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1.
Heart Vessels ; 39(1): 25-34, 2024 Jan.
Article En | MEDLINE | ID: mdl-37695543

Although angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) play critical roles in the treatment of heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF; left-ventricular ejection fraction ≤ 50%), the ideal timing for initiation in patients with acute heart failure (AHF) is unclear. We sought to clarify the timing and safety of ACEi/ARB prescription relative to hemodynamic stabilization (pre or post) in patients hospitalized with acute HFrEF/HFmrEF. This was a retrospective, observational analysis of electronic data of patients hospitalized for AHF at 17 Japanese hospitals. Among 9107 patients hospitalized with AHF, 2648 had HFrEF/HFmrEF, and 83.0% met the hemodynamic stabilization criteria within 10 days of admission. During hospitalization, 63.5% of patients with HFrEF/HFmrEF were prescribed an ACEi/ARB, 79.4% of which were prescribed pre-stabilization. In a multivariable analysis, patients treated with an ACEi/ARB pre-stabilization were more likely to have comorbid hypertension, diabetes mellitus, or ischemic heart disease. ACEi/ARB prescription timing was not associated with adverse events, including hypotension and renal impairment, and early prescription was associated with a lower incidence of subsequent worsening of HF. In clinical practice, more hospitalized patients with AHF received an ACEi/ARB before compared with after hemodynamic stabilization, and no safety concerns were observed. Moreover, early prescription may be associated with a lower incidence of worsening HF.


Angiotensin-Converting Enzyme Inhibitors , Heart Failure , Humans , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Retrospective Studies , Angiotensin Receptor Antagonists/therapeutic use , Stroke Volume , Ventricular Function, Left
2.
Health Sci Rep ; 6(6): e1316, 2023 Jun.
Article En | MEDLINE | ID: mdl-37283882

Background and Aims: This study examined the feasibility of nutritional support combined with exercise intervention for restoring muscle and physical functions in convalescent orthopedic patients. Methods: We used a crossover design in which nutritional support combined with exercise intervention was administered daily during the early (1 month) and late (1 month) cycles with a 1-week washout period. The exercise intervention was performed twice daily for 2 months in the early and late groups. The exercise intervention consisted of one set of muscle strength, stretching, and physical activity exercises for 20 min each. Nutritional interventions were administered immediately after the exercise. A 3.4 g of branched-chain amino acid supplements (BCAAs) or 1.2 g of starch was ingested. We measured the skeletal muscle mass and isometric muscle strength of the limbs and performed balance tests. After the crossover, the BCAA and Placebo groups were compared. Results: The ratio of improvement in the echo intensity of the rectus femoris (RF) was significantly higher in the BCAA group. A comparison of the order of nutritional intervention showed a significant effect on the RF echo intensity in both groups only when BCAAs were administered. Conclusion: This study's results suggest that the proposed combined intervention improves muscle quality and mass in convalescent orthopedic patients.

3.
Transplant Proc ; 55(4): 1055-1058, 2023 May.
Article En | MEDLINE | ID: mdl-37208224

When COVID-19 affects patients with risk factors such as chronic kidney disease or on immunosuppressive drugs, they often rapidly become seriously ill. We describe a 50-year-old man who was affected with SARS-CoV-2 and had undergone an ABO-compatible living-donor kidney transplantation from his father 14 years ago because of end-stage renal failure due to hypertensive nephrosclerosis. He had continued on immunosuppressive drugs and completed vaccination twice (9 months ago and 6 months ago) with messenger RNA (mRNA) vaccines against SARS-CoV-2. However, he was temporarily on a mechanical ventilator due to respiratory failure and hemodialysis due to acute kidney injury (AKI). He was finally weaned from the ventilator and hemodialysis by taking steroid and antiviral drugs. Echo-guided renal biopsy revealed myoglobin cast nephropathy. We experienced 14 outpatients after living-donor kidney transplantation infected with SARS-CoV-2, but only this case developed AKI.


Acute Kidney Injury , COVID-19 , Kidney Transplantation , Male , Humans , Middle Aged , Kidney Transplantation/adverse effects , COVID-19/complications , Myoglobin , Living Donors , COVID-19 Vaccines , SARS-CoV-2 , Immunosuppressive Agents , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology
4.
Fluids Barriers CNS ; 19(1): 43, 2022 Jun 03.
Article En | MEDLINE | ID: mdl-35659272

BACKGROUND: Cerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model. METHODS: BBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6 h OGD/24 h reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells. RESULTS: We found that treatment with 0.3-30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes. CONCLUSIONS: Our findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.


Blood-Brain Barrier , Ischemic Stroke , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/metabolism , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Animals , Astrocytes/metabolism , Blood-Brain Barrier/metabolism , Endothelial Cells/metabolism , Glucose , Humans , Rats , Tight Junction Proteins/metabolism
5.
Front Neurol ; 13: 875260, 2022.
Article En | MEDLINE | ID: mdl-35557623

Objective: To clarify the safety and efficacy of pre-operative embolization using Onyx liquid embolic agent (Onyx; ev3) compared with N-butyl cyanoacrylate (NBCA; Cordis Neurovascular, Inc.) or coils in cerebral arteriovenous malformation (AVM) surgery. Methods: This was a retrospective review of a prospectively collected clinical database of brain AVMs treated at our institute from January 2005 to March 2021. A total of 38 consecutive patients who underwent AVM resection after pre-operative embolization were included. Based on pre-operative embolization materials, the patients were divided into the pre-Onyx group (n = 16), in which NBCA or coils were used for embolization, and the Onyx group (n = 22). Patient characteristics and treatment results were compared between the two groups. Results: Patient characteristics were comparable between the two groups in terms of age, sex, and rupture status. While the Spetzler-Martin grade was also similar between the two groups, the location of the AVM nidus in the eloquent area was slightly higher in patients in the Onyx group (72.7%) than in patients in the pre-Onyx group (43.8%) (P = 0.09). The embolization rate was higher in the pre-Onyx group (mean: 63.0%; range: 12.7-100%) than in the Onyx group (mean: 50.0%; range: 15.8-100%), but the difference was not statistically significant (P = 0.06). The time needed for surgical removal was shorter in the Onyx group (mean: 354.8 min; range: 144-884 min) than in the pre-Onyx group (mean: 457.9 min; range: 240-1,294 min); however, this difference was not statistically significant (P = 0.13). The amount of intraoperative bleeding was significantly lower in the Onyx group (mean: 129.8 ml; range: 20-540 mL) than in the pre-Onyx group (mean: 448.8 mL; range: 120-1,550 ml) (P = 0.0008). The surgical complication rates were comparable between the two groups (pre-Onyx group, 18.8%; Onyx group, 4.5%; P = 0.29). Conclusions: Pre-operative embolization with Onyx can significantly reduce the amount of intraoperative bleeding in AVM resection and may contribute to safe AVM surgery.

6.
Sci Rep ; 12(1): 8715, 2022 05 24.
Article En | MEDLINE | ID: mdl-35610278

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate various genes involved in cholesterol and fatty acid synthesis. In this study, we describe that naturally occurring isothiocyanate sulforaphane (SFaN) impairs fatty acid synthase promoter activity and reduces SREBP target gene (e.g., fatty acid synthase and acetyl-CoA carboxylase 1) expression in human hepatoma Huh-7 cells. SFaN reduced SREBP proteins by promoting the degradation of the SREBP precursor. Amino acids 595-784 of SREBP-1a were essential for SFaN-mediated SREBP-1a degradation. We also found that such SREBP-1 degradation occurs independently of the SREBP cleavage-activating protein and the Keap1-Nrf2 pathway. This study identifies SFaN as an SREBP inhibitor and provides evidence that SFaN could have major potential as a pharmaceutical preparation against hepatic steatosis and obesity.


NF-E2-Related Factor 2 , Sterol Regulatory Element Binding Proteins , CCAAT-Enhancer-Binding Proteins/metabolism , Cholesterol/metabolism , Fatty Acid Synthases/metabolism , Humans , Isothiocyanates/pharmacology , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 2/metabolism , Sterol Regulatory Element Binding Proteins/metabolism , Sulfoxides
7.
Front Chem ; 10: 841313, 2022.
Article En | MEDLINE | ID: mdl-35386848

This study describes the concise exfoliation of multilayer Ti3C2T x MXene containing residual aluminum atoms. Treatment with tetramethylammonium base in a co-solvent of tetrahydrofuran and H2O produced single-layer Ti3C2T x , which was confirmed via atomic force microscopy observations, with an electrical conductivity 100+ times that of Ti3C2T x prepared under previously reported conditions. The scanning electron microscopy and X-ray diffraction measurements showed that the exfoliated single-layer Ti3C2T x MXenes were reconstructed to assembled large-domain layered films, enabling excellent macroscale electric conductivity. X-ray photoelectron spectroscopy confirmed the complete removal of residual Al atoms and the replacement of surface fluorine atoms with hydroxy groups. Using the exfoliated dispersion, a flexible transparent conductive film was formed and demonstrated in an electrical application.

8.
JCO Precis Oncol ; 6: e2000368, 2022 03.
Article En | MEDLINE | ID: mdl-35294223

PURPOSE: Lehmann et al have identified four molecular subtypes of triple-negative breast cancer (TNBC)-basal-like (BL) 1, BL2, mesenchymal (M), and luminal androgen receptor-and an immunomodulatory (IM) gene expression signature modifier. Our group previously showed that the response of TNBC to neoadjuvant systemic chemotherapy (NST) differs by molecular subtype, but whether NST affects the subtype was unknown. Here, we tested the hypothesis that in patients without pathologic complete response, TNBC subtypes can change after NST. Moreover, in cases with the changed subtype, we determined whether epithelial-to-mesenchymal transition (EMT) had occurred. MATERIALS AND METHODS: From the Pan-Pacific TNBC Consortium data set containing TNBC patient samples from four countries, we examined 64 formalin-fixed, paraffin-embedded pairs of matched pre- and post-NST tumor samples. The TNBC subtype was determined using the TNBCtype-IM assay. We analyzed a partial EMT gene expression scoring metric using mRNA data. RESULTS: Of the 64 matched pairs, 36 (56%) showed a change in the TNBC subtype after NST. The most frequent change was from BL1 to M subtypes (38%). No tumors changed from M to BL1. The IM signature was positive in 14 (22%) patients before NST and eight (12.5%) patients after NST. The EMT score increased after NST in 28 (78%) of the 36 patients with the changed subtype (v 39% of the 28 patients without change; P = .002254). CONCLUSION: We report, to our knowledge, for the first time that the TNBC molecular subtype and IM signature frequently change after NST. Our results also suggest that EMT is promoted by NST. Our findings may lead to innovative adjuvant therapy strategies in TNBC cases with residual tumor after NST.


Triple Negative Breast Neoplasms , Gene Expression Profiling , Humans , Immunotherapy , Neoadjuvant Therapy , Transcriptome , Triple Negative Breast Neoplasms/drug therapy
9.
Arch Clin Neuropsychol ; 37(4): 865-871, 2022 May 16.
Article En | MEDLINE | ID: mdl-34664637

OBJECTIVE: Simultanagnosia is a rare neuropsychological symptom characterized by difficulty recognizing global structures while preserving perception of local detail. The condition is classified into ventral and dorsal types. Clinical presentation of ventral simultanagnosia includes a reduced ability to recognize multiple visual stimuli rapidly, that is, part-by-part recognition. Here, we report a case of ventral simultanagnosia with a unique presentation; when short-duration visual stimuli were presented, the patient could perform global recognition by improving his part-by-part approach. To investigate the relationship between local and global perception bias and the duration of the present stimulus, we conducted a visual perception test using hierarchically organized Navon figures. METHODS/RESULTS: The patient was a 62-year-old right-handed man who suffered from cerebral infarction in the right occipitotemporal lobe. He had no language dysfunction but exhibited left unilateral neglect, prosopagnosia, and ventral-type simultanagnosia. We conducted a visual perception test using the Navon figures and control figures as a visual stimulus. We randomly presented the figures for intervals of 0.2 or 20 s and let the patient report all the letters (global and/or local element) that he recognized. Global elements of the Navon letter were recognized a rate of 0% and 78.3% at intervals of 20 and 0.2 s, respectively, indicating that shorter presentation made the part-by-part approach less likely to manifest. CONCLUSIONS: We assumed that the simultanagnosia in this case was caused by failure to maintain the initially perceived global information for a long period of time during visual presentation, due to right occipitotemporal damage.


Agnosia , Agnosia/complications , Humans , Male , Middle Aged , Neuropsychological Tests , Recognition, Psychology
10.
Gan To Kagaku Ryoho ; 49(13): 1531-1533, 2022 Dec.
Article Ja | MEDLINE | ID: mdl-36733125

A 66-year-old male presented with a torose lesion at the duodenal bulb, detected via endogastroduodenoscopy(EGD) during a medical check-up. It was histopathologically diagnosed as a low-grade adenoma. He was referred to the Department of Gastroenterology for follow-up observation. An endoscopic mucosal resection(EMR)was performed due to the increasing tumor size. The pathological findings of the resected specimen showed a tubular adenoma. The patient was then followed up as an outpatient. Two months later, a follow-up EGD revealed a mass lesion, suspected to be a remnant tumor. A laparoscopic distal gastrectomy, #3, #4sb, #5, #6 dissection, and Billroth Ⅱ+Braun anastomosis reconstruction were performed. Pathological examination showed a tubular adenocarcinoma in adenoma, tub1, with depth M, and no lymph node metastasis. Non-papillary duodenal carcinoma is a rare disease that has no established guidelines for radical surgery and the extent of lymph node dissection. Pancreaticoduodenectomy is often performed in advanced cases. However, due to the increasing number of patients and the risk of complications, limited resection should be considered as an alternative management option.


Adenocarcinoma , Laparoscopy , Stomach Neoplasms , Male , Humans , Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Gastroenterostomy , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Gastrectomy
11.
Pharmaceutics ; 13(8)2021 Aug 17.
Article En | MEDLINE | ID: mdl-34452232

Neurointervention with contrast media (CM) has rapidly increased, but the impact of CM extravasation and the related side effects remain controversial. This study investigated the effect of CM on blood-brain barrier (BBB) integrity. We established in vitro BBB models using primary cultures of rat BBB-related cells. To assess the effects of CM on BBB functions, we evaluated transendothelial electrical resistance, permeability, and tight junction (TJ) protein expression using immunohistochemistry (IHC) and Western blotting. To investigate the mechanism of iopamidol-induced barrier dysfunction, the role of mitogen-activated protein (MAP) kinases in brain endothelial cells was examined. We assessed the effect of conditioned medium derived from astrocytes and pericytes under iopamidol treatment. Short-term iopamidol exposure on the luminal side induced transient, while on the abluminal side caused persistent BBB dysfunction. IHC and immunoblotting revealed CM decreased the expression of TJ proteins. Iopamidol-induced barrier dysfunction was improved via the regulation of MAP kinase pathways. Conditioned medium from CM-exposed pericytes or astrocytes lacks the ability to enhance barrier function. CM may cause BBB dysfunction. MAP kinase pathways in brain endothelial cells and the interactions of astrocytes and pericytes mediate iopamidol-induced barrier dysfunction. CM extravasation may have negative effects on clinical outcomes in patients.

12.
Breast Cancer Res Treat ; 189(2): 455-461, 2021 Sep.
Article En | MEDLINE | ID: mdl-34131830

PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.


Breast Neoplasms , Biomarkers, Tumor/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Chemotherapy, Adjuvant , Female , Gene Expression Profiling , Humans , Neoplasm Recurrence, Local/genetics , Prognosis , Receptor, ErbB-2/genetics , Receptors, Estrogen/genetics , Retrospective Studies
13.
Gan To Kagaku Ryoho ; 48(4): 587-589, 2021 Apr.
Article Ja | MEDLINE | ID: mdl-33976057

A 78‒year‒old man was admitted to our hospital with the chief complaint of 5 kg weight loss in 6 months. An esophagogastroduodenoscopy revealed a 0‒Ⅱa lesion in the posterior wall of the antrum, and biopsy findings showed a well‒differentiated adenocarcinoma. Endoscopic ultrasonography did not show an obvious invasion of the submucosal layer. Contrast‒ enhanced abdominal computed tomography(CT)revealed an enlargement of the #11p lymph node to approximately 30 mm, and positron emission tomography(PET)‒CT showed an accumulation in the same lymph node. Since no other apparent distant metastases were observed, laparoscopic distal gastrectomy and D2 dissection were performed. The postoperative pathological diagnosis was L, 7×8 mm, 0‒Ⅱa, tub1, pT1a, ly0, v0, pPM0(73 mm), pDM0(35 mm), N2, and pStage ⅡA. We report this case because the successful laparoscopic resection of a differentiated gastric mucosal cancer with lymph node metastasis has been considered to be extremely rare.


Laparoscopy , Stomach Neoplasms , Aged , Gastrectomy , Gastric Mucosa , Humans , Lymph Nodes , Lymphatic Metastasis , Male , Stomach Neoplasms/surgery
14.
Gan To Kagaku Ryoho ; 48(3): 397-399, 2021 Mar.
Article Ja | MEDLINE | ID: mdl-33790167

A 75-year-old man presented to a local clinic with anal pain, and a palpable anal tumor on was found on digital examination of the rectum. A biopsy led to the diagnosis of neuroendocrine carcinoma. Besides the anal tumor, an right-inguinal lymph node was revealed on computed tomography(CT). Positron emission tomography-CT showed abnormal uptake in the 2 regions. He was diagnosed with lymph node metastases from anal canal carcinoma, and an abdominoperineal resection was performed. The resected specimen included the anal canal tumor with a size of 27×18 mm in diameter. On immunohistochemistry, the anal canal tumor was strongly positive for synaptophysin and positive for chromogranin A, with a Ki- 67 positivity index of 70%. After the surgery, he was administered chemotherapy with 4 courses of cisplatin and CPT-11. One year after the surgery, CT revealed lymph node recurrence. Therefore, cisplatin and CPT-11 therapy was repeated. After 11 courses of the cisplatin and CPT-11 treatment, tumor regrowth was still detected. The treatment protocol was changed to an amrubicin monotherapy regimen. However, the patient's general condition worsened after the therapies, and he died 38 months after the surgery.


Anus Neoplasms , Carcinoma, Neuroendocrine , Aged , Anal Canal , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/drug therapy , Anus Neoplasms/surgery , Carcinoma, Neuroendocrine/drug therapy , Carcinoma, Neuroendocrine/surgery , Humans , Male , Neoplasm Recurrence, Local
15.
Gan To Kagaku Ryoho ; 48(3): 400-402, 2021 Mar.
Article Ja | MEDLINE | ID: mdl-33790168

The patient was a 58-year-old man who had undergone wide gastrectomy for gastric ulcer at 22 years of age. Endoscopic examination revealed an advanced type 3 gastric cancer in the anastomotic region. We performed total gastrectomy and D1 lymph node dissection because of the bleeding from the tumor, although peritoneal dissemination was found during the surgery. A post-operative pathological diagnosis of gastric cancer pT4b(SI, abdominal wall)N0M1(PER), pStage Ⅳ, was made. After the surgery, he was administered chemotherapy with S-1 and cisplatin. After 9 courses of the treatment, the treatment protocol was changed to an S-1 therapy regimen because of general fatigue. Four years and 8 months after the surgery, the tumor marker had increased, and CT scans revealed a dissemination nodule at the left back side of the bladder. Therefore, PTX plus Rmab therapy was administered as a second-line chemotherapy. Treatment with PTX plus Rmab resulted in tumor reduction, with an improvement of the QOL of the patient; partial response was maintained for 12 months. After 16 courses of the PTX plus Rmab treatment, tumor regrowth was detected. The treatment protocol was changed again to a nivolumab regimen. After 4 courses, the tumor marker was normalized, and CT scans revealed that the peritoneal dissemination had shrunk. Although the prognosis of gastric cancer with dissemination is very poor, it is possible to prolong survival with chemotherapy.


Stomach Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Drug Combinations , Gastrectomy , Humans , Male , Middle Aged , Oxonic Acid/therapeutic use , Quality of Life , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery
16.
Antibodies (Basel) ; 10(1)2021 Feb 01.
Article En | MEDLINE | ID: mdl-33535554

Antibody-drug conjugates (ADCs), which are currently being developed, may become promising cancer therapeutics. Folate receptor α (FOLR1), a glycosylphosphatidylinositol-anchored membrane protein, is an attractive target of ADCs, as it is largely absent from normal tissues but is overexpressed in malignant tumors of epithelial origin, including ovarian, lung, and breast cancer. In this study, we tested the effects of novel anti-FOLR1 antibody-eribulin conjugate MORAb-202 in breast cancer and non-small cell lung cancer (NSCLC) cell lines. FOLR1 expression, cell proliferation, bystander killing effects, and apoptosis were evaluated in seven breast cancer and nine NSCLC cell lines treated with MORAb-202. Tumor growth and FOLR1 expression were assessed in T47D and MCF7 orthotopic xenograft mouse models after a single intravenous administration of MORAb-202 (5 mg/kg). MORAb-202 was associated with inhibited cell proliferation, with specific selectivity toward FOLR1-expressing breast cancer cell lines. Eribulin, the payload of MORAb-202, was unleashed in HCC1954 cells, diffused into intercellular spaces, and then killed the non-FOLR1-expressing MCF7 cells in co-culture systems. In orthotopic xenograft mouse models, FOLR1-expressing T47D tumors and non-FOLR1-expressing MCF7 tumors were suppressed upon MORAb-202 administration. The novel anti-FOLR1 antibody-eribulin conjugate MORAb-202 has potential antitumor effects in breast cancer.

17.
J Neurosurg Case Lessons ; 1(26): CASE21169, 2021 Jun 28.
Article En | MEDLINE | ID: mdl-35854902

BACKGROUND: Pituitary apoplexy associated with aneurysmal rupture is extremely rare and may be misdiagnosed as primary pituitary adenoma apoplexy. The authors present a case of a patient with pituitary apoplexy caused by rupture of an anterior cerebral artery aneurysm embedded within a giant pituitary adenoma, and they review the relevant literature. OBSERVATIONS: A 78-year-old man experienced sudden headache with progressive vision loss. Magnetic resonance imaging (MRI) revealed a giant pituitary tumor with abnormal signal intensity. Magnetic resonance angiography immediately before surgery showed a right A1 segment aneurysm, suggesting coexisting pituitary apoplexy and ruptured aneurysm. The patient underwent urgent transsphenoidal surgery for pituitary apoplexy. The tumor was partially removed, but the perianeurysmal component was left behind. Subsequent cerebral angiography showed a 5-mm right A1 aneurysm with a bleb that was successfully embolized with coils. Retrospective review of preoperative dynamic MRI showed extravasation of contrast medium from the ruptured aneurysm into the pituitary adenoma. Histopathologic examination showed gonadotroph adenoma with hemorrhagic necrosis. Postoperatively, the patient's visual function improved. LESSONS: MRI identification of pituitary apoplexy caused by aneurysmal rupture has not been reported previously. Aneurysmal rupture should be considered in the differential diagnosis of pituitary apoplexy. When a ruptured aneurysm is encountered, the authors recommend treating it before addressing pituitary apoplexy.

18.
J Neuroendovasc Ther ; 15(3): 157-163, 2021.
Article En | MEDLINE | ID: mdl-37502737

Objective: Rupture of blood blister-like aneurysm (BBA) of the internal carotid artery (ICA) may result in fatal subarachnoid hemorrhage (SAH). Open surgery including bypass surgery has been performed to treat the aneurysm. Recently, endovascular treatment is developing for the treatment of cerebral aneurysm. Here, we report a case of ruptured BBA of the ICA, treated by endovascular trapping and review the literatures. Case Presentation: A 37-year-old woman was brought to our hospital to treat SAH. Computed tomography (CT) angiography showed no apparent cause of the hemorrhage except for the minor dilation of the C2 portion of the left ICA. After 3 days, the CT angiography demonstrated progression of the dilation with the formation of a bleb. Evaluating collateral circulation through anterior communicating artery, endovascular trapping of the ICA was performed. Although she suffered minor ischemic stroke postoperatively, the symptoms recovered completely and discharged without neurological deficit. Review of Literatures: we reviewed the 11 cases of ruptured BBA treated by endovascular trapping. The results of ICA occlusion based on the evaluation of collateral circulation were satisfactory because rebleeding as well as regrowth of the aneurysm were prevented. However, hemodynamic compromise and treatment for vasospasm following SAH are considered. Conclusion: Rebleeding from BBA of the ICA should be prevented first and ischemic complication is avoided secondary. Endovascular trapping following evaluation of the collateral circulation is definitive treatment of BBA of the ICA.

19.
Sci Rep ; 10(1): 21173, 2020 12 03.
Article En | MEDLINE | ID: mdl-33273622

BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P < 0.001), nuclear grade III (76.1% vs. 48.4%, P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P < 0.001). Five-year disease free survival (DFS) (54.0% vs. 88.0%, P < 0.001) and overall survival (OS) (76.3% vs. 93.1%, P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184-7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618-11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.


BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Germ-Line Mutation , Humans , Kaplan-Meier Estimate , Middle Aged , Neoadjuvant Therapy , Prognosis , Proportional Hazards Models
20.
NMC Case Rep J ; 7(4): 147-150, 2020 Sep.
Article En | MEDLINE | ID: mdl-33062559

An onset of cervical myelopathy due to ossification of the posterior atlantoaxial membrane (PAAM) is extremely rare in older patients, and its clinical characteristics are still unclear. We report an onset of ossification of PAAM with congenital atlas hypoplasia in an 81-year-old man who presented with a 2-year history of progressive cervical myelopathy. Cervical computed tomography (CT) revealed canal stenosis secondary to a hypoplastic posterior arch of the atlas with a diameter of 20.3 mm between the anterior and posterior process. Magnetic resonance imaging showed marked spinal cord compression at the level of C1-2 secondary to atlas hypoplasia as well as ossification of PAAM. The patient underwent laminectomy of C1 and partial C2, as well as removal of the ossification, without atlantoaxial fusion. His neurological status improved 1 year postoperatively. In older patients, cervical myelopathy secondary to PAAM ossification, in the absence of trauma and atlantoaxial instability, may be induced by age-related pathophysiology associated with congenital atlas hypoplasia.

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