Drugs targeting the bone microenvironment: new therapeutic tools in Ewing's sarcoma?

Introduction: Ewing's sarcoma (ES) is the second most frequent malignant primary bone tumour in children, adolescents and young adults. The overall survival is 60 – 70% at 5 years but still very poor for patients with metastases, disease relapse or for those not responding to chemotherapy. For these high risk patients, new therapeutic approaches are needed beyond conventional therapies (chemotherapy, surgery and radiation) such as targeted therapies. Areas covered: Transcriptomic and genomic analyses in ES have revealed alterations in genes that control signalling pathways involved in many other cancer types. To set up more specific approaches, it is reasonable to think that the particular microenvironment of these bone tumours is essential for their initiation and progression, including in ES. To support this hypothesis, preclinical studies using drugs targeting bone cells (bisphosphonate zoledronate, anti-receptor activator of NF-κB ligand strategies) showed promising results in animal models. This review will discuss the new targeted therapeutic options in ES, focusing more particularly on the ones modulating the bone microenvironment. Expert opinion: Targeting the microenvironment represents a new option for patients with ES. The proof-of-concept has been demonstrated in preclinical studies using relevant animal models, especially for zoledronate, which induced a strong inhibition of tumour progression in an orthotopic bone model

Eschar and neck lymphadenopathy caused by Francisella tularensis after a tick bite: a case report

<p>Abstract</p> <p>Introduction</p> <p>In 25 to 35% of cases, the aetiological agent of scalp eschar and neck lymphadenopathy after a tick bite remains undetermined. To date, <it>Rickettsia slovaca</it>, <it>Rickettsia raoultii </it>and more recently <it>Bartonella henselae </it>have been associated with this syndrome.</p> <p>Case presentation</p> <p>A four-year-old Caucasian boy was admitted to hospital with fever, vomiting and abdominal pain. On physical examination, an inflammatory and suppurating eschar was seen on the scalp, with multiple enlarged cervical lymph nodes on both sides. Although no tick was found in this scalp lesion, a diagnosis of tick-borne lymphadenopathy was suggested, and explored by serology testing and polymerase chain reaction of a biopsy from the eschar. <it>Francisella tularensis </it>DNA was found in the skin biopsy and the serology showed titres consistent with tularaemia.</p> <p>Conclusion</p> <p>This is, to the best of our knowledge, the first reported case of scalp eschar and neck lymphadenopathy after tick bite infection caused by <it>F. tularensis.</it></p

NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma

Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15–76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4 to 85 months (mean, 35 months). Five patients were alive without evidence of disease, two were alive with disease and two died 8 months after the initial diagnosis. cEMCs were from three males and two females with an age range of 37–82 years (mean, 57 years); they presented in extremities, shoulder and paravertebral/cervical. Follow-up, available for four patients, ranged from 6 to 220 months (mean, 61 months). All patients were alive, two with recurrences and/or metastases and two without evidence of disease. Morphologically, the distinction between these two entities was difficult since all cases exhibited features typically seen in myoepithelial tumours. Immunohistochemically, MECs expressed pan-keratin (80 %), epithelial membrane antigen (EMA; 57 %), S100 (50 %), alpha-smooth muscle actin (ASMA; 75 %), calponin (67 %) and p63 (25 %). S100 and EMA were expressed in 40 % of cEMC cases respectively with additional immunoreactivity for p63, ASMA and glial fibrillary acidic protein in one case. Pan-keratin was negative in all neoplasms. NR4A3 rearrangement was present in four of four cEMCs and in none of the MECs. In contrast, three of nine (33 %) MECs and four of five (80 %) cEMCs showed an EWSR1 rearrangement. In summary, MECs and cEMCs share clinical, morphological, immunohistochemical and genetic characteristics. The pathognomic rearrangement of NR4A3 is a useful diagnostic feature in identifying cEMCs

Spindle cell embryonal rhabdomyosarcoma of the prostate in an adult patient – case report and review of clinicopathological features

BACKGROUND: Embryonal rhabdomyosarcoma of the prostate in an adult is a very rare event with only a few cases published. Diagnosis usually occurs with advanced disease frequently already with metastatic spread. In adults prognosis is very poor, therefore early diagnosis is crucial. To date, only three cases of spindle cell subtype of embryonal rhabdomyosarcoma of the prostate in an adult have been published. CASE PRESENTATION: We report an additional case of prostatic spindle cell embryonal rhabdomyosarcoma subtype in an adult. CONCLUSIONS: We discuss relevant clinicopathological features of spindle cell embryonal rhabdomyosarcoma of the prostate in adult patients in the context of the literature

Identification of an erythropoietin-sensitive cell line

The murine lymphoblastic cell line DA-1 has been characterized as dependent upon both interleukin-3 (IL-3, multicolony-stimulating factor [multi-CSF]) and granulocyte-macrophage colony-stimulating factor (GM- CSF) for survival and growth. Here we demonstrate that it is responsive to a third hematopoietic factor, the erythroid-specific hormone, erythropoietin (Epo). DA-1 cells are stimulated to proliferate by partly purified natural murine and human Epo, and pure recombinant human Epo. Antibody to Epo specifically blocks Epo-stimulated growth. Maximal growth stimulated by Epo and GM-CSF is similar, and considerably less than that stimulated by multi-CSF. Proliferation stimulated by Epo and GM-CSF is transient, decreasing within 24 to 48 hours of exposure. However, Epo acts cooperatively with GM-CSF to sustain proliferation. With or without GM-CSF, no obvious erythroid differentiation of DA-1 cells occurs after exposure to Epo for up to 72 hours. This is the first report of a growth factor-dependent cell line also responsive to Epo for survival and growth. The availability of this cell line model should greatly facilitate biochemical analysis of the mechanism of Epo growth-stimulating action.</jats:p

Identification of an erythropoietin-sensitive cell line

Abstract The murine lymphoblastic cell line DA-1 has been characterized as dependent upon both interleukin-3 (IL-3, multicolony-stimulating factor [multi-CSF]) and granulocyte-macrophage colony-stimulating factor (GM- CSF) for survival and growth. Here we demonstrate that it is responsive to a third hematopoietic factor, the erythroid-specific hormone, erythropoietin (Epo). DA-1 cells are stimulated to proliferate by partly purified natural murine and human Epo, and pure recombinant human Epo. Antibody to Epo specifically blocks Epo-stimulated growth. Maximal growth stimulated by Epo and GM-CSF is similar, and considerably less than that stimulated by multi-CSF. Proliferation stimulated by Epo and GM-CSF is transient, decreasing within 24 to 48 hours of exposure. However, Epo acts cooperatively with GM-CSF to sustain proliferation. With or without GM-CSF, no obvious erythroid differentiation of DA-1 cells occurs after exposure to Epo for up to 72 hours. This is the first report of a growth factor-dependent cell line also responsive to Epo for survival and growth. The availability of this cell line model should greatly facilitate biochemical analysis of the mechanism of Epo growth-stimulating action.</jats:p