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1.
Thorac Cancer ; 15(7): 575-577, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38366805

ABSTRACT

A 63-year-old woman was admitted to our department for the investigation of superior vena cava (SVC) syndrome. Computed tomography revealed an azygos tumor extending into the SVC. Video-assisted thoracic surgery (VATS) was performed to remove the distal end of the azygos vein in the left lateral position, followed by complete resection of the entire tumor under median sternotomy in the supine position. The histological diagnosis was a primary angiosarcoma of the azygos vein. The patient was discharged without any complications and is now alive and tumor-free 24 months after surgery. In addition, contrast-enhanced computed tomography revealed no graft occlusion in the two reconstructed brachiocephalic veins. Thoracoscopic surgery in the lateral position is useful for safe and reliable complete resection of a tumor arising from the azygos vein.


Subject(s)
Hemangiosarcoma , Superior Vena Cava Syndrome , Female , Humans , Middle Aged , Azygos Vein/surgery , Vena Cava, Superior/surgery , Hemangiosarcoma/surgery , Brachiocephalic Veins/surgery , Superior Vena Cava Syndrome/etiology
2.
FASEB J ; 38(5): e23504, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38421271

ABSTRACT

The function of kidney podocytes is closely associated with actin cytoskeleton regulated by Rho small GTPases. Loss of actin-driven cell adhesions and processes is connected to podocyte dysfunction, proteinuria, and kidney diseases. FilGAP, a GTPase-activating protein for Rho small GTPase Rac1, is abundantly expressed in kidney podocytes, and its gene is linked to diseases in a family with focal segmental glomerulosclerosis. In this study, we have studied the role of FilGAP in podocytes in vitro. Depletion of FilGAP in cultured podocytes induced loss of actin stress fibers and increased Rac1 activity. Conversely, forced expression of FilGAP increased stress fiber formation whereas Rac1 activation significantly reduced its formation. FilGAP localizes at the focal adhesion (FA), an integrin-based protein complex closely associated with stress fibers, that mediates cell-extracellular matrix (ECM) adhesion, and FilGAP depletion decreased FA formation and impaired attachment to the ECM. Moreover, in unique podocyte cell cultures capable of inducing the formation of highly organized processes including major processes and foot process-like projections, FilGAP depletion or Rac1 activation decreased the formation of these processes. The reduction of FAs and process formations in FilGAP-depleted podocyte cells was rescued by inhibition of Rac1 or P21-activated kinase 1 (PAK1), a downstream effector of Rac1, and PAK1 activation inhibited their formations. Thus, FilGAP contributes to both cell-ECM adhesion and process formation of podocytes by suppressing Rac1/PAK1 signaling.


Subject(s)
Podocytes , Actins , Kidney , GTPase-Activating Proteins/genetics , Extracellular Matrix
3.
Ann Thorac Cardiovasc Surg ; 30(1)2024 Jan 26.
Article in English | MEDLINE | ID: mdl-36927845

ABSTRACT

Systemic arterial blood supply to a normal lung is a rare anatomical abnormality. Surgery is usually indicated because this abnormality leads to pulmonary hypertension. Herein, we report our experience and ideas for safe vessel dissection. Case 1 was a woman in her 50s. We performed a left lower lobectomy following percutaneous coil embolization. The aberrant artery with emboli was confirmed intraoperatively by cone-beam computed tomography (CBCT) to safely dissect under thoracoscopic surgery (TS). Case 2 was a man in his 40s. Following percutaneous endovascular plug occlusion, we performed a left partial resection using indocyanine green fluorescence navigation. Intraoperatively, CBCT imaging demonstrated the aberrant artery and exact position of the emboli. This combination technique of interventional radiology and TS with CBCT imaging was considered safe and more secure for the treatment of anomalous systemic arterial blood supply to a normal lung.


Subject(s)
Lung , Tomography, X-Ray Computed , Humans , Male , Female , Lung/diagnostic imaging , Lung/surgery , Lung/blood supply , Treatment Outcome , Arteries/abnormalities , Cone-Beam Computed Tomography
4.
IJU Case Rep ; 6(6): 398-401, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37928304

ABSTRACT

Introduction: Retroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations. Case presentation: A 72-year-old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27-mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast-enhanced computed tomography revealed a heterogeneously enhanced tumor with well-defined borders. Dynamic contrast-enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling-in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation. Conclusion: Herein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.

5.
Nat Commun ; 14(1): 4955, 2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37591840

ABSTRACT

The Totten Glacier in East Antarctica, with an ice volume equivalent to >3.5 m of global sea-level rise, is grounded below sea level and, therefore, vulnerable to ocean forcing. Here, we use bathymetric and oceanographic observations from previously unsampled parts of the Totten continental shelf to reveal on-shelf warm water pathways defined by deep topographic features. Access of warm water to the Totten Ice Shelf (TIS) cavity is facilitated by a deep shelf break, a broad and deep depression on the shelf, a cyclonic circulation that carries warm water to the inner shelf, and deep troughs that provide direct access to the TIS cavity. The temperature of the warmest water reaching the TIS cavity varies by ~0.8 °C on an interannual timescale. Numerical simulations constrained by the updated bathymetry demonstrate that the deep troughs play a critical role in regulating ocean heat transport to the TIS cavity and the subsequent basal melt of the ice shelf.

6.
Cell Struct Funct ; 48(2): 161-174, 2023 Sep 23.
Article in English | MEDLINE | ID: mdl-37482421

ABSTRACT

Invadopodia are protrusive structures that mediate the extracellular matrix (ECM) degradation required for tumor invasion and metastasis. Rho small GTPases regulate invadopodia formation, but the molecular mechanisms of how Rho small GTPase activities are regulated at the invadopodia remain unclear. Here we have identified FilGAP, a GTPase-activating protein (GAP) for Rac1, as a negative regulator of invadopodia formation in tumor cells. Depletion of FilGAP in breast cancer cells increased ECM degradation and conversely, overexpression of FilGAP decreased it. FilGAP depletion promoted the formation of invadopodia with ECM degradation. In addition, FilGAP depletion and Rac1 overexpression increased the emergence of invadopodia induced by epidermal growth factor, whereas FilGAP overexpression suppressed it. Overexpression of GAP-deficient FilGAP mutant enhanced invadopodia emergence as well as FilGAP depletion. The pleckstrin-homology (PH) domain of FilGAP binds phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], which is distributed on membranes of the invadopodia. FilGAP localized to invadopodia in breast cancer cells on the ECM, but FilGAP mutant lacking PI(3,4)P2-binding showed low localization. Similarly, the decrease of PI(3,4)P2 production reduced the FilGAP localization. Our results suggest that FilGAP localizes to invadopodia through its PH domain binding to PI(3,4)P2 and down-regulates invadopodia formation by inactivating Rac1, inhibiting ECM degradation in invasive tumor cells.Key words: invadopodia, breast carcinoma, Rac1, FilGAP, PI(3,4)P2.


Subject(s)
Breast Neoplasms , Podosomes , Humans , Female , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Podosomes/metabolism , Podosomes/pathology , rho GTP-Binding Proteins/metabolism , Cell Line, Tumor , Extracellular Matrix/metabolism , Extracellular Matrix/pathology
7.
J Ovarian Res ; 16(1): 112, 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37316921

ABSTRACT

BACKGROUND: Granulosa cell tumors (GCTs) account for approximately 2% of ovarian malignancies and are considered a rare type of ovarian cancer. GCTs are characterized by irregular genital bleeding after menopause due to female hormone production as well as late recurrence around 5-10 years after initial treatment. In this study, we investigated two cases of GCTs to find a biomarker that can be used to evaluate the treatment and predict recurrence. CASE PRESENTATION: Case 1 was a 56-year-old woman who presented to our hospital with abdominal pain and distention. An abdominal tumor was found, and GCTs were diagnosed. Serum vascular endothelial growth factor (VEGF) levels decreased after surgery. Case 2 involved a 51-year-old woman with refractory GCTs. Carboplatin-paclitaxel combination therapy and bevacizumab were administered after the tumor resection. After chemotherapy, a decline in VEGF levels was observed, but serum VEGF levels increased again with disease progression. CONCLUSIONS: VEGF expression may be of clinical importance in GCTs as a clinical biomarker for disease progression, which may be used to determine the efficacy of bevacizumab against GCTs.


Subject(s)
Granulosa Cell Tumor , Ovarian Neoplasms , Female , Humans , Middle Aged , Granulosa Cell Tumor/diagnosis , Vascular Endothelial Growth Factor A , Bevacizumab/therapeutic use , Vascular Endothelial Growth Factors , Ovarian Neoplasms/diagnosis , Disease Progression
8.
J Clin Med ; 12(10)2023 May 14.
Article in English | MEDLINE | ID: mdl-37240566

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with coagulopathy. However, the underlying mechanisms are not completely understood. We evaluated the association between COVID-19 coagulopathy and extracellular vesicle (EV) levels. We hypothesized that several EV levels would be higher in COVID-19 coagulopathy patients than in non-coagulopathy patients. This prospective observational study was conducted in four tertiary care faculties in Japan. We enrolled 99 COVID-19 patients (48 with coagulopathy and 51 without coagulopathy) aged ≥20 years who required hospitalization, and 10 healthy volunteers; we divided the patients into coagulopathy and non-coagulopathy groups according to the D-dimer levels (≥1 µg/mL and <1 µg/mL, respectively). We used flow cytometry to measure the tissue-factor-bearing, endothelium-derived, platelet-derived, monocyte-derived, and neutrophil-derived EV levels in platelet-free plasma. The EV levels were compared between the two COVID-19 groups as well as among the coagulopathy patients, non-coagulopathy patients, and healthy volunteers. No significant difference was found in EV levels between the two groups. Meanwhile, the cluster of differentiation (CD) 41 + EV levels were significantly higher in COVID-19 coagulopathy patients than in healthy volunteers (549.90 [255.05-984.65] vs. 184.3 [150.1-254.1] counts/µL, p = 0.011). Therefore, CD41+ EVs might play an essential role in COVID-19 coagulopathy development.

9.
Plast Reconstr Surg Glob Open ; 11(5): e4968, 2023 May.
Article in English | MEDLINE | ID: mdl-37180983

ABSTRACT

We report the case of an adult with fibula regeneration after below-the-knee amputation. Fibula regeneration conventionally occurs at the donor site of children after autogenous fibula transplantation when the periosteum is preserved. However, the patient was an adult, and the regenerated fibula was 7-cm long and grew directly from the stump. A 47-year-old man was referred to the plastic surgery department owing to stump pain. He had an open comminuted fracture of the right fibula and tibia due to a traffic accident when he was 44 years old and underwent below-the-knee amputation and negative pressure wound therapy for skin defects. The patient recovered and was able to walk using a prosthetic limb. Upon radiography, the fibula was found to have regenerated 7 cm directly from the stump. Pathological examination revealed that the regenerated fibula contained normal bone tissue and neurovascular bundles in the cortex. The periosteum, mechanical stimuli with limb proteases, and negative pressure wound therapy were suspected to have accelerated bone regeneration. He had no inhibitory factors for bone regeneration, including diabetes mellitus, peripheral arterial disease, or active smoking status. After the resection of the regenerated fibula, the patient was ambulatory without further bone regeneration or pain. This case report suggests that bone regeneration may occur even in adults. The surgeon should not leave any part of the periosteum behind in patients undergoing amputation. In adult amputees complaining of stump pain, the possibility of bone regeneration may be considered.

10.
Cytopathology ; 34(4): 337-345, 2023 07.
Article in English | MEDLINE | ID: mdl-36946097

ABSTRACT

INTRODUCTION: Cancer-associated fibroblasts (CAFs) in the tumour microenvironment play a key role in tumour development, proliferation, invasion, and metastasis. The cytological features of spindle cells including CAFs-defined as stromal spindle cells (SSCs) adjacent to cancer cells-are frequently encountered in pulmonary adenocarcinomas. This study aimed to investigate the association between the presence of SSCs in cytological specimens and the clinicopathological features. METHODS: We evaluated 211 patients with pulmonary adenocarcinoma who underwent surgical resection. All participants had cytological specimens corresponding to the histological specimens available for review. RESULTS: Of the 211 cases examined, 89 were SSC-positive (SSC+ ) and 122 were SSC-negative (SSC- ). SSC+ cases were more frequently associated with higher pathological stage (P < 0.001), lymph node metastasis (P = 0.002), anaplastic lymphoma kinase (ALK) gene rearrangement (P = 0.04), high tumour grade (P < 0.001), solid and micropapillary predominant pattern (P = 0.02), and lymphatic vessel (P = 0.003), blood vessel (P < 0.001), and pleural invasion (P = 0.03) as compared to SSC- cases. Patients with SSC+ adenocarcinoma had a significantly shorter recurrence-free survival than those with SSC- adenocarcinoma (P = 0.009). Cytologically, necrotic background (P = 0.002), mucinous cancer cells (P = 0.02), pleomorphic cells (P < 0.001), and mutual cell inclusions (P = 0.01) were observed more frequently in SSC+ adenocarcinomas. CONCLUSIONS: The presence of SSCs could be an important cytological feature for predicting poor prognosis in lung adenocarcinomas.


Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Prognosis , Adenocarcinoma of Lung/diagnosis , Adenocarcinoma of Lung/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Lymphatic Metastasis , Neoplasm Staging , Retrospective Studies , Tumor Microenvironment
11.
Int Cancer Conf J ; 12(1): 14-18, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36605833

ABSTRACT

Pulmonary capillary hemangiomatosis (PCH) is a rare disease characterized by a proliferation of capillaries in the alveolar septa, bronchial and venous walls, pleura, and regional lymph nodes. However, the etiology of the disease remains unknown due to its rarity. Therefore, we present a case of a solitary PCH lesion without symptoms in a 38-year-old female patient. According to computed tomography, she was diagnosed with lung carcinoma, indicated by a tiny nodule with ground-glass opacity detected in her right upper lung. However, no other lesions were detected on systemic examination. Consequently, partial lung resection was conducted, since the lesion was suspected of lung adenocarcinoma. Pathologic results showed that the thick alveolar septa were caused by capillary growth without cellular atypia and hardly any infiltration of inflammatory cells. Finally, we diagnosed the pulmonary lesion as PCH, although solitary PCH has previously been reported in a few case reports. Therefore, further case studies are essential to clarify the causes of PCH.

12.
CEN Case Rep ; 12(1): 84-90, 2023 02.
Article in English | MEDLINE | ID: mdl-35927545

ABSTRACT

Exacerbations or de novo autoimmune/autoinflammatory disease have been reported after COVID-19 vaccination. A young male presented with cutaneous IgA vasculitis with glomerular hematuria, diarrhea and pericarditis following his second COVID-19 mRNA vaccination. He also showed positivity for proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) and anti-cardiolipin antibody. Skin biopsy was compatible to IgA vasculitis. His purpura subsided and hematuria spontaneously disappeared. Treatment with anti-inflammatory medications and prednisolone resolved the pericarditis. He had a history of persistent diarrhea, and colonic biopsies showed possible ulcerative colitis without vasculitis. Kidney biopsy after prednisolone therapy revealed minor glomerular abnormalities without any immune reactants and did not show vasculitis. After prednisolone treatment, PR3-ANCA decreased in a medium degree despite of improvement of symptoms and inflammatory data, suggesting that his PR3-ANCA may be associated with ulcerative colitis. The cause of the transient glomerular hematuria was unclear, however, it might be caused by focal glomerular active lesions (glomerular vasculitis) due to vaccine-induced IgA vasculitis with nephritis. This case highlights that COVID-19 mRNA vaccination can activate multiple autoimmune/autoinflammatory systems. The conditions might help us better understand the mutual mechanisms of the relevant disorders.


Subject(s)
COVID-19 , Colitis, Ulcerative , IgA Vasculitis , Pericarditis , Vasculitis , Humans , Male , Hematuria/etiology , Antibodies, Antineutrophil Cytoplasmic , COVID-19 Vaccines/adverse effects , Vasculitis/diagnosis , Vasculitis/etiology , Myeloblastin , Prednisolone/therapeutic use , Diarrhea , Vaccination , RNA, Messenger
13.
Cancer Sci ; 114(1): 152-163, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36102493

ABSTRACT

Recent comprehensive analyses of mtDNA and orthogonal RNA-sequencing data revealed that in numerous human cancers, mtDNA copy numbers and mtRNA amounts are significantly reduced, followed by low respiratory gene expression. Under such conditions (called mt-Low), cells encounter severe cell proliferation defects; therefore, they must acquire countermeasures against this fatal disadvantage during malignant transformation. This study elucidated a countermeasure against the mt-Low condition-induced antiproliferative effects in hepatocellular carcinoma (HCC) cells. The mechanism relied on the architectural transcriptional regulator HMGA2, which was preferably expressed in HCC cells of the mt-Low type in vitro and in vivo. Detailed in vitro analyses suggest that HMGA2 regulates insulin-like growth factor binding protein 1 (IGFBP1) expression, leading to AKT activation, which then phosphorylates the cyclin-dependent kinase inhibitor (CKI), P27KIP1, and facilitates its ubiquitin-mediated degradation. Accordingly, intervention in the HMGA2 function by RNAi resulted in an increase in P27KIP1 levels and an induction of senescence-like cell proliferation inhibition in mt-Low-type HCC cells. Conclusively, the HMGA2/IGFBP1/AKT axis has emerged as a countermeasure against P27KIP1 CKI upregulation under mt-Low conditions, thereby circumventing cell proliferation inhibition and supporting the tumorigenic state. Notably, similar to in vitro cell lines, HMGA2 was likely to regulate IGFBP1 expression in HCC in vivo, thereby contributing to poor patient prognosis. Considering the significant number of cases under mt-Low or the threat of CKI upregulation cancer-wide, the axis is noteworthy as a vulnerability of cancer cells or target for tumor-agnostic therapy inducing irreversible cell proliferation inhibition via CKI upregulation in a large population with cancer.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , RNA , Proto-Oncogene Proteins c-akt/metabolism , Liver Neoplasms/pathology , DNA, Mitochondrial , Insulin-Like Growth Factor Binding Protein 1 , Cell Proliferation/genetics , Protein Kinase Inhibitors/pharmacology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic
14.
Anticancer Res ; 42(12): 5763-5771, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36456117

ABSTRACT

BACKGROUND/AIM: Rho small GTPases regulate cancer cell adhesion, migration and invasion through reorganization of the actin cytoskeleton. Rho GTPase Activating Protein 22 (ARHGAP22) is a Rac-specific GAP and suppresses Rac-dependent lamella formation and cell spreading. We have previously shown that ARHGAP22 localizes at endosomes in human melanoma A7 cells. The aim of the present study was to demonstrate the functional significance of its localization at the endosomes in melanoma cells. MATERIALS AND METHODS: The lamella formation and cell spreading were monitored using human melanoma A7 cells. The effect of inhibition of endosome recycling pathway was examined. RESULTS: We found that dominant negative Rab11 S25N mutant inhibits RacGAP activity of ARHGAP22 and blocks ARHGAP22-dependent suppression of lamella formation and melanoma cell spreading. Furthermore, deletion of 19 amino acid residues at the C-terminal region of ARHGAP22 abolished the localization of ARHGAP22 at enlarged vesicles and stimulated RacGAP activity of ARHGAP22. The deletion mutant accumulated at enlarged vesicles when endosome recycling pathway was blocked either by co-transfection of the Rab11 S25N mutant or treatment of the cells with N-ethylmaleimide, which blocks endosomal vesicular fusion to the plasma membrane. On the other hand, deletion of the pleckstrin homology (PH) domain of ARHGAP22 abolished its RacGAP activity and localization at the plasma membrane. CONCLUSION: ARHGAP22 localizes at endosomes and is transported to the plasma membrane to inactivate Rac and suppresses lamella formation and spreading of melanoma cells.


Subject(s)
GTPase-Activating Proteins , Melanoma , Humans , GTPase-Activating Proteins/genetics , Melanoma/genetics , Biological Transport , Amino Acids , Cell Membrane , rho GTP-Binding Proteins
15.
Heart Lung ; 56: 70-73, 2022.
Article in English | MEDLINE | ID: mdl-35780572

ABSTRACT

One of the major issues encountered during the coronavirus disease 2019 (COVID-19) pandemic has been the shortage of intravenous anesthetics. Moreover, patients undergoing extracorporeal membrane oxygenation (ECMO) need large quantities of intravenous anesthetics for sedation. We report the case of a 52-year-old man who was admitted to our hospital due to acute respiratory distress syndrome by COVID-19 and treated with ECMO. As controlling sedation with intravenous anesthetics was challenging, we attempted to administer inhaled anesthetics via the gas flow of ECMO. We decreased the quantity of intravenous anesthetics and opioids. This method might help overcome the shortage of intravenous anesthetics.


Subject(s)
Boidae , COVID-19 , Extracorporeal Membrane Oxygenation , Male , Animals , Humans , Middle Aged , Sevoflurane , Anesthetics, Intravenous , Analgesics, Opioid
16.
Front Med (Lausanne) ; 8: 718641, 2021.
Article in English | MEDLINE | ID: mdl-34631741

ABSTRACT

Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) because of limited effective therapies. During infection, the accumulation and activation of macrophages and monocytes in the lungs induce inflammatory mediators and contribute to tissue injury, leading to ARDS. However, therapeutic strategies that directly target activated macrophage and monocytes have not been reported. Combination treatment with etoposide (a cytotoxic agent) and a corticosteroid has been widely used for treating hemophagocytic lymphohistiocytosis characterized by the systemic activation of macrophages with overwhelming inflammation. Herein, we present five cases of COVID-19-associated ARDS treated with etoposide and corticosteroids. Three of the five patients were over 65 years of age and had various underlying diseases, including multiple myeloma. Four patients required invasive mechanical ventilation (MV), and one patient refused to be placed on MV due to underlying diseases. All patients were pre-treated with antiviral and/or other anti-inflammatory agents, but their condition deteriorated and hyperinflammation was noted. All five patients responded well to treatment and had an immediate response, as reflected by improvement in their respiratory condition and inflammatory marker levels and rapid resolution of fever after etoposide administration; however, some patients required a second dose of etoposide and longer course of steroids. All patients recovered, and there were no severe adverse events related to the drugs. Following successful treatment in these five patients, we plan to conduct a clinical trial to evaluate the efficacy and safety of combination therapy with etoposide and corticosteroid for treating COVID-19 patients in Japan.

17.
World Neurosurg X ; 11: 100106, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34142079

ABSTRACT

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated systemic angiocentric and angiodestructive lymphoproliferative disorder. It commonly involves the lungs and can also affect the skin, liver, kidney, and central nervous system. It can rarely occur in the spine, however, the details are unclear. We performed a systematic review of published cases (including our 1 case) of spinal LYG. We performed a systematic search of studies in English on spinal LYG, focusing on its clinical features, imaging, and treatments, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on the PubMed database. We identified 14 patients from the literature. We also found 1 case of isolated cervical LYG (grade 3) who was treated with steroid and radiation therapy for the spinal lesion after pathologic diagnosis. We performed a pooled analysis of these 15 cases. The mean age was 43.4 years, and 13 of the 15 patients were male. Brain lesions were present in 11 of 12 intramedullary spinal lesions, and only 1 was an isolated spinal LYG case. Regarding the diagnostic methods, 1 case was not described. Of the 14 cases described, 12 patients underwent biopsies (7 brain, 4 lung, and 1 spinal cord lesion) and 2 underwent surgical removal for an extramedullary lesion. In the overall prognosis from a mean follow-up period of 21.6 months, 4 patients died despite several treatments. Spinal LYG, particularly isolated spinal LYG, is rare. Thus further accumulation of cases may be necessary to better understand its characteristics.

18.
FASEB J ; 35(4): e21508, 2021 04.
Article in English | MEDLINE | ID: mdl-33710706

ABSTRACT

Migrating tumor cells are characterized by a sustained front-rear asymmetry, with a front enriched in filamentous actin, which is induced by Rho small GTPase Rac. Regulation of Rac activity by its regulators should be required for effective motility. Here, we show that FilGAP, a GTPase-activating protein (GAP) for Rac, controls front-rear polarity and contributes to maintain effective tumor cell migration through the extracellular matrix (ECM). Overexpression of FilGAP in breast cancer cells induced polarized morphology and led to increased migration speed in collagen matrices, while depletion of FilGAP impaired the cell polarity and migration. FilGAP localizes to the cell front through its pleckstrin-homology (PH) domain in a phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent manner and appears to inactivate Rac at its site. We found that the affinity of PH domain to PIP3 is critically involved in the maintenance of cell polarity. Moreover, small GTPase ADP-ribosylation factor 6 (Arf6), which binds to the FilGAP PH domain, also regulates FilGAP-mediated cell polarity and migration of breast cancer cells. We propose that FilGAP regulates front-rear polarity through its PIP3 and Arf6 binding in tumor cell migration through the ECM.


Subject(s)
Cell Movement/physiology , Cell Polarity/physiology , GTPase-Activating Proteins/metabolism , ADP-Ribosylation Factor 6 , Actin Cytoskeleton/metabolism , Cell Line, Tumor , Extracellular Matrix/metabolism , Humans , rho-Associated Kinases/metabolism
19.
Microorganisms ; 10(1)2021 Dec 23.
Article in English | MEDLINE | ID: mdl-35056467

ABSTRACT

Patients with severe Coronavirus disease 2019 (COVID-19) are at high risk for secondary infection with multidrug-resistant organisms (MDROs). Secondary infections contribute to a more severe clinical course and longer intensive care unit (ICU) stays in patients with COVID-19. A man in his 60s was admitted to the ICU at a university hospital for severe COVID-19 pneumonia requiring mechanical ventilation. His respiratory condition worsened further due to persistent bacteremia caused by imipenem-non-susceptible Klebsiella aerogenes and he required VV-ECMO. Subsequently, he developed a catheter-related bloodstream infection (CRBSI) due to Candida albicans, ventilator-associated pneumonia (VAP) due to multidrug-resistant Pseudomonas aeruginosa (MDRP), and a perianal abscess due to carbapenem-resistant K. aerogenes despite infection control procedures that maximized contact precautions and the absence of MDRO contamination in the patient's room environment. He was decannulated from VV-ECMO after a total of 72 days of ECMO support, and was eventually weaned off ventilator support and discharged from the ICU on day 138. This case highlights the challenges of preventing, diagnosing, and treating multidrug-resistant organisms and healthcare-associated infections (HAIs) in the critical care management of severe COVID-19. In addition to the stringent implementation of infection prevention measures, a high index of suspicion and a careful evaluation of HAIs are required in such patients.

20.
NMC Case Rep J ; 8(1): 529-534, 2021.
Article in English | MEDLINE | ID: mdl-35079513

ABSTRACT

Intracranial dermoid cysts are rare congenital lesions that result from abnormal sequestration of ectodermal cells during neural tube formation. These tumors are especially rare in lateral areas such as in the temporal lobe. In this study, we report a case of dermoid cyst located in the right temporal lobe. A 50-year-old man was referred for further treatment of a tumor. CT revealed a low-density mass lesion in the right temporal lobe, with calcification. MRI showed the lesion with high signal intensity on diffusion-weighted imaging, high-low mixed signal intensity on T1-weighted imaging, and iso-high signal mixed intensity on T2-weighted imaging; the capsule was enhanced with gadolinium. Differential diagnosis included dermoid cyst, epidermoid cyst, teratoma, and neurenteric cyst. We decided to perform surgery for the improvement of his symptom, histopathological diagnosis, and radical cure. A right temporal craniotomy was performed, and the tumor was found adherent to the surrounding brain tissue. The tumor was completely removed under subpial dissection. Hair was confirmed in the tumor content. On histopathology, the cyst wall was lined with stratified squamous epithelium, sebaceous glands, small vessel aggregates, and inflammatory infiltrate. Keratinized material and hair were found in the lumen. The patient was discharged 7 days after surgery with no new neurologic deficits. This case was unusual in terms of the effect of gadolinium enhancement on MRI, and the presence of adipose tissue and calcification were useful for diagnosis. It is vital to consider prevention of chemical meningitis due to intrathecal dissemination of the tumor content intraoperatively.

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