Publications by authors named "Riko Kitazawa"

145 Publications

Hypoxia-induced phenotypic transition from highly invasive to less invasive tumors in glioma stem-like cells: Significance of CD44 and osteopontin as therapeutic targets in glioblastoma.

Transl Oncol 2021 May 27;14(8):101137. Epub 2021 May 27.

Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.

The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence, GSCs with highly invasive and highly migratory activities must assume a less-motile state and proliferate to regenerate tumor mass. Elucidating the molecular mechanism underlying this transition from a highly invasive phenotype to a less-invasive, proliferative tumor could facilitate the identification of effective molecular targets for treating GBM. Here, we demonstrate that severe hypoxia (1% O) upregulates CD44 expression via activation of hypoxia-inducible factor (HIF-1α), inducing GSCs to assume a highly invasive tumor. In contrast, moderate hypoxia (5% O) upregulates osteopontin expression via activation of HIF-2α. The upregulated osteopontin inhibits CD44-promoted GSC migration and invasion and stimulates GSC proliferation, inducing GSCs to assume a less-invasive, highly proliferative tumor. These data indicate that the GSC phenotype is determined by interaction between CD44 and osteopontin. The expression of both CD44 and osteopontin is regulated by differential hypoxia levels. We found that CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. Mouse brain tumors generated from CD44-knockdown GSCs exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene decreased GSC proliferation. These results suggest that interaction between CD44 and osteopontin plays a key role in tumor progression in GBM; inhibition of both CD44 and osteopontin may represent an effective therapeutic approach for suppressing tumor progression, thus resulting in a better prognosis for patients with GBM.
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http://dx.doi.org/10.1016/j.tranon.2021.101137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175402PMC
May 2021

Identification of calmodulin-like protein 5 as tumor-suppressor gene silenced during early stage of carcinogenesis in squamous cell carcinoma of uterine cervix.

Int J Cancer 2021 May 17. Epub 2021 May 17.

Division of Diagnostic Pathology, Ehime University Hospital, Toon City, Ehime, Japan.

In the course of identifying the molecular mechanism that is related to strong cell-cell adhesion in stratified structures of the squamous epithelium, calmodulin-like protein 5 (CALML5) was identified as a spinous structure-associated protein by producing monoclonal antibodies with the use of the crude intercellular portion of squamous tissue as an immunogen and by subsequent morphologic screening. By electrophoretic mobility shift assay (EMSA) and a series of mutagenesis studies, two transcription factors, ZNF750 and KLF4, by binding in line to the CALML5 gene promoter, were found to play a central role in CALML5 transcription. Knockdown of CALML5 by siRNA in the A431 cell line that expresses high levels of CALML5 resulted in the acceleration of wound confluence in a scratch assay, indicating that CALML5 functions as a tumor-suppressor in uterine cervical cancer. Immunohistochemical evaluation of squamous intraepithelial lesions, carcinoma in situ (CIS) and invasive uterine cancer, revealed a reduction in CALML5 expression during the stages of CIS through various molecular pathways including the blockage of the nuclear translocation of KLF4. Conversely, restoration of the nuclear translocation of KLF4 by inhibiting ERK-signaling reactivated CALML5 expression in ME180 cells expressing low levels of CALML5. Thus, alteration of the p63-ZNF750-KLF4 axis may result in critical functional loss of CALM-related genes during cancer progression. Although the morphological association of CALML5 with the spiny-structure in relation to cell motility is not clear, evaluation of CALML5 expression provides a useful diagnostic indicator of differentiating dysplasia, preinvasive and invasive cervical cancers.
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http://dx.doi.org/10.1002/ijc.33687DOI Listing
May 2021

The m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting ATG5 in seminoma.

Transl Androl Urol 2021 Apr;10(4):1711-1722

Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, China.

Background: Our previous work shows Autophagy enhanced resistance to cisplatin in seminoma. The expression of the N6-methyladenosine (m6A) methyltransferases METTL3 was significantly increased in the cisplatin-resistant TCam-2 cell line of seminoma. We aimed to investigate the role of m6A methylation in autophagy and the chemosensitivity of seminoma cells.

Methods: Plasmid and siRNA were used to overexpress and knockdown METTL3. Autophagy was detected by western blot and immunofluorescence, respectively. The expression of downstream targets of METTL3 was detected by quantitative real-time PCR (qRT-PCR) and western blot, and the m6A level of them was detected by MeRIP-qPCR. Chemosensitivity of the TCam-2 cell line was identified through MTT assay.

Results: Upon METTL3 overexpression, autophagy of TCam-2 cell line was enhanced and its sensitivity to cisplatin was decreased. The use of autophagy inhibitors 3-methyladenine (3-MA) could reverse the protective effect of METTL3 on TCam-2 cells. We found that the up-regulation of METTL3 could increase the m6A modification level of ATG5 transcript, thus increased expression of ATG5. Moreover, knockdown of ATG5 reduced METTL3-induced autophagy, suggesting that ATG5 was a potential target for METTL3 to promote autophagy.

Conclusions: In summary, our research unveiled the unique mechanism by which m6A methylation regulates autophagy and chemosensitivity of the TCam-2 cell line and METTL3 was a potential target to overcome the cisplatin resistance of seminoma.
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http://dx.doi.org/10.21037/tau-20-1411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100844PMC
April 2021

CD44 expression in the tumor periphery predicts the responsiveness to bevacizumab in the treatment of recurrent glioblastoma.

Cancer Med 2021 03 5;10(6):2013-2025. Epub 2021 Feb 5.

Department of Neurosurgery, Ehime University School of Medicine, Toon, Japan.

Antiangiogenic therapy with bevacizumab (Bev), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is a common treatment for recurrent glioblastoma (GBM), but its survival benefit is limited. Resistance to Bev is thought to be a major cause of ineffectiveness on Bev therapy. To optimize Bev therapy, identification of a predictive biomarker for responsiveness to Bev is required. Based on our previous study, we focused on the expression and functions of CD44 and VEGF in the Bev therapy. Here, we analyze a relationship between CD44 expression and responsiveness to Bev and elucidate the role of CD44 in anti-VEGF therapy. CD44 and VEGF expression in the tumor core and periphery of 22 GBMs was examined, and the relationship between expression of these molecules and progression-free time on Bev therapy was analyzed. The degree of CD44 expression in the tumor periphery was evaluated by the ratio of the mRNA expression in the tumor periphery to that in the tumor core (P/C ratio). VEGF expression was evaluated by the amount of the mRNA expression in the tumor periphery. To elucidate the roles of CD44 in the Bev therapy, in vitro and in vivo studies were performed using glioma stem-like cells (GSCs) and a GSC-transplanted mouse xenograft model, respectively. GBMs expressing high P/C ratio of CD44 were much more refractory to Bev than those expressing low P/C ratio of CD44, and the survival time of the former was much shorter than that of the latter. In vitro inhibition of VEGF with siRNA or Bev-activated CD44 expression and increased invasion of GSCs. Bev showed no antitumor effects in mice transplanted with CD44-overexpressing GSCs. The P/C ratio of CD44 expression may become a useful biomarker predicting responsiveness to Bev in GBM. CD44 reduces the antitumor effect of Bev, resulting in much more highly invasive tumors.
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http://dx.doi.org/10.1002/cam4.3767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957167PMC
March 2021

New Insights into Development of Female Reproductive Tract-Hedgehog-Signal Response in Wolffian Tissues Directly Contributes to Uterus Development.

Int J Mol Sci 2021 Jan 26;22(3). Epub 2021 Jan 26.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan.

The reproductive tract in mammals emerges from two ductal systems during embryogenesis: Wolffian ducts (WDs) and Mullerian ducts (MDs). Most of the female reproductive tract (FRT) including the oviducts, uterine horn and cervix, originate from MDs. It is widely accepted that the formation of MDs depends on the preformed WDs within the urogenital primordia. Here, we found that the WD mesenchyme under the regulation of Hedgehog (Hh) signaling is closely related to the developmental processes of the FRT during embryonic and postnatal periods. Deficiency of Sonic hedgehog (Shh), the only Hh ligand expressed exclusively in WDs, prevents the MD mesenchyme from affecting uterine growth along the radial axis. The in vivo cell tracking approach revealed that after WD regression, distinct cells responding to WD-derived Hh signal continue to exist in the developing FRT and gradually contribute to the formation of various tissues such as smooth muscle, endometrial stroma and vascular vessel, in the mouse uterus. Our study thus provides a novel developmental mechanism of FRT relying on WD.
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http://dx.doi.org/10.3390/ijms22031211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865753PMC
January 2021

Unilateral lower limb atrophy associated with glomus tumors: a case report.

J Med Case Rep 2021 Jan 13;15(1). Epub 2021 Jan 13.

Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.

Background: Glomus tumors are soft tissue neoplasms comprised of glomus cells, vasculature, and smooth muscle cells, which occur commonly in a single subungual area of the digits, and their main clinical features include severe paroxysmal pain, localized tenderness, and cold hypersensitivity.

Case Presentation: A 47-year-old Japanese man had suffered from chronic progressive paroxysmal shooting pain in his right leg since childhood. He avoided putting weight on his right foot whenever he walked. The frequency of paroxysmal pain and the number of tender points both gradually increased with age, and his right leg gradually atrophied. Magnetic resonance imaging of the lower extremity demonstrated multiple gadolinium-enhanced nodules that corresponded with his tender points. Excisional biopsy relieved his pain and provided a histopathological diagnosis of glomus tumors.

Conclusion: This case suggests that small glomus tumors located in deep tissue may cause disuse atrophy because of their long delay before diagnosis. Clinicians should consider the potential for glomus tumors when patients exhibit unilateral lower limb muscular atrophy with pain.
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http://dx.doi.org/10.1186/s13256-020-02616-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805226PMC
January 2021

Enhanced Masses on Contrast-Enhanced Breast: Differentiation Using a Combination of Dynamic Contrast-Enhanced MRI and Quantitative Evaluation with Synthetic MRI.

J Magn Reson Imaging 2021 02 11;53(2):381-391. Epub 2020 Sep 11.

Department of Radiology, Ehime University Graduate School of Medicine, Toon, Japan.

Background: The addition of synthetic MRI might improve the diagnostic performance of dynamic contrast-enhanced MRI (DCE-MRI) in patients with breast cancer.

Purpose: To evaluate the diagnostic value of a combination of DCE-MRI and quantitative evaluation using synthetic MRI for differentiation between benign and malignant breast masses.

Study Type: Retrospective, observational.

Population: In all, 121 patients with 131 breast masses who underwent DCE-MRI with additional synthetic MRI were enrolled.

Field Strength/sequence: 3.0 Tesla, T -weighted DCE-MRI and synthetic MRI acquired by a multiple-dynamic, multiple-echo sequence.

Assessment: All lesions were differentiated as benign or malignant using the following three diagnostic methods: DCE-MRI type based on the Breast Imaging-Reporting and Data System; synthetic MRI type using quantitative evaluation values calculated by synthetic MRI; and a combination of the DCE-MRI + Synthetic MRI types. The diagnostic performance of the three methods were compared.

Statistical Tests: Univariate (Mann-Whitney U-test) and multivariate (binomial logistic regression) analyses were performed, followed by receiver-operating characteristic curve (AUC) analysis.

Results: Univariate and multivariate analyses showed that the mean T relaxation time in a breast mass obtained by synthetic MRI prior to injection of contrast agent (pre-T ) was the only significant quantitative value acquired by synthetic MRI that could independently differentiate between malignant and benign breast masses. The AUC for all enrolled breast masses assessed by DCE-MRI + Synthetic MRI type (0.83) was significantly greater than that for the DCE-MRI type (0.70, P < 0.05) or synthetic MRI type (0.73, P < 0.05). The AUC for category 4 masses assessed by the DCE-MRI + Synthetic MRI type was significantly greater than that for those assessed by the DCE-MRI type (0.74 vs. 0.50, P < 0.05).

Data Conclusion: A combination of synthetic MRI and DCE-MRI improves the accuracy of diagnosis of benign and malignant breast masses, especially category 4 masses. Level of Evidence 4 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:381-391.
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http://dx.doi.org/10.1002/jmri.27362DOI Listing
February 2021

Tricks and traps of ICG endoscopy for effectively applying endoscopic transsphenoidal surgery to pituitary adenoma.

Neurosurg Rev 2020 Sep 5. Epub 2020 Sep 5.

Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

Differentiating tumor from normal pituitary gland is very important for achieving complete resection without complications in endoscopic endonasal transsphenoidal surgery (ETSS) for pituitary adenoma. To facilitate such surgery, we investigated the utility of indocyanine green (ICG) fluorescence endoscopy as a tool in ETSS. Twenty-four patients with pituitary adenoma were enrolled in the study and underwent ETSS using ICG endoscopy. After administering 12.5 mg of ICG twice an operation with an interval > 30 min, times from ICG administration to appearance of fluorescence on vital structures besides the tumor were measured. ICG endoscopy identified vital structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Elapsed times for internal carotid arteries did not differ according to tumor size. Conversely, as tumor size increased, elapsed times for normal pituitary gland were prolonged but those for the tumor were reduced. ICG endoscopy revealed a clear boundary between tumors and normal pituitary gland and enabled confirmation of no more tumor. ICG endoscopy could provide a useful tool for differentiating tumor from normal pituitary gland by evaluating elapsed times to fluorescence in each structure. This method enabled identification of the boundary between tumor and normal pituitary gland under conditions of a low-fluorescence background, resulting in complete tumor resection with ETSS. ICG endoscopy will contribute to improve the resection rate while preserving endocrinological functions in ETSS for pituitary adenoma.
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http://dx.doi.org/10.1007/s10143-020-01382-4DOI Listing
September 2020

Localization of DLL1- and NICD-positive osteoblasts in cortical bone during postnatal growth in rats.

Biochem Biophys Res Commun 2020 08 22;529(2):186-190. Epub 2020 Jun 22.

Laboratory of Veterinary Anatomy, Nippon Veterinary and Life Science University, 1-7-1 Kyonan-cho, Musashino City, Tokyo, 180-8602, Japan.

The long bone midshaft expands by forming primary osteons at the periosteal surface of cortical bone in humans and rodents. Osteoblastic bone formation in the vascular cavity in the center of primary osteons is delayed during cortical bone development. The mechanisms of the formation of primary osteons is not fully understood, however. Focusing on NOTCH1 signaling, an inhibitory signaling on osteoblastic bone formation, our immunohistochemical analysis revealed Delta like1 (DLL1), a ligand of NOTCH1, and the NOTCH1 intracellular domain (NICD, an activated form of NOTCH1) immunoreactivity, in the cuboidal osteoblasts lining the bone surface in the vascular cavity of primary osteons during postnatal growth in rats. Interestingly, five days after treatment of primary osteoblasts with ascorbic acid and β glycerophosphate, protein levels of both DLL1 and NICD increased transiently, indicating that DLL1 activates NOTCH1 in primary cultured osteoblasts. Thus, the results imply that DLL1-NOTCH1 signaling in osteoblasts is associated with primary osteonal bone formation.
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http://dx.doi.org/10.1016/j.bbrc.2020.06.039DOI Listing
August 2020

Intracranial anaplastic solitary fibrous tumor/hemangiopericytoma: immunohistochemical markers for definitive diagnosis.

Neurosurg Rev 2021 Jun 15;44(3):1591-1600. Epub 2020 Jul 15.

Department of Neurosurgery, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

Intracranial anaplastic hemangiopericytoma (AHPC) is a rare and malignant subset of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) as per the WHO 2016 Classification of Tumors of the Central Nervous System. AHPC portends a poor prognosis and is associated with higher rates of recurrence/metastasis in comparison with SFT/HPC. Accordingly, it is critical to continue to define the clinical course of patients with AHPC and in so doing further refine clinicopathologic/immunohistochemical (IHC) criteria needed for definitive diagnosis. Herein, we describe clinical/histological characteristics of six patients with AHPC. In addition, we reviewed and analyzed the expression of various IHC markers reported within the literature (i.e., a total of 354 intracranial SFT/HPCs and 460 meningiomas). Histologically, tumors from our six patients were characterized by a staghorn-like vascular pattern, mitotic cells, and strong nuclear atypia. Immunohistochemically, all tumors displayed positive nuclear staining for STAT6; other markers, including CD34 and Bcl-2, were expressed only in three patients. Analysis of IHC expression patterns for SFT/HPC and meningioma within the literature revealed that nuclear expression of STAT6 had the highest specificity (100%) for SFT/HPC, followed by ALDH1 (97.2%) and CD34 (93.6%). Of note, SSTR2A (95.2%) and EMA (85%) displayed a high specificity for meningioma. Anaplastic SFT/HPC is a tumor with poor prognosis that is associated with higher rates of recurrence and metastasis in comparison with SFT/HPC. Given that anaplastic SFT/HPC requires more aggressive treatment than meningioma despite of a similar presentation on imaging, it is crucial to be able to distinguish between these tumors.
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http://dx.doi.org/10.1007/s10143-020-01348-6DOI Listing
June 2021

Clinical features and endoscopic findings of granular cell tumor of the sellar region: A case report and review of the literature.

Surg Neurol Int 2020 9;11:101. Epub 2020 May 9.

Departments of Neurosurgery, Ehime University School of Medicine, Shitsukawa, Toon, Ehime, Japan.

Background: Granular cell tumor (GCT) of the sellar region is a rare tumor of the sellar and suprasellar regions that originate from the neurohypophysis. This tumor is very difficult to differentiate from other pituitary neoplasms, such as pituitary adenoma, pituicytoma, and spindle cell oncocytoma. We report a rare case of GCT arising from the posterior pituitary of the sellar region and suggest a useful indicator for accurate diagnosis and pitfalls for surgical procedures.

Case Description: A 42-year-old woman was admitted to our hospital with bitemporal hemianopsia. Neuroimaging showed a large pituitary tumor in the sellar and suprasellar regions with a hypointense part on T2-weighted magnetic resonance imaging, and the enhanced anterior pituitary gland was displaced anteriorly. Laboratory findings showed mild hyperprolactinemia. Subtotal resection of the tumor was achieved using an endoscopic endonasal transsphenoidal approach. Histological findings showed round or polygonal cells with abundant granular eosinophilic cytoplasm staining strongly for thyroid transcription factor 1. The tumor was, therefore, diagnosed as a GCT of the sellar region, belonging to tumors of the posterior pituitary. After surgery, visual impairment and anterior pituitary function were improved. Follow-up neuroimaging after 1 year showed no signs of recurrence.

Conclusion: GCT of the sellar region is difficult to diagnose on routine neuroimaging. Therefore, accurate diagnosis requires careful identification of clinical signs, magnetic resonance imaging including hypointensity on T2-weighted imaging, and analysis of combined morphological and immunohistochemical studies.
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http://dx.doi.org/10.25259/SNI_111_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265469PMC
May 2020

New Insights into the Pathogenesis of Diabetic Nephropathy: Proximal Renal Tubules Are Primary Target of Oxidative Stress in Diabetic Kidney.

Acta Histochem Cytochem 2020 Apr 25;53(2):21-31. Epub 2020 Apr 25.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan.

Diabetic nephropathy is a major source of end-stage renal failure, affecting about one-third cases of diabetes mellitus. It has long been accepted that diabetic nephropathy is mainly characterized by glomerular defects, while clinical observations have implied that renal tubular damage is closely linked to kidney dysfunction at the early stages of diabetic nephropathy. In this study, we conducted pathohistological analyses focusing on renal tubular lesions in the early-stage diabetic kidney with the use of a streptozotocin (STZ)-induced diabetes mellitus mouse model. The results revealed that histological alterations in renal tubules, shown by a vacuolar nucleic structure, accumulations of PAS-positive substance, and accelerated restoration stress, occur initially without the presence of glomerular lesions in the early-stage diabetic kidney, and that these tubular defects are localized mainly in proximal renal tubules. Moreover, enhanced expression of RAGE, suggesting an aberrant activation of AGEs-RAGE signaling pathway, and accumulation of oxidative modified mitochondria through the impaired autophagy/lysosome system, were also seen in the damaged diabetic proximal renal tubules. Our findings indicate that proximal tubular defects are the initial pathological events increasingly linked to the progression of diabetic nephropathy, and that controlling renal tubular damage could be an effective therapeutic strategy for the clinical treatment of diabetic nephropathy.
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http://dx.doi.org/10.1267/ahc.20008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212204PMC
April 2020

Malignant Ovarian Steroid Cell Tumor, Not Otherwise Specified, Causes Virilization in a 4-Year-Old Girl: A Case Report and Literature Review.

Case Rep Oncol 2020 Jan-Apr;13(1):358-364. Epub 2020 Apr 2.

Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Japan.

We report a case of a 4-year-old girl with an ovarian steroid cell tumor, not otherwise specified (SCT-NOS). She was admitted to the hospital with progressing virilization and Cushing's syndrome, which included abnormality of the perineum, hirsutism, hypertrichosis, flushing of face, hoarseness, and weight gain. Blood testing showed a significantly increased testosterone level and slightly increased cortisol level. Computed tomography scan revealed an 8.0 × 5.0 × 5.0 cm tumor of the right ovary. The patient underwent right salpingo-oophorectomy, and pathological examination showed malignant potential. Three courses of bleomycin, etoposide, and cisplatin were administered as postoperative chemotherapy. After tumor resection, her testosterone decreased to undetectable levels. However, during the course of the treatment, the patient suffered from adrenal insufficiency resulting in the need for hydrocortisone replacement therapy. Although SCT-NOS in childhood are typically benign, pathological findings should be carefully observed for potential malignancy. In cases of cortisol-producing SCT-NOS, serum levels should be monitored, and hydrocortisone replacement therapy should be considered before resection.
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http://dx.doi.org/10.1159/000506044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184839PMC
April 2020

Hedgehog Inhibitors Suppress Osteoclastogenesis in In Vitro Cultures, and Deletion of in Macrophage/Osteoclast Lineage Prevents Age-Related Bone Loss.

Int J Mol Sci 2020 Apr 15;21(8). Epub 2020 Apr 15.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan.

The functional role of the Hedgehog (Hh)-signaling pathway has been widely investigated in bone physiology/development. Previous studies have, however, focused primarily on functions in bone formation, while its roles in bone resorption have not been fully elucidated. Here, we found that cyclopamine (smoothened (Smo) inhibitor), GANT-58 (GLI1 inhibitor), or GANT-61 (GLI1/2 inhibitor) significantly inhibited RANKL-induced osteoclast differentiation of bone marrow-derived macrophages. Although the inhibitory effects were exerted by cyclopamine or GANT-61 treatment during 0-48 h (early stage of osteoclast differentiation) or 48-96 h (late stage of osteoclast differentiation) after RANKL stimulation, GANT-58 suppressed osteoclast formation only during the early stage. These results suggest that the Smo-GLI1/2 axis mediates the whole process of osteoclastogenesis and that GLI1 activation is requisite only during early cellular events of osteoclastogenesis. Additionally, macrophage/osteoclast-specific deletion of Smo in mice was found to attenuate the aging phenotype characterized by trabecular low bone mass, suggesting that blockage of the Hh-signaling pathway in the osteoclast lineage plays a protective role against age-related bone loss. Our findings reveal a specific role of the Hh-signaling pathway in bone resorption and highlight that its inhibitors show potential as therapeutic agents that block osteoclast formation in the treatment of senile osteoporosis.
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http://dx.doi.org/10.3390/ijms21082745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216259PMC
April 2020

Altered features of monocytes in adult onset leukoencephalopathy with axonal spheroids and pigmented glia: A clue to the pathomechanism of microglial dyshomeostasis.

Neurobiol Dis 2020 07 7;140:104867. Epub 2020 Apr 7.

Department of Neurology, Kansai Medical University Medical Center, 10-15 Fumizono, Moriguchi 570-8507, Japan. Electronic address:

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an autosomal-dominant type of leukoencephalopathy caused by gene mutation of colony stimulating factor 1 receptor, which is expressed mainly on monocyte lineage cells such as monocytes in the peripheral blood and microglia in the brain. Hence, microglial dysfunction is regarded as critical in the pathogenesis of ALSP. However, functional changes in these cells have not been elucidated. In this study, we report the phenotypic and functional alterations of monocytes in four patients with ALSP. Flow cytometric analysis revealed altered expression of antigen presentation- and migration-related molecules, an inflammatory shift in cytokine production and phagocytic impairment in ALSP monocytes. We speculate that the observed altered features of monocytes are mostly shared by microglial cells, leading to the clinical history and pathological characteristics of ALSP. Our analysis of PB monocytes provides novel insights into the pathogenesis of ALSP.
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http://dx.doi.org/10.1016/j.nbd.2020.104867DOI Listing
July 2020

Met-PET uptake index for total tumor resection: identification of C-methionine uptake index as a goal for total tumor resection including infiltrating tumor cells in glioblastoma.

Neurosurg Rev 2021 Feb 15;44(1):587-597. Epub 2020 Feb 15.

Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

Glioblastoma multiforme (GBM) is largely due to glioma stem cells (GSCs) that escape from total resection of gadolinium (Gd)-enhanced tumor on MRI. The aim of this study is to identify the imaging requirements for maximum resection of GBM with infiltrating GSCs. We investigated the relationship of tumor imaging volume between MRI and C-methionine (Met)-PET and also the relationship between Met uptake index and tumor activity. In ten patients, tumor-to-contralateral normal brain tissue ratio (TNR) was calculated to evaluate metabolic activity of Met uptake areas which were divided into five subareas by the degrees of TNR. In each GBM, tumor tissue was obtained from subareas showing the positive Met uptake. Immunohistochemistry was performed to examine the tumor proliferative activity and existence of GSCs. In all patients, the volume of Met uptake area at TNR ≦ 1.4 was larger than that of the Gd-enhanced area. The Met uptake area at TNR 1.4 beyond the Gd-enhanced tumor was much wider in high invasiveness-type GBMs than in those of low invasiveness type, and survival was much shorter in the former than the latter types. Immunohistochemistry revealed the existence of GSCs in the area showing Met uptake at TNR 1.4 and no Gd enhancement. Areas at TNR > 1.4 included active tumor cells with relatively high Ki-67 labeling index. In addition, it was demonstrated that GSCs could exist beyond the border of Gd-enhanced tumor. Therefore, to obtain maximum resection of GBMs, including infiltrating GSCs, aggressive surgical excision that includes the Met-positive area at TNR 1.4 should be considered.
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http://dx.doi.org/10.1007/s10143-020-01258-7DOI Listing
February 2021

Epithelioid glioblastoma presenting as multicentric glioma: A case report and review of the literature.

Surg Neurol Int 2020 17;11. Epub 2020 Jan 17.

Department of Neurosurgery, Ehime University School of Medicine.

Background: Epithelioid glioblastoma is a rare aggressive variant of glioblastoma multiforme (GBM), which was formally recognized by the World Health Organization classification of the central nervous system in 2016. Clinically, epithelioid GBMs are characterized by aggressive features, such as metastases and cerebrospinal fluid dissemination, and an extremely poor prognosis. A rare case of epithelioid GBM that was discovered as a multicentric glioma with different histopathology is reported.

Case Description: A 78-year-old man was admitted to our hospital with mild motor weakness of the right leg. Neuroimaging showed small masses in the left frontal and parietal lobes on magnetic resonance imaging. The abnormal lesion had been increasing rapidly for 3 weeks, and a new lesion appeared in the frontal lobe. 11C-methionine positron emission tomography (PET) showed abnormal uptake corresponding to the lesion. To reach a definitive diagnosis, surgical excision of the right frontal mass lesion was performed. Histological findings showed diffuse astrocytoma. Only radiotherapy was planned, but the left frontal and parietal tumors progressed further within a short period. Therefore, it was thought that these tumors were GBM, and a biopsy of the left parietal tumor was performed. The histological diagnosis was epithelioid GBM. Immunohistochemistry showed that most tumor cells were negatively stained for p53 and isocitrate dehydrogenase 1. V600E mutations were not identified, but promoter mutations were identified. Immediately after surgery, the patient was given chemotherapy using temozolomide, extended local radiotherapy and then bevacizumab. After 6 months, he showed no signs of recurrence.

Conclusion: Epithelioid GBM is one of the rarest morphologic subtypes of GBM and has a strongly infiltrative and aggressive nature. Therefore, careful identification of preoperative imaging studies and detailed evaluation of genetic studies are necessary to select the appropriate treatment for epithelioid GBM.
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http://dx.doi.org/10.25259/SNI_544_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969379PMC
January 2020

Knockdown of Lrp1 in RAW264 cells inhibits osteoclast differentiation and osteoclast-osteoblast interactions in vitro.

Biochem Biophys Res Commun 2020 03 19;523(4):961-965. Epub 2020 Jan 19.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime, 791-0295, Japan.

Low density lipoprotein receptor-related protein 1 (LRP1), a multifunctional cell surface protein, is expressed in bone marrow-derived macrophages. While LRP1 is thought to be a suppressor of osteoclast differentiation at late stages, its function at early stages remains unclear. Here we demonstrate that Lrp1 stable knockdown by lentiviral short hairpin RNA in macrophage cell line RAW264 cells inhibited RANKL-induced osteoclast formation and osteoclastic master transcription factor Nfatc1 mRNA expression as assessed by quantitative RT-PCR. Furthermore, knockdown of the Lrp1 gene suppressed not only differentiation, but also proliferation, and inhibitory effects on osteoblastic ALP activity by osteoclast-derived humoral factors. Thus, we propose that LRP1 in macrophages is required for both differentiation into osteoclasts and osteoclast-osteoblast interactions.
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http://dx.doi.org/10.1016/j.bbrc.2020.01.065DOI Listing
March 2020

Prognostic significance of immunohistochemical subtypes based on the stage of B-cell differentiation in primary CNS lymphoma.

Int J Clin Exp Pathol 2019 1;12(4):1457-1467. Epub 2019 Apr 1.

Department of Neurosurgery, Ehime University School of Medicine 454 Shitsukawa, Toon, Ehime 791-0295, Japan.

Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but the prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. We also analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. Tumors from 32 PCNSL patients were immunohistochemically evaluated for expression of cluster of differentiation (CD) 10, B-cell lymphoma-6 (BCL-6), and multiple myeloma oncogene-1 (MUM-1) and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months) (P<0.05). Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing sensitivity to HD-MTX therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947071PMC
April 2019

Recent Insights into Long Bone Development: Central Role of Hedgehog Signaling Pathway in Regulating Growth Plate.

Int J Mol Sci 2019 Nov 20;20(23). Epub 2019 Nov 20.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City 791-0295, Japan.

The longitudinal growth of long bone, regulated by an epiphyseal cartilaginous component known as the "growth plate", is generated by epiphyseal chondrocytes. The growth plate provides a continuous supply of chondrocytes for endochondral ossification, a sequential bone replacement of cartilaginous tissue, and any failure in this process causes a wide range of skeletal disorders. Therefore, the cellular and molecular characteristics of the growth plate are of interest to many researchers. Hedgehog (Hh), well known as a mitogen and morphogen during development, is one of the best known regulatory signals in the developmental regulation of the growth plate. Numerous animal studies have revealed that signaling through the Hh pathway plays multiple roles in regulating the proliferation, differentiation, and maintenance of growth plate chondrocytes throughout the skeletal growth period. Furthermore, over the past few years, a growing body of evidence has emerged demonstrating that a limited number of growth plate chondrocytes transdifferentiate directly into the full osteogenic and multiple mesenchymal lineages during postnatal bone development and reside in the bone marrow until late adulthood. Current studies with the genetic fate mapping approach have shown that the commitment of growth plate chondrocytes into the skeletal lineage occurs under the influence of epiphyseal chondrocyte-derived Hh signals during endochondral bone formation. Here, we discuss the valuable observations on the role of the Hh signaling pathway in the growth plate based on mouse genetic studies, with some emphasis on recent advances.
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http://dx.doi.org/10.3390/ijms20235840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928971PMC
November 2019

Dual-energy computed tomography for evaluation of breast cancer: value of virtual monoenergetic images reconstructed with a noise-reduced monoenergetic reconstruction algorithm.

Jpn J Radiol 2020 Feb 4;38(2):154-164. Epub 2019 Nov 4.

Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.

Purpose: To evaluate the image quality and lesion visibility of virtual monoenergetic images (VMIs) reconstructed using a new monoenergetic reconstruction algorithm (nMERA) for evaluation of breast cancer.

Materials And Methods: Forty-two patients with 46 breast cancers who underwent 4-phasic breast contrast-enhanced computed tomography (CT) using dual-energy CT (DECT) were enrolled. We selected the peak enhancement phase of the lesion in each patient. The selected phase images were generated by 120-kVp-equivalent linear blended (M120) and monoenergetic reconstructions from 40 to 80 keV using the standard reconstruction algorithm (sMERA: 40, 50, 60, 70, 80) and nMERA (40 +, 50 +, 60 +, 70 +, 80 +). The contrast-to-noise ratio (CNR) was calculated and objectively analyzed. Two independent readers subjectively scored tumor visibility and image quality each on a 5-point scale.

Results: The CNR at 40 + and tumor visibility scores at 40 + and 50 + were significantly higher than those on M120. The CNR at 50 + was not significantly different from that on M120. However, the overall image quality score at 40 + was significantly lower than that at 50 + and on M120 (40 + vs M120, P < 0.0001 and 40 + vs 50 +, P = 0.0001).

Conclusions: VMI reconstructed with nMERA at 50 keV is preferable for evaluation of patients with breast cancer.
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http://dx.doi.org/10.1007/s11604-019-00897-1DOI Listing
February 2020

Wilson Disease With Giant Splenic Artery Aneurysms Caused by Fibromuscular Dysplasia During Living Donor Liver Transplantation: A Case Report.

Transplant Proc 2019 Nov 11;51(9):3131-3135. Epub 2019 Oct 11.

Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.

Liver cirrhosis can cause splenic artery aneurysms (SAA) that pose a threat to patients undergoing liver transplantation. However, liver transplantation with multiple visceral artery aneurysms including giant SAA caused by arterial fragility has never been reported. We describe a 36-year-old man with decompensated liver cirrhosis due to Wilson disease that was complicated by giant SAA and multiple aneurysms in the bilateral renal arteries caused by fibromuscular dysplasia (FMD). The maximal diameter of the triple snowball-shaped SAA was 11 cm. We planned a 2-stage strategy consisting of a splenectomy with distal pancreatectomy to treat the SAA and subsequent living donor liver transplantation (LDLT) to address the liver cirrhosis. This strategy was selected to prevent fatal postoperative infectious complications caused by the potential development of pancreatic fistula during simultaneous procedures and to histopathologically diagnose the arterial lesion before LDLT to promote safe hepatic artery reconstruction. However, a postoperative pancreatic fistula did not develop after a splenectomy with distal pancreatectomy, and the pathologic findings of the artery indicated FMD. The patient underwent ABO-identical LDLT with a right lobe graft donated by his brother. Other than postoperative rupture of the aneurysm in the left renal artery requiring emergency interventional radiology, the patient has remained free of any other arterial complications and continues to do well at 2 years after LDLT.
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http://dx.doi.org/10.1016/j.transproceed.2019.06.005DOI Listing
November 2019

Modulation of αβ Integrin via Transactivation of β Integrin Gene on Murine Bone Marrow Macrophages by 1,25(OH)D, Retinoic Acid and Interleukin-4.

Acta Histochem Cytochem 2019 Aug 10;52(4):77-83. Epub 2019 Aug 10.

Department of Molecular Pathology, Ehime University Graduate School of Medicine.

The interleukin (IL)-4, 1,25(OH)D and retinoic acid, increase surface expression of functional integrin αβ on murine osteoclast precursors. All three agonists stimulate transcription of the β gene, leading to increased steady-state levels of mRNA this protein. By contrast, mRNA levels of α remain unchanged. In each instance, the increase in the surface expression of the integrin results in increased migration of the cells onto an αβ substrate. Because β subunit, except platelet where β subunit conform a dimer with α, associates solely with α subunit monogamously, while promiscuous α subunit combines with various subunit, our present data support the idea that the β subunit governs the surface-expressed functional integrin complex.
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http://dx.doi.org/10.1267/ahc.19015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773611PMC
August 2019

Testis developmental related gene 1 regulates the chemosensitivity of seminoma TCam-2 cells to cisplatin via autophagy.

J Cell Mol Med 2019 11 9;23(11):7773-7784. Epub 2019 Sep 9.

Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

We previously identified testis developmental related gene 1 (TDRG1), a gene implicated in proliferation of TCam-2 seminoma cells. Recent evidence has revealed that autophagy influences the chemosensitivity of cancer cells to chemotherapy. However, whether TDRG1 protein regulates autophagy in seminoma cells and influences their sensitivity to cis-dichlorodiammine platinum (CDDP) remains unknown. In this study, we used TCam-2 cells and male athymic BALB/c nude mice with xenografts of TCam-2 cells to investigate autophagy, cell viability, apoptosis and the p110β/Rab5/Vps34 (PI3-kinase Class III) pathway under the conditions of TDRG1 overexpression or knockdown and with or without CDDP treatment. We found that TDRG1 upregulation promoted autophagy in both TCam-2 cells and seminoma xenografts via p110β/Rab5/Vps34 activation. Inhibition of autophagy reduced cell viability and promoted apoptosis during CDDP treatment of TCam-2 cells. Similarly, TDRG1 knockdown inhibited autophagy, reduced cell viability and promoted apoptosis during CDDP treatment of TCam-2 cells. TDRG1 knockdown inhibited tumour growth and promoted apoptosis in TCam-2 cell xenografts, whereas TDRG1 overexpression had the opposite effect. According to these results, we propose that high expression of TDRG1 promotes autophagy through the p110β/Rab5/Vps34 pathway in TCam-2 cells. TDRG1 overexpression promotes autophagy and leads to CDDP resistance, whereas TDRG1 knockdown inhibits autophagy and promotes chemosensitivity to CDDP both in vivo and in vitro. This study has uncovered a novel role of TDRG1 in reducing chemoresistance during CDDP treatment and provides potential therapeutic strategies for the treatment of human seminoma.
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http://dx.doi.org/10.1111/jcmm.14654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815826PMC
November 2019

Activation of protein kinase C accelerates murine osteoclastogenesis partly via transactivation of RANK gene through functional AP-1 responsive element in RANK gene promoter.

Biochem Biophys Res Commun 2019 07 28;515(2):268-274. Epub 2019 May 28.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime, 791-0295, Japan; Division of Diagnostic Molecular Pathology, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-1, Kobe, 650-0017, Japan. Electronic address:

Receptor activator of NF-κB (RANK) expressed on osteoclasts and their precursors is a receptor for RANK ligand (RANKL). Signals transduced by RANKL-RANK interaction induce genes essential for the differentiation and function of osteoclasts. We have cloned a basic promoter region of the mouse RANK gene and have analyzed the transcription machinery by transcription factors such as PU.1 (-480), and MITF (-100). Here, we examined the regulatory mechanisms of RANK gene transcription through AP-1 binding site, agagctca (-240). RANK mRNA expression in pre-osteoclastic RAW264.7 cells was induced by Phorbol12-myristate13-acetate (PMA) and suppressed by protein kinase C (PKC) inhibitor calphostin C. In RAW264.7 cells, Fos knockdown by siRNA blocked the inducible effect of PMA on RANK expression. By EMSA, an oligonucleotide (-246/-238) showed DNA protein binding, the specificity of which was confirmed by block-shift assay with an anti-Fos antibody and by the addition of the excess of a cold consensus probe. Co-transfection with a Fos expression vector showed that Fos increased RANK promoter activity 6-fold in RAW264.7 cells, and the addition of PU.1 and MITF superinduced the activity more than twenty-fold by the addition of PU.1 and MITF. Mutagenesis of the putative AP-1 site (-240) blocked the inducible effect of Fos on promoter activity. Taken together, these results indicate that during the differentiation of bone marrow mono-nucleated cells into osteoclast precursors, RANK transcription is positively regulated by Fos/AP-1 through the binding element of its gene promoter, supporting the concept that Fos activation by continuous CSF-1 stimulation on macrophages triggers initial expression of RANK and, later, a positive feedback loop by RANKL-RANK interaction.
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http://dx.doi.org/10.1016/j.bbrc.2019.05.144DOI Listing
July 2019

Nonocclusive Mesenteric Ischemia Rescued by Immediate Surgical Exploration in a Boy with Severe Neurodevelopmental Disability.

Case Rep Pediatr 2019 19;2019:5354074. Epub 2019 Feb 19.

Department of Pediatrics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.

Background: Nonocclusive mesenteric ischemia (NOMI) defines acute mesenteric ischemia without occlusion of the mesenteric arteries. The most common cause of NOMI is vasoconstriction or vasospasm of a mesenteric artery. NOMI generally affects patients >50 years of age, and few cases have been reported in children.

Case Presentation: A 15-year-old boy with severe neurodevelopmental disability developed sudden-onset fever, abdominal distention, and dyspnea. Laboratory and radiological findings indicated acute intestinal obstruction and prerenal failure. He developed transient cardiopulmonary arrest and hypovolemic shock. Emergent laparotomy was performed, which revealed segmentally necrotic intestine from the jejunum to the ascending colon with pulsation of peripheral intestinal arteries, leading to a diagnosis of NOMI. The necrotic intestine was resected, and stomas were created. He was discharged on postoperative day 334 with short bowel syndrome as a complication.

Conclusions: NOMI should be considered a differential diagnosis for intestinal symptoms with severe general conditions in both adults and children with underlying disease. Immediate surgical exploration is essential with NOMI to save a patient's life.
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http://dx.doi.org/10.1155/2019/5354074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399550PMC
February 2019

SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9.

J Cell Physiol 2019 08 19;234(10):17280-17294. Epub 2019 Feb 19.

Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.

Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High-level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.
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http://dx.doi.org/10.1002/jcp.28346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617759PMC
August 2019

Intraosseous synovial sarcoma of the distal ulna: a case report and review of the literature.

BMC Cancer 2019 Feb 1;19(1):116. Epub 2019 Feb 1.

Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.

Background: Synovial sarcoma is a relatively rare type of soft tissue sarcoma. The commonly observed symptom is a deep-seated palpable mass accompanied by pain or tenderness. Thus, it is considered a soft tissue sarcoma and rarely occurs primarily in bone. However, only few studies have been reported on intraosseous synovial sarcoma, and reports on cases with cytogenetic or molecular confirmation are even rarer. We report a case of intraosseous synovial sarcoma of the distal ulna that has been confirmed using histopathological examination and molecular analysis.

Case Presentation: A 77-year-old female was referred to our hospital with a 1-month history of right wrist pain after housework. Clinical and imaging findings suggested a benign bone tumor that was enhanced by Gd-DTPA. It was thought that the tumor was possibly an enchondroma. Initially, we planned to evaluate the benignancy of the tumor with intraoperative frozen section, followed by curettage and bone graft at one stage However, when considering carefully, characteristics of the tumor did not perfectly match those of any diagnostic categories including enchondroma. Therefore, an incisional biopsy was performed and revealed that the tumor was synovial sarcoma. Following an elaborate plan, the patient underwent a wide resection of the tumor at the distal part of the right ulna. Reverse transcription-polymerase chain reaction (RT-PCR) from the resected specimen and sequencing of RT-PCR products demonstrated a chimeric SYT-SSX1 transcript, confirming the diagnosis of synovial sarcoma.

Conclusions: Synovial sarcoma is seldom considered in differential diagnosis of bone tumors because it is difficult to line up such an unusual diagnosis as a differential diagnosis. When the lesion does not perfectly fit into any diagnostic category, when the initial image diagnosis appears unconvincing, biopsy and pathology are indicated, recalling Jaffe's triangle. According to these diagnostic processes, the patient successfully completed the treatment for this rare intraosseous synovial sarcoma, following a careful plan based on the preoperative diagnosis.
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http://dx.doi.org/10.1186/s12885-019-5325-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359868PMC
February 2019

Usefulness of neuroimaging and immunohistochemical study for accurate diagnosis of chordoid glioma of the third ventricle: A case report and review of the literature.

Surg Neurol Int 2018 2;9:226. Epub 2018 Nov 2.

Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.

Background: Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology within the third ventricular region, but with radiological and histopathological features mimicking benign lesions such as meningioma. We report a case of chordoid glioma of the third ventricle and suggest a useful indicator for accurate diagnosis.

Case Description: A previously healthy 46-year-old woman was admitted to our hospital with mild headache. Neuroimaging revealed a large tumor measuring approximately 18 mm in the suprasellar region, and perifocal edema in the optic tract and internal capsule on magnetic resonance imaging. Laboratory findings revealed no pituitary dysfunction including diabetes insipidus. Gross total resection of the tumor was performed by the interhemispheric translamina terminalis approach. Histological findings revealed nests of regular epithelioid cells with large nuclei and abundant eosinophilic cytoplasm within myxoid stroma. Immunohistochemical studies demonstrated diffuse cytoplasmic expression of glial fibrillary acidic protein (GFAP) and CD34, and strong nuclear staining for thyroid transcription factor 1 (TTF-1). We, therefore, histologically classified the tumor as chordoid glioma of the third ventricle. Headache improved immediately postoperatively, and follow-up neuroimaging after 12 months showed no signs of recurrence.

Conclusions: Chordoid glioma of the third ventricle is a very rare tumor that is difficult to diagnose on routine neuroimaging. Accurate diagnosis requires detailed analysis of neuroimaging and immunohistochemical studies using CD34 and TTF-1 staining.
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http://dx.doi.org/10.4103/sni.sni_306_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238323PMC
November 2018