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Biomedical subjects

M V Seiden

Publications and source records attributed to M V Seiden.

At least 19 recordsLinked to original sources
PubMed1999

TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line.

The mechanisms responsible for the development of the taxol resistance phenotype are unclear, and are likely explained by multiple mechanisms. To understand the molecular changes associated with drug resistance more fully, a taxol-resistant subline, derived from the human ovarian cancer cell line SKOV-3, was established through selection by culture in incrementally increasing taxol concentrations. Comparison of SKOV-3 to SKOV-3TR by differential display identifies a new gene, TRAG-3 (Taxol Resistance Associated Gene- 3). In comparison to the parental line, SKOV-3, TRAG-3 mRNA is overexpressed in the taxol-resistant cell line SKOV-3TR. The nucleotide sequence of the TRAG-3 cDNA contains an open reading frame of 333bp that predicts for a protein product of 110 amino acids. A GenBank search identifies a cosmid clone containing a genomic sequence corresponding to that of TRAG-3. DNA and protein analysis reveals that TRAG-3 has no homology to any known cDNAs or proteins. Northern analysis demonstrates that TRAG-3 is overexpressed in the taxol-resistant breast cancer cell line MDA 435TR as well as the doxorubicin-resistant multiple myeloma cell lines 8226/DOX40 and 8226/MDR10V. A survey of normal tissue shows minimal or absent TRAG-3 mRNA expression. Screening of a wide variety of cancer cell lines demonstrates TRAG-3 expression in many cell lines derived from different tissue types. In summary, TRAG-3 is a novel gene whose expression is associated with the chemotherapy-resistant and neoplastic phenotype.

Amino Acid Sequence↗
PubMed1999

High dose chemotherapeutic strategies in the treatment of epithelial ovarian carcinoma.

High dose chemotherapy with stem cell rescue has been used in an attempt to overcome chemotherapy resistance and increase survival in patients with poor prognosis epithelial ovarian cancer. Untreated patients with advanced stage disease and those with chemosensitive recurrent disease do better in terms of response rates as well as duration of response and overall survival. Newer strategies using multiple cycles of dose intense therapy may improve results although it will be difficult to document changes in the natural history of advanced ovarian cancer without the completion of randomized phase III trials.

Antineoplastic Agents↗
PubMed1998

Ovarian cancer: an update on genetics and therapy.

This article reviews the important aspects of the management of both early and advanced ovarian cancer with a particular emphasis on genetic predisposition and recent and anticipated advances in treatment.

Combined Modality Therapy↗
PubMed1996

Stem cell purging ex vivo.

Over the last several years there has been significant progress in developing several techniques designed to detect contaminating tumor cells in bone marrow (BM) and peripheral blood progenitor cells (PBPC). These techniques include immunohistochemistry, in situ hybridization (ISH), flow cytometry, clonogenic tumor assays, and polymerase chain reaction (PCR) based assays. These assays have detection capabilities ranging from 1 tumor cell in 100 normal cells (ISH) to 1 tumor cell in a million tumor cells (RT-PCR). These techniques have confirmed that BM and PBPC are frequently contaminated with tumor cells, with most studies suggesting higher tumor contamination in the BM as compared to the PBPC. Comparison of immunocytochemistry with the clonogenic assay has demonstrated good but not perfect correlation of these two techniques. Gene marking studies have confirmed that these tumor cells are viable and capable of contributing to disease relapse. Many of the assays are at least semiquantitative and are effective at monitoring for persistent residual tumor cell contamination after ex vivo processing of autografts including purging strategies and/or positive selection techniques. Preliminary data are conflicting, although some data suggest that patients receiving autografts with residual tumor cell contamination do worse than patients receiving autografts free of detectable tumor cells. Many purging techniques are capable of reducing tumor contamination by 3 to 5 logs; positive selection techniques are probably slightly less effective, reducing tumor contamination by 3 to 4 logs. The clinical benefit of purging remains to be demonstrated in randomized clinical trials.

Blood Component Removal↗
PubMed1995

Lymphomagenesis in the SCID-hu mouse involves abundant production of human interleukin-10.

Both human (hu) and viral (v) interleukin-10 (IL-10) appear to be important cofactors in the survival and growth of lymphoblastoid cell lines infected with Epstein-Barr virus (EBV). When mice with severe combined immune deficiency (SCID) are injected with human peripheral blood lymphocytes (PBL) from normal individuals who are seropositive for EBV, the majority of hu-PBL-SCID mice will develop an EBV-associated lymphoproliferative disease (EBV-LPD) of human B-cell origin, not unlike some cases of EBV-LPD that are seen in immunocompromised individuals. The role of huIL-10 or vIL-10 in this chimeric mouse model of EBV-LPD is unknown. In the present study, we show that hu-PBL-SCID mice that develop EBV-LPD have significant elevation of serum huIL-10 levels compared with mice that do not develop EBV-LPD (P = .005). vIL-10 was undetectable in all animals. The EBV+ tumor samples express transcript for huIL-10 and huIL-10 receptor, express huIL-10 protein by immunohistochemical staining, and show specific binding of recombinant (r) huIL-10. In vitro analysis of the functional consequences of rhuIL-10 binding to IL-10 receptors on fresh EBV+ tumor cells shows that rhuIL-10 can prevent programmed cell death as well as promote proliferation and can do so at concentrations of huIL-10 found in vivo. Thus, huIL-10 production by EBV+ tumor cells may contribute directly to their malignant outgrowth in the hu-PBL-SCID mouse by two autocrine mechanisms: prevention of programmed cell death and proliferation. The implications of such findings with regard to EBV-LPD in humans is discussed.

Animals↗
PubMed1995

Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma.

This report describes the clinical characteristics, treatment associated toxicity, and follow-up of fifty-eight patients with plasma cell--dyscrasias treated with high dose chemotherapy and total body irradiation (TBI) at a single institution. Following TBI, 36 patients received anti-B cell monoclonal antibody (MoAb)-treated autologous bone marrow, 21 patients received anti-CD6 cell MoAb-treated allogeneic bone marrow to deplete T cells, and one patient received unpurged bone marrow from a syngeneic donor. Evaluation after high dose chemotherapy and bone marrow transplantation (BMT) demonstrated 26 complete responses (CR), 26 partial responses (PR), 2 non-responders, 1 not yet evaluated, and three toxic deaths. Fourteen of 36 patients who underwent autologous BMT are alive free from progression at 18 (range 5 to 68) months post transplant (post-BMT); of these, 11 remain in continuous complete response at 16 (range 5 to 68) months post-BMT. Seven of 21 patients who underwent allogeneic BMT are alive free from progression at 30 (range 4 to 44) months post-BMT; of these, three patients remain in continuous complete response at 43 (range 33 to 45) months post-BMT. These data suggest that high dose chemotherapy with TBI followed by MoAb purged BM can be performed with acceptable toxicity and high tumor response rates.

Adult↗
PubMed1994

Multiple myeloma.

The mortality associated with multiple myeloma is due to the progressive accumulation of a clonal population of plasma cells in the bone marrow. Tumor cells may also be found in the blood and other extramedullary sites, especially in the terminal stages of the disease. During disease progression, numerous effects lead to significant morbidity, including immunosuppression, increased bone turnover, anemia, and renal deterioration. For more than two decades it has been realized that chemotherapy and radiotherapy could provide effective temporary relief from the pain and suffering associated with this malignancy. Unfortunately, these benefits are usually short lived, and essentially all patients experience recurrent disease that is usually refractory to additional therapy.

Chromosome Aberrations↗
PubMed1994

Detection of circulating tumor cells in men with localized prostate cancer.

PURPOSE: Using prostate-specific antigen (PSA) mRNA as a marker for prostatic epithelial cells, we have developed a sensitive technique that involves reverse transcription and polymerase chain reaction (RT-PCR) to detect circulating tumor cells in the peripheral blood of men with prostatic carcinoma (CaP). PATIENTS AND METHODS: A sensitive RT-PCR assay was used to evaluate the peripheral blood of 135 men with a history of CaP. Fourteen men with benign prostate disease, many of whom had elevated serum PSA levels, were used as a control group. RESULTS: All patients with benign prostate disease had a negative result in the RT-PCR assay. Of particular interest was a subgroup of 65 patients with clinically localized CaP evaluated before definitive local therapy. Five of these patients had detectable PSA mRNA by RT-PCR, suggesting circulating tumor cells. Within this group, systemic disease was detected by RT-PCR in some men with PSA levels less than 10 ng/mL and clinical stage B disease. Blood from men with hormone-refractory and progressive CaP demonstrated a higher frequency of PSA mRNA detectable by RT-PCR (10 of 20 patients). In contrast, none of seven patients with newly diagnosed metastatic prostate cancer and only one of seven patients with metastatic, hormone-responsive disease had blood that was positive for PSA mRNA by RT-PCR. CONCLUSION: Circulating tumor cells can be detected in the blood of a subset of patients with clinically localized CaP and a larger subset of patients with progressive metastatic disease.

Base Sequence↗
PubMed1993

Molecular genetic analysis of post-transplant lymphoproliferative disorders.

Lymphoproliferative disorders developing in the post-transplant setting are a devastating set of diseases with major implications for the patients who develop them. On the other hand, they have provided us with an opportunity to better understand the basic biology of these disorders and malignant lymphomas in general. Molecular gene rearrangement studies and the Epstein-Barr virus, which is found in the genome of most of the abnormal lymphocytes in these disorders, have been investigated to further our understanding of the development and progression of these diseases.

Gene Rearrangement↗
PubMed1992

Pulmonary toxicity associated with high dose chemotherapy in the treatment of solid tumors with autologous marrow transplant: an analysis of four chemotherapy regimens.

We retrospectively reviewed the pulmonary toxicity of six high dose chemotherapy protocols using four chemotherapy regimens in the treatment of solid tumors. All protocols used either high dose cyclophosphamide or ifosfamide in combination with one to three additional chemotherapeutic agents. In each protocol autologous bone marrow was reinfused post chemotherapy to shorten the period of severe myelosuppression. Of 178 patients there were 20 cases of fatal or life-threatening pulmonary toxicity including nine cases of pneumonia, nine cases of interstitial pneumonitis and two cases of pulmonary hemorrhage. Pulmonary function tests revealed modest changes in FEV1 and DLCO in the majority of patients, although 24 patients had more dramatic changes in DLCO suggesting interstitial damage. Significant decrements in FEV1 were seen in the BCNU containing regimen. Statistically significant or nearly significant decreases in DLCO were seen after all cyclophosphamide containing regimens. A regimen containing ifosfamide, carboplatin, and etoposide had minimal associated pulmonary toxicity.

Adolescent↗
PubMed1990

Vasculitis with recurrent pulmonary hemorrhage in a long-term survivor after autologous bone marrow transplantation.

We report an unusual vasculitic syndrome in a long-term survivor of autologous bone marrow transplant. Clinical and pathologic studies revealed a cutaneous and pulmonary leukocytoclastic vasculitis complicated by recurrent pulmonary hemorrhage. Serologic studies revealed an elevated anti-neutrophil cytoplasmic antibody titer. The vasculitis has been successfully controlled with prednisone, cyclophosphamide, and trimethoprim/sulfamethoxazole.

Adult↗
PubMed1986

JH1 peptide induces antibodies to a common immunoglobulin determinant as detected by cell-binding analysis.

In order to more accurately determine the distribution of antigenic determinants detected by antisera to hypervariable-region and JH1 peptides, we measured the frequency of lymphocytes stained with these sera by flow cytometry. None of the sera specific for HV1, HV2 or HV3 peptides stained significant numbers of lymphocytes, but those specific for JH1 reacted with nearly all B-cells.

Animals↗
PubMed1986

Hypervariable region peptides variably induce specific anti-idiotypic antibodies: an approach to determining antigenic dominance.

Rats and rabbits were immunized with synthetic peptides corresponding to the VH hypervariable regions of several alpha (1----3) dextran-specific antibodies from mice to study the efficacy of synthetic peptides in the generation of site-specific anti-idiotypic reagents. Synthetic peptides were made which corresponded to the HV1, HV2, and HV3 hypervariable regions of the heavy chain of M104 (IdX+, IdI-(M104)+), HV2 of HDex 14 (IdX-), and HV3 of J558 (IdX+, IdI(J558)+). The HV1(M104) peptide sequence is found in all dextran-specific immunoglobulins examined and the HV2 and the HV3 peptides span the regions implicated in IdX and IdI expression, respectively. Sera from many rabbits and rats indicate that all five peptides are immunogenic. Antisera to HV3 peptides show excellent binding to the appropriate myeloma proteins, with antisera to the HV3(M104) peptide demonstrating little binding to proteins that differ in HV3 sequence. Antisera generated against HV1(M104) and both HV2 peptides show weak cross-reaction to the appropriate proteins; however, these sera are not idiotypic because they cross-react with immunoglobulins with very limited sequence homology. Thus, it appears that some, but not all synthetic peptides from hypervariable regions will be capable of generating antisera with useful anti-idiotypic specificities. This may reflect differences in the intrinsic antigenicity of various parts of the VH region.

Amino Acid Sequence↗
PubMed1984

Chemical synthesis of idiotopes. Evidence that antisera to the same JH1 peptide detect multiple binding site-associated idiotopes.

In an attempt to better understand the molecular basis of idiotypy, we have generated several site-specific antisera through immunization of animals with synthetic peptides corresponding to the (JH1) heavy chain joining segment 1 of the mouse heavy chain variable (VH) region. These anti-peptide sera identify several idiotypic determinants present on intact hybridoma and myeloma immunoglobulins. Expression of at least three of these idiotopes is correlated with the antigen specificity of the family of immunoglobulins bearing the determinant. Use of synthetic peptides may prove a powerful technique in the generation of molecularly defined antiidiotypic reagents.

Amino Acid Sequence↗
PubMed1983

Synthetic idiotypes: the third hypervariable region of murine anti-dextran antibodies.

Synthetic peptides with the sequence of the third hypervariable region of either M104 or J558 murine myeloma proteins have been used to immunize rabbits. Most of the resulting antisera distinguished the two proteins in a specific manner corresponding to the sequence of the immunizing peptide. Thus synthetic peptides have been used to elicit antisera specific for particular idiotypes. These studies have significant implications for our understanding of the molecular basis of idiotypy.

Animals↗