In a retrospective cohort, seven patients with multiple myeloma carrying the BRAF V600E mutation ... more In a retrospective cohort, seven patients with multiple myeloma carrying the BRAF V600E mutation had significantly shorter overall survival and higher prevalence of extramedullary disease than 251 BRAF wild type (wt) controls (Andrulis et al Cancer Discov 2013). Three case reports are in concordance with this view (Bohn et al and Sharman et al, Clin Lymphoma Myeloma Leuk, 2014). We conducted this study to further investigate the clinical and biological implications of this mutation in multiple myeloma. We used mutation-specific quantitative real-time PCR (qPCR) to screen biopsies from 209 myeloma patients, of which 185 were taken prior to first relapse. The BRAF V600E mutation was detected in 13 (6.2 %) of the patients. 10 of them also expressed the corresponding protein as evaluated by immunohistochemistry (IHC) using the BRAF V600E specific VE1 antibody, and 2 patients had simultaneous mutations in BRAF and NRAS/KRAS. RAS mutations are of particular interest because in vitro studi...
A comparative study was performed to examine the lethal effects of several cytokines injected int... more A comparative study was performed to examine the lethal effects of several cytokines injected into mice sensitized with actinomycin D (Act-D). Consistent with published data, human tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) (0.2-5 micrograms) caused the death of the animals within 8-12 hr after injection. Human interleukin-6 (IL-6) and interleukin-8 (IL-8) (0.6-6 micrograms) known to be induced by TNF-alpha did not show any lethal effects, indicating that TNF-alpha-associated lethality is not mediated by IL-6 or IL-8. Human tumor necrosis factor-beta (TNF-beta) (also called lymphotoxin), which shares structural and functional properties with TNF-alpha, was as potent as TNF-alpha in its lethal effects. Murine interferon-gamma (IFN-gamma) (0.04-5 micrograms) was also tested and showed no lethal effects in this model. In addition, a synthetic peptide corresponding to amino acid residues 163-171 of IL-1 beta, and which has been shown to lack the inflammat...
A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She th... more A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She thought that the rash might be caused by irritation from a label inside the collar of her coat. The next day she noticed lymph-node enlargement on both sides of her neck. Because she worked in a surgical department, she asked a surgeon about the lumps. The surgeon at once thought of the possibility of malignant lymphoma and removed one of the lymph nodes for histopathological investigation. The pathologist diagnosed a high-grade B-cell non-Hodgkin’s lymphoma. Computed tomography of her thorax and abdomen was negative, and lactate dehydrogenase was normal. 2 weeks later she was sent to a University Hospital for further investigations and treatment. A bone-marrow biopsy specimen was normal. By that time her other lymph nodes had returned almost to normal. Microscopy of the lymph node removed showed a partly effaced structure caused by paracortical expansion and proliferation of blasts (figure A). In some areas, sinuses were preserved and dilated, suggesting an inflammatory reaction. Immunohistochemical investigation showed many blasts positive for anti-CD20 (figure B) and anti-CD30 (figure C) in the expanded paracortex. Differential diagnoses were T-cell-rich B-cell lymphoma, lymphocyte-predominant Hodgkin’s disease, and virus lymphadenitis. Serological investigations did not show any sign of virus infection. PCR investigation of DNA extracted from sections of the lymph-node biopsy showed a polyclonal reaction for immunoglobulin genes (IgH) and T-cell receptor genes (TCR).
Primary (AL) amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloi... more Primary (AL) amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloidosis of the stomach is even more seldom. We present the case of a patient who was referred to upper endoscopy because of weight loss, nausea, and vomiting. Large areas of intramucosal hemorrhages were seen, and biopsies resulted in profuse bleeding stopped with endoscopic clips. The biopsies showed amyloid depositions and further workup revealed that the patient also had cardiac and neuropathic involvements. The patient started treatment with dexamethasone, melphalan and bortezomib. After treatment was started the nausea and epigastric discomfort improved, and a reduction in the biochemical markers troponin T, NT-proBNP, and M-component was observed. Gastric amyloidosis is rarely seen at upper endoscopy in patients without a previously established diagnosis, but the unusual endoscopic findings and bleeding tendency after biopsy should be kept in mind by gastroenterologists.
A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She th... more A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She thought that the rash might be caused by irritation from a label inside the collar of her coat. The next day she noticed lymph-node enlargement on both sides of her neck. Because she worked in a surgical department, she asked a surgeon about the lumps. The surgeon at once thought of the possibility of malignant lymphoma and removed one of the lymph nodes for histopathological investigation. The pathologist diagnosed a high-grade B-cell non-Hodgkin’s lymphoma. Computed tomography of her thorax and abdomen was negative, and lactate dehydrogenase was normal. 2 weeks later she was sent to a University Hospital for further investigations and treatment. A bone-marrow biopsy specimen was normal. By that time her other lymph nodes had returned almost to normal. Microscopy of the lymph node removed showed a partly effaced structure caused by paracortical expansion and proliferation of blasts (figure A). In some areas, sinuses were preserved and dilated, suggesting an inflammatory reaction. Immunohistochemical investigation showed many blasts positive for anti-CD20 (figure B) and anti-CD30 (figure C) in the expanded paracortex. Differential diagnoses were T-cell-rich B-cell lymphoma, lymphocyte-predominant Hodgkin’s disease, and virus lymphadenitis. Serological investigations did not show any sign of virus infection. PCR investigation of DNA extracted from sections of the lymph-node biopsy showed a polyclonal reaction for immunoglobulin genes (IgH) and T-cell receptor genes (TCR).
d cytoplasm or nuclei pathologic feature and most probably also a common pathogenic mechanism for... more d cytoplasm or nuclei pathologic feature and most probably also a common pathogenic mechanism for a variety of clinical conditions, some of which are highly prevalent (e.g. Alzheimer’s disease), severe, and fatal (1). bring new clues to the prevention and treatment The deposited proteins exhibit diVerent morpholof these devastating disorders, caused by naughty ogic features: amorphous masses, granular patterns, proteins that won’t stay where they should, but gather crystals, plaques or brils. All apparently represent at improper places to form guerilla troups committing more or less de ned assemblies or aggregates to a organized crime against their host. great extent made up by a single protein type Although the composition and structure of the (Table I ). We should, therefore, consider that formadeposited proteins and their respective genes are tion and deposition of brils typical of amyloid is quite well established in many cases (1–4), several not obligatory for a protein to confer tissue toxicity. questions still remain unanswered regarding the In addition, proteins exhibiting brillar structures pathogenesis of PDD. may be present without causing disease. It appears to be time for researchers to direct their 1. Why and how do these proteins assemble? focus also on phenomena other than brillogenesis 2. Why and how do they deposit ‘‘out of place’’ in in vivo or in vitro as far as studies of pathogenic certain tissues and organs to cause local or sysmechanisms for PDD are concerned (2–4). temic disease manifestation? Attention to the wider concept of PDD of which 3. How do they exert their toxicity to cells and tissues amyloidosis is nevertheless an important actor, might following deposition? 4. How can their production, assembly and deposGunnar Husby, Centre for Rheumatic Diseases, The National ition be arrested? Hospital University of Oslo, NO-0027 Oslo, Norway. 5. How can the deposits be resolved and removed? E-mail g.a.husby@klinmed.uio.no 6. Are they, after all, only insigni cant epiphenomena
We report on an in vivo model of human myeloma producing bone disease in irradiated severe combin... more We report on an in vivo model of human myeloma producing bone disease in irradiated severe combined immunodeficiency disease mice using the human myeloma cell line JJN-3 and its subline JJN-3 T1. The cell lines are not Epstein-Barr virus transformed and produce large amounts of hepatocyte growth factor (HGF). Mice had radiological signs of osteolysis and mild hypercalcemia. Xenografted cells were predominantly found in bone marrow and brown adipose tissue, but also in meninges and liver. Take was documented by histopathological examination, immunophenotyping of cultured bone marrow, and radiography. HGF was detected in serum and bone marrow plasma. Disease generally occurred within 45 days of intravenous inoculation and was signaled by paraparesis or signs of intracranial neoplasia. More than 90% of the mice had take of xenografts. The subline JJN-3 T1 gave more reproducible bone marrow take than the native cell line. Bone histomorphometric examination revealed a 99% reduction in osteoblast counts and a 33% reduction in osteoclast counts in areas of tumor growth. Bone formation rates were reduced by 53%. The results suggest that osteoblastopenia and reduced bone formation is of importance for the occurrence of osteolytic lesions in this model.
Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cell... more Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as “proliferation,” “low bone disease,” and “MMSET/FGFR3.” PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in th...
Male Sprague Dawley rats were exposed to inhalation of n-C9 to n-C13 alkanes close to air saturat... more Male Sprague Dawley rats were exposed to inhalation of n-C9 to n-C13 alkanes close to air saturation at 20 degrees (4438, 1369, 442, 142 and 41 p.p.m., respectively) for 8 hours and observed for the following 14 days. In addition, exposure to higher and lower concentrations of n-C9 was performed. The concentration of alkane in the brain after exposure exceeded that of blood for the lower alkanes, while the higher alkanes possessed a brain/blood ratio equal to or less than unity. Gross ataxia, general and focal seizure and spasms were observed in animals exposed to n-C9 in the range from 5280 to 3560 p.p.m. No toxic effects were observed in animals exposed to 2414 p.p.m. of n-C9 or to the other alkanes. An LC50 value for n-C9 of 4467 +/- 189 p.p.m. was estimated. Despite the clinical improvement in animals surviving the n-C9 exposure of 4438 p.p.m. (6/10), severe cerebellar damages were found at autopsy at the end of the observation period, with a loss of Purkinje cells as the most prominent feature. Immediate post mortem examination (4/10) showed marked vascular congestion of the liver as well as slight fatty degeneration but no cerebellar damage. No abnormalities were observed in animals exposed to the other alkanes. The significant distribution in the brain of the n-C9 alkane, the clinical signs of cerebellar dysfunction and the damage of cerebellar neurons would suggest CNS to be a possible target organ for the toxic effects of the n-C9 alkane.
We report on an in vivo model of human myeloma producing bone disease in irradiated severe combin... more We report on an in vivo model of human myeloma producing bone disease in irradiated severe combined immunodeficiency disease mice using the human myeloma cell line JJN-3 and its subline JJN-3 T1. The cell lines are not Epstein-Barr virus transformed and produce large amounts of hepatocyte growth factor (HGF). Mice had radiological signs of osteolysis and mild hypercalcemia. Xenografted cells were predominantly found in bone marrow and brown adipose tissue, but also in meninges and liver. Take was documented by histopathological examination, immunophenotyping of cultured bone marrow, and radiography. HGF was detected in serum and bone marrow plasma. Disease generally occurred within 45 days of intravenous inoculation and was signaled by paraparesis or signs of intracranial neoplasia. More than 90% of the mice had take of xenografts. The subline JJN-3 T1 gave more reproducible bone marrow take than the native cell line. Bone histomorphometric examination revealed a 99% reduction in osteoblast counts and a 33% reduction in osteoclast counts in areas of tumor growth. Bone formation rates were reduced by 53%. The results suggest that osteoblastopenia and reduced bone formation is of importance for the occurrence of osteolytic lesions in this model.
In a retrospective cohort, seven patients with multiple myeloma carrying the BRAF V600E mutation ... more In a retrospective cohort, seven patients with multiple myeloma carrying the BRAF V600E mutation had significantly shorter overall survival and higher prevalence of extramedullary disease than 251 BRAF wild type (wt) controls (Andrulis et al Cancer Discov 2013). Three case reports are in concordance with this view (Bohn et al and Sharman et al, Clin Lymphoma Myeloma Leuk, 2014). We conducted this study to further investigate the clinical and biological implications of this mutation in multiple myeloma. We used mutation-specific quantitative real-time PCR (qPCR) to screen biopsies from 209 myeloma patients, of which 185 were taken prior to first relapse. The BRAF V600E mutation was detected in 13 (6.2 %) of the patients. 10 of them also expressed the corresponding protein as evaluated by immunohistochemistry (IHC) using the BRAF V600E specific VE1 antibody, and 2 patients had simultaneous mutations in BRAF and NRAS/KRAS. RAS mutations are of particular interest because in vitro studi...
A comparative study was performed to examine the lethal effects of several cytokines injected int... more A comparative study was performed to examine the lethal effects of several cytokines injected into mice sensitized with actinomycin D (Act-D). Consistent with published data, human tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) (0.2-5 micrograms) caused the death of the animals within 8-12 hr after injection. Human interleukin-6 (IL-6) and interleukin-8 (IL-8) (0.6-6 micrograms) known to be induced by TNF-alpha did not show any lethal effects, indicating that TNF-alpha-associated lethality is not mediated by IL-6 or IL-8. Human tumor necrosis factor-beta (TNF-beta) (also called lymphotoxin), which shares structural and functional properties with TNF-alpha, was as potent as TNF-alpha in its lethal effects. Murine interferon-gamma (IFN-gamma) (0.04-5 micrograms) was also tested and showed no lethal effects in this model. In addition, a synthetic peptide corresponding to amino acid residues 163-171 of IL-1 beta, and which has been shown to lack the inflammat...
A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She th... more A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She thought that the rash might be caused by irritation from a label inside the collar of her coat. The next day she noticed lymph-node enlargement on both sides of her neck. Because she worked in a surgical department, she asked a surgeon about the lumps. The surgeon at once thought of the possibility of malignant lymphoma and removed one of the lymph nodes for histopathological investigation. The pathologist diagnosed a high-grade B-cell non-Hodgkin’s lymphoma. Computed tomography of her thorax and abdomen was negative, and lactate dehydrogenase was normal. 2 weeks later she was sent to a University Hospital for further investigations and treatment. A bone-marrow biopsy specimen was normal. By that time her other lymph nodes had returned almost to normal. Microscopy of the lymph node removed showed a partly effaced structure caused by paracortical expansion and proliferation of blasts (figure A). In some areas, sinuses were preserved and dilated, suggesting an inflammatory reaction. Immunohistochemical investigation showed many blasts positive for anti-CD20 (figure B) and anti-CD30 (figure C) in the expanded paracortex. Differential diagnoses were T-cell-rich B-cell lymphoma, lymphocyte-predominant Hodgkin’s disease, and virus lymphadenitis. Serological investigations did not show any sign of virus infection. PCR investigation of DNA extracted from sections of the lymph-node biopsy showed a polyclonal reaction for immunoglobulin genes (IgH) and T-cell receptor genes (TCR).
Primary (AL) amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloi... more Primary (AL) amyloidosis of the gastrointestinal tract is relatively rare, and symptomatic amyloidosis of the stomach is even more seldom. We present the case of a patient who was referred to upper endoscopy because of weight loss, nausea, and vomiting. Large areas of intramucosal hemorrhages were seen, and biopsies resulted in profuse bleeding stopped with endoscopic clips. The biopsies showed amyloid depositions and further workup revealed that the patient also had cardiac and neuropathic involvements. The patient started treatment with dexamethasone, melphalan and bortezomib. After treatment was started the nausea and epigastric discomfort improved, and a reduction in the biochemical markers troponin T, NT-proBNP, and M-component was observed. Gastric amyloidosis is rarely seen at upper endoscopy in patients without a previously established diagnosis, but the unusual endoscopic findings and bleeding tendency after biopsy should be kept in mind by gastroenterologists.
A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She th... more A nurse aged 55 years had flu-like symptoms and a vesicular rash on her neck, about 44 cm. She thought that the rash might be caused by irritation from a label inside the collar of her coat. The next day she noticed lymph-node enlargement on both sides of her neck. Because she worked in a surgical department, she asked a surgeon about the lumps. The surgeon at once thought of the possibility of malignant lymphoma and removed one of the lymph nodes for histopathological investigation. The pathologist diagnosed a high-grade B-cell non-Hodgkin’s lymphoma. Computed tomography of her thorax and abdomen was negative, and lactate dehydrogenase was normal. 2 weeks later she was sent to a University Hospital for further investigations and treatment. A bone-marrow biopsy specimen was normal. By that time her other lymph nodes had returned almost to normal. Microscopy of the lymph node removed showed a partly effaced structure caused by paracortical expansion and proliferation of blasts (figure A). In some areas, sinuses were preserved and dilated, suggesting an inflammatory reaction. Immunohistochemical investigation showed many blasts positive for anti-CD20 (figure B) and anti-CD30 (figure C) in the expanded paracortex. Differential diagnoses were T-cell-rich B-cell lymphoma, lymphocyte-predominant Hodgkin’s disease, and virus lymphadenitis. Serological investigations did not show any sign of virus infection. PCR investigation of DNA extracted from sections of the lymph-node biopsy showed a polyclonal reaction for immunoglobulin genes (IgH) and T-cell receptor genes (TCR).
d cytoplasm or nuclei pathologic feature and most probably also a common pathogenic mechanism for... more d cytoplasm or nuclei pathologic feature and most probably also a common pathogenic mechanism for a variety of clinical conditions, some of which are highly prevalent (e.g. Alzheimer’s disease), severe, and fatal (1). bring new clues to the prevention and treatment The deposited proteins exhibit diVerent morpholof these devastating disorders, caused by naughty ogic features: amorphous masses, granular patterns, proteins that won’t stay where they should, but gather crystals, plaques or brils. All apparently represent at improper places to form guerilla troups committing more or less de ned assemblies or aggregates to a organized crime against their host. great extent made up by a single protein type Although the composition and structure of the (Table I ). We should, therefore, consider that formadeposited proteins and their respective genes are tion and deposition of brils typical of amyloid is quite well established in many cases (1–4), several not obligatory for a protein to confer tissue toxicity. questions still remain unanswered regarding the In addition, proteins exhibiting brillar structures pathogenesis of PDD. may be present without causing disease. It appears to be time for researchers to direct their 1. Why and how do these proteins assemble? focus also on phenomena other than brillogenesis 2. Why and how do they deposit ‘‘out of place’’ in in vivo or in vitro as far as studies of pathogenic certain tissues and organs to cause local or sysmechanisms for PDD are concerned (2–4). temic disease manifestation? Attention to the wider concept of PDD of which 3. How do they exert their toxicity to cells and tissues amyloidosis is nevertheless an important actor, might following deposition? 4. How can their production, assembly and deposGunnar Husby, Centre for Rheumatic Diseases, The National ition be arrested? Hospital University of Oslo, NO-0027 Oslo, Norway. 5. How can the deposits be resolved and removed? E-mail g.a.husby@klinmed.uio.no 6. Are they, after all, only insigni cant epiphenomena
We report on an in vivo model of human myeloma producing bone disease in irradiated severe combin... more We report on an in vivo model of human myeloma producing bone disease in irradiated severe combined immunodeficiency disease mice using the human myeloma cell line JJN-3 and its subline JJN-3 T1. The cell lines are not Epstein-Barr virus transformed and produce large amounts of hepatocyte growth factor (HGF). Mice had radiological signs of osteolysis and mild hypercalcemia. Xenografted cells were predominantly found in bone marrow and brown adipose tissue, but also in meninges and liver. Take was documented by histopathological examination, immunophenotyping of cultured bone marrow, and radiography. HGF was detected in serum and bone marrow plasma. Disease generally occurred within 45 days of intravenous inoculation and was signaled by paraparesis or signs of intracranial neoplasia. More than 90% of the mice had take of xenografts. The subline JJN-3 T1 gave more reproducible bone marrow take than the native cell line. Bone histomorphometric examination revealed a 99% reduction in osteoblast counts and a 33% reduction in osteoclast counts in areas of tumor growth. Bone formation rates were reduced by 53%. The results suggest that osteoblastopenia and reduced bone formation is of importance for the occurrence of osteolytic lesions in this model.
Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cell... more Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as “proliferation,” “low bone disease,” and “MMSET/FGFR3.” PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in th...
Male Sprague Dawley rats were exposed to inhalation of n-C9 to n-C13 alkanes close to air saturat... more Male Sprague Dawley rats were exposed to inhalation of n-C9 to n-C13 alkanes close to air saturation at 20 degrees (4438, 1369, 442, 142 and 41 p.p.m., respectively) for 8 hours and observed for the following 14 days. In addition, exposure to higher and lower concentrations of n-C9 was performed. The concentration of alkane in the brain after exposure exceeded that of blood for the lower alkanes, while the higher alkanes possessed a brain/blood ratio equal to or less than unity. Gross ataxia, general and focal seizure and spasms were observed in animals exposed to n-C9 in the range from 5280 to 3560 p.p.m. No toxic effects were observed in animals exposed to 2414 p.p.m. of n-C9 or to the other alkanes. An LC50 value for n-C9 of 4467 +/- 189 p.p.m. was estimated. Despite the clinical improvement in animals surviving the n-C9 exposure of 4438 p.p.m. (6/10), severe cerebellar damages were found at autopsy at the end of the observation period, with a loss of Purkinje cells as the most prominent feature. Immediate post mortem examination (4/10) showed marked vascular congestion of the liver as well as slight fatty degeneration but no cerebellar damage. No abnormalities were observed in animals exposed to the other alkanes. The significant distribution in the brain of the n-C9 alkane, the clinical signs of cerebellar dysfunction and the damage of cerebellar neurons would suggest CNS to be a possible target organ for the toxic effects of the n-C9 alkane.
We report on an in vivo model of human myeloma producing bone disease in irradiated severe combin... more We report on an in vivo model of human myeloma producing bone disease in irradiated severe combined immunodeficiency disease mice using the human myeloma cell line JJN-3 and its subline JJN-3 T1. The cell lines are not Epstein-Barr virus transformed and produce large amounts of hepatocyte growth factor (HGF). Mice had radiological signs of osteolysis and mild hypercalcemia. Xenografted cells were predominantly found in bone marrow and brown adipose tissue, but also in meninges and liver. Take was documented by histopathological examination, immunophenotyping of cultured bone marrow, and radiography. HGF was detected in serum and bone marrow plasma. Disease generally occurred within 45 days of intravenous inoculation and was signaled by paraparesis or signs of intracranial neoplasia. More than 90% of the mice had take of xenografts. The subline JJN-3 T1 gave more reproducible bone marrow take than the native cell line. Bone histomorphometric examination revealed a 99% reduction in osteoblast counts and a 33% reduction in osteoclast counts in areas of tumor growth. Bone formation rates were reduced by 53%. The results suggest that osteoblastopenia and reduced bone formation is of importance for the occurrence of osteolytic lesions in this model.
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