BACKGROUND: Morphologically noninvolved mucosa in patients with head and neck cancer is altered by carcinogens. These alterations may include chromosome alterations, gene mutations, and other molecular abnormalities which may explain very high incidence of second tumors in this group of patients. The purpose of this study was to investigate the in vivo proliferative characteristics in epithelial tissues adjacent to the tumor in a series of patients with head and neck cancer. METHODS: Twenty-one patients with head and neck tumors received IV infusions of iododeoxyuridine (IdUrd) and/or bromodeoxyuridine (BrdUrd). Surgical specimens containing normal-appearing epithelium adjacent to the tumor were selected and stained with the respective monoclonal antibody. The percentage of S-phase cells (labeling index, LI) was counted in the basal and suprabasal layers of the epithelium. RESULTS: In 27 samples of oral epithelium obtained from 14 previously untreated patients, labeled (S-phase) cells were predominantly located in suprabasal layers with LI 31.6 +/- 3.1% (range 13.5-73.2%). In contrast, the LI of the basal layer was very low: 1.6 +/- 0.2% (range 0.5%-8.8%). There was no statistically significant difference between normal appearing and dysplastic samples (p > 0.05). In 10 samples obtained from 7 patients whose biopsies were studied 2 days to 2 month after concomitant radiation and chemotherapy, the LI of the oral mucosa basal layer was significantly higher (21.0 +/- 4.1%, range 6.3-39.2%). The LI of the suprabasal layer in treated patients was 14.3 +/- 2.4% (range 5.9-31.1%). The LI of nasal pseudostratified epithelium (4 samples) was 11.2%. The average LI of "basal" cells was 8.3% (range 5.9-11.9%) and that of "suprabasal" cells was 13.8% range (3.2-29.5%). The basal layer of the skin (5 samples) contained 9.3% labeled cells (range 3.3-16.3%); the LI of suprabasal layers of skin was 21.3% (range 7.8-33.2%). CONCLUSION: Both the frequency and the spatial distribution of S-phase cells are disordered in noninvolved epithelia in patients with head and neck tumors. These observations suggest that disordered proliferation may be an early consequence of field cancerization, a consequence that occurs prior to appearance of morphologically apparent hyperplasia or dysplasia.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

The myelodysplastic syndromes in 1996: complex stem cell disorders confounded by dual actions of cytokines.

Based upon recent studies of apoptosis, proliferation, cytokines and genic abnormalities, a new hypothesis regarding the pathology of myelodysplastic syndromes is being proposed. The transforming abnormality which affects an early progenitor hemopoietic stem cell is poorly defined so far but confers a growth advantage on this cell eventually leading to monoclonal hemopoiesis at least affecting the non-lymphoid bone marrow cells. Several cytokines confound the picture by exerting dual effects of stimulating the proliferation of immature cells while inducing the apoptosis in their maturing progeny thereby producing the clinical syndrome of cytopenias despite cellular marrows. Since a number of these offending cytokines share the same common lipid intracellular signalling pathway, interfering with the generation of specific phospholipid second messengers should hypothetically result in a dual effect as well. Alleviation of cytopenias (due to attenuation of apoptosis) should be accompanied by a decrease in the progeny of the transformed stem cell (due to suppression of proliferation) eventually allowing for resumption of polyclonal hemopoiesis.

Acute Disease↗

PubMedDate not supplied

The effects of 13-cis retinoic acid and interferon-alpha in chronic myelogenous leukemia cells in vivo in patients.

The effects of the administration of a 3-day course of 13-cis retinoic acid in combination with interferon a [RA/IFN] on the leukemia cells was measured in vivo in 43 patients with chronic myelogenous leukemia. The administration of RA/IFN was associated with a significant fall in the white blood cell count of patients with chronic-phase disease and with a fall in the percentage S-phase cells in CML patients regardless of the stage of their leukemia. In two thirds of the patients studied the administration of RA/IFN was also associated with an increase in marrow apoptosis. The cytokine combination also suppressed bcl-2 and myc expression in a minority of patients and such expression appears to be associated with response to a treatment regimen which includes RA/IFN. These studies are the first to directly assess the effects of the combination of RA/IFN on chronic myelogenous leukemia cells in vivo in patients. These effects, if seen in other malignant diseases, could account for the therapeutic benefit which has been associated with the administration of this combination of biological agents to patients with malignant disease.

Adult↗

PubMedDate not supplied

The CD34 hemopoietic progenitor cell associated antigen: biology and clinical applications.

CD34, which was first detected in hemopoietic and lymphopoietic progenitors, is a heavily glycosylated Type I transmembrane protein that does not share any significant similarity with other transmembrane proteins. Its functions are still unknown. Several monoclonal antibodies were raised against CD34, and at least 4 different epitopes could be recognized. CD34 expression is confined to a few cell lines, to 1-4% of adult bone marrow mononuclear cells (including marrow-repopulating cells, all multipotent and committed myeloid progenitors, B and T lymphoid precursors, osteoclast precursors, and most likely the precursors for stromal cells), and to less than 1% of peripheral blood mononuclear cells. In non-lymphohemopoietic tissues its expression is confined to endothelial cells and to some cells of the skin. In malignancies, CD34 expression is not fully elucidated. Immature hemolymphopoietic malignancies (namely acute leukemias) and the blast cells of chronic myeloid leukemia are frequently positive. Chronic lymphoproliferative disorders and lymphomas are negative. Among other tumors, only vascular derived tumors are positive. Clinical applications of CD34+ cells include autologous transplantation of putative CD34+ stem cells isolated by positive selection from the bone marrow, and transplantation of autologous peripheral blood stem cells, using the proportion and number of CD34+ cells as a guideline for the harvesting procedure.

Antibodies↗

PubMedDate not supplied

CD34-positive cell selection by immunomagnetic beads and chymopapain.

BACKGROUND: Pluripotent hemopoietic stem cells, progenitors of all hemolymphopoietic lineages, and clonogenic cells from many patients with acute nonlymphocytic leukemia (ANLL) and chronic myeloid leukemia (CML) express the CD34 antigen on their surface. Isolation of these cell populations is of primary experimental and clinical importance. METHODS: Six bone marrow (BM) and 10 peripheral blood (PB) samples were obtained from 2 normal individuals, 3 patients with CML and 9 with ANLL. The CD34+ cell fraction was isolated using MY10 antibody, sheep anti-mouse immunomagnetic beads and the enzyme chymopapain. Indirect immunofluorescence and semisolid culture were employed to evaluate the percentage of CD34+ cells and that of clonogenic cells in each cell fraction. RESULTS: The frequency of CD34+ cells in the original unseparated populations was (mean +/- SE) 24.3 +/- 7.3%, and reached 85.0 +/- 2.7% in the isolated CD34-positive fractions; in the negative fractions it was only 2.7 +/- 1.7%. According to these results, the great majority of clonogenic cells was separated in the CD34-positive fractions and depleted in those CD34-negative. Moreover, chymopapain was shown to be non-toxic to the clonogenic cells. CONCLUSIONS: Positive immunoselection using My10 Ab, immunomagnetic beads and chymopapain is a method for isolating almost pure progenitors from the BM and PB of normal individuals and patients with myeloid leukemias.

Antigens, CD↗

PubMedDate not supplied

Evaluation of c-myc proto-oncogene in primary human breast carcinomas.

The expression of the c-myc proto-oncogene product was examined by immunohistochemistry in 11 normal breast tissues, 31 invasive and 14 non-invasive breast carcinomas. The c-myc product was detected in all breast carcinoma specimens and in seven of 11 normal breast tissues. Invasive tumors stained more frequently with the anti-myc monoclonal antibody (MAb) than non-invasive tumors, while the level of expression in normal breast tissue was much less than that in a breast cancer. Marked heterogeneity in the c-myc expression was seen among different tumors and within individual tumors. None of the eight invasive tumors with a high protein level of the c-myc showed evidence of gene amplification by Southern blot analysis.

Antibodies, Monoclonal↗