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Biomedical subjects

R Dummer

Publications and source records attributed to R Dummer.

At least 73 records · Page 4Linked to original sources
PubMed2001

Expression of TCL1 in hematologic disorders.

OBJECTIVE: TCL1, MTCP1 and TCL1b are three members of a new family of oncogenes that are expressed in T cell leukemias of ataxia telangiectasia patients (T-PLL, T-CLL). TCL1 is located at 14q32.1 and activated by juxtaposition to the alpha/delta-locus at 14q11 or beta-locus at 7q35 of the T cell receptor during the reciprocal translocations t(14;14)(q11;q32), t(7;14)(q35;q32), or inversion inv(14)(q11;q32). TCL1 encodes a predominantly cytoplasmic protein of 114 aa (14 kD) of unknown function. Recent studies suggest that TCL1 promotes cell survival rather than stimulating cell proliferation, as previously proposed. METHODS: In an attempt to clarify the contexts in which TCL1 is expressed, we investigated TCL1 expression in 114 lymphoma and leukemia patients by Northern blot, RT-PCR and immunohistochemistry. RESULTS: TCL1 expression is restricted to lymphoid cells, and is found in neoplastic (T and B cell neoplasms, and Hodgkin's disease) and nonneoplastic proliferations (reactive lesions). Out of 114 cases, 18 neoplasms of myeloid and 4 cases of epithelial origin were TCL1-negative. In lesions of the lymphoid system, both low- and high-grade lymphomas were found to express TCL1. CONCLUSIONS: We propose that TCL1 expression especially in high-grade B cell non-Hodgkin's lymphomas might interfere with B cell differentiation and promote the transition from low- to high-grade lymphoma.

Blotting, Northern↗
PubMed2001

Skin cancers in organ transplant recipients: two cases of virus-induced neoplasms.

Immunosuppression profoundly influences the prevalence of skin disorders in transplant recipients. Skin tumors occur with high incidence and constitute a major part of transplantation-related morbidity and mortality. We report on 2 immunosuppressed patients presenting with rapidly growing epithelial and mesenchymal neoplasms after renal transplantation. The diagnostic approach, differential diagnosis and treatment options are discussed emphasizing the characteristics of cutaneous lesions in immunosuppressed transplant recipients.

Adult↗
PubMed2001

Swiss guidelines for the treatment and follow-up of cutaneous melanoma.

Melanoma is the most common lethal cutaneous neoplasm. There is major controversy over the best management of this malignancy. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated. They have been approved by all Swiss medical societies involved in the care of melanoma patients.

Continuity of Patient Care↗
PubMed2001

GVAX (Cell Genesys).

Cell Genesys (formerly Somatix Therapy Corp) is developing GVAX as a potential cancer vaccine for various tumor types. Clinical trials have commenced for melanoma, renal tumor, lung tumor, pancreatic tumor, prostate tumor and multiple myeloma [191143], [287470], [298308], [367408], [401114]; trials are planned for 2001 in leukemia (phase I) and pancreatic cancer (phase II) [366918], [388814]. A worldwide collaboration was signed with Japan Tobacco in December 1998, covering the application of GVAX in prostate cancer trials [312213]. This collaboration may be extended to lung cancer and melanoma, depending on the clinical trial results for prostate cancer [309873], [311835]. The Japanese clinical trials were put on hold on 21 September 2000 due to problems with the mass production of cells by Cell Genesys [384885]. Somatix was developing GVAX until its merger with Cell Genesys in June 1997 [248422]. In April 2001, Cell Genesys initiated the first in a series of trials of a high-potency version of GVAX prostate cancer vaccine following encouraging phase II data reported for its first-generation product. The high-potency form of GVAX is similar to the first-generation product except that it releases an increased quantity of immune system stimulant [405932].

Animals↗
PubMed2000

Reduction of tumor burden and stabilization of disease by systemic therapy with anti-CD20 antibody (rituximab) in patients with primary cutaneous B-cell lymphoma.

BACKGROUND: Primary cutaneous B-cell lymphoma (CBCL) is characterized by restriction to the skin, a high incidence of recurrence after various treatment modalities, and a variable but mostly favorable prognosis. METHODS: Ten patients with long standing primary CBCL (3 with follicular CBCL, 5 with cutaneous, large B-cell lymphoma, 1 with diffuse large cell lymphoma, and 1 with extranodal large cell lymphoma) were treated by intravenous application of a chimeric antibody against the CD20 transmembrane antigen that is present on malignant and normal B-cells. In 6 of 10 patients, several treatment attempts either had failed or could not be used due to severe side effects or underlying disease. RESULTS: The treatment regimen resulted in two complete regressions, five partial responses, and one mixed response, and two patients did not respond to the treatment. No severe side effects occurred, except for slight pain in the nodules after infusion and an urticarial reaction at the tumor sites. A prolonged, complete disappearance of B-cells from the peripheral blood was observed. The immunoglobulin serum levels and inflammatory markers were unchanged. Histologic examination of biopsies from two regressing tumor nodes showed necrotic tumor cells and infiltration with CD8 positive cells. CONCLUSIONS: Intravenous therapy with the anti-CD20 antibody rituximab is a nontoxic and effective treatment for patients with primary cutaneous B-cell lymphoma.

Adult↗
PubMed2000

[Immuno-intervention in cutaneous lymphomas].

Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders. Most of the cutaneous lymphomas present a rather good prognosis because they disseminate to internal organs late in the disease process, if at all. Since radiotherapy and intensive chemotherapy have limited efficacy, immunological interventions are regularly used in this disease group. These interventions include unspecific treatment modalities such as Interferon-alpha, Interleukin-2, but also rather specific interventions like photopheresis, fusion toxins and as a new development, antigen-loaded dendritic cells. A new humanized anti CD20-antibody can be used for patients with cutaneous B-cell lymphomas, expressing the B-cell antigen CD20 in most of the cases. We expect that new information on the immunobiology of these diseases will allow more specific immunological interventions, providing the basis for a better therapy with optimal tolerability for patients suffering from cutaneous lymphomas.

Humans↗
PubMed2000

Intralesional therapy with anti-CD20 monoclonal antibody rituximab in primary cutaneous B-cell lymphoma.

BACKGROUND: We report the use of a new treatment modality in 2 patients with primary cutaneous B-cell lymphoma. In a 58-year-old woman with progressive nodular lesions on the scalp and face, several treatment attempts either failed or could not be used because of severe adverse effects and underlying epilepsy. The patient declined radiotherapy. A 30-year-old man presented with recurrence of tumor nodules occipitally, thoracically, on the arm, and on the right thigh after several excisions. OBSERVATIONS: Intralesional injection of rituximab, a chimeric antibody directed against the CD20 transmembrane antigen present in malignant and normal B cells, resulted in partial regression of tumor nodules. No adverse effects occurred except pain during or shortly after injection and, in one patient, a slight rise in body temperature. Due to the treatment a prolonged complete disappearance of B cells from peripheral blood samples was observed. CONCLUSION: Intralesional rituximab therapy is a nontoxic and effective treatment for cutaneous B-cell lymphoma that deserves further investigation in larger clinical trials.

Adult↗
PubMed2000

Pathogenesis of cutaneous lymphomas.

Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders derived from T cells, B cells and, in rare cases, natural killer cells. The precise mechanisms of the lymphomagenesis are still obscure. However, there are various factors involved. These factors include environmental, especially infectious factors, translocations, mutations and genetic instability. The special microenvironment in the skin is responsible for the peculiar behavior of these neoplasms by providing various key factors, such as adhesion molecules and cytokines. Newly identified molecular disturbances in cutaneous lymphomas might be targeted by specific molecular or immunologic interventions in the future.

Cell Transformation, Neoplastic↗
PubMed2000

Allelic deletion at 9p21-22 in primary cutaneous CD30(+) large cell lymphoma.

The genetic alterations responsible for the development of cutaneous lymphoma are largely unknown. Chromosome region 9p21 contains a gene locus encoding an inhibitor of cyclin-dependent kinase 4, and heterozygous deletions of this tumor suppressor gene (p16) have been shown in a variety of malignant tumors. We studied 11 randomly selected cutaneous CD30-positive large cell lymphomas. Several areas containing 20-50 CD30-positive lymphocytes were microdissected in each case and subjected to single-step DNA extraction. Loss of heterozygosity analysis was performed using polymorphic markers at 9p21 (IFNA, D9S171, D9S169) and 17p13 (TP53). Samples from normal cells apart from CD30-positive lymphocytes, e.g., CD30-negative lymphohistiocytic infiltrates and normal epidermal layer, were also obtained in all cases from the same slide for comparison with the tumor samples. Expression of CD30 and T-lineage antigens (CD3, CD45Ro) was confirmed in all cases. Immunohistochemical staining for p16 and p53 was performed using the monoclonal antibodies sc-1661 and DO-7, respectively. Of the 11 informative cases, seven (64%) exhibited loss of heterozygosity at least for one marker at 9p21 (p16), whereas no allelic deletions were found for the polymorphic marker at 17p13 (p53). On immunohistochemistry loss of the p16 protein was detected in two of 11 cases. Nuclear staining for p53 protein was found in four of 11 cases. Here, we provide the first evidence of the involvement of the tumor suppressor gene p16 in primary cutaneous large cell lymphoma. Whether p16 deletion in these lymphomas is associated with disease progression and whether this method could serve as an early marker to detect lymphomas at an early stage needs to be addressed in future studies. J Invest Dermatol 115:1104-1107 2000

Adult↗
PubMed2000

Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was carried out in patients with metastatic melanoma or breast cancer with increased p53 protein immunoreactivity in pretreatment tumor biopsies. The biological activity of the injected wt p53 was assayed by reverse transcriptase-polymerase chain reaction in tumor tissue. A total of six (five melanoma and one breast adenocarcinoma) patients were treated at dose levels dependent upon tumor size/dose escalation sequence. Five of six patients became positive for the transfer of wt p53 into tumor tissue 2 days after injection of the vector. Of the four patients assayed, all developed anti-adenoviral antibodies. Adverse reactions associated with i.t. injection were mild, with no obvious correlation between the incidence, severity, or relationship of the events and drug dose. p53 gene therapy by i.t. injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective (with respect to transduction frequency) in patients with either metastatic melanoma or breast cancer.

Adenocarcinoma↗
PubMed2000

CD4 + /CD7- T cell frequency and polymerase chain reaction-based clonality assay correlate with stage in cutaneous T cell lymphomas.

In cutaneous T cell lymphomas, tumor cells can be found in skin and in other compartments. A precise definition of extracutaneous spread including blood involvement is necessary for staging and treatment design. We investigated peripheral blood in 51 patients with various types of cutaneous T cell lymphomas by the analysis of blood smears for Sézary cells, the CD4 + /CD7- T helper cell frequency in the peripheral blood by fluorescence activated cell sorter analysis and by polymerase chain reaction for the T cell receptor gamma-chain followed by denaturing gradient gel electrophoresis. Eleven polymerase chain reaction products were sequenced. Thirty-five per cent of patients with stage Ia-IIb cutaneous T cell lymphomas presented a peripheral blood T cell clone. In patients with stage III-IVb cutaneous T cell lymphomas 75% were positive for clonality in the peripheral blood by polymerase chain reaction. Interestingly, three of 13 Sézary patients showed a TCR-gamma joining region pseudogene (JgammaP1/JgammaP2) usage. CD4 + /CD7- cell counts were significantly higher in patients with advanced cutaneous T cell lymphomas than in patients with early cutaneous T cell lymphomas. There was a correlation between increased percentage of circulating CD4 + /CD7- cells and detection of clonality by polymerase chain reaction (p = 0.001). There was no significant correlation between the polymerase chain reaction data and the percentage of Sézary cells on blood smears. A significant correlation between CD4 + /CD7- cells and Sézary cells was found, however. Stepwise logistic regression analysis showed that the CD4 + /CD7- cell count and clonal T cell detection in peripheral blood are independently correlated with stage. The combination of both parameters gives more information than each one separately. In conclusion, our data indicate that fluorescence activated cell sorter analysis of peripheral blood and polymerase chain reaction-based clonality assays can improve the accuracy of staging investigations in cutaneous T cell lymphomas patients.

Antigens, CD7↗
PubMed2000

Upregulation of interleukin-12 receptor on peripheral blood mononuclear cells and HLA class I, HLA class II or ICAM-1 on melanoma cells by B7.1 and interleukin-12: a mechanism for immunostimulatory impact of melanoma cells adenovirally transfected with B7.1 and IL12?

Melanoma is an immunogenic tumour and may express both HLA class I and class II molecules. These can be recognized by cytotoxic T-cells. Melanoma cells can evade immunosurveillance due to the lack of co-stimulatory molecules such as B7.1 or B7.2. Interleukin-12 (IL12) exerts antitumour effects, and B7.1 and IL12 synergistically induce effective antitumour immunity. We investigated the immunostimulatory potential of melanoma cells adenovirally transduced with B7.1, IL12 or B7.1 plus IL12. We observed that: (i) melanoma cells transduced with B7.1 plus IL12 can elicit a strong proliferative response from peripheral blood mononuclear cells (PBMCs); (ii) a high level of TH1 cytokine production from PBMCs was induced by melanoma cells transduced with Adv-B7.1 plus Adv-IL12; (iii) the expression of HLA class I antigens, HLA class II antigens or ICAM-1 antigens was higher on melanoma cells transduced with Adv-lL12 or Adv-B7.1 plus IL12 than those transduced with Adv-LacZ or wild-type melanoma cells; and (iv) the expression of IL12 receptors on PBMCs was upregulated by melanoma cells transfected with Adv-IL12 or Adv-B7.1 plus IL12. Thus, melanoma cells transduced with both Adv-lL12 and B7.1 may represent another clinical approach for antimelanoma gene therapy.

Adenoviridae↗