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1.
Kyobu Geka ; 77(3): 163-168, 2024 Mar.
Article in Japanese | MEDLINE | ID: mdl-38465486

ABSTRACT

PURPOSE: We investigated the relationship between aortic remodeling and timing of thoracic endovascular aortic repair( TEVAR) in patients with uncomplicated Stanford type B aortic dissection. METHODS: 29 patients with sub-acute and early chronic uncomplicated Stanford type B aortic dissection underwent TEVAR between February 2019 and August 2022 in our hospital. We retrospectively compared aortic remodeling between 19 patients in the sub-acute( SA) group( 15-90 days from onset) and 10 patients in the early chronic( ECh) group( 91-365 days from onset) using the false luminal area reduction rate using computed tomography imagings. RESULTS: The false lumen area reduction rates at the level of the carina in the SA and ECh groups were 21.9±13.5% and 7.0±21.2% (p=0.04) around 3-8 days after TEVAR, 91.8±13.8% and 62.6±48.4 % (p=0.26) at 6 months, 96.6±7.2% and 68.7±42.5% (p=0.14) at 12 months, and 96.2±10.0% and 79.2±37.6% (p=0.62) at 18 months respectively. There were no significant differences between the two groups regarding any complication. CONCLUSION: Preemptive TEVAR for sub-acute and early chronic uncomplicated Stanford type B aortic dissection resulted in good remodeling and it may provide a good prognosis, especially in the subacute stage.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Endovascular Aneurysm Repair , Retrospective Studies , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Treatment Outcome , Aortic Dissection/diagnostic imaging , Aortic Dissection/surgery , Risk Factors
2.
Breast Cancer ; 30(4): 584-595, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36930419

ABSTRACT

BACKGROUND: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. METHODS: A total of 47 patients with Stage I-III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. RESULTS: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). CONCLUSIONS: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.


Subject(s)
Biomarkers, Tumor , DNA Copy Number Variations , Triple Negative Breast Neoplasms , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/genetics , Biomarkers, Tumor/genetics , Humans , Female , Adult , Middle Aged , Aged , Disease-Free Survival
3.
J Vasc Surg Cases Innov Tech ; 8(1): 107-110, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35146220

ABSTRACT

Cerebrospinal fluid drainage is recommended for high-risk patients to prevent spinal cord ischemia during aortic surgery; however, it is associated with complications. We report a case of a late-onset spinal subdural hematoma that developed after removal of the cerebrospinal fluid drainage tube from a patient who undergon thoracic endovascular aortic repair. Spinal hematoma usually develop 2 to 3 days after tube removal; however, in our patient's case, it developed after 7 days. Therefore, a spinal subdural hematoma can occur ≤1 week after drainage tube removal, necessitating prompt magnetic resonance imaging for patients with lower limb weakness or back pain.

4.
Kyobu Geka ; 74(5): 383-387, 2021 May.
Article in Japanese | MEDLINE | ID: mdl-33980801

ABSTRACT

A mobile thrombus in the ascending aorta is extremely rare. A 57-year-old man was referred to our hospital with suspected esophageal cancer. Following thorough evaluation, he was diagnosed with esophageal cancer( UtMt type0-Ⅱa T1b, Mt type0-Ⅱc T1a N0M0 cStageⅠ) and tongue cancer in situ. He was administered preoperative chemotherapy comprising fluorouracil and cisplatin. The patient developed fever on day four of the first course of the chemotherapy. Contrast-enhanced chest and abdominal computed tomography revealed a mobile thrombus in the ascending aorta with bilateral partial renal infarction. We initiated intravenous unfractionated heparin and oral warfarin as anticoagulant therapy. The thrombus did not disappear despite ten-day treatment;therefore, he underwent aortic thrombectomy under hypothermic circulatory arrest with retrograde cerebral perfusion. Intraoperatively, we detected a pedunculated mobile thrombus attached to the aorta. His postoperative course was uneventful and he was treated at discharge with warfarin. He underwent video-assisted thoracoscopic esophagectomy postoperatively and was discharged without any complication. Currently, he showed no recurrent thrombus or cancer.


Subject(s)
Esophageal Neoplasms , Thrombosis , Aorta , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/surgery , Heparin , Humans , Male , Middle Aged , Thrombectomy , Thrombosis/diagnostic imaging , Thrombosis/surgery
5.
Kyobu Geka ; 74(3): 202-205, 2021 Mar.
Article in Japanese | MEDLINE | ID: mdl-33831873

ABSTRACT

Idiopathic aortic rupture is a rare but often fatal condition that requires urgent attention and repair. I have performed thoracic endovascular aortic repair ( TEVAR) in two cases of idiopathic aortic rupture and have achieved positive results. It can be difficult to identify the site of rupture in these cases. Therefore, it is necessary to lengthen treatment and to determine the potential for spinal cord ischemia and associated paralysis of the lower extremities. Given its association with a favorable postoperative recovery, TEVAR can be considered as a minimally-invasive option that can be used early to treat this condition, including those associated with hemodynamic instability and in patients who are at high risk for complications.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Rupture , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/surgery , Aortic Rupture/diagnostic imaging , Aortic Rupture/surgery , Humans , Postoperative Complications , Retrospective Studies , Risk Factors , Treatment Outcome
6.
Chromosome Res ; 29(1): 95-106, 2021 03.
Article in English | MEDLINE | ID: mdl-33694044

ABSTRACT

Scanning probe microscopy (SPM) uses a probing tip which scans over a sample surface for obtaining information on the sample surface characteristics. Among various types of SPM, atomic force microscopy (AFM) has been widely applied to imaging of biological samples including chromosomes. Scanning ion conductance microscopy (SICM) has been also introduced for visualizing the surface structure of biological samples because it can obtain "contact-free" topographic images in liquid conditions by detecting ion current flow through a pipette opening. However, we recently noticed that the consistent imaging of chromosomes is difficult by SICM. In this paper, the behaviors of the ion current on the sample surfaces were precisely investigated for obtaining SICM images of isolated muntjac metaphase chromosomes more consistently than at present. The present study revealed that application of positive potential to the pipette electrode was acceptable for obtaining the topographic image of chromosomes, while application of negative potential failed in imaging. The approach curves were then studied for analyzing the relationship between the ion current and the tip sample distance when the pipette is approaching chromosomes. The current-voltage (I-V) curve further provided us the accurate interpretation of the ion current behavior during chromosome imaging. These data were further compared with those for SICM imaging of HeLa cells. Our findings indicated that chromosomes are electrically charged and the net charge is strongly negative in normal Dulbecco's phosphate buffered saline. We finally showed that the ion concentration of the bath electrolyte is important for imaging chromosomes by SICM.


Subject(s)
Chromosomes , Microscopy , HeLa Cells , Humans , Metaphase
7.
J Gastrointest Surg ; 25(9): 2231-2241, 2021 09.
Article in English | MEDLINE | ID: mdl-33420656

ABSTRACT

BACKGROUND: Activin A receptor type 2A (ACVR2A) is one of the most frequently mutated genes in microsatellite instability-high (MSI-H) gastric cancer. However, the clinical relevance of the ACVR2A mutation in MSI-H gastric cancer patients remains unclear. The aims of this study were to explore the effect of ACVR2A mutation on the tumor behavior and to identify the clinicopathological characteristics of gastric cancer patients with ACVR2A mutations. METHODS: An in vitro study was performed to investigate the biological role of ACVR2A via CRISPR/Cas9-mediated ACVR2A knockout MKN74 human gastric cancer cells. One hundred twenty-four patients with gastric cancer were retrospectively analyzed, and relations between MSI status, ACVR2A mutations, and clinicopathological factors were evaluated. RESULTS: ACVR2A knockout cells showed less aggressive tumor biology than mock-transfected cells, displaying reduced proliferation, migration, and invasion (P < 0.05). MSI mutations were found in 10% (13/124) of gastric cancer patients, and ACVR2A mutations were found in 8.1% (10/124) of patients. All ACVR2A mutations were accompanied by MSI. The 5-year overall survival rates of ACVR2A wild-type patients and ACVR2A-mutated patients were 57% and 90%, respectively (P = 0.048). Multivariate analysis revealed that older age (P = 0.015), distant metastasis (P < 0.001), and ACVR2A wild-type status (P = 0.040) were independent prognostic factors for overall survival. CONCLUSIONS: Our study demonstrated that gastric cancer patients with ACVR2A mutation have a significantly better prognosis than those without. Dysfunction of ACVR2A in MKN74 human gastric cancer cells caused less aggressive tumor biology, indicating the importance of ACVR2A in the progression of MSI-H tumors.


Subject(s)
Microsatellite Instability , Stomach Neoplasms , Activin Receptors, Type II , Activins , Aged , Biology , Humans , Mutation , Retrospective Studies , Stomach Neoplasms/genetics
8.
J Surg Res ; 256: 645-656, 2020 12.
Article in English | MEDLINE | ID: mdl-32810665

ABSTRACT

BACKGROUND: Although previous experiments have implicated sphingosine-1-phosphate (S1P) as a links between immune reactions and cancer progression, the exact mechanism of this interaction has not comprehensively studied in clinical human samples. This study sought to evaluate the S1P regulation by sphingosine kinase 1 (SPHK1), an S1P-producing enzyme, in the immunity/immuno-reactivity of clinical human breast cancer surgical specimens. METHODS: S1P levels were examined in tumor, peritumoral, and normal human breast samples using mass spectrometry. Genomics Data Commons data portal of The Cancer Genome Atlas cohort was used to assess the expression of S1P-related and immune-related genes. RESULTS: S1P levels were significantly higher in tumor samples compared to peritumoral (P < 0.05) or normal human breast samples (P < 0.001). SPHK1 gene expression was elevated in tumoral samples compared to normal breast samples (P < 0.01). Furthermore, the elevated expression of SPHK1 in breast cancer tissue was associated with an increased expression of the different kinds of immune-related genes, such as CD68, CD163, CD4, and FOXP3 (forkhead box P3), in HER2-negative breast cancer. Network analysis showed the central role of SPHK1 in the interaction of S1P signaling and expression of immune cell-related proteins. CONCLUSIONS: We demonstrated that S1P is mainly produced by tumor tissue, rather than peritumoral tissue, in breast cancer patients. Our data revealed the involvement of S1P signaling in the regulation of immune-related genes, suggesting the links between S1P and complicated immune-cancer interactions in breast cancer patients.


Subject(s)
Breast Neoplasms/immunology , Breast/pathology , Gene Expression Regulation, Neoplastic/immunology , Lysophospholipids/analysis , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Sphingosine/analogs & derivatives , Breast/immunology , Breast Neoplasms/pathology , Cell Line, Tumor , Chromatography, High Pressure Liquid , Cohort Studies , Datasets as Topic , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Lysophospholipids/metabolism , Phosphotransferases (Alcohol Group Acceptor)/analysis , Protein Interaction Maps/genetics , Protein Interaction Maps/immunology , Signal Transduction/genetics , Signal Transduction/immunology , Spectrometry, Mass, Electrospray Ionization , Sphingosine/analysis , Sphingosine/metabolism , Tandem Mass Spectrometry
9.
Biochem Biophys Res Commun ; 531(4): 515-521, 2020 10 22.
Article in English | MEDLINE | ID: mdl-32807491

ABSTRACT

Light is an important cue for resetting the circadian clock. In mammals, light signals are thought to be transmitted to the cAMP response element (CRE) via a binding protein (CREB) to induce the expression of Per1 and Per2 genes in the mammalian circadian pacemaker, the suprachiasmatic nuclei (SCN). Several in vitro studies have suggested candidate CRE sites that contribute to the Per1 and Per2 induction by light, resulting in a phase shift of the circadian rhythm. However, it remains unclear whether the CREs are responsible for the light-induced Per1/2 induction. To address this question, we generated CRE-deleted mice in the Per1 and Per2 promoter regions. Deletion of a cAMP-responsive CRE in the Per1 promoter blunted light-induced Per1 expression in the SCN at night, while deletion of an ATF4 (CREB-2)-associated CRE in the Per2 promoter had no effect on its expression. These results suggested that the CRE in the Per1 promoter works for light induction but not CRE in the Per2 promoter. Behavioral rhythms observed under some light conditions were not affected by the CRE-deletion in Per1 promoter, suggesting that the attenuated Per1 induction did not affect the entrainment in some light conditions.


Subject(s)
Cyclic AMP/genetics , Period Circadian Proteins/genetics , Response Elements/physiology , Suprachiasmatic Nucleus/physiology , Animals , CRISPR-Cas Systems , Female , Gene Expression Regulation , Light , Locomotion/physiology , Male , Mice, Inbred C57BL , Mice, Mutant Strains , Promoter Regions, Genetic
10.
Case Rep Vasc Med ; 2020: 4726381, 2020.
Article in English | MEDLINE | ID: mdl-32095311

ABSTRACT

Both spontaneous superior mesenteric artery dissection (SMAD) and spontaneous renal artery dissection (SRAD) are very rare conditions. Their etiologies and natural histories are not precisely defined, but they are thought to be associated with underlying conditions. In this report, we describe an extremely rare case of SRAD in a man who had a history of spontaneous SMAD. We successfully treated SRAD with endovascular intervention. Isolated spontaneous SMAD and SRAD are both rare conditions. Their optimal treatment has not been established due to their rare entities, but endovascular treatment is a good option because it can prevent both advancement of infarction and renovascular hypertension, and it has become safer as device technology has improved. Patients with isolated visceral artery dissection should be carefully followed up.

11.
Oral Dis ; 26(1): 234-237, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31621985

ABSTRACT

OBJECTIVE: To investigate associated risk factors for oral candidiasis in elderly patients hospitalized in a community-based acute-care hospital with no dental units. METHODS: Two hundred and twenty-eight elderly patients (male: 105, female: 123), who were hospitalized with several systemic diseases in a community-based acute-care hospital from May 2014 to October 2016, were retrospectively analysed by multiple logistic regression. RESULTS: Multiple logistic regression analysis shows that bacterial pneumonia has a statistically strong relationship with oral candidiasis (p = 0.000, OR: 5.173, 95% CI: 2.368-11.298). The order followed is poor oral hygiene (p = 0.001, OR: 6.095, 95% CI: 2.003-18.545) and severe dry mouth (p = 0.043, OR: 2.507, 95% CI: 1.031-6.098). Other correlated factors including diabetes mellitus, denture wearer, dysphagia, malnutrition, requiring care and use of inhalation steroids, were not statistically significant in this study. CONCLUSIONS: Bacterial pneumonia correlates with oral candidiasis.


Subject(s)
Candidiasis, Oral/complications , Pneumonia, Bacterial/complications , Aged , Aged, 80 and over , Deglutition Disorders , Dentures , Diabetes Mellitus , Female , Hospitalization , Hospitals, Community , Humans , Male , Malnutrition , Oral Hygiene , Retrospective Studies , Risk Factors , Steroids/administration & dosage , Xerostomia/complications
12.
J Surg Case Rep ; 2019(11): rjz343, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31824639

ABSTRACT

Intrapericardial rupture of an aortic arch aneurysm is a rare and catastrophic event that requires emergency treatment. Recent development of thoracic endovascular repair has contributed to improved outcomes for the treatment of ruptured aneurysm of the thoracic aorta. However, when there is an aneurysm that involves the arch vessels, the treatment strategy, including conventional open surgery and endovascular stenting, is still controversial. We performed life-saving emergency total arch replacement using a modified elephant-trunk procedure for two cases of intrapericardial rupture of an aortic arch aneurysm. Prompt institution of cardiopulmonary bypass is effective for reducing the risk of re-rupture. Hybrid operation caries the risk of re-rupture during the procedure because it is performed under heparinization without blood pressure control. Open surgery is still a good option for such cases.

13.
Case Rep Dent ; 2019: 4945921, 2019.
Article in English | MEDLINE | ID: mdl-31934463

ABSTRACT

Professional oral health care (POHC) is known to prevent aspiration pneumonia in patients with dysphagia and/or those at the perioperative stage of surgery. However, the effect of POHC on patients suffering from aspiration pneumonia remains unknown. Here, we report a case where continual POHC intervention improved severe aspiration pneumonia. A 74-year-old male patient with a brain infarction suffered from severe aspiration pneumonia (PSI: IV, A-DROP: 3) complicated by vascular dementia and severe dysphagia. Because an antimicrobial approach following the treatment guidelines for pneumonia was not effective, we started a POHC intervention to improve his poor oral condition at the request of the attending doctor and the patient's family. The severe pneumonia markedly improved after continual POHC by the dental team. This case suggests that continual POHC intervention by a dental hygienist may improve severe aspiration pneumonia.

14.
J Surg Res ; 232: 186-194, 2018 12.
Article in English | MEDLINE | ID: mdl-30463717

ABSTRACT

BACKGROUND: Pancreatic cancer is a disease with poor prognosis, and development of new treatments is necessary. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays a critical role in progression of many types of cancer. However, little is known about the role of sphingosine kinases in pancreatic cancer. This study investigated the roles of sphingosine kinases in pancreatic cancer progression. MATERIALS AND METHODS: S1P levels in pancreatic cancer and noncancerous pancreatic tissue were measured in 10 patients. We generated PAN02 murine pancreatic cancer cell lines with a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system genes 9 (Cas9)-mediated deletion of SphK1 or SphK2 and assessed cell growth and migration. In an animal model, we assessed the survival of mice injected with PAN02 cells intraperitoneally. RESULTS: S1P levels in the pancreatic cancer tissue were significantly higher than those in noncancerous tissue. SphK1 knockout (KO) cells showed greater proliferation and migration than wild type (WT) cells, and SphK2 KO cells showed less proliferation and migration than WT cells. Animal experiments showed that the survival of mice injected with SphK1 KO cells was significantly shorter than those injected with WT cells, and the survival of mice injected with SphK2 KO cells was longer than those injected with WT cells. Surprisingly, cytotoxic assay using gemcitabine showed that SphK1 KO cells survived less than WT cells, and SphK2 KO cells survived more than WT cells. CONCLUSIONS: S1P produced by SphK1 and SphK2 may have different functions in pancreatic cancer cells. Targeting both SphK1 and SphK2 may be a potential strategy for pancreatic cancer treatment.


Subject(s)
Pancreatic Neoplasms/enzymology , Phosphotransferases (Alcohol Group Acceptor)/physiology , Animals , Cell Line, Tumor , Cell Proliferation , Disease Progression , Humans , Lysophospholipids/physiology , Male , Mice , Mice, Inbred C57BL , Pancreas/enzymology , Pancreatic Neoplasms/pathology , Phosphotransferases (Alcohol Group Acceptor)/analysis , Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors , Sphingosine/analogs & derivatives , Sphingosine/physiology
15.
J Surg Res ; 231: 323-330, 2018 11.
Article in English | MEDLINE | ID: mdl-30278948

ABSTRACT

BACKGROUND: Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that is generated by sphingosine kinase 1 (SphK1) and is known to play an important role in inflammation and cancer progression. Moreover, SphK1 and S1P act as upstream mediators of proinflammatory cytokine interleukin 6 (IL-6) and signal transducer and activator of transcription-3 (STAT3). We hypothesized that the expression levels of phosphorylated SphK1 (pSphK1), phosphorylated STAT3 (pSTAT3), and IL-6 are universally higher in CAC patients than in sporadic colorectal cancer (CRC) patients because all of these factors are associated with inflammation. In this study, we determined the expression levels of pSphK1 in patients with sporadic CRC and CAC and clarified the importance of S1P in CAC patients. MATERIALS AND METHODS: We randomly selected 10 sporadic CRC patients and 10 CAC patients who underwent curative resection, and we examined their surgical specimens by immunohistochemistry. We determined the expression levels of pSphK1, pSTAT3, and IL-6 in these samples. RESULTS: We found pSphK1 expression to be more prevalent in CAC patients (P = 0.019) and to have a higher immunohistochemistry score (P = 0.005) than in sporadic CRC patients. However, the expression of pSTAT3 and IL-6 did not differ between the patient groups. CONCLUSIONS: To our knowledge, this is the first report comparing pSphK1 expression levels in CAC with those in sporadic CRC. The high levels of pSphK1 expression in CAC suggest an important role of S1P in the disease process of CAC.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Biomarkers, Tumor/metabolism , Colitis, Ulcerative/complications , Colorectal Neoplasms/metabolism , Up-Regulation , Adult , Aged , Aged, 80 and over , Case-Control Studies , Colitis, Ulcerative/metabolism , Colorectal Neoplasms/etiology , Female , Humans , Immunohistochemistry , Interleukin-6/metabolism , Lysophospholipids/metabolism , Male , Middle Aged , Retrospective Studies , STAT3 Transcription Factor/metabolism , Sphingosine/analogs & derivatives , Sphingosine/metabolism
16.
Cancer Res ; 78(7): 1713-1725, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29351902

ABSTRACT

Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here, we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors. Targeting the SphK1/S1P/S1PR1 axis with FTY720/fingolimod attenuated key proinflammatory cytokines, macrophage infiltration, and tumor progression induced by obesity. S1P produced in the lung premetastatic niche by tumor-induced SphK1 increased macrophage recruitment into the lung and induced IL6 and signaling pathways important for lung metastatic colonization. Conversely, FTY720 suppressed IL6, macrophage infiltration, and S1P-mediated signaling pathways in the lung induced by a high-fat diet, and it dramatically reduced formation of metastatic foci. In tumor-bearing mice, FTY720 similarly reduced obesity-related inflammation, S1P signaling, and pulmonary metastasis, thereby prolonging survival. Taken together, our results establish a critical role for circulating S1P produced by tumors and the SphK1/S1P/S1PR1 axis in obesity-related inflammation, formation of lung metastatic niches, and breast cancer metastasis, with potential implications for prevention and treatment.Significance: These findings offer a preclinical proof of concept that signaling by a sphingolipid may be an effective target to prevent obesity-related breast cancer metastasis. Cancer Res; 78(7); 1713-25. ©2018 AACR.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Adenocarcinoma/pathology , Breast Neoplasms/pathology , Lysophospholipids/metabolism , Obesity/pathology , Receptors, Lysosphingolipid/metabolism , Sphingosine/analogs & derivatives , Animals , Cell Line, Tumor , Culture Media, Conditioned/pharmacology , Cytokines/antagonists & inhibitors , Diet, High-Fat , Disease Models, Animal , Female , Fingolimod Hydrochloride/pharmacology , Humans , Immunosuppressive Agents/pharmacology , Inflammation/pathology , Interleukin-6/metabolism , Lung/immunology , Lung/pathology , Macrophages/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Sphingosine/metabolism , Sphingosine-1-Phosphate Receptors
17.
Article in English | MEDLINE | ID: mdl-32529167

ABSTRACT

PURPOSE: It has been suggested that the biological characteristics of breast cancer may differ among different geographic or ethnic populations. Indeed, triple-negative breast cancer (TNBC), the most lethal breast cancer subgroup, has been reported to show a higher incidence in Japan than in the US. However, most genomic studies of these tumors are from Western countries and the genomic landscape of TNBC in an Asian population has not been thoroughly investigated. Here, we sought to elucidate the geographic and ethnic diversity of breast cancer by examining actionable driver alterations in TNBC tumors from Japanese patients and comparing them with The Cancer Genome Atlas (TCGA) database, which gather data primarily from non-Asian patients. MATERIALS AND METHODS: We performed comprehensive genomic profiling, including an analysis of 435 known cancer genes on Japanese TNBC patients (N=53) and compared the results to independent data obtained from TCGA (N=123). RESULTS: Driver alterations were identified in 51 out of 53 Japanese patients (96%). Although the overall alteration spectrum of Japanese patients was similar to that of the TCGA, we found significant differences in the frequencies of alterations in MYC and PTK2. We identified three patients (5.7%) with a high tumor mutation burden, although no microsatellite instability was observed in any of the Japanese patients. Importantly, pathway analysis revealed that 66.0% (35/53) of Japanese patients, as well as 66.7% (82/123) of the TCGA cohort, had alterations in at least one actionable gene targetable by an FDA-approved drug. CONCLUSION: Our study identified actionable driver alterations in Japanese patients with TNBC, revealing new opportunities for targeted therapies in Asian patients.

18.
Micron ; 104: 21-25, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29049927

ABSTRACT

Since a three-dimensional (3D) cellular ultrastructure is significant for biological functions, it has been investigated using various electron microscopic techniques. Although transmission electron microscopy (TEM)-based techniques are traditionally used, cells must be embedded in resin and sliced into ultrathin sections in sample preparation processes. Block-face observation using a scanning electron microscope (SEM) has also been recently applied to 3D observation of cellular components, but this is a destructive inspection and does not allow re-examination. Therefore, we developed electron tomography using a transmission electron imaging technique called Plate-TEM. With Plate-TEM, the cells cultured directly on a scintillator plate are inserted into a conventional SEM equipped with a Plate-TEM observation system, and their internal structures are observed by detecting scintillation light produced by electrons passing through the cells. This technology has the following four advantages. First, the cells cultured on the plate can be observed at electron-microscopic resolution since they remain on the plate. Second, both surface and internal information can be obtained simultaneously by using electron- and photo-detectors, respectively, because a Plate-TEM detector is installed in an SEM. Third, the cells on the scintillator plate can also be inspected using light microscopy because the plate has transparent features. Finally, correlative observation with other techniques, such as conventional TEM, is possible after Plate-TEM observation because Plate-TEM is a non-destructive analysis technique. We also designed a sample stage to tilt the samples for tomography with Plate-TEM, by which 3D organization of cellular structures can be visualized as a whole cell. In the present study, Mm2T cells were investigated using our tomography system, resulting in 3D visualization of cell organelles such as mitochondria, lipid droplets, and microvilli. Correlative observations with various imaging techniques were also conducted by successive observations with light microscopy, SEM, Plate-TEM, and conventional TEM. Consequently, the Plate-TEM tomography technique encourages understanding of cellular structures at high resolution, which can contribute to cellular biological research.


Subject(s)
Cells, Cultured/ultrastructure , Electron Microscope Tomography/methods , Epithelial Cells/ultrastructure , Imaging, Three-Dimensional/methods , Intravital Microscopy/methods , Microscopy, Electron, Transmission/methods , Animals , Microscopy/methods , Muntjacs
19.
Semin Cell Dev Biol ; 73: 125-131, 2018 01.
Article in English | MEDLINE | ID: mdl-28939037

ABSTRACT

Scanning ion conductance microscopy (SICM), which belongs to the family of scanning probe microscopy, regulates the tip-sample distance by monitoring the ion current through the use of an electrolyte-filled nanopipette as the probing tip. Thus, SICM enables "contact-free" imaging of cell surface topography in liquid conditions. In this paper, we applied hopping mode SICM for obtaining topographical images of convoluted tissue samples such as trachea and kidney in phosphate buffered saline. Some of the SICM images were compared with the images obtained by scanning electron microscopy (SEM) after drying the same samples. We showed that the imaging quality of hopping mode SICM was excellent enough for investigating the three-dimensional surface structure of the soft tissue samples. Thus, SICM is expected to be used for imaging a wide variety of cells and tissues - either fixed or alive- at high resolution under physiologically relevant liquid conditions.


Subject(s)
Kidney Glomerulus/cytology , Kidney Glomerulus/ultrastructure , Microscopy/methods , Trachea/cytology , Trachea/ultrastructure , Animals , Surface Properties
20.
Gan To Kagaku Ryoho ; 45(13): 1854-1856, 2018 Dec.
Article in Japanese | MEDLINE | ID: mdl-30692376

ABSTRACT

A 33-year-old woman underwent resection of a right breast mass, which was diagnosed as a fibroadenoma 15 years ago. Ten years later, a right breast mass appeared again, and it was diagnosed as a fibroadenoma based on core needle biopsy. After observation for a while, the mass increased in size, and she underwent resection of the tumor, which was diagnosed as a borderline-malignant phyllodes tumor. A mass appeared again in the right breast and rapidly expanded. A malignant phyllodes tumor was suspected, and right mastectomy was performed. The pathological diagnosis revealed a benign phyllodes tumor. Four years ago, a left breast mass was also detected. Because the mass was suspected to be a fibroadenoma, it has been observed for a few years. The mass has increased in size since 1 year ago, and another mass emerged 2 months ago. Core needle biopsy of the 2 masses revealed that both were phyllodes tumors. She underwent left mastectomy, and the pathological examination revealed that both masses were benign phyllodes tumors. We report this rare case of metachronal phyllodes tumors that presented bilaterally.


Subject(s)
Breast Neoplasms , Fibroadenoma , Phyllodes Tumor , Adult , Biopsy, Large-Core Needle , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Female , Fibroadenoma/diagnosis , Fibroadenoma/surgery , Humans , Mastectomy , Phyllodes Tumor/diagnosis , Phyllodes Tumor/surgery
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