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Pristane induces an indomethacin inhibitable inflammatory influx of CD4+ T cells and IFN-gamma production in plasmacytoma-susceptible BALB/cAnPt mice.

In BALB/cAnPt (BALB/c) mice, the intraperitoneal injection of pristane induces the formation of chronic oil granulomatous tissue and a high incidence of plasmacytomas (PCT). DBA/2N (DBA) and (BALB/c x DBA)F1 hybrid (CDF1) mice develop oil granulomas but no PCT. Recent studies comparing pristane-injected conventionally housed BALB/c mice with specific pathogen-free BALB/c mice (SPF) demonstrated a significant reduction in both the incidence of PCT and the T cell infiltration of oil granulomatous tissue in SPF mice. In this study, FACS analysis was performed to determine the proportion of myeloid, T. and B cells present in pristane-induced peritoneal exudate (PE), and oil granulomas (OG) of BALB/c, DBA, and CDF1 mice. At all time points studied, the majority of cells recovered from the PE and OG of all three strains of mice were Mac-1+, presumably macrophages and neutrophils. Neither Ly-5(B220)+ B cells nor CD8+ T cells were significantly altered by pristane injection. BALB/c mice had a dramatic influx of CD4+ T lymphocytes (three- to fivefold) more than 50 days after the initial injection of pristane. The PCT-resistant DBA and CDF1 mice did not. This increase in CD4+ cells in BALB/c mice was not significantly affected by a second injection of pristane nor was it induced by a second injection in DBA mice. Indomethacin, which has been shown to prevent the development of PCT in BALB/c mice, prevented the infiltration of CD4+ T cells. In addition, pristane-induced levels of interferon-gamma greater than controls were found in the peritoneal lavages of BALB/c mice at all time points tested but not in DBA or indomethacin-treated BALB/c mice. In contrast, pristane injection increased levels of interleukin-5 in DBA but not BALB/c mice.

Animals↗

Rapid generation of antibodies against the HTLV-II external envelope protein by growth of mouse plasmacytomas in SCID mice.

Recombinant human T-cell leukemia virus type II (HTLV-II) envelope external glycoprotein, gp46-II, was expressed using a vaccinia virus vector. A recombinant gp46-II fused to an epitope of the influenza virus hemagglutinin, YPYDVPDYA, was purified by immunoaffinity chromatography. The purified glycoprotein was used to immunize Balb/c mice, and antibodies against gp46-II were detected by Western blot analysis and syncytium inhibition assays. We transformed spleen cells from the immunized mice by retroviral infection with ABL-MYC (psi 2) and intraperitoneally transplanted the infected cells into syngeneic Balb/c and severe combined immunodeficient (SCID) mice. The plasmacytomas established ascitic tumors that produced antibodies directed against HTLV-II gp46-II. Ascites developed more rapidly in SCID mice than in normal syngeneic mice. This procedure provides a general means to generate antibodies rapidly.

Amino Acid Sequence↗

Myeloma proteins that bind Hsp65 (GroEL) are polyreactive and are found in high incidence in pristine induced plasmacytomas.

The myeloma proteins produced by 44 plasmacytomas (PCTs) recently induced by pristane in BALB/cAnPt and closely related PCT susceptible congenic strains of mice were isolated chromatographically and screened against a panel of 10 protein, nucleic acid and lipid antigens. This sample was highly unusual because 82% of the proteins had IgG isotopes. Nine of the proteins bound to Hsp65 (GroEL), and all of these were polyreactative. Twenty-one of the myeloma proteins were polyreactive and bound two or more antigens in the panel, and five were monoreactive. Thus, an antigen binding activity was determined for 59% of these myeloma proteins.

Animals↗

An exceptional mouse plasmacytoma with a new kappa/N-myc [T(6; 12) (C1; B)] translocation expresses N-myc but not c-myc.

Mouse plasmacytomas (MPC) carry one of three reciprocal translocations that juxtapose c-myc to one of the three immunoglobulin (Ig) loci. Here we describe an exceptional MPC, induced by pristane oil and Abelson (A-MuLV) virus. It does not carry any of the three c-myc/Ig translocations, but contains a previously unknown reciprocal T(6;12) translocation affecting the bands known to carry the IgK (6C/1) and N-myc (12B) loci, respectively. Northern blot analysis showed high N-myc but no c-myc expression. This is consistent with the constitutive activation of N-myc by a juxtaposition of the IgK and N-myc loci. Reciprocal translocation in B-cell derived tumors are believed to involve the Ig loci by the action of some enzyme that participates in the physiological rearrangement of the Ig loci. Only transcriptionally active chromatin regions are accessible to such recombinases (Alt et al. 1987). N-myc is not expressed in B-cells, but it is transcriptionally active during the early pro- and pre-B cell stage, whereafter it and the surrounding chromatin region becomes inactive (Smith et al. 1992). It is therefore most likely that the N-myc/Kappa translocation has arisen at an early stage of B-cell differentiation. This would imply that the myc/Ig translocations do not block B-cell differentiation. They also reaffirm the functional equivalence of N- and c-myc in relation to B-cell carcinogenesis, as shown by our previous work on tumor induction in N-myc transgenic mice (Wang et al. 1992).

Animals↗

The difference between 5-fluorouracil and melphalan in their ability to promote antitumor immune response against MOPC-315 plasmacytoma.

The anticancer chemotherapeutic drugs melphalan (L-phenylalanine mustard; L-PAM), 5-fluorouracil (5-FU), methotrexate (MTX), and daunorubicin (DAU) were tested for their toxic activity against MOPC-315 tumor cells in vitro. L-PAM, 5-FU, and DAU had a marked toxic effect whereas MTX did not affect the rate of thymidine incorporation in the tumor cells. L-PAM (7.5 mg/kg) induced permanent regression of large s.c. MOPC-315 plasmacytoma tumors, 5-FU (200-250 mg/kg) induced transient regression of MOPC-315 tumors with reappearance starting on the 6th day after the 5-FU injection and DAU (5 mg/kg) was not effective. L-PAM treatment restored the cytotoxic potential of spleen cells of tumor-bearing mice against target MOPC-315 tumor cells whereas spleen cells from tumor-bearing mice treated with 5-FU were unable to mount a cytotoxic response. L-PAM and 5-FU were also assayed for their effect in vitro on induction of suppressor T cells by ConA. L-PAM treatment in vitro markedly reduced the induction of suppressor T cells by ConA whereas 5-FU had no effect. It is suggested that anticancer chemotherapeutic drugs can be classified in "immunopromoting" (L-PAM as prototype) and "nonimmunopromoting" (5-FU as prototype) on the basis of their effect in vivo on established tumors and their effect on induction of suppressor T cells by ConA.

Adjuvants, Immunologic↗

Potentiation by amphotericin B of the cytotoxicity of anticancer agents against MOPC-315 plasmacytoma and Lewis lung carcinoma.

The ability of amphotericin B (AmB) to potentiate the cytotoxicity of several different anticancer agents against two murine tumor models was examined. A spleen colony assay was used to quantitate the cytotoxicity of BCNU, CCNU, and L-PAM, either alone or in combination with AmB against the MOPC-315 plasmacytoma. A high level of potentiation of the effects of CCNU and L-PAM by AmB occurred, but AmB did not increase the cytotoxicity of BCNU. Tumor growth curves and calculation of cell survival demonstrated significant potentiation of the cytotoxicity of CCNU by AmB against SC Lewis lung carcinoma.

Amphotericin B↗

Primary extramedullary orbital plasmacytoma in a child.

We describe a rare case of extramedullary plasmacytoma of the orbit in an 11-year-old boy. Immunoperoxidase staining of the tissue was positive for IgG, kappa chain and negative for lambda chain. Serum and urine electrophoresis showed no M spike. Systemic examination and bone marrow aspirate failed to show generalised involvement. The tumour was completely excised and radiotherapy given postoperatively.

Child↗

Angiography in myeloma (plasmacytoma). A correlated angiographic and histologic study.

Angiography was performed in ten cases of myeloma (plasmacytoma), of which nine were solitary on admission. All lesions were hypervascular bone tumors with extension of neoplastic growth into adjacent soft tissue. Contrast uptake of the tumors occurred regularly and usually was non-homogeneous. In nearly all cases irregular tumor vessels and early venous drainage was evident with arteriovenous shunting in three. Pathologic-anatomic correlation demonstrated 'tumor vessels' to be newly formed vascular spaces lacking the normal constituents of vessel walls. The contrast uptake presumably was caused by passage of contrast into the newly formed, slit-like capillary vascular spaces. Angiography usually permitted separation of myeloma from benign, hypervascular bone lesions. The procedure proved to be of particular value in indicating definite malignancy, since myeloma was considered initially as the probable diagnosis in only one of the series. It was not possible, however, to differentiate myeloma from other malignant tumors by plain radiography or angiography. Irreversible renal failure occurred in one patient after angiography.

Adult↗

Solitary plasmacytoma of the skull. A case report.

A case of solitary plasmacytoma of the skull is presented. The tumor was radically removed. There was no systemic involvement and the patient was not submitted to radiotherapy. Lytic lesions of the skull are discussed.

Adult↗

[Diagnostic and therapeutic aspects of solitary extramedullary plasmacytomas (author's transl)].

The rare solitary extramedullary Plasmacytoma is discussed and compared to the more common disseminated form. Based upon the pertinent literature, some diagnostic problems, clinical and pathological features as well as prognostic and therapeutic aspects of the solitary lesion in the ENT field are reviewed. In connection to one personal case, the authors analyze Trotter's Median Labiomandibular Glossotomy.

Brain Neoplasms↗

Immunoglobulin gene expression in a coupled transcription/translation system from mouse plasmacytoma cell-free extracts.

Mouse plasmacytoma cytoplasmic extracts and sonicated nuclei have been incubated under conditions which resulted in translation and transcription, respectively. When the cell-free systems were combined, incorporation of radioactive precursors into RNA and protein was enhanced and extended. Coupling of transcription and translation was indicted by the inhibition of protein synthesis, and specifically immunoglobulin synthesis, by actinomycin D and alpha-amanitin. When immunoglobulin synthesis was investigated in MOPC-104E cells Which contain both lambda and K mRNAs but secrete only lambda light chains, the extracts synthesized both K and Lambda light chains. These results indicated that the unexpressed MOPC-104E K mRNA could be translated on homologous ribosomes under the appropriate conditions and suggested that postranscriptional controls may play a role in k-chain gene expression in MOPC-104E cells.

Animals↗

A murine plasmacytoma MOPC 104E resistant to cyclophosphamide is resistant to immunotherapy.

A murine plasmacytoma MOPC 104E (MOPC) is highly sensitive to chemotherapeutic agents such as cyclophosphamide and mitomycin C as well as to immunotherapy (OK-432-combined adoptive immunotherapy using interleukin-2-cultured killer cells). In the present study, we prepared cyclophosphamide-resistant MOPC cells (MOPC-CPA/R) by serial in vivo passage of tumor cells following cyclophosphamide treatment. The in vivo sensitivity of MOPC-CPA/R to mitomycin C or to immunotherapy (OK-432-combined adoptive immunotherapy) was significantly decreased compared to the parent MOPC. In vitro experiments showed that MOPC-CPA/R were more resistant (five-fold) to lysis by cultured immune spleen cells than MOPC. Inhibition of the lytic activity of cultured immune spleen cells against MOPC was significantly increased (P less than 0.05) by the addition of unlabeled MOPC compared to unlabeled MOPC-CPA/R. These results suggest that MOPC-CPA/R express weaker antigenicity than MOPC. However, the transfer of immune spleen cells cultured with tumor extract derived from MOPC-CPA/R significantly prolonged the survival of MOPC-CPA/R-inoculated mice. Thus, by repeated cyclophosphamide treatment, tumor cells with low-antigenicity were selected. These tumor cells had lower sensitivity to another chemotherapeutic agent and immunotherapy. Such an immunological response may play an important role in cancer therapy.

Animals↗

Therapeutic efficacy of sequential therapy with OK-432, cyclophosphamide, IL2-cultured lymphocytes and in vivo IL2 against advanced murine plasmacytoma.

BALB/c mice inoculated IP with a syngeneic plasmacytoma MOPC104E were treated with a combination of a streptococcal preparation, OK-432 (1 KE, 0.1 mg/mouse), low-dose of cyclophosphamide (CPA, 1 mg/kg) and adoptive transfer of tumor-bearer-spleen cells (2 x 10(7) cells) cultured with IL2 and sonicated tumor extract (adoptive immunotherapy; AIT). The consecutive protocol of OK-432 (day 8, 9 post inoculation) - CPA (day 10) - AIT (day 11) was the most effective. Rate of complete remission was highest when recombinant (r-) IL2 was injected to the mice after AIT. Moreover, another bacterial preparation, Nocardia rubra cell wall skeleton and another low-dose chemotherapy, Mitomycin C could be used successfully instead of OK-432 or CPA. Transfer test of intraperitoneal cells (tumor cells plus host cells) of mice on day 11 post inoculation (on the day of AIT) revealed that OK-432 augmented the susceptibility of peritoneal cells to cultured lymphocytes in inhibition of transplantability, and that CPA after OK-432 augmented the anti-tumor effect of tumor-bearer-spleen cells which act synergistically with cultured lymphocytes. This therapy schedule seems to be the best model to augment the effect of AIT with minimal side effect.

Animals↗

Anaplastic solitary extramedullary plasmacytoma of the cecum. Report of a case confirmed by immunoperoxidase staining.

Solitary extramedullary plasma cell tumors, although uncommon, have been reported with increasing frequency over the last few years. Approximately 5 to 10 percent of the tumors arise in the gastrointestinal tract. This report demonstrates that a solitary anaplastic cecal extramedullary plasmacytoma can mimic a polypoid carcinoma, both grossly and, to an extent, microscopically. Immunoperoxidase stains for cytoplasmic immunoglobulin proved useful in establishing the correct diagnosis.

Aged↗

Non-secretory solitary plasmacytoma of the spleen.

A case of primary nonsecretory plasmacytoma of the spleen is reported. On laparotomy and splenectomy a 920 g spleen was removed, measuring 16 x 14 x 6 cm. The cut surface of the entire spleen showed that the tumour occupied most of the splenic tissue. A bone marrow aspirate and trephine, skeletal survey showed no signs of myeloma. Biopsy of the liver and regional lymph nodes was normal. Immunocytochemistry of the splenic tumour showed positivity for pan-B and plasma cell markers. After splenectomy the patient was treated with chemotherapy according to protocol VBCMP (M2).

Antineoplastic Combined Chemotherapy Protocols↗

Disseminated peritoneal plasmacytoma following cardiac transplantation.

Posttransplant lymphoproliferative disorders (PTLD) are an important comorbidity in immunosuppressed transplant patients. We describe a unique case of PTLD, a disseminated peritoneal plasmacytoma in a 56-year-old cardiac transplant patient presenting with ascites. The associated computed tomographic findings include omental thickening, mesenteric stranding, and ascites.

Ascites↗

Characterization of Wue-1, a novel monoclonal antibody that stimulates the growth of plasmacytoma cell lines.

A new monoclonal antibody, Wue-1, which specifically recognizes normal and malignant plasma cells, is characterized. Biochemical studies showed that monoclonal antibodies (mAbs) recognize a protein of 94 kDa. Using triple-staining flow cytometry and double-labeling immunohistochemical techniques, two populations of plasma cells, i.e. lymphoplasmocytoid plasma cells located in the germinal center of lymphoid organs and reticular plasma cells at the paracortex or medullary cords of secondary lymphoid tissues, were distinguished. Wue-1 is expressed when B-cell markers become lost and secretory activity with plasma cell morphology appears. Cell surface markers were identified on normal plasma cells and compared with their malignant counterpart in vivo. Terminal plasma-cellular differentiation of malignant low- and high-grade B-cell lymphoma and anaplastic plasmacytoma, otherwise difficult to identify with conventional B-cell markers on tissue sections or fluorescence-activated cell sorter analyses, were detectable by Wue-1. In cell culture, Wue-1 enhanced the proliferation of myeloma cell lines but not normal plasma cells in a dose-dependent manner. Since Wue-1-induced proliferation was increased by interleukin (IL)-6, Wue-1 recognizes a so far unidentified antigen with functional properties. Therefore, Wue-1 represents a useful new tool for therapy and for the in vivo and in vitro studying of B-cell lymphomas and the mechanisms of B-cell differentiation.

Animals↗