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J Casper

Publications and source records attributed to J Casper.

At least 55 records · Page 3Linked to original sources
PubMed1997

Comparative cytotoxicity of oxaliplatin and cisplatin in non-seminomatous germ cell cancer cell lines.

Approximately 70-80% of patients with metastatic testicular cancer will become disease free with cisplatin-based chemotherapy and most of these patients will be long-term survivors. Despite these impressive results, the two limitations of cisplatin are its severe and potentially long-term side-effects, and the emergence of drug resistance which prevents a small proportion of these patients from achieving long-term remission. Oxaliplatin has an improved toxicity profile compared to cisplatin and contains the diaminocyclohexane (DACH) substituent known to be correlated with a lack of cross-resistance with cisplatin. A phase II study has shown interesting activity when used in combination with cisplatin in cisplatin-refractory testicular cancer patients. Here we report the results of the first in vitro study investigating whether oxaliplatin as a single agent exhibits cross-resistance to cisplatin in a panel of non-seminomatous germ cell tumor (NSGCT) cell lines using short and long-term drug exposures in a five-day sulfhodamine B in vitro cytotoxicity assay. Oxaliplatin cytotoxicity was significantly superior to cisplatin in cell lines with both acquired (H12DDP) and intrinsic (1777NRp Cl-A) intermediate level resistance to cisplatin. Following 24 h or 96 h drug exposure the fold resistance in H12DDP and 1777NRp Cl-A was 1.7-2.2 with oxaliplatin compared to 3.9-6.1 with cisplatin. The cytotoxic activity of oxaliplatin was not significantly different from that of cisplatin in cisplatin-sensitive cell lines or in cell lines with a high level (10-20 fold) of cisplatin resistance. The results of this study suggest that further preclinical studies in NSGCT are of interest, particularly in combination with cisplatin, ifosfamide and etoposide. Furthermore, the in vitro results support the use of an oxaliplatin administration schedule giving prolonged drug exposure, such as the flat or circadian rhythm-modulated schedule already under investigation for oxaliplatin.

Adult↗
PubMed1997

Pre-clinical activity of taxol in non-seminomatous germ cell tumor cell lines and nude mouse xenografts.

Taxol (Paclitaxel) is a novel anti-cancer drug which has shown excellent clinical activity in a variety of solid tumors, particularly in metastatic breast and ovarian cancer. 70-80% of patients with metastatic non-seminomatous germ cell tumor (NSGCT) attain disease-free status with standard cisplatin-based combination chemotherapy but the emergence of drug resistance still prevents a small proportion of these patients from achieving long-term remission. Here we report the results of pre-clinical studies investigating whether taxol exhibits cross-resistance to cisplatin or ifosfamide in human NSGCT cell lines and in a cisplatin refractory xenograft model of human NSGCT. Following 96-h drug exposure in a 5-day sulphohodamine B (SRB) in vitro assay, taxol demonstrated potent cytotoxicity in cell lines which were cisplatin sensitive (577 LM, H32, H12.1; mean IC50s 1.5-3.0 nM) or those with acquired or intrinsic cisplatin resistance (H12DDP, H23.1; mean IC50s 2.5 nM). Compared to the drug-sensitive cell line, H12.1, the IC50 values of taxol were increased in cell line 1777NRp Cl-A with intermediate level resistance to cisplatin and ifosfamide (4.7 nM; p > 0.05) and significantly elevated in cell line 1411HP, with a high level of cisplatin resistance (6.9 nM; p < 0.01). The latter 2 cell lines may represent models corresponding to patients relapsing after high-dose platinum-based chemotherapy who seem to be resistant to taxol therapy. The IC50s of taxol in H32 and H12DDP were approximately 100-fold lower following drug exposure times exceeding 24 hours compared with short exposure times (1-6 h). Dose-dependent anti-tumor activity was observed with taxol in a cisplatin-refractory xenograft model of NSGCT (H23.1), with significant anti-tumor activity observed at a dose of 15 mg/kg/d injected intravenously on days 1 through 5. The results of this study are in accordance with the most recent clinical data which showed that taxol is a useful drug in relapsed or cisplatin-refractory testicular germ cell cancer, with significant anti-tumor activity being observed in 25% of patients, but poor activity in patients previously treated with high-dose therapy. Further pre-clinical research, especially using models such as 1411HP and 1777NRp Cl-A, on the combinations of taxol with other regimens are required to enable successful treatment of the most drug-resistant relapsed germ cell tumors.

Animals↗
PubMed1997

Association of donor-derived host-reactive cytolytic and helper T cells with outcome following alternative donor T cell-depleted bone marrow transplantation.

Recipients of marrow from alternative donors (unrelated or HLA-mismatched related donors) have a higher incidence of post-transplant complications compared to recipients of marrow from HLA-identical siblings. HLA disparity undetected by routine typing techniques has been suggested as one cause for the increased complications observed. Limiting dilution analysis (LDA) of donor-derived, host-reactive T cell precursor frequency prior to transplant has been proposed as a surrogate indicator of underlying HLA disparity which might be used to predict transplant outcome and aid in donor selection. We compared results of LDA of host-reactive IL-2 producing helper T lymphocytes (HTLp) and/or cytolytic T lymphocytes (CTLp) in 77 alternative marrow donor/recipient pairs with transplant outcome using univariate and multivariate analysis. All donor grafts were depleted ex vivo of mature T cells. Median patient age was 15 years (1-53). Donor selection was based on serologic typing for HLA class I and high resolution oligotyping for HLA-DRB1-DRB5, and HLA-DQB1. HLA-A and HLA-B locus antigens were retrospectively defined by one dimensional isoelectric focusing (IEF). Cox proportional hazards regression models were used to assess the impact of frequency and estimated cell dose of CTLp and HTLp on outcome. The CTLp assay was most sensitive to HLA-A and HLA-B locus disparity detected by serology or IEF. The HTLp assay detected class I disparity but was most strongly reactive in the presence of HLA-DRB1 disparity. Univariate analysis indicated a significant association of CTLp frequency and dose with severe (grades 3-4) acute graft-versus-host disease (GVHD), and of CTLp dose with chronic GVHD. Both assays were associated with survival and neither assay was associated with relapse. After adjustment for other significant covariables including known HLA disparity, the association of CTLp with acute GVHD was lost, however, CTLp frequency and CTLp dose remained associated with survival and HTLp frequency was associated with chronic GVHD. These data support the hypothesis that post-BMT complications may be influenced not only by T cell dose but by the alloreactive potential of the cells infused. LDA of alloreactive potential was useful in detecting disparity and in predicting survival or chronic GVHD in recipients of alternative donor TCD marrow grafts.

Adolescent↗
PubMed1997

Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation.

T cell depletion using the murine monoclonal antibody (moAb) T10B9 is unique in that the T cell receptor (TCR)gamma delta bearing subset is relatively spared compared to the TCR alpha beta + subset. We evaluated the probabilities of engraftment, acute and chronic graft-versus-host disease (GVHD), relapse, and survival in 273 recipients of marrow T cell depleted using T10B9. Sixty-two patients received marrow from an HLA-identical sibling, 54 patients received partially matched related donor marrow and 157 patients received unrelated donor marrow. Limiting dilution analysis (LDA) was used to estimate total clonable T cell dose in all patients and a modified LDA using moAb-coated immunomagnetic beads was used to estimate TCR alpha beta +, CD4+, and CD8+ T cells in a subset of patients. TCR gamma delta + cell dose was estimated by flow cytometry. Cox proportional hazards regression models were used to assess the impact of T cell subset dose/kg of body weight on outcome. We found a significant association of TCR gamma delta + T cell dose (P = 0.004), but not TCR alpha beta + T cell dose or total clonable T cell dose, with the probability of engraftment. TCR alpha beta +, CD4+, CD8+ and total clonable T cell dose were significantly associated (P < 0.001) with the risks of grade 2-4 acute GVHD in recipients of marrow from related donors but not in recipients of marrow from unrelated donors. Neither total clonable T cell dose nor any T cell subset dose was found to be significantly associated with chronic GVHD, relapse or survival. The results confirm preclinical studies showing TCR gamma delta + T cells promote engraftment. TCR gamma delta + T cells are not associated with an increased risk of acute GVHD while TCR alpha beta T cells are associated with acute GVHD but not engraftment in recipients of marrow grafts T cell depleted using T10B9. These findings support the hypothesis that T cell subsets differentially contribute to alloengraftment and GVHD.

Adolescent↗
PubMed1997

Analysis of the MHC class I antigen presentation machinery in human embryonal carcinomas: evidence for deficiencies in TAP, LMP and MHC class I expression and their upregulation by IFN-gamma.

The expression of the major histocompatibility complex (MHC) class I antigens is suppressed in early post-implantation embryonic cells as well as in embryonal carcinoma (EC) cells, but could be upregulated by treatment with interferon (IFN)-gamma or retinoic acid. In a number of human and murine tumours, defects in the expression of the different components of the MHC class I antigen processing machinery, such as the proteasomal subunits LMP-2 and LMP-7 and the peptide transporters TAP-1 and TAP-2, account for impaired MHC class I surface expression. Here, we analysed the constitutive and IFN-gamma regulated mRNA and protein expression of the LMP, TAP and MHC class I molecules in the human EC line 577LM. In comparison to lymphoblastoid control cells, poor constitutive mRNA and protein expression of LMP-7, TAP-1, HLA class I, and beta 2-microglobulin, but not of TAP-2 and LMP-2, was detected in 577LM cells. The lack of MHC class I surface expression on 577LM cells could not be enhanced either by culturing cells at low temperature or by their incubation with exogenous MHC class I specific binding peptides: thus, the defective MHC class I surface expression was not only caused by impaired generation and processing of antigenic peptides. IFN-gamma treatment of 577LM resulted in a significant increase of MHC class I surface expression which was preceded by an upregulation of TAP, LMP and MHC class I transcripts as well as of TAP-1 and TAP-2, but not of LMP-2 and LMP-7, protein expression. These data suggest that human EC cell lines show a stable expression of a MHC class I low/deficient phenotype. The deficiencies associated with this phenotype involve different levels of the MHC class I restricted antigen presentation machinery and could be modified by treatment with IFN-gamma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Comparative analysis of cell surface antigens expressed by cell lines derived from human germ cell tumours.

The pattern of cell surface antigen expression of a set of cell lines derived from human germ cell tumours and corresponding to various cell phenotypes found within these tumours was studied using immunofluorescence. Twenty-two different antibodies were used. Many of these antibodies have been noted to recognise epitopes that are either preferentially expressed by embryonal carcinoma (EC) cells, or by more differentiated cell types. Using scatter plots and rank correlations, 6 groups of antibodies were distinguished with respect to their staining patterns on the cell lines tested. Several antibodies showed a specific staining pattern in relation to the differentiation state of the cells. Two groups of antibodies included those recognising high m.w. glycoproteins (antibodies TRA-1-60, TRA-1-81, GCTM2, 3-177, K4 and K21) and the ganglioseries glycolipid antigens SSEA-3 and -4 (antibodies MC631 and MC813-70). These antibodies mostly stained EC cells but not other cell types, confirming previously published data. However, one of these groups, comprising antibodies K4 and MC631, was more exclusively associated with the EC cell phenotype than was the other group. Antibodies recognising the liver isozyme of alkaline phosphatase (TRA-2-49 and TRA-2-54) also reacted strongly with most EC cell lines, although they reacted significantly with a number of other cell lines as well, whereas antibodies to the placental isozyme tended to react only weakly with EC cells. The antibodies recognising the ganglioseries glycolipids GD2 and GD3 (VIN2PB22 and VINIS56) preferentially stained cells with neuroectodermal characteristics. Other antibodies showed a heterogeneous staining pattern for the cell lines with different phenotypes. The data obtained from the cell lines were, in general, similar to data obtained from immunohistochemical studies on tissue sections of primary germ cell tumours of the adult testis, including carcinoma in situ.

Adult↗
PubMed1996

[10 years transplantation of bone marrow and hematopoietic stem cells in adults at the Hannover Medical School].

PATIENTS AND METHODS: From January 1986 until August 1995 230 adult patients received an allogeneic or autologous transplantation of bone marrow or hematopoietic blood stem cells. The conditioning and myeloablative treatment regimens were chosen according to the underlying disease and type of transplant. RESULTS: The observation period comprises 1 to 115 months after transplantation. After allogeneic transplantation from HLA-identical family donors, the probabilities of disease-free survival were for acute myeloid leukemia in first complete remission (CR) (n = 35) 77%, for acute lymphoid leukemia in 1st CR (n = 7) 72% and in 2nd CR (n = 10) 40%, in first chronic phase of chronic myeloid leukemia (n = 34) 50% and in severe aplastic anemia (n = 7) 100%. Following myeloablative therapy and autologous transplantation the probabilities of disease-free survival were 47% in relapsed Hodgkin's disease (n = 22) and 42% for relapsed high-grade non-Hodgkin's lymphoma (n = 12). Eight of 10 patients with acute myeloid and 7 of 8 with acute lymphoid leukemia suffered a leukemic relapse after autologous bone marrow transplantation. Three of 8 patients with relapsed testicular cancer survived relapse-free. Treatment failures were due to more advanced acute graft versus host disease after allogeneic transplantation and caused by relapse after autologous transplantation. Current protocols evaluate the allogeneic transplantation of enriched CD34+ blood stem cells. In chronic myeloid leukemia the autologous transplantation of blood stem cells after myeloablative therapy is being studied.

Adolescent↗
PubMed1996

Unrelated donor bone marrow transplantation to treat severe aplastic anaemia in children and young adults.

Alternative donor bone marrow transplantation (BMT) to treat severe aplastic anaemia (SAA) in children and young adults has been complicated by high rates of graft rejection and severe graft-versus-host disease (GVHD). We hypothesized that increased immunosuppression combined with T-cell depletion of the marrow graft would enable successful use of unrelated donor BMT in this disease. Preconditioning consisted of cytosine arabinoside, cyclophosphamide, and total body irradiation (TBI). T-cell depletion was with the anti-CD3 antibody T10B9. GVHD prophylaxis consisted of cyclosporine A. 28 previously transfused patients were transplanted. Nine donor/recipient pairs were HLA matched. As of 1 January 1996, 15/28 (54%) patients are alive, transfusion independent and well with a range of follow-up of 13 months to 8 years (median 2.75 years). Fatalities include all three patients with nonengraftment and all three patients with grade III/IV GVHD. Other fatalities were due to infections or therapy-related toxicity. The incidence >or= grade II acute GVHD was 28%. These data show that in children with SAA who have failed immunosuppression, unrelated donor BMT offers a reasonable hope of long-term survival.

Adolescent↗
PubMed1996

Amifostine does not alter the antitumor activity of cisplatin in a pre-clinical model of testicular cancer.

Testicular germ cell tumors are so exquisitely sensitive to cisplatin that the majority of patients with this cancer are now cured with modern platinum-based chemotherapy. In contrast to some other tumor types, testicular germ cell tumors are known to express alkaline phosphatases (ALP). Amifostine is an aminothiol pro-drug which is rapidly dephosphorylated by ALP at the ell surface of healthy tissues and which exerts a clinically proven protective effect against chemotherapy associated toxicity. The aim of this pre-clinical study was to assess the potential of amifostine to protect platinum-sensitive non-seminomatous germ cell tumor (NSGCT) nude mouse xenografts established from an ALP-positive embryonal carcinoma (EC) cell line, from the cytotoxicity of cisplatin when both were administered at their individual maximally tolerated doses (MTD). The %T/C values calculated at day 30 for nude mice carrying H12.1 NSGCT xenografts treated with amifostine alone, amifostine plus cisplatin or cisplatin alone were, respectively, 93, 3 or 3%. Mean tumor volumes were not significantly different between mice treated with the combination versus cisplatin alone at day 14 or 30. The results of this study revealed no evidence of tumor protection by amifostine, confirming previous results in other tumor types.

Adult↗
PubMed1996

Management of other non-cisplatin-induced emesis.

A number of non-cisplatin cytotoxic regimens induce moderate to severe nausea and emesis. Moreover, the majority of these regimens are given to outpatients where an effective, well-tolerated anti-emetic therapy is particularly important to maintain patients' well-being. This review focuses on the management of nausea and emesis induced by non-cisplatin chemotherapy particularly regimens that do not contain cyclophosphamide or carboplatin, as these are reviewed elsewhere in this volume. For patients receiving highly emetogenic cytotoxic therapy such as dacarbazine, total body irradiation or hemi-body irradiation, a 5-HT3 receptor antagonist plus a corticosteroid may provide optimal control of emesis and nausea. High-dose single-fraction and fractionated radiotherapy to the upper abdomen induces moderate emesis. Traditional anti-emetics prevent emesis in approximately 50% of patients; 5-HT3 receptor antagonists provide a more effective anti-emetic therapy for these patients. Studies evaluating anti-emetics in specific chemotherapy regimens will give clear guidelines for the management of emesis in different patient populations.

Antiemetics↗
PubMed1995

Combined transplantation of allogeneic bone marrow and CD34+ blood cells.

Allogeneic peripheral blood progenitor cells (PBPCs) were transplanted after immunoselection of CD34+ cells. Two patient groups were studied: group I patients received immunoselected blood CD34+ cells and unmanipulated marrow cells from the same donor. Group II patients were given immunoselected blood and bone marrow (BM) CD34+ cells. One to 6 weeks before bone marrow transplantation (BMT), PBPCs from HLA-identical and MLC- sibling donors were mobilized with granulocyte colony-stimulating factor (G-CSF) (5 micrograms/kg twice daily subcutaneously) for 5 days. Aphereses were performed at days 4 and 5 of G-CSF application. CD34+ cells were separated from the pooled PBPC concentrates by immunoadsorption onto avidin with the biotinylated anti-CD34 monoclonal antibody 12.8 and then stored in liquid nitrogen. BM was procured on the day of transplantation. Patients were conditioned with either busulfan (16 mg/kg) or total body irradiation (12 Gy) followed by cyclophosphamide (120 mg/kg). Cyclosporin A and short methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. After transplantation, all patients received 5 micrograms G-CSF/kg/d from day 1 until greater than 500 neutrophils/microL were reached and 150 U erythropoietin/kg/d from day 7 until erythrocyte transfusion independence for 7 days. Group I consisted of patients with acute myeloid leukemia (AML) (n = 2), chronic myeloid leukemia (CML) (n = 2), and T-gamma-lymphoproliferative syndrome and BM aplasia (n = 1). The patients received a mean of 3.3 x 10(6) CD34+ and 3.7 x 10(5) CD3+ cells/kg body weight of PBPC origin and 4.5 x 10(6) CD34+ and 172 x 10(5) cells/kg body weight of BM origin. Group II consisted of five patients (two AML, two CML, one non-Hodgkin's lymphoma). They received a mean of 3.3 x 10(6) CD34+ and 3.2 x 10(5) CD3+ cells/kg from PBPC and 1.4 x 10(6) CD34+ and 0.6 x 10(5) CD3+ cells from BM. A matched historical control group (n = 12) transplanted with a mean of 5.2 x 10(6) CD34+ and 156 x 10(5) CD3+ cells/kg from BM alone was assembled for comparison. In group I, the median time to neutrophil recovery to > 100, > 500, and > 1,000/microL was 12, 15, and 17 days, respectively. Patients from group II reached these neutrophil levels at days 13, 15 and 17 post BMT. Neutrophil recovery in the control patient group occurred at days 17, 18, and 20 respectively. Group I patients were given platelet transfusions within 18 days and red blood cells within 10 days, whereas for group II patients, these time points were 26 and 17 days, respectively. These same transfusions could be ceased within 38 and 24 days, respectively, in control patients. The addition of about 2% more peripheral blood CD3+ cells (group I patients) did not result in higher grades of acute GVHD (median grade II) as compared with the controls (median grade II). Four of five group II patients showed no signs of acute GVHD. These data suggest that the addition of immunoselected allogeneic CD34+ progenitor cells to BM cells may accelerate hematopoietic recovery.

Adult↗
PubMed1995

Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia.

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.

Actuarial Analysis↗
PubMed1995

Physiological characteristics of the supported singing voice. A preliminary study.

The purpose of this study was to develop a definition of the supported singing voice based on physiological characteristics by comparing the subjects' concepts of a supported voice with objective measurements of their supported and unsupported voice. This preliminary report presents findings based on data from eight classically trained singers. Subjects answered questions about their concepts of the characteristics of the supported singing voice and how it is produced. Samples of the supported and unsupported singing voice produced at low, medium, and high pitches at a comfortable loudness level were collected for acoustic, spectral, airflow, electroglottographic, air volume, and stroboscopic analyses. Significant differences between the supported and unsupported voice were found for sound pressure level (SPL), peak airflow, subglottal pressure (Ps), glottal open time, and frequency of the fourth formant (F4). Mean flow and F2 frequency differences were sex and pitch related. Males adjusted laryngeal configuration to produce supported voice, whereas glottal configuration differences were greater in females. Breathing patterns were variable and not significantly different between supported and unsupported voice. Subjects in this study believe that the supported singing voice is resonant, clear, and easy to manage and is produced by correct breath management. Results of data analysis show that the supported singing voice has different spectral characteristics from and higher SPL, peak airflow, and Ps than the unsupported voice. Singers adjust laryngeal and/or glottal configuration to account for these changes, but no significant differences in breathing activity were found.

Acoustics↗
PubMed1995

Stroboscopic signs associated with benign lesions of the vocal folds.

Stroboscopic signs were systematically rated for a group of 80 patients with benign vocal fold lesions, most of whom had either a nodule or a polyp. Each group revealed a characteristic pattern of ranking of signs and exhibited differences of most predominant signs. The results of the ratings were submitted to a multiple discriminant analysis to determine if post hoc stroboscopic ratings could be used to correctly classify patients into one of four diagnostic groups and into one of two treatment groups. All patients except one were correctly classified into the diagnostic groups, and all were correctly classified into the treatment groups. The important signs for classifying patients into the diagnostic groups were roughness of the edge of the affected vocal fold, phase closure pattern, and phase symmetry. The important signs for classifying patients into the treatment groups were roughness of the edge of the affected vocal fold, glottal closure configuration, and vibration characteristics of the affected (or more affected) vocal fold. The results suggest that objective evaluation of stroboscopic examinations can be valuable in correctly diagnosing patients and in selecting the proper treatment regimen for the patient.

Cysts↗
PubMed1995

Endoscopic microsuture repair of vocal fold defects.

The presence of a nonvibratory segment of vocal folds after microlaryngeal surgery is often a cause of poor voice result. The etiology of a nonvibratory segment is due to full thickness epithelial defect followed by secondary wound closure and scar contracture. To reduce scar contracture and nonvibratory segment of the vocal folds, primary repair with a 6-0 chromic endo-knot suture technique was used to close defects and approximate microflaps of the vocal folds. This was done in 18 patients with epithelial defects after resection of benign vocal fold lesions. The pathologic findings included severe polypoid degeneration (n = 7), fusiform laryngeal polyps (n = 5), sulcus vocalis (n = 2), cyst (n = 2), and keratosis (n = 2). Voice was improved in all patients after surgery. Comparison of vocal fold vibration before and after surgery showed improvements in configuration, amplitude, and mucosal wave. Vocal folds that were sutured all had good vibratory characteristics; none had a nonvibrating segment at the site of suture placement. Voice and healing after microsuture technique were near normal by Day 10 and return of mucosal wave was often complete by Day 14. Endoscopic microsuture closure of microflaps of the vocal folds edge is safe and affords the surgeon an opportunity for primary repair with improved functional result.

Endoscopy↗
PubMed1994

Glycolipids of germ cell tumors: extended globo-series glycolipids are a hallmark of human embryonal carcinoma cells.

Glycolipids of human germ cell tumor lines were analyzed to define the most common immunohistochemical profiles of embryonal carcinoma (EC), differentiated derivatives of EC, yolk sac carcinoma (YC) and choriocarcinoma (CC). Glycolipid composition was examined by high-performance thin-layer chromatography (HPTLC) combined with immunostaining with a panel of anti-carbohydrate monoclonal antibodies (MAbs). All EC cell lines were found to contain high levels of globo-series glycolipids, including globotriosylceramide (Gb3), globoside (Gb4), Gb5 (Gal beta 1-->3Gb4) and GL7 (sialyl Gal beta 1-->3Gb4). Somatic differentiated derivatives (e.g., EC cells treated with retinoic acid) contained decreased levels of globo-series glycolipids and increased levels of lacto- and ganglio-series glycolipids, including GD3, GT3 and GD2. CC cell lines contained relatively large amounts of Gb3 but did not contain extended globo-series glycolipids Gb5 and GL7. CC cell lines also contained a macroglycolipid reactive with the antibody to SSEA-1 (Lex). Glycolipids were not detected in two YC cell lines, while other YC cell lines contained globo-series core glycolipids (Gb3 and Gb4) and gangliosides. We conclude that EC, YC and CC have distinct patterns of membrane glycolipid expression that can be identified by HPTLC and immunostaining. Our results indicate that globo-series glycolipids Gb5 and GL7, which carry stage-specific embryonic antigens 3 and 4 (SSEA-3 and SSEA-4), are a hallmark of human EC cells. Cell lines derived from human germ cell tumors that do not express Gb5 and GL7 deserve to be re-evaluated, since they may represent different stem cells, most likely equivalent to somatic cells and their developmentally committed precursors (e.g., neuroblasts).

Biomarkers, Tumor↗
PubMed1994

Efficacy of fluorescence in situ hybridization for detecting PML/RARA gene fusion in treated and untreated acute promyelocytic leukemia.

OBJECTIVE: To test the efficacy of fluorescence in situ hybridization (FISH) for detection of fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARA) genes in patients with treated or untreated acute promyelocytic leukemia (APL). DESIGN: We conducted a retrospective blind study on a series of stored bone marrow specimens from normal subjects and patients with APL. MATERIAL AND METHODS: Conventional cytogenetic and FISH analyses were done on interphase and metaphase cells in specimens from 31 normal subjects and 19 patients with untreated or treated APL. RESULTS: From 25 of the normal specimens, we calculated a normal cutoff of 10% for interphase cells and 0% for metaphase cells. With use of these criteria, the other six specimens from normal subjects showed normal findings, and each of the seven specimens from patients with untreated APL was abnormal by FISH analysis. The specimens from four patients in clinical relapse or with residual APL were abnormal. Of the eight specimens from patients in clinical remission, three were abnormal; two of these patients had a relapse within 8 months, and the other patient had received 1 month of chemotherapy and was entering remission. Of the other five patients in remission, four had normal FISH results and have now been in remission for 2.5 to 10 years. The other patient in remission with normal FISH results had a relapse within 6 months. PML/RARA fusion was detectable in three patients with hypogranular APL and in three with a cytogenetic variant of the t(15;17). CONCLUSION: The results of this study suggest that FISH with PML and RARA probes can be used to diagnose APL and may be useful for monitoring treated patients.

Antineoplastic Agents↗