow of two patients during chemotherapy. None of the seven PBSC specimens contained tumor cells. We conclude that ovarian cancer micrometastases have the potential to contaminate BM, as is also the case in patients with other epithelial malignancies. In the limited number of specimens analyzed, PBSC harvests appeared to provide a less tumor-contaminated source of hematopoietic stem cells for autologous transplantation.


Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Células Sanguíneas , Exame de Medula Óssea/métodos , Neoplasias da Medula Óssea/secundário , Transplante de Medula Óssea/métodos , Medula Óssea/patologia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Neoplásicas , Neoplasias Ovarianas/patologia , Anticorpos Monoclonais/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Medula Óssea/patologia , Transplante de Medula Óssea/efeitos adversos , Contraindicações , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Sensibilidade e Especificidade , Transplante Autólogo , Células Tumorais Cultivadas
16.
Blood ; 85(4): 1138-43, 1995 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-7849302

RESUMO

The effect of priming on occult tumor cell involvement of peripheral blood (PB) and PB progenitor cell (PBPC) collections is poorly characterized. Using sensitive immunocytochemistry (ICC) and tumor clonogenic assays (TCA) specific for epithelial-derived tumor cells, hematopoietic specimens were analyzed for PBPC and occult tumor cell involvement in 28 patients with chemotherapy-sensitive stage IIIB or IV breast cancer. Before PBPC priming, tumor was detected by ICC in PB of 1 of 23 (4%) patients and in bone marrow (BM) harvests of 4 of 27 (15%) patients. Fifteen days after cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF) priming, 2 of 28 (7%) patients had ICC-positive PBPC collections. The median amplification of CD34+ PBPC during this time was over 19-fold (range, < 1 to 199). One patient had pretreatment tumor involvement of both PB and BM. One patient grew tumor colonies in TCA; the PB and BM were ICC- and TCA-positive, but the PBPC collection was ICC-positive and TCA-negative. After cytoreduction with conventional-dose chemotherapy, patients with advanced breast cancer and histologically negative BM biopsy specimens have rare tumor cell involvement of PB and BM. Despite effective PBPC priming with cyclophosphamide and GM-CSF, clonogenic breast cancer cells were not found in the PBPC collection performed on day 15.


Assuntos
Medula Óssea/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Ciclofosfamida/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/patologia , Adulto , Purging da Medula Óssea/métodos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e Especificidade
17.
Cancer Res ; 54(9): 2366-71, 1994 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-8162582

RESUMO

Tumor contamination of hematopoietic stem cell grafts may influence the outcome of breast cancer patients treated with high-dose chemotherapy. The goals of this study were: (a) to evaluate the prevalence of tumor contamination of bone marrow (BM) harvests in patients responding to systemic chemotherapy; (b) to evaluate reduction of BM tumor contamination by ex vivo purging with 4-hydroperoxycyclophosphamide (4HC); and (c) to compare the tumor contamination of peripheral blood progenitor cell collections and BM in advanced-stage breast cancer patients designated for peripheral blood progenitor cell infusion. We evaluated pre- and post-4HC purge BM specimens from 20 patients for tumor contamination using immunocytochemistry and for in vitro growth potential of tumor cells using a tumor cell clonogenic assay. Pre-4HC purge BM specimens from 15 of 20 (75%) patients were immunocytochemistry and tumor cell clonogenic assay negative. The remaining 5 BM specimens were immunocytochemistry positive, but only 3 of 5 specimens were tumor cell clonogenic assay positive. In vitro tumor colony growth was not observed in any post-4HC purge BM specimens. We also evaluated nine patients with bone or BM metastases from the start of induction chemotherapy. We found less tumor involvement of peripheral blood progenitor cell collections than of simultaneously obtained bone marrow aspirates. We conclude that bone marrow micrometastases occur with low frequency in women with chemotherapy-sensitive breast cancer and that ex vivo purging with 4HC may render tumor cells nonviable.


Assuntos
Purging da Medula Óssea/métodos , Medula Óssea/patologia , Neoplasias da Mama/patologia , Ciclofosfamida/análogos & derivados , Ciclofosfamida/uso terapêutico , Adulto , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaio Tumoral de Célula-Tronco
18.
Urology ; 43(1): 68-73, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7506855

RESUMO

OBJECTIVE: To test the hypothesis that prostate cancer lymph node (LN) micrometastases, undetected by standard histology, might be found using sensitive immunohistologic methods and may correlate to preoperative prostate-specific antigen (PSA) levels. METHOD: Archival paraffin blocks of pelvic lymphadenectomy specimens from radical prostatectomy were blindly submitted for immunostaining using pan-cytokeratin monoclonal antibody SB-3, as well as antibodies directed against PSA. Automated immunostaining was performed on a Ventana Medical Systems 320 immunostainer. As a positive control, 7 cases with known nodal metastases by standard histology were blindly analyzed and all has detectable micrometastases by this methodology. RESULTS: For 13 patients with PSA < 10.1 (8%) had LN micrometastases detected. For 10 patients with PSA between 10 and 20 and for 9 patients with PSA > 20, no occult metastases were detected. We did find previously undetected prostate cancer (CaP) LN micrometastases in 1 of 32 (3%) clinically localized prostate cancer patients who had undergone radical prostatectomy. In many LNs, cytokeratin stains cross-reacted and stained individual plasma cells, whereas in the positive metastatic case, a cluster/nest of CaP cells were reactive. To the unfamiliar observer, the pitfall of false-positive results because of nonspecific cytokeratin staining must be considered. These results are in exact agreement with another recent study which also found only a 3 percent incidence of unsuspected pelvic lymph node micrometastases in clinically localized CaP utilizing similar methods. CONCLUSIONS: Our hypothesis was not substantiated: LN micrometastases were uncommon and did not correlate to serum PSA. Unlike studies with breast cancer, occult micrometastatic nodal disease not appreciated by standard methods appears to be uncommon in clinically localized prostatic carcinoma.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pelve , Cuidados Pré-Operatórios , Neoplasias da Próstata/sangue
19.
Blood ; 82(9): 2605-10, 1993 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8219214

RESUMO

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.


Assuntos
Neoplasias da Mama/patologia , Células-Tronco Hematopoéticas/patologia , Ensaio Tumoral de Célula-Tronco , Adulto , Idoso , Medula Óssea/patologia , Separação Celular , Sobrevivência Celular , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
20.
J Hematother ; 1(3): 225-32, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1365029

RESUMO

Peripheral blood stem cell (PBSC) reinfusions are being used with increasing frequency in lieu of, or in addition to, autologous bone marrow transplantation (ABMT) to rescue cancer patients from the myeloablative effects of high-dose chemotherapy. However, the incidence and quantity of tumor cell contamination in PBSC collections has not been widely investigated. This paper reviews the existing data and presents new information to demonstrate that tumor cells are detectable in PBSC harvests from patients with a variety of malignancies. Furthermore, their presence in peripheral blood may have prognostic and clinical significance. Areas of future research and applications for PBSC technologies are also discussed.


Assuntos
Células-Tronco Hematopoéticas/patologia , Neoplasias/patologia , Manejo de Espécimes/métodos , Doenças da Medula Óssea/patologia , Humanos , Fatores de Risco
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