Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors.

Background: Inherited mutations in the BRCA1 gene may be responsible for almost half of inherited breast carcinomas. However, somatic (acquired) mutations in BRCA1 have not been reported, despite frequent loss of heterozygosity (LOH or loss of one copy of the gene) at the BRCA1 locus and loss of BRCA1 protein in tumors. To address whether BRCA1 may be inactivated by pathways other than mutations in sporadic tumors, we analyzed the role of hypermethylation of the gene's promoter region.

Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis.

Objective: In many patients with chronic myeloid leukemia (CML), a residual population of primitive normal (Ph-negative) progenitors persists despite the marked expansion of the leukemic (Ph-positive) clone. These cells may be found in the blood of patients studied soon after diagnosis or during the period of endogenous hematopoietic recovery that follows myeloreductive therapy. Based on those observations, we have developed a clinical protocol that allows collection of Ph-negative peripheral blood progenitor cells (PBPC) with transplantable hematopoietic regenerative potential.

Littoral cell angioma with severe thrombocytopenia.

Littoral cell angioma (LCA) is a recently described splenic vascular tumor. We present a new case in a 62-year-old woman with severe thrombocytopenia and mild bleeding diathesis, but without palpable splenomegaly. Abdominal ultrasound and magnetic resonance showed multiple nodular images, suggesting splenic hemangiomas.

Cytogenetic response to autografting in chronic myelogenous leukemia correlates with the amount of BCR-ABL positive cells in the graft.

Objective: An important step in successful autografting of patients with chronic myelogenous leukemia is the delivery of a leukemia-free graft. We conducted this study to determine whether the cytogenetic response after autografting was correlated with the number of BCR ABL-positive cells present within the stem cell grafts.

Materials And Methods: By BCR-ABL mRNA quantification, we studied the serial pheresis products from 40 Philadelphia (Ph)-positive patients who received ICE/mini-ICE mobilization therapy and underwent autologous stem cell transplantation.

DNA image cytometry. An alternative method in osteoblast proliferation assays.

Objective: To assess whether DNA image cytometry can be used as an alternative method to tritiated thymidine uptake quantification in osteoblast proliferation assays. STUD DESIGN: Proliferation of normal human osteoblasts incubated with normal human serum at 0%, 2.5%, 5%, 10%, 20% and 40% was quantified by tritiated thymidine uptake quantification and DNA image cytometry.

Chronic myeloid leukemia with expression of ALL-type BCR/ABL transcript: a case-report and review of the literature.

CML with exclusive expression of ALL-type bcr/abl has only been rarely described. In some cases, the presence of this fusion gene has been associated to a differentiated subtype of CML that share some features with CMML, while in another case this molecular hallmark has been associated to a bad prognosis of the disease with a blast phase as clinical presentation or an early transformation to blast phase. We report a case of a 30-year-old woman who was diagnosed of CML in chronic phase in May 1989.

Quantitative competitive reverse transcriptase-polymerase chain reaction for BCR-ABL on Philadelphia-negative leukaphereses allows the selection of low-contaminated peripheral blood progenitor cells for autografting in chronic myelogenous leukemia.

The Philadelphia (Ph) translocation t(9;22) results in the creation of the BCR-ABL gene, which is now regarded as central to the mechanism that underlies the chronic phase of chronic myelogenous leukemia (CML). From a clinical point of view, BCR-ABL mRNA detection has become the basis for the study of minimal residual disease in CML, particularly when a complete cytogenetic remission is achieved after interferon-alpha (IFN-alpha) therapy or allogeneic stem cell transplantation. We have recently demonstrated that it is possible to mobilize normal peripheral blood progenitor cells (PBPC) in higher rates if this procedure is performed during the early chronic phase.

Autografting with philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia.

Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high-dose therapy. Hematopoietic recovery to greater than 0.

Rescreening of atypical cervicovaginal smears using PAPNET.

Background: Atypical squamous cells of undetermined significance (ASCUS) is a cytopathologic term used to describe cases without specific pathologic substratum. Between 10-60% of ASCUS cases correspond to squamous intraepithelial lesions (SIL).

Methods: The objectives of this study were: 1) to detect the pathologic significance of ASCUS in study patients, 2) to determine whether PAPNET identifies these cases, and 3) to compare the results of PAPNET with those of a second conventional screening.

Engraftment of HLA-matched sibling hematopoietic stem cells after immunosuppressive conditioning regimen in patients with hematologic neoplasias.

Background And Objective: The main objective of this pilot study was to assess the possibility of achieving engraftment of HLA-matched sibling donor mobilized hematopoietic stem cells after immunosuppressive non-myeloablative therapy. The second objective was to verify whether high-dose therapy with autologous stem cells rescue followed by allografting conditioned by only an immunosuppressive regimen, can be combined in order to achieve the reduction of tumor burden after autografting and the control of residual disease with immune-mediated effects after allografting.

Design And Methods: To enter the pilot study the patients had to fulfil the following criteria: advanced resistant disease, presence of an HLA matched sibling donor, no general contraindications to stem cell transplantation.

Evidence of cytogenetic and molecular remission by allogeneic cells after immunosuppressive therapy alone.

An immunosuppressive but not myeloablative regimen followed by HLA-matched donor mobilized haemopoietic stem cell transplantation was employed in two high-risk patients. The first patient had refractory anaemia with excess blasts (RAEB) and cytogenetic evidence of translocation 1;3(p36;q21). The second patient had Philadelphia-negative but p190 BCR-ABL chimaeric gene positive chronic myelogenous leukaemia in accelerated phase (AP-CML).

K-ras gene mutations in the diagnosis of fine-needle aspirates of pancreatic masses: prospective study using two techniques with different detection limits.

Detection of K-ras mutations may be useful in the evaluation of pancreatic cancer. The aim of this study was to assess, in a prospective design, the diagnostic utility of K-ras mutation analysis in 62 consecutive fine-needle aspirates of pancreatic masses, using two PCR-based techniques-standard and enriched-with detection limits of a mutant allele in the presence of 10(2) or 10(3) wild-type alleles, respectively. Cytology alone offered a diagnostic sensitivity of 75%.

Effective mobilization of Philadelphia-chromosome-negative cells in chronic myelogenous leukaemia patients using a less intensive regimen.

To determine if reducing the intensity of the mobilizing chemotherapy protocol used would alter the number and/or quality of the progenitors mobilized in patients with chronic myelogenous leukaemia (CML), we undertook a pilot study. 36 consecutive CML patients previously treated only with hydroxyurea were given mobilization therapy within 12 months of diagnosis. 17 patients were treated by the ICE protocol and 19 patients received the mini-ICE protocol.

Clear cell tumors of the female genital tract.

Clear cell adenocarcinomas of the vagina, cervix, endometrium, and ovaries show very similar histological features. Several other tumors and tumor-like lesions of the female genital tract may also contain clear cells and may occasionally be misinterpreted as clear cell adenocarcinomas. These conditions include microglandular hyperplasia, mesonephric hyperplasia, Arias-Stella change, smooth muscle tumors containing clear cells, dysgerminoma, yolk sac tumor, metastatic renal cell carcinoma, steroid cell tumors, hepatoid carcinomas, signet-ring-cell stromal tumors, and trophoblastic tumors.

Stem-cell mobilization for autografting in chronic myeloid leukemia.

In this article, the rationale for autografting in chronic myeloid leukemia is reviewed, and alternative therapeutic approaches to the use of granulocyte-colony stimulating factor and chemotherapy-mobilized peripheral blood stem cells are discussed. The data from patients treated using the original ICE (idarubicin, cytarabine, etoposide), or the shorter course mini-ICE protocols are considered, with special emphasis on those patients who received their chemotherapy regimens soon after diagnosis and prior to any treatment with interferon alpha. The appropriate design of a trial to test the value of autografting in chronic myeloid leukemia is discussed, as is the optimal timing of collections to achieve the maximal yield and purity of Ph-negative peripheral blood stem cells.

Aspiration cytology of lung metastasis of monophasic synovial sarcoma. Report of a case.

Background: Synovial sarcoma usually arises in the extremities of young adults and metastasizes in about 50% of the cases. Fine needle aspiration can reveal those metastases.

Case: A 65-year-old female presented with a solid mass in the left lung from which a fine needle aspirate was taken.

New insights in biology and current therapeutic options for patients with chronic myelogenous leukemia.

Background And Objective: From the discovery of the Ph-chromosome, there has been an extraordinary progress in our understanding of chronic myeloid leukemia (CML). During the last three decades, new findings arising from dissection of the genetic abnormalities at a molecular level have received the most attention, but there have also been important new observations arising from studies of the biologic behaviour of normal and leukemic stem cells and, more recently, from clinical investigations. In this review we first report the most important observations relevant to understanding the oncogenic potential of the BCR-ABL chimeric gene, and the behaviour and the relationships of normal and leukemic stem cells.

Mobilization and transplantation of Philadelphia-negative peripheral-blood progenitor cells early in chronic myelogenous leukemia.

Purpose: Mobilization of Philadelphia (Ph) chromosome-negative progenitors is now possible in many Ph1-positive chronic myelogenous leukemia (CML) patients who had received interferon alfa (IFN-alpha) with no cytogenetic response. In this pilot study, we used this approach in patients without prior IFN-alpha therapy to determine if the number and quality of mobilized progenitors would be increased and to evaluate the potential effect of these cells as autografts.

Patients And Methods: Twenty-two untreated patients were mobilized within 12 months of diagnosis.

Prognostic value of S-phase fraction in lymph-node-negative breast cancer by image and flow cytometric analysis.

Cellular DNA content and proliferation rates have been suggested as prognostic factors in breast carcinomas. A series of 271 lymph-node negative breast carcinoma patients without adjuvant therapy was reviewed (mean follow-up, 108 mo). Tumor cells from the same paraffin-embedded block tissue (Hedley's method) were analyzed by image analysis (IA) in Feulgen-stained smears and by flow cytometric analysis (FC).

In vivo mobilization of karyotypically normal peripheral blood progenitor cells in high-risk MDS, secondary or therapy-related acute myelogenous leukaemia.

We have previously reported that mobilization of Philadelphia (Ph) chromosome-negative progenitors is possible in a significant number of Ph1-positive acute lymphoblastic leukaemia (ALL) and chronic myelogenous leukaemia (CML) patients. In this pilot study we employed the same approach for patients with RAEB-t, secondary AML (sAML) and therapy-related AML (t-AML). All patients except one had double or complex cytogenetic abnormalities in marrow cells before mobilization therapy.

Fine needle aspiration cytology in pancreatic pathology.

Objective: To assess the sensitivity and specificity of pancreatic fine needle aspiration.

Study Design: Two hundred five fine needle aspirates were obtained from 149 patients over seven years. After excluding 40 patients lacking biopsy or follow-up, 125 aspirates from 109 patients were selected to analyze the accuracy of this method.

Autografting Ph-negative blood precursor cells in chronic myeloid leukaemia.

The study was devised to evaluate whether it was possible to collect Philadelphia-negative precursor cells in patients with chronic myeloid leukaemia. The approach was based on previous experience showing that complete remission (Ph-negative bone marrow cells) is rarely achieved after chemotherapy and is very short-lasting. We decided to explore whether it was possible to collect Ph-negative precursor cells in peripheral blood during the early phase of haemopoietic recovery.

Diagnostic utility of K-ras mutations in fine-needle aspirates of pancreatic masses.

Background & Aims: Mutations at codon 12 of the K-ras gene are present in 65%-100% of carcinomas of human exocrine pancreas and could be used as a potential tumor marker at the tissue level. The purpose of this study was to assess, in large series of patients, the utility of K-ras mutation analysis to evaluate fine-needle aspirates of pancreatic masses.

Methods: One hundred fifteen fine-needle aspirates obtained from 93 patients were evaluated retrospectively.

Long-term risk of sarcoma following radiation treatment for breast cancer.

At the hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 3,120 patients with breast carcinoma were submitted to radiation between 1976 and 1994. Among them there were three patients (0.06%) in whom malignant neoplasm developed in areas of prior irradiation.