Vascular anomalies are classified according to the ISSVA classification into vascular tumors with endothelial proliferation and vascular malformations without proliferation. Infantile hemangioma is a vascular tumor that is diagnosed by GLUT-1 immunoreactivity. GLUT-1 positivity is reportedly sometimes observed in angiosarcoma, but the clinical significance remains unclear. Here, immunohistochemistry was performed on tissue samples from patients with angiosarcoma (n = 10), pyogenic granuloma (n = 9), and senile hemangioma (n = 10), with infantile hemangioma serving as a positive control. GLUT-1 expression was detected in the cytoplasm and/or cell membrane of tumor cells in all cases of angiosarcoma (100%), as well as in the cytoplasm of some cases of pyogenic granuloma (44.4%) and senile hemangioma (40%). Double immunofluorescent staining for GLUT-1 and CD34 revealed co-expression in tumor endothelial cells of angiosarcoma. Clinically, cases of angiosarcoma with strong membranous GLUT-1 expression tended to be associated with tumor progression, while those with weak or mild cytoplasmic expression showed a better response to treatment. These findings suggest that GLUT-1 may serve as a useful marker of tumor progression for angiosarcoma, and as a potential therapeutic target in vascular tumors.

Nestin-expressing stem cells located in the bulge area of the hair follicle can give rise to multiple cell types. In the present study, we subcutaneously transplanted red fluorescent protein (RFP)-labeled SK-MEL-5 human melanoma cells into nestin-driven green fluorescent protein (ND-GFP)-nude mice. Nestin-GFP-positive cells differentiated into CD31-positive endothelial cells and αSMA-positive pericytes, and βIII-tubulin-positive neurons, forming blood vessel-like and nerve-like structures within the transplanted melanoma. Bevacizumab, a vascular endothelial growth factor (VEGF)-targeting monoclonal antibody, suppressed nestin-positive blood-vessel structures and nerve structures from forming within the tumor but did not significantly inhibit tumor growth. Due to bevacizumab treatment, blood-vessel-like and nerve-like structures expressing CD31, αSMA, and βIII tubulin formed without the expression of nestin in the transplanted melanoma but remained RFP-positive, suggesting that they trans-differentiated from melanoma cells. Relative mRNA expression of VEGFA also significantly decreased in the melanoma after bevacizumab treatment of the mice. In contrast, VEGFR2 and FGF6, markers that are related to blood vessels, significantly increased compared with the non-treated mice. In the bevacizumab-treated mice, mRNA expression of Tuj1, BDNF, and IGF1 markers related to nerves significantly increased within the melanoma. In the bevacizumab-treated mice, nestin expression was not detected, but RFP was maintained in the blood-vessel-like and nerve-like structures in the melanoma. Since nestin was not detected and RFP was maintained, it suggests these structures trans-differentiated from the melanoma cells. The present study suggests that both the host and cancer cells can differentiate into blood-vessel-like and nerve-like structures in the melanoma.

This is an English-translated version of the Japanese Dermatological Association's clinical practice guidelines for alopecia areata (AA) 2024. It includes the sections of summary, pathogenesis and epidemiology, evaluation and diagnosis, and treatment of AA. Updates based on recent evidence/advances were made in each part. The treatment part contains the statements of recommendation for 25 clinical questions (CQs) with respective recommendation/evidence levels. AA-cube, a graphic illustration conceptualizing the treatment strategy based on individual patients' factors, was newly proposed. Taking into account the recent approval of a JAK inhibitor and a JAK3/TEC family kinase selective inhibitor, a CQ for these modalities was also added. These guidelines aim to support evidence-based management of AA as well as prompt understanding of disease etiopathogenesis.

Immune checkpoint inhibitor (ICI) therapy serves as a standard treatment for advanced or recurrent malignant melanoma. Tumour neoantigenicity is an important factor for the effectiveness of the ICI therapy. However, the absence of reliable biomarkers to predict ICI therapy efficacy remains an unresolved challenge. REV7 is a subunit of mutagenic DNA polymerase ζ and plays a role in generating genetic alterations following DNA damage. In this study, we examined REV7 as a potential predictive biomarker for ICI therapy in melanoma. Using RNA in situ hybridisation, we assessed REV7 expression in melanomas from 42 patients who received ICI therapy. Our analysis revealed that high REV7 expression correlated significantly with improved progression-free survival, durable clinical benefit and favourable clinical outcomes according to response evaluation criteria in solid tumours. These findings suggest that REV7 may be a potential predictive biomarker for ICI therapy response in melanoma.

Although AA amyloidosis is primarily caused by inflammatory conditions, associations between AA amyloidosis and solid cancers have occasionally been described. Herein, we report the case of a 48-year-old man in whom resection of a proliferating pilomatricoma with deposition of AA amyloid resulted in remission of concomitant AA gastrointestinal amyloidosis. A rapidly growing, giant, reddish, ulcerated tumor measuring 16 × 13 cm in size was identified on the upper left arm on a visit to our hospital. Gastrointestinal AA amyloidosis was diagnosed from colorectal mucosal biopsy at the same time, and weight loss and profuse diarrhea were clinically evident. As treatment, the tumor was resected with a 10-mm surgical margin. Histologically, the tumor predominantly comprised a lobular proliferation of basophilic cells peripherally, filled with eosinophilic, cornified material and shadow cells with mitoses observed in basophilic cells. Specimens revealed eosinophilic, homogeneous deposits around tumor nests, which were confirmed as amyloid deposits by positive staining with Congo red stain. These deposits were immunohistochemically positive on staining with anti-serum amyloid A antibody. Collectively, proliferating pilomatricoma with AA amyloidosis was diagnosed. After tumor resection, chronic diarrhea resolved and no amyloid deposition was apparent in colorectal biopsy. It is important to remember that if amyloid deposition is present in a tumor, aggressive tumor excision may alleviate systemic amyloidosis.

There has been only limited success to differentiate adult stem cells into cardiomyocyte subtypes. In the present study, we have successfully induced beating atrial and ventricular cardiomyocytes from rat hair-follicle-associated pluripotent (HAP) stem cells, which are adult stem cells located in the bulge area. HAP stem cells differentiated into atrial cardiomyocytes in culture with the combination of isoproterenol, activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF), and cyclosporine A (CSA). HAP stem cells differentiated into ventricular cardiomyocytes in culture with the combination of activin A, BMP4, bFGF, inhibitor of Wnt production-4 (IWP4), and vascular endothelial growth factor (VEGF). Differentiated atrial cardiomyocytes were specifically stained for anti-myosin light chain 2a (MLC2a) antibody. Ventricular cardiomyocytes were specially stained for anti-myosin light chain 2v (MLC2v) antibody. Quantitative Polymerase Chain Reaction (qPCR) showed significant expression of MLC2a in atrial cardiomyocytes and MLC2v in ventricular cardiomyocytes. Both differentiated atrial and ventricular cardiomyocytes showed characteristic waveforms in Ca 2+ imaging. Differentiated atrial and ventricular cardiomyocytes formed long myocardial fibers and beat as a functional syncytium, having a structure similar to adult cardiomyocytes. The present results demonstrated that it is possible to induce cardiomyocyte subtypes, atrial and ventricular cardiomyocytes, from HAP stem cells.

Diabetes often results in chronic ulcers that fail to heal. Effective treatment for diabetic wounds has not been achieved, although stem-cell-treatment has shown promise. Hair-follicle-associated-pluripotent (HAP)-stem-cells from bulge area of mouse hair follicle have been shown to differentiate into keratinocytes, vascular endothelial cells, smooth muscle cells, and some other types of cells. In the present study, we developed HAP-cell-sheets to determine their effects on wound healing in type-2 diabetes mellitus (db/db) C57BL/6 mouse model. Flow cytometry analysis showed cytokeratin 15 expression in 64% of cells and macrophage expression in 3.6% of cells in HAP-cell-sheets. A scratch cell migration assay in vitro showed the ability of fibroblasts to migrate and proliferate was enhanced when co-cultured with HAP-cell-sheets. To investigate in vivo effects of the HAP-cell-sheets, they were implanted into 10 mm circular full-thickness resection wounds made on the back of db/db mice. Wound closure was facilitated in the implanted group until day 16. The thickness of epithelium and granulation tissue volume at day 7 were significantly increased by the implantation. CD68 positive area and TGF-β1 positive area were significantly increased; meanwhile, iNOS positive area was reduced at day 7 in the HAP-cell-sheets implanted group. After 21 days, CD68 positive areas in the implanted group were reduced to under the control group level, and TGF-β1 positive area had no difference between the two groups. These observations strongly suggest that the HAP-cell-sheets implantation is efficient to facilitate early macrophage activity and to suppress inflammation level. Using immuno-double-staining against CD34 and α-SMA, we found more vigorous angiogenesis in the implanted wound tissue. The present results suggest autologous HAP-cell-sheets can be used to heal refractory diabetic ulcers and have clinical promise.

Wounds in diabetic patients are often difficult to heal (refractory wounds), leading to infection and necrosis, requiring to skin graft surgery or lower extremity amputation. Hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of the hair follicle. HAP stem cells can differentiate into keratinocytes, vascular endothelial cells, cardiomyocytes, neurons, pigment cells, smooth muscle cells, and glial cells. HAP stem cells are readily accessible to everyone, and can be used for autologous transplantation without immunosuppression, do not form tumors, and can be cryopreserved without loss of pluripotency, and are bankable. HAP stem cell sheets are formed by culturing the upper part of the hair follicle containing the hair follicle stem cell region. In the present study, we developed autologous stem cell sheets for rapid wound healing in diabetic db/db mouse models. The whisker pad from the upper lip of db/db mice was harvested and the upper parts of the whisker hair follicles were cultured in medium for 4 weeks to generate HAP stem cell sheets. The HAP stem cell sheets were transplanted into 10 mm circular full thickness excisional wounds established on the back of db/db mice. The wound was regularly photographed, and the size of the wound was measured daily. After 14 days, tissue was collected from the wound site and the wound healing efficacy of HAP stem cell sheet transplantation was demonstrated. The present results suggest autologous HAP stem cells can be used to heal refractory diabetic ulcers.

Cellular hair growth therapy is an emerging approach to alopecia. Recently, Tsuboi et al. (J Am Acad Dermatol. 2020;83,109–116.) have observed hair-growth stimulation by dermal-sheath-cup cells in patients with androgenic alopecia. Hair follicle-associated pluripotent (HAP) stem cells, originate in the bulge area and express nestin, have been shown to differentiate to multiple cell types including keratinocytes, neurons and numerous other cell types. In the present study, we tested if HAP stem cells could stimulate hair growth in athymic nu/nu nude mice. The upper part of whisker follicles from nestin-driven green-fluorescent protein (GFP) transgenic mice, containing GFP-expressing HAP stem cells, were transplanted in the dorsal area of the nude mice which can not produce normal hair shafts. Fluorescence microscopy and immunostaining showed that the transplanted HAP stem cells jumped and targeted the bulge area and hair bulb and other areas of the resident nude-mouse pelage follicles. The jumping HAP stem cells differentiated to keratinocytes, thereby transforming the twisted abnormal nude-mouse hair follicles to a normal-like morphology which produced normal mature hair shafts for at least 2 hair cycles. The present results demonstrate that HAP stem cells can normalize nude-mouse hair follicles and thereby stimulate hair growth, suggesting the potential of HAP stem cells for hair-loss cellular therapy.

Intracerebral hemorrhage (ICH) is a leading cause of mortality with ineffective treatment. Hair-follicle-associated pluripotent (HAP) stem cells can differentiate into neurons, glial cells and many other types of cells. HAP stem cells have been shown to repair peripheral-nerve and spinal-cord injury in mouse models. In the present study, HAP stem cells from C57BL/6J mice were implanted into the injured brain of C57BL/6J or nude mice with induced ICH. After allo transplantation, HAP stem cells differentiated to neurons, astrocytes, oligodendrocytes, and microglia in the ICH site of nude mice. After autologous transplantation in C57BL/6J mice, HAP stem cells suppressed astrocyte and microglia infiltration in the injured brain. The mRNA expression levels of IL-10 and TGF-β1, measured by quantitative Real-Time RT-PCR, in the brain of C57BL/6J mice with ICH was increased by HAP-stem-cell implantation compared to the non-implanted mice. Quantitative sensorimotor function analysis, with modified limb-placing test and the cylinder test, demonstrated a significant functional improvement in the HAP-stem-cell-implanted C57BL/6J mice, compared to non-implanted mice. HAP stem cells have critical advantages over induced pluripotent stem cells, embryonic stem cells as they do not develop tumors, are autologous, and do not require genetic manipulation. The present study demonstrates future clinical potential of HAP-stem-cell repair of ICH, currently a recalcitrant disease.

Chronic spinal cord injury (SCI) is a highly debilitating and recalcitrant disease with limited treatment options. Although various stem cell types have shown some clinical efficacy for injury repair they have not for SCI. Hair-follicle-associated pluripotent (HAP) stem cells have been shown to differentiate into neurons, Schwan cells, beating cardiomyocytes and many other type of cells, and have effectively regenerated acute spinal cord injury in mouse models. In the present report, HAP stem cells from C57BL/6J mice, encapsulated in polyvinylidene fluoride membranes (PFM), were implanted into the severed thoracic spinal cord of C57BL/6J or athymic nude mice in the early chronic phase. After implantation, HAP stem cells differentiated to neurons, astrocytes and oligodendrocytes in the regenerated thoracic spinal cord of C57BL/6J and nude mice. Quantitative motor function analysis, with the Basso Mouse Scale for Locomotion (BMS) score, demonstrated a significant functional improvement in the HAP-stem-cell-implanted mice, compared to non-implanted mice. HAP stem cells have critical advantages over other stem cells: they do not develop teratomas; do not loose differentiation ability when cryopreserved and thus are bankable; are autologous, readily obtained from anyone; and do not require genetic manipulation. HAP stem cells therefore have greater clinical potential for SCI repair than induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs)/neural progenitor cells (NPCs) or embryonic stem cells (ESCs). The present report demonstrates future clinical potential of HAP-stem-cell repair of chronic spinal cord injury, currently a recalcitrant disease.

Stimulation of hair growth in hair loss has been a difficult goal to achieve. Hair follicle-associated pluripotent (HAP) stem cells express nestin and have been shown to differentiate to multiple cell types including keratinocytes, neurons, beating cardiac muscles and numerous other cell types. HAP stem cells originate in the bulge area of the hair follicle and have been shown to migrate within and outside the hair follicle. In the present study, the upper part of vibrissa follicles from nestin-driven green-fluorescent protein (GFP) transgenic mice, containing GFP-expressing HAP stem cells, were transplanted in the dorsal area of athymic nude mice. Fluorescence microscopy and immunostaining showed the transplanted HAP stem cells jumped and targeted the bulge and hair bulb and other areas of the resident nude mouse pelage follicles where they differentiated to keratinocytes. These results indicate that transplanted nestin-GFP expressing HAP stem cells jumped from the upper part of the whisker follicles and targeted nude-mouse hair follicles, which are genetically deficient to grow normal hair shafts, and differentiated to keratinocytes to produce normal mature hair shafts. The resident nude-mouse pelage follicles targeted by jumping whisker HAP stem cells produced long hair shafts from numerous hair follicles for least 2 hair cycles during 36 days, demonstrations that HAP stem cells can stimulate hair growth. The present results for hair loss therapy are discussed.

Cardiomyocytes have been differentiated from various stem cells such as human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), but it is difficult to produce mature cardiomyocytes. We showed rat hair-follicle-associated pluripotent (HAP) stem cells have pluripotency and produced mature beating cardiomyocyte sheets differentiated from rat HAP stem cells. The upper parts of rat vibrissa hair follicles were cultured in 10% FBS DMEM and stained with antibodies of the ectoderm, mesoderm, endoderm system to show the differentiation of multiple cell types. Moreover, HAP stem cells were cultured under three different conditions to decide the most suitable culture conditions for making beating cardiomyocyte sheets. The beating cardiomyocyte sheets were shown to be mature by staining sarcomere structures. Isoproterenol alone and the combination of isoproterenol, activin A, bone morphogenetic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) effectively induced beating long-fiber cardiomyocytes, which formed beating sheets, only in the presence of all four agents. Flexible substrates were essential for the differentiation of sheets of mature beating cardiomyocytes for HAP stem cells. The features of the cardiomyocytes differentiated from HAP stem cells demonstrate they have clinical potential for heart regeneration.

Abstract BackgroundPatients frequently experience physical, mental, and even financial distress because of acute or chronic wounds to the skin. In severe situations, the skin scars can be quite noticeable, cause persistent discomfort, restrict joint motion, or be mentally taxing. Hair-follicle-associated pluripotent (HAP) stem cells were discovered by our laboratory, in the bulge area of hair follicle; and can differentiate to neurons, glia, beating cardiomyocytes, keratinocyte and nascent vessel. In the present study, we determined if HAP stem cells can accelerate cutaneous wound healing in a mouse model.MethodsHAP stem cells which were grown from the upper part of vibrissa follicle and formed a sheet in culture were implanted to dorsal wounds in a mouse model. After HAP-stem-cell-sheet-implantation, progression of wound closure with time was evaluated. After wound closure, scar morphology, infiltration of dermal inflammatory cell such as macrophage and fibrocyte and dermal fibrosis were observed histologically. mRNA of TGF-β1, type I collagen alpha 2 (COL1A2) and type III collagen alpha 1 (COL3A1) expression levels in the wound were measured by quantitative real-time PCR (RT-PCR) to assess dermal inflammation and fibrosis.ResultsHAP stem cells formed sheet which differentiated to keratinocytes, macrophages and endothelial cells in culture. After HAP-stem-cell-sheet-implantation to the dorsal wound in the mice model, it accelerated the wound closure, increased capillary-vessel-formation and suppressed macrophage and fibrocyte infiltration and collagen deposition in the dermis compared with non-implanted control mice. Also, mRNA of TGF-β1, COL1A2 and COL3A1 expression levels in the wound were decreased in the HAP-stem-cell-implanted mice compared with non-implantation control mice.ConclusionsImplantation of HAP stem cells differentiated to keratinocytes, macrophages and endothelial cells accelerated wound closure and suppressed scar formation in a mouse model, indicating clinical potential of scar-free wound healing.

•Diagnosis of CCE-CI is challenging due to nonspecific neurological symptoms.•Brain DWI revealed multiple small ischemic lesions among patients with CCE-CI.•CCE-CI was associated with atherosclerotic plaques in the ascending aorta and arch.•CCE-CI was also associated with lower eGFR and higher blood eosinophil count.•CCE-CI is associated with aortic aneurysm morbidity.

Hair-follicle-associated pluripotent (HAP) stem cells are located in the bulge area of hair follicles from mice and humans and have been shown to differentiate to neurons, glia, keratinocytes, smooth muscle cells, melanocytes and beating cardiac muscle cells in vitro. Subsequently, we demonstrated that HAP stem cells could effect nerve and spinal-cord regeneration in mouse models, differentiating to Schwann cells and neurons in this process. HAP stem cells can be banked by cryopreservation and preserve their ability to differentiate. In the present study, we demonstrated that mouse HAP stem cells cultured in neural-induction medium can extensively differentiate to dopaminergic neurons, which express tyrosine hydroxylase and secrete dopamine. These results indicate that the dopaminergic neurons differentiated from HAP stem cells may be useful in the future to improve the symptoms of Parkinson’s disease in the clinic.

The Journal of DermatologyVolume 48, Issue 7 p. e345-e346 LETTER TO THE EDITOR Successful treatment of non-AIDS Kaposi’s sarcoma with eribulin Mamiko Masuzawa, Corresponding Author masuderm@med.kitasato-u.ac.jp orcid.org/0000-0001-7116-211X Department of Dermatology, Kitasato University School of Medicine, Kanagawa, Japan Correspondence Mamiko Masuzawa, Department of Dermatology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, Japan. Email: masuderm@med.kitasato-u.ac.jpSearch for more papers by this authorKazuya Yamashita, Department of Pathology, Kitasato University Hospital, Kanagawa, JapanSearch for more papers by this authorYuichi Horigome, Department of Hematology, Kitasato University School of Medicine, Kanagawa, JapanSearch for more papers by this authorYasuyuki Amoh, Department of Dermatology, Kitasato University School of Medicine, Kanagawa, JapanSearch for more papers by this author Mamiko Masuzawa, Corresponding Author masuderm@med.kitasato-u.ac.jp orcid.org/0000-0001-7116-211X Department of Dermatology, Kitasato University School of Medicine, Kanagawa, Japan Correspondence Mamiko Masuzawa, Department of Dermatology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, Japan. Email: masuderm@med.kitasato-u.ac.jpSearch for more papers by this authorKazuya Yamashita, Department of Pathology, Kitasato University Hospital, Kanagawa, JapanSearch for more papers by this authorYuichi Horigome, Department of Hematology, Kitasato University School of Medicine, Kanagawa, JapanSearch for more papers by this authorYasuyuki Amoh, Department of Dermatology, Kitasato University School of Medicine, Kanagawa, JapanSearch for more papers by this author First published: 21 April 2021 https://doi.org/10.1111/1346-8138.15925 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume48, Issue7July 2021Pages e345-e346 RelatedInformation

Hair-follicle-associated pluripotent (HAP) stem cells express nestin, and are located in the bulge area of hair follicles and can differentiate to numerous types of cells. In the present study, we demonstrate that rat HAP stem cells simultaneously differentiated to mature cardiomyocytes and atrial myocytes. The addition of isoproterenol, activin A, bone morphogenetic protein 4 (BMP 4), basic fibroblast growth factor (bFGF), and cyclosporin A (CSA), induced simultaneously differentiation of HAP stem cells to c-kit-positive cardiomyocytes and MLC-2a-expressing atrial myocytes. The results of the present study suggest that HAP stem cells differentiating to cardiomyocytes and atrial myocytes have future clinical potential for heart regeneration.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL-NT), is a rare subtype of non-Hodgkin lymphoma associated with Epstein-Barr virus. This type of lymphoma is rare in Western countries but is more frequent in East Asia and Latin America. ENKTL-NT mostly occurs in the nose and paranasal area, including the upper aerodigestive tract. The skin is the second-most commonly involved organ. ENKTL-ET is characterized by an angiocentric, angiodestructive pattern of growth with ulceration and necrosis evident on histopathological examination. We provide the first description of ENKTL-NT presenting with intravascular localization of tumor cells in skin biopsies from both plaque and normal-appearing skin. Random skin biopsy might thus be useful for early diagnosis, staging, and estimation of prognosis in ENKTL-NT. Moreover, the current case indicates that ENKTL-NT and intravascular natural killer/T-cell lymphoma may represent related diseases.

Angiosarcoma is a rare malignant tumor derived from endothelial cells, and its prognosis is poor because advanced angiosarcoma is often resistant to taxane therapy. Endoglin (CD105) acts as a coreceptor for TGF-beta signaling and is overexpressed in tumor-associated endothelial cells and enhances tumor angiogenesis. Numerous clinical trials are testing the effectiveness of anti-endoglin antibodies in various types of malignancies. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether endoglin inhibition results in antitumor activity. Endoglin was overexpressed in angiosarcoma, and its inhibition was effective in promoting apoptosis and the suppression of migration, invasion, tube formation, and Warburg effect in angiosarcoma cells. Knockdown of endoglin activated caspase 3/7 that is essential for apoptosis, reduced survivin levels, and decreased paxillin and vascular endothelial cadherin phosphorylation and matrix metalloproteinase 2 and matrix metalloproteinase 9 activities in angiosarcoma cells. Although endoglin is a coreceptor that regulates TGF-beta signaling, the antitumor effect of endoglin in angiosarcoma was not based on Smad signaling regulation but on non-Smad TGF-beta signaling. Taken together, these results indicated that endoglin could be a novel therapeutic target for angiosarcoma.