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Biomedical subjects

A Kanbour

Publications and source records attributed to A Kanbour.

At least 19 recordsLinked to original sources

Cytomorphologic features of classic and variant lobular carcinoma: A comparative study.

There are several subtypes of lobular carcinoma (LC), and their cytomorphologic features differ from classic lobular carcinoma (CLC). The finer details of the differences between CLC and variant lobular carcinoma (VLC) have not been adequately studied. A comparative study of 54 cases of CLC and VLC was done in order to verify any statistically significant differences between them. All cases had histologic confirmation of the diagnosis. Six parameters, which included cellularity, signet-ring cells, intracytoplasmic lumina (ICL), anisonucleosis, cell size, and prominent nucleoli, were studied. The only statistically significant findings were cellularity and cell size when compared to CLC. The cellularity in VLC was higher and the cells in VLC were larger when compared to CLC. There are no definite diagnostic features to identify VLC; however, in a cellular specimen with plenty of large cells with other features of LC, one should have a high index of suspicion of VLC.

Biopsy, Needle↗

In situ hybridisation for cytokine gene transcripts in the solid tumour microenvironment.

To determine if mononuclear cells (MNC) infiltrating various types of human solid tumours express genes for cytokines, in situ hybridisation with 35S-labelled cDNA antisense probes for interleukin 2 (IL2), interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), interleukin 1-beta (IL1-beta), transforming growth factor beta (TGF-beta) and interleukin 2-receptors (IL2R) was performed. Fresh-frozen tissue samples of ovarian carcinomas (n = 13), breast carcinomas (n = 12), and squamous cell carcinomas of the head and neck (SCCHN, n = 7) were evaluated for the presence and localization in the tumour of MNC positive for cytokine genes. In ovarian tumours and those breast carcinomas producing little or no mucin, only rare positive MNC were observed. In contrast, breast carcinomas producing mucin and all SCCHN contained numerous MNC expressing gene transcripts for IL2, IFN-gamma, TNF-alpha, IL2R as well as TGF-beta. In tumour-involved lymph nodes of patients with SCCHN, MNC expressing genes for cytokines were found around tumour metastases but not in non-involved areas. These data suggest that tumours expressing immunogenic antigens (e.g. mucin) contain many activated MNC, while other tumours either fail to activate or suppress functions of infiltrating MNC. In SCCHN or tumour-draining lymph nodes, local down-regulation of antitumour responses might be mediated by TGF-beta produced by activated tumour-infiltrating MNC.

Breast Neoplasms↗

Tumor-infiltrating lymphocytes from ovarian tumors of low malignant potential.

Tumor-infiltrating lymphocytes (TIL) from human ovarian tumors of low malignant potential (LMP) were studied in situ by immunohistology and characterized functionally after isolation from tumors. In comparison to ovarian carcinomas, borderline (LMP) ovarian tumors contained significantly fewer infiltrating leukocytes. Phenotypically, TIL from LMP tumors contained significantly fewer activated (HLA-DR+ or CD25+) lymphocytes than did fresh TIL from ovarian carcinomas. Also, percentages of CD3-CD56+ natural killer cells were higher in LMP than in ovarian carcinomas. TIL obtained from LMP tumors proliferated well in vitro in the presence of interleukin 2 (IL2) and tumor necrosis factor alpha (TNF alpha) but did not show a selective enrichment in CD3+CD8+T lymphocytes generally observed with TIL from ovarian carcinomas. Antitumor cytotoxicity against a panel of tumor cell targets of cultured TIL from LMP tumor did not parallel that of effectors generated from autologous peripheral blood lymphocytes. However, no significant enrichment in reactivity against autologous tumor cells was observed in long-term cultures of TIL from LMP tumors. Thus, considerable differences were observed between phenotypic and functional characteristics of lymphoid cells infiltrating LMP tumors and invasive ovarian carcinomas.

Adult↗

Expression of mRNA for cytokines in tumor-infiltrating mononuclear cells in ovarian adenocarcinoma and invasive breast cancer.

Cytokine gene expression in tumor-infiltrating lymphocytes (TIL) in frozen-tissue sections of 2 types of human solid tumor--ovarian adenocarcinoma and invasive breast cancer--was examined by in situ hybridization with 35S-labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense c-DNA probes for interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or receptors for IL-2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNF alpha mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10-20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor-infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNF alpha, IL2 or IFN gamma. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL-2, TNF alpha and IL-2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL-2, TNF alpha, IFN gamma and IL-2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin-producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL.

Adenocarcinoma↗

Choriocarcinoma in a term placenta with maternal metastases.

Choriocarcinoma of the nonmolar placenta is presumptively a rare entity and is usually associated with widespread maternal metastases at the time of diagnosis. Nonmetastatic disease goes unrecognized and undiagnosed because placental carcinoma can be limited to a few villi, and grossly evident disease is often misinterpreted as a placental infarct. The optimal treatment for patients with choriocarcinoma of the placenta is not known but aggressive combination chemotherapy is suggested for patients with metastatic disease. Historically, the prognosis for both mother and infant has been poor.

Adult↗

Lymphocytes infiltrating human ovarian tumors: synergy between tumor necrosis factor alpha and interleukin 2 in the generation of CD8+ effectors from tumor-infiltrating lymphocytes.

Tumor-infiltrating lymphocytes (TIL) were isolated by enzymatic digestion and gradient centrifugation from 18 human ovarian carcinomas. These cells were cultured in a complete medium supplemented with recombinant interleukin 2 (IL2) alone or recombinant IL2 plus recombinant tumor necrosis factor alpha (TNF-alpha), and their growth and antitumor cytotoxicity were determined. TIL cultured in the presence of IL2 plus TNF-alpha (1000 units/ml each) for 6 days showed significantly higher cytotoxicity against fresh autologous tumor targets than did TIL cultured with IL2 alone (e.g., mean lytic units/10(7) cells for 8 TIL preparations were 290 versus 74; P less than 0.05). No differences in [3H]thymidine uptake or natural killer cell activity were observed among these TIL cultures. In titration experiments, optimal synergistic concentrations of IL2 and TNF-alpha were determined as 10(2) and 10(3) units/ml, respectively. Using these concentrations for culturing the TIL, effector cells developed which preferentially lysed autologous tumor and displayed a CD8+ phenotype (up to 75% positive). However, the autologous tumor cytotoxicity mediated by these cultured TIL on day 6 was short lived. By day 12, it was replaced by non-major histocompatibility complex-restricted, lymphokine-activated killer cell-like activity mediated by CD3-CD56+ effector cells. Simultaneously, the production of gamma-interferon and interleukin 1 decreased in these cultures. In contrast to TNF-alpha, anti-CD3 antibody synergized with IL2 to increase 2-3-fold TIL proliferation but not their cytotoxic activity against autologous tumor cell targets. These data suggest that TNF-alpha and IL2 synergize early in culture to induce tumor-reactive CD8+ effectors, some of which may be specific for autologous ovarian tumor cells. However, the conditions needed to sustain the specific autologous tumor responses in long-term cultures of human TIL remain to be determined.

Antigens, Differentiation, T-Lymphocyte↗

Lymphocytes infiltrating human ovarian tumors. I. Role of Leu-19 (NKH1)-positive recombinant IL-2-activated cultures of lymphocytes infiltrating human ovarian tumors.

Tumor-infiltrating lymphocytes (TIL) were obtained from human ovarian tumors, expanded in the presence of IL-2 in culture and studied for cytotoxicity against fresh autologous and allogeneic ovarian carcinoma (CA) targets. TIL from ovarian tumors grew well in long term cultures, achieving from 8- to 682-fold expansion. TIL cultured with IL-2 were cytotoxic against both autologous and allogeneic fresh ovarian CA targets, and no specificity for autologous tumor could be demonstrated in any of the cultures. In all fresh TIL preparations, CD3+ lymphocytes were the major cell type and contained a high proportion (up to 51%) of activated (IL-2R+) cells as determined by two-color flow cytometry. Sorting of bulk TIL cultures followed by cytotoxicity assays identified the Leu-19+ cells, both CD3+ and CD3-, as effectors of cytotoxicity against autologous and allogeneic tumor cell targets. Cold target inhibition assays showed that allogeneic targets (both ovarian CA and a sarcoma) competed effectively with autologous ovarian CA targets for Leu-19+ effectors in TIL cultures. mAb to Leu-19 or Leu-2a did not block lysis of autologous targets by sorted effectors. OKT3 antibody augmented lysis of autologous targets by CD3+Leu-19- effectors only. These results show that non-MHC-restricted Leu-19+ effectors in cultures of TIL with 1000 U/ml of rIL-2 mediate lysis of autologous and allogeneic tumor cells. The CD3+Leu-19- cells, the main population in these cultures, do not mediate tumor lysis. To determine the phenotype of antitumor effectors in IL-2 cultures of TIL, cell sorting followed by functional assays are necessary.

Adult↗

Malignant fibrous histiocytoma of the head and neck. A report of 12 cases.

The clinical and pathologic features of 12 cases of malignant fibrous histiocytoma of the head and neck were studied. These tumors occurred in seven men and five women ranging in age from 21 to 75 years (average, 55 years). The sinonasal tract was the most common site (four cases), followed by the parotid area (two cases), oral cavity (two cases), soft tissues of the neck (two cases), mandible (one case), and larynx (one case). Pathologically, 11 of the tumors were subclassified as storiform-pleomorphic and one as inflammatory. All were treated initially with surgery with or without postoperative irradiation. Five (42%) of the patients experienced local recurrences, three (25%) developed distant metastases (especially to the lungs), and five (42%) died of their disease, all of the latter occurring within two years of diagnosis. No patient developed bona fide cervical lymph node metastasis, although one did have a positive paraparotid node as a result of direct extension from an adjacent tumor.

Adult↗

Differential expression of MHC class I antigens on the placenta of the rat. A mechanism for the survival of the fetal allograft.

In some mating combinations in rats, there is a maternal antibody response to the maternal antigenic components of the placenta without any previous immunization of the mother. The highest response occurs in the WF (u) female mated to the DA (a) male, and it is against a unique MHC-encoded class I antigen, the Pa antigen, and not against the major allele-specific transplantation antigen of the DA strain, RT1.Aa. The development of mAbs to the Pa and Aa antigens allowed us to localize these antigens on the placenta and to explore the reason for the differential antibody response to them using immunohistochemical and biochemical techniques. Both antibodies reacted with the WF X DA placenta and stained the endovascular and interstitial trophoblast of the decidua, the basal trophoblast, Reichert's membrane, and the yolk sac epithelium, but they did not stain the labyrinthine trophoblast. Blocking studies showed that each antibody reacted with a separate molecule in the placenta. Anti-class II mAbs reactive with the a or u haplotype did not stain the WF X DA, DA X DA, or WF X WF placenta; hence, there are no class II antigens in the placenta. Electron microscopic studies of the semiallogeneic WF X DA placenta using the immunogold technique with both single- and double-labeling showed that only the Pa antigen was expressed on the surface of the basal trophoblast, but that both the Pa and Aa antigens were in the cytoplasm of these cells; neither antigen was found in the labyrinthine trophoblast. By contrast, the placenta from the syngeneic DA X DA mating expressed both the Pa and Aa antigens on the surface of the basal trophoblast as well as in the cytoplasm; neither antigen was found in the labyrinthine trophoblast. These observations were quantified morphometrically using electron photomicrographs of single-labeled tissues. Both the Pa and Aa antigens isolated from the plasma membrane of lymphocytes have heavy chains of 46 kD, but those antigens isolated from the plasma membrane of basal trophoblast cells have heavy chains of 43 kD. Based on densitometric measurements of autoradiographs, the Pa/Aa ratio in the basal trophoblast membrane is 23.5, whereas it is 0.46 in lymphocyte membranes. These studies show that there is differential regulation of the expression of class I antigens on basal trophoblast cells in semiallogeneic pregnancies, but not in syngeneic pregnancies, such that the major allele-specific transplantation antigen is scarcely expressed on the surface of the basal trophoblast.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Electron microscopic localization of the Pa and RT1.Aa antigens on the placenta of the rat.

A major factor in the ability of the placenta to avoid allograft rejection is the differential expression of MHC class I antigens on its surface. Using monoclonal antibodies and the electron microscopic immunogold technique, we have demonstrated that only the pregnancy-associated (Pa) antigen, which carries a broadly shared antigenic determinant, is expressed on the placental surface in the rat, whereas the allele-specific classical transplantation antigens are not. Both types of antigens are, however, present in the cytoplasm of the basal trophoblast but completely absent from the labyrinthine trophoblast.

Animals↗

Vaginal adenosis and polycystic ovaries during infancy and childhood.

A histologic study of 40 postmoretem specimens of vagina, uterus, and ovaries obtained from fetuses, infants, and children revealed vaginal or ectocervical adenosis in eight cases (20.0%) and polycystic ovaries in 13 cases (32.5%). All cases of adenosis were associated with polycystic ovaries and moderate to marked theca luteinization. Five patients who had adenosis died of diseases of the central nervous system (CNS) such as cerebral injury and hydrocephalus. A total of seven of 13 cases or 53.8% with polycystic ovaries had CNS diseases. The possible roles of neurogenic and hormonal factors in the pathogenesis of these conditions are discussed.

Adolescent↗

Prehysterectomy curettage.

The efficacy of prehysterectomy curettage in ruling out an endometrial cancer was evaluated in three ways. First, by an evaluation of the extent of routine prehysterectomy curettage; second, by the assessment of the clinicians' ability to recognize endometrial cancer on the basis of curettings; and third, by evaluating the presence of a gross endometrial lesion in those uteri removed without a preoperative diagnosis of an endometrial malignancy. It was concluded that the examination of the opened excised uterus was more valuable than prehysterectomy curettage for the operative diagnosis of an endometrial malignancy.

Adenocarcinoma↗

Characterizing "blue blobs". Immunohistochemical staining and ultrastructural study.

OBJECTIVE: To investigate the nature and origin of "blue blobs" (Bbs) in atrophic Pap smears in postmenopausal women and to study their clinical significance. STUDY DESIGN: A retrospective study of 412 atrophic Pap smears from postmenopausal women was done to detect the presence of Bbs. The smears from 24 cases showing Bbs were further studied to evaluate the nature of the Bbs with special stains, immunohistochemistry and electron microscopy. RESULTS: Bbs showed a heterogeneous morphology, with variable numbers and staining intensity. The diameter of Bbs was approximately equivalent to that of a parabasal/intermediate squamous cell. Special stains showed Bbs to be positive for periodic acid-Schiff and methyl green pyronin and negative for mucicarmine and calcium. Immunohistochemistry revealed Bbs to be positive for cytokeratin, epithelial membrane antigen and carcinoembryonic antigen and negative for vimentin and muscle-specific actin. Some Bbs had residual ghost nuclear shadows. Electron microscopy revealed cellular skeletons with residual tonofilaments enmeshed within a loose cytoskeleton matrix and nuclei with variable degrees of degeneration. CONCLUSION: Special stains, immunohistochemistry and electron microscopy indicated that Bbs represent parabasal/intermediate squamous cells exhibiting various degree of degeneration. In general, Bbs appear to be of no clinical significance except as a source of potential diagnostic error.

Aged↗