Marleen Melis | ErasmusMC Rotterdam (original) (raw)
Papers by Marleen Melis
Graefe's Archive for Clinical and Experimental Ophthalmology, 2008
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Cancer Biotherapy and Radiopharmaceuticals, Feb 1, 2007
In peptide receptor radionuclide therapy (PRRT), the dose-limiting organ is, most often, the kidn... more In peptide receptor radionuclide therapy (PRRT), the dose-limiting organ is, most often, the kidney. However, the precise mechanism as well as the exact localization of kidney damage during PRRT have not been fully elucidated. We studied renal damage in rats after therapy with different amounts of [(177)Lu-DOTA(0), Tyr(3)]octreotate and investigated (99m)Tc-DMSA (dimercaptosuccinic acid) as a tool to quantify renal damage after PRRT. Twenty-nine (29) rats were divided into 3 groups and injected with either 0, 278, or 555 MBq [(177)Lu-DOTA(0), Tyr(3) ]octreotate, leading to approximately 0, 46, and 92 Gy to the renal cortex. More than 100 days after therapy, kidney damage was investigated using (99m)Tc-DMSA single-photon emission computed tomography (SPECT) autoradiography, histology, and blood analyses. In vivo SPECT with (99m)Tc-DMSA resulted in high-resolution (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1.6-mm) images. The (99m)Tc-DMSA uptake in the rat kidneys was inversely related with the earlier injected activity of [(177)Lu-DOTA(0), Tyr(3)]octreotate and correlated inversely with serum creatinine values. Renal ex vivo autoradiograms showed a dose-dependent distribution pattern of (99m)Tc-DMSA. (99m)Tc-DMSA SPECT could distinguish between the rats that were injected with 278 or 555 MBq [(177)Lu-DOTA(0), Tyr(3) ]octreotate, whereas histologic damage grading of the kidneys was nearly identical for these 2 groups. Histologic analyses indicated that lower amounts of injected radioactivity caused damage mainly in the proximal tubules, whereas as well the distal tubules were damaged after high-dose radioactivity. Renal damage in rats after PRRT appeared to start in a dose-dependent manner in the proximal tubules and continued to the more distal tubules with increasing amounts of injected activity. In vivo SPECT measurement of (99m)Tc-DMSA uptake was highly accurate to grade renal tubular damage after PRRT.
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Poster: "ECR 2014 / B-0523 / Optimisation of combination of peptide receptor radionuclide th... more Poster: "ECR 2014 / B-0523 / Optimisation of combination of peptide receptor radionuclide therapy (PRRT) and temozolomide therapy using SPECT/CT and MRI in mice" by: "S. M. Bison, J. C. Haeck, S. J. Koelewijn, M. Melis, M. R. Bernsen, M. de Jong; Rotterdam/NL"
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The Journal of Nuclear Medicine, May 1, 2010
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
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Nuclear Medicine and Biology, 2016
Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in p... more Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Since these techniques were first introduced, many improvements have been made. SSTR expression has also been reported on breast cancer (BC). Currently mammography, magnetic resonance imaging and ultrasound are the most frequent methods used for BC imaging. Since SSTR expression on BC was demonstrated, clinical studies examining the feasibility of visualizing primary BC using SSTR radioligands have been performed. However, to date SSTR-mediated nuclear imaging is not used clinically in BC patients. The aim of this review is to assess whether recent improvements made within nuclear medicine may enable SSTR-mediated imaging to play a role in BC management. For this we critically analysed results of past studies and discussed the potential of the improvements made within nuclear medicine on SSTR-mediated nuclear imaging of BC. Seven databases were searched for publications on BC imaging with SSTR radioligands. The papers found were analysed by 3 individual observers to identify whether the studies met the pre-set inclusion criteria defined as studies in which nuclear imaging using radiolabelled SST analogues was performed in patients with breast lesions. Twenty-four papers were selected for this review including studies on SSTR-mediated nuclear imaging in BC, neuroendocrine BC and other breast lesions. The analysed studies were heterogeneous with respect to the imaging method, imaging protocol, patient groups and the radiolabelled SST analogues used. Despite the fact that the analysed studies were heterogeneous, sensitivity for primary BC ranged from 36-100%. In a subset of the studies LN lesions were visualized, but sensitivity was lower compared to that for primary tumours. A part of the studies included benign lesions and specificity ranged from 22-100%. Furthermore, false negatives and false positives were reported. In the majority of the studies scan outcome was not associated with BC subtype.
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
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Qual Life Res, 2010
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2007
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EJNMMI research, 2015
Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine... more Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate ((177)Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI and SPECT/CT, we studied tumour characteristics and therapeutic responses after different (combined) administration schemes in a murine tumour model in order to identify the optimal treatment schedule for PRRT plus TMZ. We performed molecular imaging studies in mice bearing SSTR-expressing H69 (humane small cell lung cancer) tumours after single intravenous (i.v.) administration of 30 MBq (177)Lu-TATE or TMZ (oral 50 mg/kg daily for 14 days). Tumour perfusion was evaluated weekly by dynamic contrast-enhanced MRI (DCE-MRI), whereas tumour uptake of (111)In-octreotide was quantified using SPECT/CT until day 39 after treatment. ...
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Clinical nuclear medicine, Jan 12, 2015
Radiolabeled somatostatin (SST) analogs, used to visualize and treat SST receptor (SSTR)-expressi... more Radiolabeled somatostatin (SST) analogs, used to visualize and treat SST receptor (SSTR)-expressing neuroendocrine tumors, also accumulate in the spleen. There is a high interpatient variation and no significant radiation-induced splenic toxicity; however, an absorbed dose-related reduction in spleen size was detected. However, the exact localization of radioactivity and the role of SST receptors in splenic retention are unknown. Therefore, we performed ex vivo micro-SPECT of the isolated spleen from a patient with a pancreatic neoplasm after 1 GBq (27 mCi) Lu-DOTATATE administration, followed by autoradiography and immunohistochemistry. Ex vivo autoradiography demonstrated convincingly that most radioactivity accumulated in red pulp.
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Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 6, 2015
Imaging and therapy using radioligands targeting receptors overexpressed on tumor cells is succes... more Imaging and therapy using radioligands targeting receptors overexpressed on tumor cells is successfully applied in neuroendocrine tumor patients. Since expression of the gastrin releasing peptide receptor (GRPR), somatostatin receptor 2 (SSTR2) and chemokine C-X-C motif receptor 4 (CXCR4) has been demonstrated in breast cancer, targeting these receptors using radioligands might offer new imaging and therapeutic opportunities for breast cancer patients. The aim of this study was to correlate messenger RNA (mRNA) expression of GRPR, SSTR2 and CXCR4 with clinico-pathological and biological factors, with prognosis and prediction to therapy response, to identify specific breast cancer patient groups suited for the application of radioligands targeting the receptors. First, we studied GRPR and SSTR2 expression in 13 clinical breast cancer specimens by in vitro autoradiography and correlated this with corresponding mRNA levels to investigate whether mRNA levels reliably represent cell surf...
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Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2007
Ex vivo autoradiographs of healthy kidney tissue from patients who received (111)In-DTPA-octreoti... more Ex vivo autoradiographs of healthy kidney tissue from patients who received (111)In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) before nephrectomy showed very heterogeneous radioactivity patterns in the kidneys. The consequences of the reported inhomogeneities have been evaluated for radionuclide therapy with (90)Y- DOTA-Tyr(3)-octreotide (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), (177)Lu-DOTA-Tyr(3)-octreotate, and (111)In-DTPA-octreotide by calculating dose distributions and dose-volume histograms (DVHs) for the kidneys. Monte Carlo radiation transport calculations were performed by using the MCNP code version 5. The autoradiography data were used in a 2-dimensional model of the kidney tissue sections. A voxel structure inside the MIRD Pamphlet 19 multiregion kidney model was developed to generate a 3-dimensional representation of the autoradiographs. Dose distributions were calculated for the beta-emitter (90)...
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Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2007
Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP) receptors. This observati... more Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP) receptors. This observation suggests that GRP receptors may be used as new visualization and treatment modalities for these tumors. Radiolabeled GRP receptor-targeting analogs of GRP and bombesin (BN) have successfully been developed for these purposes. Expression of GRP receptors in human prostate tumors is, however, primarily evaluated in early stages of tumor development and information on expression in the more progressive prostate tumors is uncertain. To evaluate GRP receptor expression in all stages of PC, we investigated GRP receptor expression using a panel of 12 established human PC xenograft models representing the different stages of human PC and the effect of antiandrogen treatment (castration). Human PC xenografts were grown in male nude mice, and GRP receptor density in the tumors was evaluated using displacement receptor autoradiography with the universal BN receptor analog (125)I-[D-Tyr(6),beta-A...
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Cancer Biotherapy and Radiopharmaceuticals, 2014
Gastrin-releasing peptide receptors (GRPR) and GRP-derived analogs have attracted attention due t... more Gastrin-releasing peptide receptors (GRPR) and GRP-derived analogs have attracted attention due to high receptor expression in frequently occurring human neoplasia. The authors recently synthesized a series of GRPR-affine peptide analogs based on the 27-mer GRP and derivatized with the DOTA chelator at the N-terminus for (111)In-labeling. In this study, the authors evaluated the most promising from these series, DOTA-GRP(13-27), after radiolabeling with (177)Lu for future therapeutic applications. In addition, to improve in vivo stability of the peptide against in vivo degradation by the protease neutral endopeptidase (NEP), the authors coinjected [(177)Lu]DOTA-GRP(13-27) with the potent NEP inhibitor phosphoramidon (PA). The authors also aimed at reducing renal uptake by coadministration of lysine. In vivo stability studies were performed in Swiss albino mice. Biodistribution studies were conducted in NMRI nu/nu mice bearing prostate cancer (PC)-3 xenografts. Ex vivo autoradiography was performed using frozen sections from PC-3 xenografts and kidneys. Coadministration of PA significantly increased the percentage of intact radiopeptide in the mouse circulation. From biodistribution and ex vivo autoradiography studies, coadministration of both lysine and PA with [(177)Lu]DOTA-GRP(13-27) appeared to induce a clear improvement of tumor uptake as well as lower levels of renal radioactivity, causing a promising ninefold increase in tumor/kidney ratios.
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Journal of Nuclear Medicine, 2012
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Journal of Nuclear Medicine, 2010
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![Research paper thumbnail of Effect of Interferon- Treatment on [68Ga-DOTA,Tyr3,Thre8]Octreotide Uptake in CA20948 Tumors: A Small-Animal PET Study](https://attachments.academia-assets.com/110785590/thumbnails/1.jpg)
](Journal of Nuclear Medicine, 2011
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Journal of Leukocyte Biology, 2010
Mouse histiocytosis sarcoma virus infection induces a heterogeneous disease with characteristics ... more Mouse histiocytosis sarcoma virus infection induces a heterogeneous disease with characteristics of Mφ/DC neoplasms involving Langerin+ DC, Mφ, and precursors. Neoplastic diseases of macrophages (Mφ) and dendritic cells (DC), collectively called histiocytoses, are relatively rare. The etiology of most forms of histiocytosis is poorly understood, and the development of animal models is crucial for further research in this field. Previously, an animal model for malignant histiocytosis (MH), involving transformed histiocytic cells, has been generated by infecting mice with malignant histiocytosis sarcoma virus (MHSV). However, increased insight into the heterogeneity of Mφ and DC, and the associated reappraisal of human proliferative diseases involving these cells inspired us to re-evaluate the mouse model. We analyzed spleen, bone marrow, and lymph nodes of susceptible mice at various time points after infection. From day 11 onwards, a heterogeneous population of cells, consisting of ...
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Graefe's Archive for Clinical and Experimental Ophthalmology, 2008
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Cancer Biotherapy and Radiopharmaceuticals, Feb 1, 2007
In peptide receptor radionuclide therapy (PRRT), the dose-limiting organ is, most often, the kidn... more In peptide receptor radionuclide therapy (PRRT), the dose-limiting organ is, most often, the kidney. However, the precise mechanism as well as the exact localization of kidney damage during PRRT have not been fully elucidated. We studied renal damage in rats after therapy with different amounts of [(177)Lu-DOTA(0), Tyr(3)]octreotate and investigated (99m)Tc-DMSA (dimercaptosuccinic acid) as a tool to quantify renal damage after PRRT. Twenty-nine (29) rats were divided into 3 groups and injected with either 0, 278, or 555 MBq [(177)Lu-DOTA(0), Tyr(3) ]octreotate, leading to approximately 0, 46, and 92 Gy to the renal cortex. More than 100 days after therapy, kidney damage was investigated using (99m)Tc-DMSA single-photon emission computed tomography (SPECT) autoradiography, histology, and blood analyses. In vivo SPECT with (99m)Tc-DMSA resulted in high-resolution (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1.6-mm) images. The (99m)Tc-DMSA uptake in the rat kidneys was inversely related with the earlier injected activity of [(177)Lu-DOTA(0), Tyr(3)]octreotate and correlated inversely with serum creatinine values. Renal ex vivo autoradiograms showed a dose-dependent distribution pattern of (99m)Tc-DMSA. (99m)Tc-DMSA SPECT could distinguish between the rats that were injected with 278 or 555 MBq [(177)Lu-DOTA(0), Tyr(3) ]octreotate, whereas histologic damage grading of the kidneys was nearly identical for these 2 groups. Histologic analyses indicated that lower amounts of injected radioactivity caused damage mainly in the proximal tubules, whereas as well the distal tubules were damaged after high-dose radioactivity. Renal damage in rats after PRRT appeared to start in a dose-dependent manner in the proximal tubules and continued to the more distal tubules with increasing amounts of injected activity. In vivo SPECT measurement of (99m)Tc-DMSA uptake was highly accurate to grade renal tubular damage after PRRT.
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Poster: "ECR 2014 / B-0523 / Optimisation of combination of peptide receptor radionuclide th... more Poster: "ECR 2014 / B-0523 / Optimisation of combination of peptide receptor radionuclide therapy (PRRT) and temozolomide therapy using SPECT/CT and MRI in mice" by: "S. M. Bison, J. C. Haeck, S. J. Koelewijn, M. Melis, M. R. Bernsen, M. de Jong; Rotterdam/NL"
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The Journal of Nuclear Medicine, May 1, 2010
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
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Nuclear Medicine and Biology, 2016
Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in p... more Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Since these techniques were first introduced, many improvements have been made. SSTR expression has also been reported on breast cancer (BC). Currently mammography, magnetic resonance imaging and ultrasound are the most frequent methods used for BC imaging. Since SSTR expression on BC was demonstrated, clinical studies examining the feasibility of visualizing primary BC using SSTR radioligands have been performed. However, to date SSTR-mediated nuclear imaging is not used clinically in BC patients. The aim of this review is to assess whether recent improvements made within nuclear medicine may enable SSTR-mediated imaging to play a role in BC management. For this we critically analysed results of past studies and discussed the potential of the improvements made within nuclear medicine on SSTR-mediated nuclear imaging of BC. Seven databases were searched for publications on BC imaging with SSTR radioligands. The papers found were analysed by 3 individual observers to identify whether the studies met the pre-set inclusion criteria defined as studies in which nuclear imaging using radiolabelled SST analogues was performed in patients with breast lesions. Twenty-four papers were selected for this review including studies on SSTR-mediated nuclear imaging in BC, neuroendocrine BC and other breast lesions. The analysed studies were heterogeneous with respect to the imaging method, imaging protocol, patient groups and the radiolabelled SST analogues used. Despite the fact that the analysed studies were heterogeneous, sensitivity for primary BC ranged from 36-100%. In a subset of the studies LN lesions were visualized, but sensitivity was lower compared to that for primary tumours. A part of the studies included benign lesions and specificity ranged from 22-100%. Furthermore, false negatives and false positives were reported. In the majority of the studies scan outcome was not associated with BC subtype.
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2010
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
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Qual Life Res, 2010
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Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2007
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EJNMMI research, 2015
Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine... more Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate ((177)Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI and SPECT/CT, we studied tumour characteristics and therapeutic responses after different (combined) administration schemes in a murine tumour model in order to identify the optimal treatment schedule for PRRT plus TMZ. We performed molecular imaging studies in mice bearing SSTR-expressing H69 (humane small cell lung cancer) tumours after single intravenous (i.v.) administration of 30 MBq (177)Lu-TATE or TMZ (oral 50 mg/kg daily for 14 days). Tumour perfusion was evaluated weekly by dynamic contrast-enhanced MRI (DCE-MRI), whereas tumour uptake of (111)In-octreotide was quantified using SPECT/CT until day 39 after treatment. ...
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Clinical nuclear medicine, Jan 12, 2015
Radiolabeled somatostatin (SST) analogs, used to visualize and treat SST receptor (SSTR)-expressi... more Radiolabeled somatostatin (SST) analogs, used to visualize and treat SST receptor (SSTR)-expressing neuroendocrine tumors, also accumulate in the spleen. There is a high interpatient variation and no significant radiation-induced splenic toxicity; however, an absorbed dose-related reduction in spleen size was detected. However, the exact localization of radioactivity and the role of SST receptors in splenic retention are unknown. Therefore, we performed ex vivo micro-SPECT of the isolated spleen from a patient with a pancreatic neoplasm after 1 GBq (27 mCi) Lu-DOTATATE administration, followed by autoradiography and immunohistochemistry. Ex vivo autoradiography demonstrated convincingly that most radioactivity accumulated in red pulp.
Bookmarks Related papers MentionsView impact
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 6, 2015
Imaging and therapy using radioligands targeting receptors overexpressed on tumor cells is succes... more Imaging and therapy using radioligands targeting receptors overexpressed on tumor cells is successfully applied in neuroendocrine tumor patients. Since expression of the gastrin releasing peptide receptor (GRPR), somatostatin receptor 2 (SSTR2) and chemokine C-X-C motif receptor 4 (CXCR4) has been demonstrated in breast cancer, targeting these receptors using radioligands might offer new imaging and therapeutic opportunities for breast cancer patients. The aim of this study was to correlate messenger RNA (mRNA) expression of GRPR, SSTR2 and CXCR4 with clinico-pathological and biological factors, with prognosis and prediction to therapy response, to identify specific breast cancer patient groups suited for the application of radioligands targeting the receptors. First, we studied GRPR and SSTR2 expression in 13 clinical breast cancer specimens by in vitro autoradiography and correlated this with corresponding mRNA levels to investigate whether mRNA levels reliably represent cell surf...
Bookmarks Related papers MentionsView impact
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2007
Ex vivo autoradiographs of healthy kidney tissue from patients who received (111)In-DTPA-octreoti... more Ex vivo autoradiographs of healthy kidney tissue from patients who received (111)In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) before nephrectomy showed very heterogeneous radioactivity patterns in the kidneys. The consequences of the reported inhomogeneities have been evaluated for radionuclide therapy with (90)Y- DOTA-Tyr(3)-octreotide (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), (177)Lu-DOTA-Tyr(3)-octreotate, and (111)In-DTPA-octreotide by calculating dose distributions and dose-volume histograms (DVHs) for the kidneys. Monte Carlo radiation transport calculations were performed by using the MCNP code version 5. The autoradiography data were used in a 2-dimensional model of the kidney tissue sections. A voxel structure inside the MIRD Pamphlet 19 multiregion kidney model was developed to generate a 3-dimensional representation of the autoradiographs. Dose distributions were calculated for the beta-emitter (90)...
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Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2007
Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP) receptors. This observati... more Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP) receptors. This observation suggests that GRP receptors may be used as new visualization and treatment modalities for these tumors. Radiolabeled GRP receptor-targeting analogs of GRP and bombesin (BN) have successfully been developed for these purposes. Expression of GRP receptors in human prostate tumors is, however, primarily evaluated in early stages of tumor development and information on expression in the more progressive prostate tumors is uncertain. To evaluate GRP receptor expression in all stages of PC, we investigated GRP receptor expression using a panel of 12 established human PC xenograft models representing the different stages of human PC and the effect of antiandrogen treatment (castration). Human PC xenografts were grown in male nude mice, and GRP receptor density in the tumors was evaluated using displacement receptor autoradiography with the universal BN receptor analog (125)I-[D-Tyr(6),beta-A...
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Cancer Biotherapy and Radiopharmaceuticals, 2014
Gastrin-releasing peptide receptors (GRPR) and GRP-derived analogs have attracted attention due t... more Gastrin-releasing peptide receptors (GRPR) and GRP-derived analogs have attracted attention due to high receptor expression in frequently occurring human neoplasia. The authors recently synthesized a series of GRPR-affine peptide analogs based on the 27-mer GRP and derivatized with the DOTA chelator at the N-terminus for (111)In-labeling. In this study, the authors evaluated the most promising from these series, DOTA-GRP(13-27), after radiolabeling with (177)Lu for future therapeutic applications. In addition, to improve in vivo stability of the peptide against in vivo degradation by the protease neutral endopeptidase (NEP), the authors coinjected [(177)Lu]DOTA-GRP(13-27) with the potent NEP inhibitor phosphoramidon (PA). The authors also aimed at reducing renal uptake by coadministration of lysine. In vivo stability studies were performed in Swiss albino mice. Biodistribution studies were conducted in NMRI nu/nu mice bearing prostate cancer (PC)-3 xenografts. Ex vivo autoradiography was performed using frozen sections from PC-3 xenografts and kidneys. Coadministration of PA significantly increased the percentage of intact radiopeptide in the mouse circulation. From biodistribution and ex vivo autoradiography studies, coadministration of both lysine and PA with [(177)Lu]DOTA-GRP(13-27) appeared to induce a clear improvement of tumor uptake as well as lower levels of renal radioactivity, causing a promising ninefold increase in tumor/kidney ratios.
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Journal of Nuclear Medicine, 2012
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Journal of Nuclear Medicine, 2010
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Journal of Nuclear Medicine, 2011
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Journal of Leukocyte Biology, 2010
Mouse histiocytosis sarcoma virus infection induces a heterogeneous disease with characteristics ... more Mouse histiocytosis sarcoma virus infection induces a heterogeneous disease with characteristics of Mφ/DC neoplasms involving Langerin+ DC, Mφ, and precursors. Neoplastic diseases of macrophages (Mφ) and dendritic cells (DC), collectively called histiocytoses, are relatively rare. The etiology of most forms of histiocytosis is poorly understood, and the development of animal models is crucial for further research in this field. Previously, an animal model for malignant histiocytosis (MH), involving transformed histiocytic cells, has been generated by infecting mice with malignant histiocytosis sarcoma virus (MHSV). However, increased insight into the heterogeneity of Mφ and DC, and the associated reappraisal of human proliferative diseases involving these cells inspired us to re-evaluate the mouse model. We analyzed spleen, bone marrow, and lymph nodes of susceptible mice at various time points after infection. From day 11 onwards, a heterogeneous population of cells, consisting of ...
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