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2.
Ortop Traumatol Rehabil ; 19(2): 183-189, 2017 Apr 12.
Article in English | MEDLINE | ID: mdl-28508769

ABSTRACT

Sarcoidosis is a multiorgan inflammatory disease that rarely involves the musculoskeletal system. A typical radiographic presentation is only noted with phalangeal lesions in the hands and feet, and other skeletal sites of sarcoidosis are a diagnostic imaging challenge [1]. We describe two cases of patients with sarcoidosis in whom pathologic bone marrow lesions were diagnosed on MRI scans. The magnetic resonance findings were non-specific and metastatic lesions or multiple myeloma were suspected. The case analysis serves to point to limitations of imaging studies in diagnosing bone sarcoidosis and underline the importance of cooperation between the radiologist and the clinician. The role of magnetic resonance imaging in the diagnostic algorithm for bone sarcoidosis should mostly focus on locating lesions, indicating biopsy sites and follow-up of abnormalities.


Subject(s)
Bone Diseases/diagnostic imaging , Bone Diseases/physiopathology , Bone Marrow Neoplasms/diagnostic imaging , Bone Marrow Neoplasms/physiopathology , Magnetic Resonance Angiography , Sarcoidosis/diagnostic imaging , Sarcoidosis/physiopathology , Humans , Sarcoidosis/diagnosis
3.
J Orthop Sports Phys Ther ; 46(2): 124, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26828237

ABSTRACT

A 58-year-old man was referred to physical therapy with a primary complaint of intermittent low back pain (LBP) 2 weeks after being in a motor vehicle collision. The absence of red flags justified the initiation of treatment, but when symptoms of unrelenting LBP emerged, he was referred to his primary care physician with a request for further medical workup. Before further imaging work-up was performed, the patient presented to the emergency room with a urinary complaint; this, in combination with unrelenting LBP, prompted further imaging follow-up. Lumbar/thoracic spine magnetic resonance imaging revealed multiple compression fractures and diffuse bone marrow heterogeneity consistent with a malignant infiltrative marrow process. The patient underwent additional laboratory testing and a bone marrow aspirate and biopsy that confirmed the diagnosis of multiple myeloma.


Subject(s)
Accidents, Traffic , Bone Marrow Neoplasms/secondary , Low Back Pain/etiology , Magnetic Resonance Imaging , Multiple Myeloma/secondary , Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Fractures, Compression/etiology , Humans , Lumbar Vertebrae/injuries , Male , Middle Aged , Motor Vehicles , Multiple Myeloma/pathology , Multiple Myeloma/physiopathology , Thoracic Vertebrae/injuries
4.
J Biomed Inform ; 58: 104-113, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26453823

ABSTRACT

PURPOSE: To date the standard nosology and prognostic schemes for myeloid neoplasms have been based on morphologic and cytogenetic criteria. We sought to test the hypothesis that a comprehensive, unbiased analysis of somatic mutations may allow for an improved classification of these diseases to predict outcome (overall survival). EXPERIMENTAL DESIGN: We performed whole-exome sequencing (WES) of 274 myeloid neoplasms, including myelodysplastic syndrome (MDS, N=75), myelodysplastic/myeloproliferative neoplasia (MDS/MPN, N=33), and acute myeloid leukemia (AML, N=22), augmenting the resulting mutational data with public WES results from AML (N=144). We fit random survival forests (RSFs) to the patient survival and clinical/cytogenetic data, with and without gene mutation information, to build prognostic classifiers. A targeted sequencing assay was used to sequence predictor genes in an independent cohort of 507 patients, whose accompanying data were used to evaluate performance of the risk classifiers. RESULTS: We show that gene mutations modify the impact of standard clinical variables on patient outcome, and therefore their incorporation hones the accuracy of prediction. The mutation-based classification scheme robustly predicted patient outcome in the validation set (log rank P=6.77 × 10(-21); poor prognosis vs. good prognosis categories HR 10.4, 95% CI 3.21-33.6). The RSF-based approach also compares favorably with recently-published efforts to incorporate mutational information for MDS prognosis. CONCLUSION: The results presented here support the inclusion of mutational information in prognostic classification of myeloid malignancies. Our classification scheme is implemented in a publicly available web-based tool (http://myeloid-risk. CASE: edu/).


Subject(s)
Bone Marrow Neoplasms/genetics , Exome , Bone Marrow Neoplasms/classification , Bone Marrow Neoplasms/physiopathology , Cohort Studies , Prognosis
5.
J Neurooncol ; 120(3): 523-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25119002

ABSTRACT

To determine the risk factors for intraocular involvement in patients with primary central nervous system lymphoma (PCNSL), a retrospective chart review was performed on 136 patients who were pathologically diagnosed with PCNSL. The patients were investigated for demographics, clinical manifestation, and the profile of immunohistochemical tumor biomarkers, as well as for the presence of intraocular involvement of lymphoma at diagnosis or during follow-up. The mean age of the entire cohort was 58.6 ± 12.4 years, and the mean follow-up period was 31.1 ± 30.8 months. Twenty-nine (21 %) patients had an intraocular involvement, among which 20 (69 %) patients presented with intraocular involvement at diagnosis of PCNSL and 9 (31 %) patients developed intraocular involvement after a mean period of 32.4 ± 33.6 months. Of the patients with intraocular involvement, 8 (28 %) had no visual symptom at the diagnosis of ocular invasion. Between those with and without intraocular involvement, no significant differences were found with respect to the age, sex, and follow-up period as well as cerebrospinal fluid spread and bone marrow involvement. Among the immunohistochemical biomarkers, the Ki-67 proliferation index was significantly higher in patients with intraocular involvement than in patients without (P = 0.021), but the other investigated biomarkers did not show a significant difference between the two groups. A Ki-67 level ≥80 % was a risk factor for the intraocular involvement in patients with PCNSL (odds ratio, 2.63). Median overall survival was 39.0 months in the entire cohort and was not significantly different between those with and without intraocular involvement (P = 0.959).


Subject(s)
Central Nervous System Neoplasms/epidemiology , Central Nervous System Neoplasms/physiopathology , Eye Neoplasms/epidemiology , Eye Neoplasms/physiopathology , Lymphoma/epidemiology , Lymphoma/physiopathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Bone Marrow Neoplasms/epidemiology , Bone Marrow Neoplasms/physiopathology , Central Nervous System Neoplasms/pathology , Cohort Studies , Eye Neoplasms/pathology , Female , Follow-Up Studies , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Lymphoma/pathology , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Analysis , Young Adult
6.
Orv Hetil ; 155(10): 367-75, 2014 Mar 09.
Article in Hungarian | MEDLINE | ID: mdl-24583557

ABSTRACT

Polyclonal mesenchymal cells (fibroblasts, endothelial cells, pericytes, osteoblasts, reticular cells, adipocytes, etc.) of the bone marrow create a functional microenvironment, which actively contributes to the maintenance of hemopoesis. This takes place through cellular interactions via growth factors, cytokines, adhesion molecules and extracellular matrix components, as well as through the control of calcium and oxygen concentration. Inflammatory and neoplastic diseases of the bone marrow result in pathologic interaction between hemopoietic progenitors and stromal cells. This may lead to the activation and expansion of the stroma and to the accumulation of reticulin and collagen fibers produced by mesenchymal cells. Clinically relevant fiber accumulation, termed as myelofibrosis accompanies many diseases, although, the extent and the consequence of myelofibrosis are variable in different disorders. The aim of this review is to summarize basic features of the normal bone marrow mesenchymal environment and the pathological process leading to myelofibrosis. In addition, the special features of myelofibrosis in bone marrow diseases, including myeloproliferative neoplasia, myelodysplastic syndrome and other neoplastic conditions are discussed.


Subject(s)
Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Bone Marrow/metabolism , Hematopoietic Stem Cells , Mesenchymal Stem Cells , Primary Myelofibrosis/pathology , Primary Myelofibrosis/physiopathology , Acute Disease , Bone Marrow Neoplasms/metabolism , Calcium/metabolism , Cell Adhesion Molecules/metabolism , Collagen/metabolism , Cytokines/metabolism , Extracellular Matrix/metabolism , Hematopoiesis , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/pathology , Humans , Leukemia/pathology , Leukemia/physiopathology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/pathology , Myelodysplastic Syndromes/pathology , Myelodysplastic Syndromes/physiopathology , Oxygen/metabolism , Primary Myelofibrosis/metabolism , Reticulin/metabolism
7.
West Indian Med J ; 62(1): 89-91, 2013 Jan.
Article in English | MEDLINE | ID: mdl-24171336

ABSTRACT

Primary isolated bone marrow disease as a presenting feature of lymphoma is very rare. We describe the case of a Chinese with isolated bone marrow small B-cell lymphoma as a first manifestation. A 55-year old woman was admitted to our hospital with fever. Her peripheral blood smear and laboratory findings were suggestive of bicytopenia. Bone marrow specimen showed diffusely distributed small-sized lymphocytes. Combined with immunophenotypic and chromosomal analysis, a diagnosis of primary bone marrow B-cell non-Hodgkin's lymphoma was made. The patient was treated with R-CHOP (rituximab and cyclophosphamide, epirubicin, vindesine, and prednisone) regimen for six cycles. She had complete remission and is still alive without relapse. We concluded that primary bone marrow mature small B-cell lymphoma is a rare but distinctive subtype of lymphoma. The prognosis for this entity is poor but rituximab-based treatment is promising for improving its outcomes.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bone Marrow Neoplasms , Bone Marrow/pathology , Lymphoma, B-Cell , Antineoplastic Agents/administration & dosage , Bone Marrow Neoplasms/diet therapy , Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/pathology , Lymphoma, B-Cell/physiopathology , Middle Aged , Prednisone/administration & dosage , Remission Induction , Rituximab , Treatment Outcome , Vincristine/administration & dosage
8.
Ann Surg ; 255(6): 1105-12, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22580852

ABSTRACT

OBJECTIVE: To assess the impact of disseminated tumor cells (DTC) in bone marrow on recurrence and survival in complete resected esophageal cancer (EC). BACKGROUND: Current modalities to predict tumor recurrence and survival in EC are insufficient. Here, we evaluated in a prospective study the prognostic relevance of DTC in bone marrow for the natural postoperative course of EC. METHODS: We enrolled 370 consecutive EC patients (1995-2009). All tumors, 189 squamous cell carcinomas and 181 adenocarcinomas, were completely surgically resected (R0), and patients received neither neoadjuvant nor adjuvant therapy. Disseminated tumor cells were detected by an immunocytochemical cytokeratin assay in preoperatively taken bone marrow aspirates. The results were correlated with clinic-pathological parameters and clinical outcome. RESULTS: Overall 120 (32.4%) patients harbored DTC in their bone marrow. Presence of DTC significantly correlated with aggressive tumor biology as indicated by increased tumor size (P = 0.026), regional (P = 0.002) and distant (P = 0.012) lymph node metastases, and higher relapse rate (P < 0.001, χ test). A gradual decrease in disease-free (P < 0.001) and overall (P < 0.001, log-rank test) survival was observed between DTC-negative and DTC-positive patients and was evident in subgroup analysis stratified for nodal status, lymph node yield, lymph node ratio, and tumor subtypes. Disseminated tumor cells were identified as a strong independent prognosticator of tumor recurrence (hazard ratio [HR] 4.0, 95% confidence interval [CI]: 2.96-5.45, P < 0.001) and overall survival (HR 3.1, 95% CI: 2.37-4.09, P < 0.001, Cox regression analysis). CONCLUSIONS: The presence of DTC in bone marrow is a strong and independent prognostic factor in patients with resectable EC.


Subject(s)
Adenocarcinoma/physiopathology , Bone Marrow Neoplasms/physiopathology , Carcinoma, Squamous Cell/physiopathology , Esophageal Neoplasms/physiopathology , Neoplasm Recurrence, Local , Neoplastic Cells, Circulating , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Bone Marrow Neoplasms/secondary , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/surgery , Disease Progression , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Prospective Studies , Risk Factors , Survival Analysis
9.
Langenbecks Arch Surg ; 397(4): 535-42, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22350614

ABSTRACT

PURPOSE: More than 130 years ago, circulating tumour cells (CTCs) and disseminated tumour cells (DTCs) have been linked to metastasis. Since then, a myriad of studies attempted to characterise and elucidate the clinical impact of CTCs/DTCs, amongst others in colorectal cancer (CRC). Due to a flood of heterogeneous findings regarding CTCs/DTCs in CRC, this review aims to describe the known facts about CTC/DTC biology and clinical impact. METHODS: To identify the basic scientific literature regarding the biology and clinical impact of CTCs/DTCs in CRC, we reviewed the literature in the PubMed database. We focused on publications written in English and published until January 2012. As search terms, we used "colorectal cancer (CRC)", "colon cancer (CC)", "CTC", "DTC", "bone marrow (BM)", "lymph node (LN)", "peripheral blood (PB)", "significance" and "prognosis". RESULTS: CTC detection and quantification under standardised conditions is feasible. Several studies in large patient settings have revealed prognostic impact of CTCs in CRC. CRC-derived DTC detection and analysis in BM exhibits a more heterogeneous picture but also shows clinical value. Furthermore, the presence of DTCs in LN has a strong prognostic impact in CRC. CONCLUSIONS: Clinical relevance and prognostic significance of CTCs/DTCs in CRC have been clearly demonstrated in many experimental studies. The major challenge in CTC/DTC research is now to harmonise the various identification and detection approaches and consequently to conduct large prospective multi-institutional trials to verify the use of CTCs/DTCs as a valid prognostic and predictive biomarker for clinical routine.


Subject(s)
Colorectal Neoplasms/physiopathology , Neoplastic Cells, Circulating , Animals , Biomarkers, Tumor/genetics , Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Bone Marrow Neoplasms/secondary , Cell Proliferation , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Disease Models, Animal , Disease Progression , Epithelial-Mesenchymal Transition/physiology , Humans , Liver Neoplasms/pathology , Liver Neoplasms/physiopathology , Liver Neoplasms/secondary , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Lung Neoplasms/secondary , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Mice , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/physiopathology , Neoplastic Cells, Circulating/pathology , Prognosis
10.
Adv Clin Exp Med ; 21(6): 767-71, 2012.
Article in English | MEDLINE | ID: mdl-23457135

ABSTRACT

BACKGROUND: The development of bone marrow fibrosis is a severe complication in hematological diseases. The progress of bone marrow myelofibrosis is evaluated by a trephine examination and may be characterized by the biochemical markers of collagen turnover determination. OBJECTIVES: Investigation of serum prolidase activity and biochemical markers of collagen metabolism in order to establish its role in the development of bone marrow fibrosis. MATERIAL AND METHODS: The group of 37 patients with myeloproliferative neoplasms (MPN) before treatment, consisted of 16 patients with chronic myeloid leukemia (CML), 7 with primary myelofibrosis (PMF), 8 with essential thrombocythopenia (ET), and 6 with polycythemia vera (PV). RESULTS: It was found that the plasma activity of prolidase (Pro) was reduced to almost half together with the serum level of osteocalcin (BGL), and hydroxyproline (H-PRO) in the serum and urine of patients with MPN in comparison to the control group. In the MPN group of patients, the levels of N-terminal procollagen III peptide (PIIINP), type I procollagen (PICP) and the C-terminal telopeptide of type I collagen (ICTP) were significantly higher. CONCLUSIONS: The alteration of collagen turnover markers in the MPN patient group (the elevation of synthesis and inhibition of collagen catabolism rate) has suggested that a diminished prolidase activity may contribute to such alteration of collagen metabolism and should be consider a biomarker of MPN progress.


Subject(s)
Bone Marrow Neoplasms/enzymology , Dipeptidases/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Bone Marrow Neoplasms/physiopathology , Bone Remodeling , Case-Control Studies , Connective Tissue/pathology , Connective Tissue/physiopathology , Female , Humans , Male , Middle Aged , Young Adult
11.
Article in English | MEDLINE | ID: mdl-21264782

ABSTRACT

Metastasis is the rapid proliferation of cancer cells (secondary tumour) at a specific place, generally leading to death. This occurs at anatomical parts providing the necessary environment for vascularity, oxygen and food to hide their actions and trigger the rapid growth of cancer. Prostate and breast cancers, for example, use bone marrow for their proliferation. Bone-supporting cancer cells thus adapt to the environment, mimicking the behaviour of genetic and molecular bone cells. Evidence of this has been given in Cecchini et al. (2005, EAU Update Ser. 3:214-226), providing arguments such as how cancer cell growth is so active during bone reabsorption. This paper simulates metastasis activation in bone marrow. A mathematical model has been developed involving the activation of molecules from bone tissue cells, which are necessary for cancer to proliferate. Here, we simulate two forms of secondary tumour growth depending on the type of metastasis: osteosclerosis and osteolysis.


Subject(s)
Bone Neoplasms/secondary , Models, Biological , Neoplasm Metastasis/pathology , Neoplasm Metastasis/physiopathology , Biomedical Engineering , Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Bone Marrow Neoplasms/secondary , Bone Neoplasms/pathology , Bone Neoplasms/physiopathology , Bone Remodeling/physiology , Cell Differentiation/physiology , Cell Proliferation , Computer Simulation , Humans , Mathematical Concepts , Osteolysis/pathology , Osteolysis/physiopathology , Osteosclerosis/pathology , Osteosclerosis/physiopathology , Parathyroid Hormone-Related Protein/physiology , Somatomedins/physiology , Transforming Growth Factor beta/physiology
12.
Cell Signal ; 23(12): 1952-60, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21777670

ABSTRACT

Single disseminated tumor cells (DTC) can be detected in the bone marrow (BM) from 20% to 60% of patients with various tumors including non-small cell lung cancer (NSCLC). Detection of DTC in the BM of NSCLC patients is associated with poor prognosis and may be responsible for metastatic relapse. However, the functional properties of DTC are widely unknown. Here, we performed the first functional analysis of DTC focusing on the activation of the PI3K/Akt signalling pathway and the functional roles of Akt isoforms. In vitro kinase assays revealed a high activity of Akt3 in NSCLC-derived DTC. Proliferation and survival of DTC was reduced by depletion of Akt3 and to a lesser extend by Akt1, but not after depletion of Akt2. The major effect of Akt3 on the proliferation of DTC was associated with an Akt3-mediated regulation of both, cyclin D1 and cyclin D3, whereas Akt1 regulated the expression of cyclin D1 only. In contrast all three Akt isoforms, especially Akt2, were involved in the regulation of migration. Analysis of signalling events downstream of distinct Akt isoforms revealed that expression levels of urokinase-type plasminogen activator and its receptor were decreased after knockdown of Akt1 and Akt3. In addition, EGF-stimulated proliferative and anti-apoptotic signals are mediated by Akt1 and Akt3 in DTC. Finally, by immunofluorescence staining of primary DTC from BM samples of lung cancer patients, pAkt(S473) and Akt3 positive DTC were detected in vivo. Our data demonstrate that Akt1 and notably Akt3 regulate proliferation, survival, migration and EGF-mediated signal transduction in NSCLC-derived DTC.


Subject(s)
Cell Movement , Cell Proliferation , Cell Survival , Epidermal Growth Factor/physiology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Bone Marrow Neoplasms/metabolism , Bone Marrow Neoplasms/physiopathology , Bone Marrow Neoplasms/secondary , Breast Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/physiopathology , Carcinoma, Non-Small-Cell Lung/secondary , Cell Line, Tumor , Enzyme Assays , Epidermal Growth Factor/pharmacology , ErbB Receptors/metabolism , Female , Gene Expression , Gene Knockdown Techniques , Glycogen Synthase Kinase 3/metabolism , Humans , Isoenzymes/metabolism , Lung Neoplasms/pathology , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , RNA Interference , Receptor, ErbB-2/metabolism , Receptor, ErbB-3/metabolism , Receptors, Urokinase Plasminogen Activator/genetics , Receptors, Urokinase Plasminogen Activator/metabolism , Urokinase-Type Plasminogen Activator/genetics , Urokinase-Type Plasminogen Activator/metabolism
13.
Acta Haematol ; 126(2): 122-8, 2011.
Article in English | MEDLINE | ID: mdl-21701157

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), currently considered to originate from immature plasmacytoid dendritic cells (DC), is a rare and aggressive CD4+CD56+ neoplasm that frequently involves the skin and bone marrow. We present a case of an 80-year-old man with a CD4+CD56+ BPDCN that affected the orbital cavity and bone marrow. Although BPDCN has not been reported to express any lineage-specific markers, the neoplastic cells strongly expressed the CD13 antigen. Therefore, in addition to pathological examination, we attempted to induce in vitro morphological and surface marker changes with IL-3 and CD40 ligand. After treatment with these cytokines, the tumor cells enlarged markedly, acquired many fine dendrites, similar to mature DC, and showed enhanced expression of antigens specific to DC or antigen-presenting cells, such as CD40, CD80, CD83 and CD86. To the best of our knowledge, this is the first report of BPDCN expressing a myeloid antigen, CD13, although CD33 expression has been described in some cases. The present patient received 2 courses of combination chemotherapy consisting of cytarabine and etoposide, which resulted in complete remission. Given that the cellular origin of plasmacytoid DC is still controversial, myeloid antigen expression involving CD13 may not exclude a diagnosis of BPDCN.


Subject(s)
Anemia/etiology , Bone Marrow Neoplasms/metabolism , CD13 Antigens/metabolism , Dendritic Cells/pathology , Neoplasms, Plasma Cell/metabolism , Orbital Neoplasms/metabolism , Aged, 80 and over , Bone Marrow Neoplasms/blood , Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Humans , Male , Neoplasms, Plasma Cell/blood , Neoplasms, Plasma Cell/pathology , Neoplasms, Plasma Cell/physiopathology , Orbital Neoplasms/blood , Orbital Neoplasms/pathology , Orbital Neoplasms/physiopathology
14.
Appl Immunohistochem Mol Morphol ; 19(3): 279-82, 2011 May.
Article in English | MEDLINE | ID: mdl-21475041

ABSTRACT

Hairy cell leukemia (HCL) is a rare chronic B-cell disorder with an increased risk of second tumors. The relative risk of second cancers reported in various series of HCL patients ranged from 0.95 to 4.33, but simultaneous presentation of HCL and other epithelial malignancies is very rare. To our knowledge, we present the first case of the coexistence of signet ring carcinoma of the stomach and HCL. We report a case of the simultaneous presentation of HCL and metastasis of the primary signet ring cell carcinoma of the stomach to the bone marrow and skin. A bone marrow biopsy was performed on a patient with pancytopenia. A histologic examination with immunostaining of the bone marrow specimen showed the presence of signet ring carcinoma cells in addition to HCL. As a consequence, our patient underwent further diagnostic procedures including endo-gastro-duodenoscopy with biopsy of gastric tumor mass, which established the diagnosis of gastric signet ring cell carcinoma.


Subject(s)
Bone Marrow Neoplasms/diagnosis , Bone Marrow/pathology , Carcinoma, Signet Ring Cell/diagnosis , Leukemia, Hairy Cell/diagnosis , Skin Neoplasms/diagnosis , Stomach Neoplasms/diagnosis , Aged , Biopsy , Blood Cell Count , Bone Marrow Neoplasms/complications , Bone Marrow Neoplasms/physiopathology , Bone Marrow Neoplasms/secondary , Carcinoma, Signet Ring Cell/complications , Carcinoma, Signet Ring Cell/physiopathology , Carcinoma, Signet Ring Cell/secondary , Gastroscopy , Humans , Leukemia, Hairy Cell/complications , Leukemia, Hairy Cell/pathology , Leukemia, Hairy Cell/physiopathology , Male , Pancytopenia , Skin Neoplasms/complications , Skin Neoplasms/physiopathology , Skin Neoplasms/secondary , Splenomegaly , Stomach Neoplasms/complications , Stomach Neoplasms/pathology , Stomach Neoplasms/physiopathology
15.
Curr Opin Hematol ; 17(4): 281-6, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20473160

ABSTRACT

PURPOSE OF REVIEW: In the postnatal life, hematopoietic stem cell (HSC) niches are specialized microenvironments in the bone marrow that are essential for the maintenance and function of HSCs. The purpose of this review is to discuss the concept of HSC niche in light of recent studies that broaden its complexity and better define its molecular regulation. Also, we will discuss recent studies addressing the impact of leukemia development on HSC regulation and normal hematopoiesis, while discussing the potential regulation of leukemia-initiating cells by bone marrow niches. RECENT FINDINGS: Recent studies have identified new cellular and molecular components of the HSC niche and highlighted reciprocal interactions between the hematopoietic cells and their niches. These studies indicate that the HSC niche is not constituted by a single cell type but rather should be considered as a multicellular functional unit. Finally, advances have been made that provide promising insights into the the instructive role of the bone marrow microenvironment in hematological malignancies. SUMMARY: Increasing insights into the cell-cell cross talk between the hematopoietic system and its microenvironment in the bone marrow, and in particular in the interplay of HSCs with their niche(s), should provide new tools for combinatorial therapies in bone marrow failure and bone marrow cancers.


Subject(s)
Bone Marrow Cells/physiology , Bone Marrow Neoplasms/physiopathology , Hematopoiesis/physiology , Stem Cell Niche/physiology , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Bone Marrow Neoplasms/genetics , Bone Marrow Neoplasms/pathology , Cell Differentiation/genetics , Cell Differentiation/physiology , Cell Lineage/genetics , Cell Lineage/physiology , Gene Expression Regulation, Developmental , Hematopoiesis/genetics , Humans , Stem Cell Niche/cytology , Stem Cell Niche/metabolism
17.
Urologe A ; 46(8): 888-90, 2007 Aug.
Article in German | MEDLINE | ID: mdl-17632696

ABSTRACT

The skeletal system is the most frequent metastatic site of hematogenous spread of urologic carcinomas. Osseus metastases are classified as osteoneutral, osteolytic, osteoblastic and combinations thereof. Osteolytic metastases lead to bone resorption by activating osteoclasts, while osteoblastic metastases stimulate osteoblasts by paracrine mechanisms. The local osteoblastic effect is associated with secondary systemic bone resorption. The use of bisphosphonates is now an established supportive therapy and newer treatment strategies including targeted intervention in the pathophysiology of bone metastases and radioimmunotherapy are being applied or will be coming soon.


Subject(s)
Bone Neoplasms/secondary , Bone Resorption/physiopathology , Urologic Neoplasms/physiopathology , Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Bone Marrow Neoplasms/secondary , Bone Marrow Neoplasms/therapy , Bone Neoplasms/pathology , Bone Neoplasms/physiopathology , Bone Neoplasms/therapy , Bone Resorption/pathology , Bone Resorption/therapy , Bone and Bones/pathology , Bone and Bones/physiopathology , Cytokines/physiology , Diphosphonates/therapeutic use , Humans , Osteoblasts/pathology , Osteoblasts/physiology , Osteoclasts/pathology , Osteoclasts/physiology , Osteolysis/pathology , Osteolysis/physiopathology , Osteolysis/therapy , Osteoprotegerin/physiology , Parathyroid Hormone-Related Protein/physiology , RANK Ligand/antagonists & inhibitors , RANK Ligand/physiology , Radioimmunotherapy , Urologic Neoplasms/pathology , Urologic Neoplasms/therapy
18.
BMC Cancer ; 6: 195, 2006 Jul 21.
Article in English | MEDLINE | ID: mdl-16859559

ABSTRACT

BACKGROUND: The chemokine stromal derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 have been demonstrated to be crucial for the homing of stem cells and prostate cancers to the marrow. While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing. CD164 is known to function as a receptor that regulates stem cell localization to the bone marrow. RESULTS: Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein. Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices. Human tissue microarrays stained for CD164 demonstrated a positive correlation with prostate-specific antigen levels, while its expression was negatively correlated with the expression of androgen receptor. CONCLUSION: Our findings suggest that CD164 may participate in the localization of prostate cancer cells to the marrow and is further evidence that tumor metastasis and hematopoietic stem cell trafficking may involve similar processes.


Subject(s)
Bone Marrow Neoplasms/secondary , Endolyn/metabolism , Neoplasm Metastasis/physiopathology , Prostatic Neoplasms/pathology , Bone Marrow Neoplasms/physiopathology , Cell Adhesion , Chemokine CXCL12 , Chemokines, CXC/physiology , Gene Expression Profiling , Hematopoietic Stem Cells/physiology , Humans , Male , Prostate-Specific Antigen , Tumor Cells, Cultured
19.
Natl Med J India ; 19(2): 80-9, 2006.
Article in English | MEDLINE | ID: mdl-16756196

ABSTRACT

The management of multiple myeloma has undergone a major change during the past decade. Currently, patients < 65 years of age with advanced disease (stage II-III) are best treated with initial chemotherapy (3-4 cycles of vincristine, adriamycin and dexamethasone, or vincristine, adriamycin and methyl prednisolone, or thalidomide and dexamethasone followed by high dose chemotherapy with autologous peripheral blood stem cell transplantation. More than 50% of patients achieve complete response following this approach. The results of a number of nonrandomized and randomized studies indicate that treatment with high dose chemotherapy followed by autologous peripheral blood stem cell transplantation is associated with improved overall and event-free survival compared with conventional chemotherapy. The absence of chromosome 13 abnormalities, serum albumin levels > 3.5 g/dl and low serum b-2 microglobulin are associated with a better outcome. Almost all patients with significant bone disease or osteoporosis are candidates for therapy with bisphosphonates. About one-third of patients with relapsed or refractory myeloma benefit from therapy with thalidomide or bortezomib (a proteosome inhibitor). Recent work in the immunotherapy of myeloma suggests that some novel immune-based approaches might be useful in the management. The application of cytogenetics and molecular genetics, especially gene expression profiling, are likely to be areas of active research in future studies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Neoplasms , Multiple Myeloma , Peripheral Blood Stem Cell Transplantation , Bone Marrow Neoplasms/diagnosis , Bone Marrow Neoplasms/drug therapy , Bone Marrow Neoplasms/physiopathology , Bone Marrow Neoplasms/surgery , Dexamethasone/administration & dosage , Diphosphonates/administration & dosage , Doxorubicin/administration & dosage , Drug Therapy, Combination , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapy , Multiple Myeloma/physiopathology , Multiple Myeloma/surgery , Retrospective Studies , Vincristine/administration & dosage
20.
Exp Hematol ; 33(3): 318-28, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15730855

ABSTRACT

OBJECTIVE: We hypothesized that the presence of tumor cells in bone marrow (BM) could alter hematopoietic progenitor cell functions. Therefore, we evaluated phenotypic and in vitro functional properties of BM-derived CD34+ progenitors issued from untreated and newly diagnosed patients presenting a mature B-lymphoproliferative disorder (LPD) involving the BM (Inv+). PATIENTS AND METHODS: In vitro proliferation and differentiation capacities of primitive and committed progenitors were evaluated by cobblestone area-forming cell (CAFC) and colony-forming cell (CFC) assays, and ex vivo cell expansion. Migratory capacities of CD34+ cells were explored by chemotaxis assays using a CXCL12alpha gradient. RESULTS: Our results showed that CD34+ cells from Inv+ patients overexpressed CD117 and had a significant decrease of week-3 and -6 CAFC, and CFC frequencies, compared to cells obtained from healthy volunteers and LPD patients without BM involvement (Inv-). In addition, progenitors from Inv+ patients maintained a significantly decreased CFC capacity after ex vivo cell expansion, compared to healthy volunteers. However, the former cells held their migratory capacity in response to CXCL12alpha. CONCLUSION: Functional defects of primitive and committed CD34+ progenitors detected among LPD patients with BM tumor involvement suggest either that tumor cells may induced bystander effects on progenitors or that "unusual" CD34+ cells may exist in the BM that could belong to the proliferating tumor tissue.


Subject(s)
Antigens, CD34 , Bone Marrow Neoplasms/physiopathology , Bone Marrow/physiopathology , Bystander Effect , Hematopoietic Stem Cells , Lymphoproliferative Disorders/physiopathology , Adult , Aged , B-Lymphocytes , Bone Marrow Neoplasms/secondary , Case-Control Studies , Female , Humans , Male , Middle Aged
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