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PubMed1976

Resistance of mice to Krebs ascites tumour, sarcoma S180 and PC6 plasmacytoma after immunisation with Salmonella enteritidis 11RX.

Resistance to Krebs ascites tumour, sarcoma S180 (ascitic form) and PC6 plasmacytoma can be induced with prior immunisation with live Salmonella enteritidis 11RX. One thousand to ten thousand more tumour cells are needed to give an LD50 after immunisation. Resistance to PC6 could be recalled 137 days after intravenous immunisation with 11RX protein antigen intraperitoneally as measured by prolonged survival or monitoring the death of 5[131I]-iodo-2'-deoxyuridine labelled tumour cells in vivo. The range of tumours to which resistance can be produced by 11RX immunisation suggests that the mechanism of resistance does not involve antigens common to the tumours and Salmonella enteritidis 11RX.

Animals↗
PubMed1993

Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas.

We have screened the entire coding region of c-myc in a panel of Burkitt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the belief that c-myc is wild type in these tumours, we found that 65% of 57 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) substitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations often occur before Myc/Ig translocation in BL. In PCTs, only the mutant c-myc allele was expressed indicating a functional homozygosity, but occurrence of mutations after the translocation. Many of the observed mutations are clustered in regions associated with transcriptional activation and apoptosis, and in BLs, they frequently occur at sites of phosphorylation, suggesting that the mutations have a pathogenetic role.

Alleles↗
PubMed2002

Nonmyeloablative allogeneic peripheral blood stem cell transplantation for multifocal extramedullary plasmacytomas progressing after autologous transplantation.

Multifocal extramedullary plasmacytomas (EMP) are an uncommon manifestation of plasma cell malignancies. We report two patients with multiple EMP who developed rapidly progressive and ultimately fatal disease shortly after undergoing nonmyeloablative, matched-related donor allogeneic peripheral blood stem cell transplantation (PBSCT). We have not observed a similar course in patients transplanted for multiple myeloma without extramedullary manifestations and hypothesize that the intense immunosuppression associated with the fludarabine, busulfan and anti-thymocyte globulin conditioning regimen may have contributed to rapid disease progression in the two EMP patients. Our observations support the assertion that extramedullary disease is a marker for an aggressive, refractory plasma cell malignancy and suggest that patients should be treated intensively from the time of diagnosis. The utility of a graft-versus-tumor effect and the role of nonmyeloablative allogeneic PBSCT is yet to be defined in patients with extramedullary plasma cell malignancies, but it is logical to consider using it at the time of minimal residual disease rather than at disease relapse or progression. Nevertheless, we recommend circumspection in the administration of highly immunosuppressive conditioning regimens to patients with refractory EMP and encourage further clinical research in this area.

Adult↗
PubMed2003

High-dose melphalan followed by radical radiotherapy for the treatment of massive plasmacytoma of the chest wall.

We report three cases of massive chest wall plasmacytoma, each greater than 10 cm in diameter, without evidence of overt myeloma, whom we treated with a combination of VAD chemotherapy consolidated by high-dose melphalan and autologous peripheral blood stem cell transplantation and radical radiotherapy. All three patients completed all components of their therapy without experiencing any major side effects and one patient has had a durable remission. The other two patients have had disease progression but at sites other than the original tumour.

Antineoplastic Agents, Alkylating↗
PubMed1998

Solitary plasmacytoma of the spine associated with neurological complications.

We report eight patients with a solitary plasmacytoma of the spine associated with neurological complications. The patients included five men and three women with an average age at presentation of 59 years (range, 47 to 73 years). The tumour was confined to the thoracic spine in six cases, cervical spine in one and lumbar spine in one. Duration of symptoms ranged from 2.5 to 22 months. Treatment consisted of a combination of radiotherapy, melphalan and surgery. One patient progressed to multiple myeloma 7 years after surgery. Surgical treatment (anterior surgery in three cases and posterior surgery in five) produced neurological improvement in all patients. We stress the importance of an early diagnosis followed by appropriate treatment including surgery for this clinical entity and long-term follow-up to detect a disseminated disease.

Aged↗
PubMed1998

Plasmacytoma of dens as a cause of atlanto-axial instability.

A case of Plasmacytoma of dens (Odontoid Process) in an adult male managed by trans-oral excision and posterior fusion is reported for its rarity. The importance of neuro-imaging and the treatment options, in view of the associated instability at the atlanto-axial region and the difficulty in preoperative diagnosis are emphasized.

Adult↗
PubMed2001

Gp130 and ras mediated signaling in human plasma cell line INA-6: a cytokine-regulated tumor model for plasmacytoma.

INTRODUCTION: Cytokines of the gp130-family, particularly interleukin(IL)-6, play a crucial role in the propagation of malignant plasma cells. MATERIALS AND METHODS: The role of IL-6 and other gp130-cytokines was studied in the human plasma cell line INA-6 in vitro and in INA-6 xenografts. The proliferative response to gp130-cytokines was evaluated and activated components of gp130-signaling pathways were identified by Western blotting and DNA binding studies. Specifically, expression of IL-6 and receptors for IL-6 and leukemia inhibitory factor were analysed by RT-PCR and ELISA. RESULTS: The plasma cell line INA-6 was cultured for several years remaining strictly dependent on exogenous IL-6. Other gp130-cytokines had no significant effect on INA-6 cell proliferation in vitro. Due to an activating mutation in the N-ras gene, mitogen-activated protein kinases (MAPK) were constitutively phosphorylated. In contrast, signal transducer and activator of transcription(STAT)-3 activation was dependent on stimulation with IL-6. Blocking of either one of these pathways resulted in a significant decrease of INA-6 cell proliferation. Remarkably, INA-6 xenografts did not require exogeneous IL-6 for proliferation in vivo. Instead, an autocrine IL-6 loop and, in certain tumor sublines, responsiveness to additional gp130-cytokines was induced during in vivo growth. CONCLUSION: Activation of the gp130 signal transducer is mandatory for INA-6 cell growth in vitro and in vivo. Both the MAPK and the Jak/STAT pathway are operative in malignant plasma cells and either one is essential for plasma cell growth. The INA-6 cell line provides a preclinical model to study growth regulation of human plasmacytoma cells and to evaluate novel therapeutic strategies.

Aged↗
PubMed1975

Determination of polyadenylate-rich ribonucleic acid in the nucleus and in the cytoplasm of plasmacytoma cells.

A number of parameters affecting the adsorption of rRNA and poly(A)-containing RNA to Millipore filters were investigated separately. Binding of both types of RNA to the filter was dependent on the concentration of RNA, pH and Mg2+ concentration of the reaction mixture. Both types of RNA bound to the filter optimally at slightly acid pH values. The binding of poly(A)-containing RNA to the filter exhibited a broad pH-dependence compared with that of rRNA. The ratio of poly(A)-rich RNA/rRNA retained by the filter was maximal between pH7 and 8. The presence of 1 mM-EDTA or a high concentration of NaCl (over 0.5M) decreased the affinity of RNA for the filter. The amount of poly(A)-containing RNA in the nucleus and in the cytoplasm of a plasmacytoma cell line (MPC-11) labelled with [32P]Pi was determined by the Millipore-filter technique under conditions that minimized contamination by rRNA. These data were compared with the estimations made by oligo(dT)-cellulose chromatography. The results obtained by these two methods were in good agreement for RNA labelled for short periods (up to 2h). In long labelling and pulse-chase experiments, however, contamination of the filter by rRNA of increasing specific radioactivity in the cytoplasm gave an erroneous value for poly(A)-containing RNA by the Millipore-filter technique. Determinations made on the nuclear fraction by these two methods did not show significant variation in short- and long-term labelling experiments.

Animals↗
PubMed2001

Thalidomide in multiple myeloma: lack of response of soft-tissue plasmacytomas.

Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.

Aged↗
PubMed2003

Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma.

Malignant plasma cells generally grow within the bone marrow microenvironment; however, they can also grow at extramedullary sites. To identify the tumour-specific alterations required for extramedullary growth, we analysed the expression profiles of a series of plasma cell neoplasms including primary multiple myeloma (MM), plasma cell leukaemia (PCL) and extramedullary plasmacytoma (EPC). Hierarchical clustering analysis segregated the EPCs from the remaining samples, and revealed an expression pattern associated with angiogenesis in the EPCs, involving higher expression of the genes TIE2, NOTCH3, CD31 and endoglin. Direct comparison of EPC samples with the MM samples identified 156 genes significantly upregulated and 85 genes significantly downregulated (P < 0.005, t-test) in the EPCs, including several genes involved in angiogenesis and adhesion that were upregulated (including angiopoietin 1, SPARC, Notch3 and fibronectin 1). Immunohistochemical staining demonstrated CD31 and endoglin protein expression in the EPC tumour cells, which are both angiogenesis related and could confer malignant plasma cells with the ability to grow outside the normal bone marrow environment. Defining how malignant plasma cell growth is regulated in the bone marrow versus at extramedullary sites will help to delineate the mechanisms underlying the dependence of tumour cell growth on angiogenesis and cell adhesion.

Cell Division↗
PubMed2002

Multiple cutaneous plasmacytomas following an autologous peripheral stem cell transplant.

We describe the unusual development of multiple cutaneous plasmacytomas following treatment of IgA lambda myeloma with myeloablative therapy and a peripheral blood stem cell autograft. Cutaneous metastatic spread was evident despite bone marrow remission. Treatment with an autograft may have contributed to the cutaneous relapse.

Hematopoietic Stem Cell Transplantation↗
PubMed1998

Solitary plasmacytoma of the lung with light chain extracellular deposits: a case report and review of the literature.

AIMS: We present the clinical and histopathological findings of an unusual pulmonary plasmacytoma associated with light chain deposits. METHODS AND RESULTS: The tumour was located in the main left stem bronchus 40 mm from the carina. Histologically, it was composed of sheets of well differentiated plasma cells. Large extracellular deposits of amorphous material were observed in the tumour. These deposits were Congo red negative and contained kappa light chains. They were electron dense granular and non-filamentous. No plasmacytosis was identified by bone marrow biopsy and no monoclonal spike was shown by serum and urine electrophoresis. CONCLUSIONS: Our case is unusual in being endobronchial and showing light chain deposition.

Aged↗
PubMed1996

Early B-cell factor (EBF) down-regulates immunoglobulin heavy chain intron enhancer function in a plasmacytoma cell line.

The immunoglobulin heavy chain intron enhancer contains two potential binding sites for early B-cell factor (EBF). To investigate the functional properties of these, EBF was expressed in the EBF non-expressing S194 plasmacytoma cell line and found to down-regulate the activity of a co-transfected immunoglobulin heavy chain intron enhancer reporter construct. The expression of an unrelated reporter construct was unaltered. Dividing the immunoglobulin heavy chain intron enhancer into two subregions showed that the EBF mediated down-regulation of expression was mediated by at least two independent sites. These data indicate a role for EBF in the regulation of immunoglobulin gene expression.

Animals↗
PubMed1996

Suppression of tumour-specific cytotoxic T-cell responses against the syngeneic BALB/c plasmacytoma ADJ-PC-5 by tumour-induced CD8+ regulatory T cells via IFN-gamma.

The mechanisms of tolerance induction by tumour cells during early stages of tumourigenesis were analysed in a murine model system using the highly immunogenic BALB/c plasmacytoma ADJ-PC-5. Early stages of tumourigenesis were simulated in syngeneic BALB/c mice by repeated intraperitoneal injections with subimmunogenic doses of X-irradiated ADJ-PC-5 tumour cells. This treatment causes a state of tumour-specific tolerance in a high percentage of mice, involving a population of CD8+ peritoneal T cells which are able to suppress a protective tumour-specific Tc response against this tumour. Using a primary mixed lymphocyte tumour cell culture (MLTC) as an in vitro system to study suppressive mechanisms of such regulatory T cells, the role of production or consumption of a number of cytokines was analysed. The data presented here demonstrate that inhibition of a protective Tc response against ADJ-PC-5 tumour cells is due to IFN-gamma production by suppressive T cells from tolerized mice, but not to IL-2 consumption. In contrast to typical CD8+ Tc cells, ADJ-PC-5-specific CD8+ Tc cells do not produce IFN-gamma and are furthermore suppressed by IFN-gamma. Thus, tumour-induced suppressive T cells and tumour-specific Tc cells seem to represent functionally and phenotypically different subsets of CD8+ T cells, possibly pointing towards a differential activation of type-1 and type-2 CD8+ T cells depending on the dose of tumour cells.

Animals↗
PubMed1999

Solitary bone plasmacytoma: management of isolated local relapse following radiotherapy.

Radiotherapy is the prime treatment modality for solitary plasmacytomas of bone (SPB). Although local control rates are excellent, progression to multiple myeloma is frequent, albeit with varying latency. Local failure in the absence of dissemination is rare and thus management is poorly documented. We discuss such a patient who presented 3 years after local radiation for a pelvic SPB and review the relevant literature. Radiation doses, portals employed and prognostic factors that may predict progression to myeloma are discussed. This report shows that an isolated recurrence of SPB in a previously irradiated field was successfully treated with orthopaedic surgery. This resulted in good pain relief and mobility for the patient, who remains free of disease 6 months after operation.

Acetabulum↗
PubMed1978

[Plasmacytoma of the stomach (author's transl)].

Over a period of two years, enlarged folds in the gastric antrum were found on several occasions, during barium meals, in a 50-year old patient. On gastroscopy and biopsy, the diagnosis of superficial gastritis was made. Six and a half years later the radiological examination, gastroscopy, and biopsy were repeated with suspicion of a malignant tumour. Following histological examination of the resected specimen, the diagnosis of gastric plasmacytoma was made. The features of this rare contition are described and the literature is reviewed.

Biopsy↗
PubMed2000

[Locally recurring extramedullary plasmacytoma of the upper aerodigestive tract].

BACKGROUND: Extramedullary plasmacytomas (EMP) are plasma cell tumors in which by definition the primary tumor is extramedullary. Most of them are found in the upper aerodigestive tract. PATIENTS: In this study we describe 3 patients with EMP. The first case is a locally recurrent EMP with recurrent involvement of cervical lymph nodes. The first manifestation of EMP was 31 years ago. Hence, this is one of the longest clinical courses of recurrent EMP ever described in the literature. Case 2 is a locally aggressive recurrent EMP. Case 3 is a localized solitary EMP that could be successfully treated by surgery alone. RESULTS AND CONCLUSIONS: Different classifications of EMP described in the literature are discussed. If these classifications are applied to our cases neither the tumor stage nor the histological picture allow definite conclusions about the prognoses to be drawn. Metastases in regional lymph nodes do not necessarily mean a worse prognosis. Overall, compared to MM with a ten year survival rate of 18% the prognosis is more favorable in EMP with a ten year survival rate of 50%. After a generalized plasma cell neoplasia has been excluded EMP in the head and neck should be treated like a locally aggressive and potentially metastatic tumor. From our experiences we recommend a primary surgical therapy followed by radiation therapy if necessary.

Aged↗