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1.
Gan To Kagaku Ryoho ; 51(4): 442-444, 2024 Apr.
Article Ja | MEDLINE | ID: mdl-38644316

The aim of this study was to investigate the short-term outcomes of surgery for colorectal cancer(CRC)in the elderly aged over 90 years old. We retrospectively analyzed 1,043 patients with stage Ⅰ-Ⅳ CRC who underwent curative surgery in our institutions between 2013 and 2022. The patients were divided into the super older(aged ≥90 years, 20 patients) and non-super older groups(aged 80-89 years, 243 patients). The short-term outcomes were compared between the 2 groups. There were no significant differences in tumor location, stage, surgical approach, duration of operation and blood loss. The incidence of severe postoperative complications did not differ between the 2 groups. In conclusion, our study suggested that surgery for colorectal cancer could be as safely performed in super elderly patients as in non-super elderly patients.


Colorectal Neoplasms , Humans , Aged, 80 and over , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Male , Female , Treatment Outcome , Retrospective Studies , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Neoplasm Staging
2.
Br J Cancer ; 130(2): 336-345, 2024 02.
Article En | MEDLINE | ID: mdl-38036665

BACKGROUND: Conventional chemotherapy is based on the maximum tolerated dose (MTD) and requires treatment-free intervals to restore normal host cells. MTD chemotherapy may induce angiogenesis or immunosuppressive cell infiltration during treatment-free intervals. Low-dose metronomic (LDM) chemotherapy is defined as frequent administration at lower doses and causes less inflammatory change, whereas MTD chemotherapy induces an inflammatory change. Although several LDM regimens have been applied, LDM cisplatin (CDDP) has been rarely reported. This study addressed the efficacy of LDM CDDP on tumour endothelial cell phenotypic alteration compared to MTD CDDP. METHODS: Tumour growth and metastasis were assessed in bladder cancer-bearing mice treated with LDM or MTD gemcitabine (GEM) and CDDP. To elucidate the therapeutic effects of LDM CDDP, the change of tumour vasculature, tumour-infiltrating immune cells and inflammatory changes were evaluated by histological analysis and mRNA expression in tumour tissues. RESULTS: Tumour growth and bone metastasis were more suppressed by LDM CDDP + MTD GEM treatment than MTD CDDP + MTD GEM. Myeloid-derived suppressor cell accumulation was reduced by LDM CDDP, whereas inflammatory change was induced in the tumour microenvironment by MTD CDDP. CONCLUSION: LDM CDDP does not cause inflammatory change unlike MTD CDDP, suggesting that it is a promising strategy in chemotherapy.


Cisplatin , Neoplasms , Animals , Mice , Gemcitabine , Drug Administration Schedule , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Tumor Microenvironment
3.
Aging Cell ; 23(2): e14050, 2024 Feb.
Article En | MEDLINE | ID: mdl-38098255

Thrombosis is the major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the pathology of vascular endothelial cells (ECs) has received much attention. Although there is evidence of the infection of ECs in human autopsy tissues, their detailed pathophysiology remains unclear due to the lack of animal model to study it. We used a mouse-adapted SARS-CoV-2 virus strain in young and mid-aged mice. Only mid-aged mice developed fatal pneumonia with thrombosis. Pulmonary ECs were isolated from these infected mice and RNA-Seq was performed. The pulmonary EC transcriptome revealed that significantly higher levels of viral genes were detected in ECs from mid-aged mice with upregulation of viral response genes such as DDX58 and IRF7. In addition, the thrombogenesis-related genes encoding PLAT, PF4, F3 PAI-1, and P-selectin were upregulated. In addition, the inflammation-related molecules such as CXCL2 and CXCL10 were upregulated in the mid-aged ECs upon viral infection. Our mouse model demonstrated that SARS-CoV-2 virus entry into aged vascular ECs upregulated thrombogenesis and inflammation-related genes and led to fatal pneumonia with thrombosis. Current results of EC transcriptome showed that EC uptake virus and become thrombogenic by activating neutrophils and platelets in the aged mice, suggesting age-associated EC response as a novel finding in human severe COVID-19.


COVID-19 , Pneumonia , Thrombosis , Humans , Mice , Animals , Middle Aged , Aged , SARS-CoV-2 , Endothelial Cells , Lung/pathology , Inflammation/pathology , Pneumonia/pathology , Thrombosis/pathology
4.
Anticancer Res ; 43(12): 5637-5644, 2023 Dec.
Article En | MEDLINE | ID: mdl-38030213

BACKGROUND/AIM: To evaluate the safety of colorectomy in elderly colorectal cancer patients with high American Society of Anesthesiologists (ASA) scores compared to those with low scores. PATIENTS AND METHODS: Two hundred patients with stage I-IV colorectal cancer aged ≥80 years were retrospectively analyzed. Short- and long-term outcomes were compared between 136 patients with ASA scores ≤2 (low ASA group) and 64 patients with scores ≥3 (high ASA group). RESULTS: The incidence of postoperative complications, duration of postoperative hospital stay, and 5-year overall and cancer-specific survival rates did not differ significantly between the groups. Laparoscopic surgery was significantly associated with a lower incidence of postoperative complications than open surgery in the high ASA score group (p=0.041), whereas no difference was observed in the low ASA score group (p=0.639). In the high ASA group, open surgery (p=0.024) and higher body mass index (p=0.040) were independent risk factors for postoperative complications. CONCLUSION: Colorectal cancer resection can be safely performed in elderly patients with high ASA scores. Moreover, laparoscopic surgery may have a stronger contribution to the reduction of postoperative complications in elderly patients with colorectal cancer with high ASA scores than in those with low ASA scores.


Colorectal Neoplasms , Laparoscopy , Aged , Humans , Retrospective Studies , Anesthesiologists , Laparoscopy/adverse effects , Postoperative Complications/etiology , Treatment Outcome
5.
Front Oncol ; 13: 973871, 2023.
Article En | MEDLINE | ID: mdl-37124539

Background: Tumor blood vessels play a key role in tumor metastasis. We have previously reported that tumor endothelial cells (TECs) exhibit abnormalities compared to normal endothelial cells. However, it is unclear how TECs acquire these abnormalities. Tumor cells secrete extracellular vesicles (EVs) to create a suitable environment for themselves. We have previously identified miR-1246 to be more abundant in high metastatic melanoma EVs than in low metastatic melanoma EVs. In the current study, we focused on miR-1246 as primarily responsible for acquiring abnormalities in TECs and examined whether the alteration of endothelial cell (EC) character by miR-1246 promotes cancer metastasis. Methods: We analyzed the effect of miR-1246 in metastatic melanoma, A375SM-EVs, in vivo metastasis. The role of tumor EV-miR-1246 in the adhesion between ECs and tumor cells and the EC barrier was addressed. Changes in the expression of adhesion molecule and endothelial permeability were examined. Results: Intravenous administration of A375SM-EVs induced tumor cell colonization in the lung resulting in lung metastasis. In contrast, miR-1246 knockdown in A375SM decreased lung metastasis in vivo. miR-1246 transfection in ECs increased the expression of adhesion molecule ICAM-1 via activation of STAT3, followed by increased tumor cell adhesion to ECs. Furthermore, the expression of VE-Cadherin was downregulated in miR-1246 overexpressed EC. A375SM-EV treatment enhanced endothelial permeability. VE-Cadherin was validated as the potential target gene of miR-1246 via the target gene prediction database and 3' UTR assay. Conclusion: miR-1246 in high metastatic tumor EVs promotes lung metastasis by inducing the adhesion of tumor cells to ECs and destroying the EC barrier.

6.
Gan To Kagaku Ryoho ; 50(1): 93-95, 2023 Jan.
Article Ja | MEDLINE | ID: mdl-36759997

We reported a case in which a pancreatic resection was performed for pancreatic metastasis of renal cell carcinoma 24 years after nephrectomy, and a residual pancreatectomy was performed 4 years later for residual pancreatic recurrence. The patient was a 72-year-old. In 1991, he underwent right nephrectomy for right renal cell carcinoma. During follow-up, in 2015, mass lesions were noted in the pancreatic tail and distal pancreatectomy was performed on suspicion of pancreatic neuroendocrine tumor(NET). Pathological examination diagnosed metastasis of renal cell carcinoma. In 2019, mass lesions were noted in the residual pancreas and total pancreatectomy was performed. Pathological examination diagnosed metastasis of renal cell carcinoma. There was 5 cases in Japan, including an our case, in which pancreatectomy was performed again after pancreatectomy for pancreatic metastasis of renal cancer, and the average time until the first pancreatic metastasis was pointed out was 11.8 years, and the average time until pancreatic recurrence was 9.4 years. Pancreatic metastasis of renal cell carcinoma shows heterochronic and multiple metastasis occurs, requiring long-team follow-up. When determining the extent of resection, it was suggested that the minimum number of repetitions necessary may lead to a long-term prognosis, taking into account the patient's age, background.


Carcinoma, Renal Cell , Kidney Neoplasms , Pancreatic Neoplasms , Male , Humans , Aged , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/secondary , Pancreatectomy , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/secondary , Nephrectomy , Pancreas/pathology
7.
Sensors (Basel) ; 23(2)2023 Jan 06.
Article En | MEDLINE | ID: mdl-36679484

Few studies have dealt with lower-limb kinematics during the timed up and go (TUG) test in subjects with locomotive syndrome (LS). This study aimed to evaluate the characteristics of lower-limb kinematics during the TUG test in subjects with LS using the wearable sensor-based H-Gait system. A total of 140 participants were divided into the non-LS (n = 28), the LS-stage 1 (n = 78), and LS-stage 2 (n = 34) groups based on the LS risk test. Compared with the non-LS group, the LS-stage 1 and LS-stage 2 groups showed significantly smaller angular velocity of hip and knee extension during the sit-to-stand phase. The LS-stage 2 group showed significantly smaller peak angles of hip extension and flexion during the walking-out phase compared to the non-LS group. These findings indicate that the evaluation of the lower-limb kinematics during the TUG test using the H-Gait system is highly sensitive to detect LS, compared with the evaluation of the lower-limb kinematics when simply walking.


Gait , Wearable Electronic Devices , Humans , Biomechanical Phenomena , Walking , Lower Extremity
8.
Gan To Kagaku Ryoho ; 50(13): 1897-1899, 2023 Dec.
Article Ja | MEDLINE | ID: mdl-38303245

We reported a case of an advanced gastric cancer patient with gastric outlet obstruction and malnutrition who successfully underwent neoadjuvant chemotherapy with enteral feeding. The patient is a 72-year-old man. The diagnosis was advanced gastric cancer with pyloric stenosis. Both decompression and enteral nutrition was performed with a W-ED®. Chemotherapy was markedly effective and nutritional status improved. He underwent robot-assisted distal gastrectomy(D2)and Billroth Ⅱ reconstruction under good nutritional status after neoadjuvant chemotherapy with intragastric decompression and nutritional management using a W-ED® tube. W-ED® tube is a useful tool for the proper nutritional management of patients with advanced gastric cancer who have pyloric stenosis by adequate decompression and enteral feeding.


Gastric Outlet Obstruction , Malnutrition , Pyloric Stenosis , Stomach Neoplasms , Male , Humans , Aged , Enteral Nutrition , Stomach Neoplasms/therapy , Stomach Neoplasms/surgery , Neoadjuvant Therapy , Gastric Outlet Obstruction/etiology , Gastric Outlet Obstruction/surgery
9.
Gan To Kagaku Ryoho ; 50(13): 1381-1383, 2023 Dec.
Article Ja | MEDLINE | ID: mdl-38303281

We investigated the safety and efficacy of UDON(5-FU, docetaxel and nedaplatin), a similar DCF therapy, as neoadjuvant chemotherapy for advanced esophageal cancer. Twelve patients who underwent radical esophagectomy after neoadjuvant chemotherapy for esophageal cancer at our department from June 2021 to December 2022 were retrospectively evaluated. One patient had Grade Ⅲ or higher neutropenia(8%)and 2 patients had anorexia(15%)as adverse events, but they could be safely treated. Nutritional status and ADL were maintained in all patients, and surgery was performed after 2-3 courses of neoadjuvant chemotherapy. The median postoperative hospital stay was 14 days, and no severe postoperative complications were observed. The histological effect to chemotherapy was Grade 3 in 3 patients(23%). UDON therapy is a safe and effective treatment.


Esophageal Neoplasms , Neutropenia , Organoplatinum Compounds , Humans , Docetaxel , Neoadjuvant Therapy , Retrospective Studies , Fluorouracil , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Neutropenia/chemically induced , Treatment Outcome , Cisplatin
10.
Cancer Sci ; 113(11): 3980-3994, 2022 Nov.
Article En | MEDLINE | ID: mdl-35997541

Recent studies have demonstrated a relationship between oral bacteria and systemic inflammation. Endothelial cells (ECs), which line blood vessels, control the opening and closing of the vascular barrier and contribute to hematogenous metastasis; however, the role of oral bacteria-induced vascular inflammation in tumor metastasis remains unclear. In this study, we examined the phenotypic changes in vascular ECs following Streptococcus mutans (S. mutans) stimulation in vitro and in vivo. The expression of molecules associated with vascular inflammation and barrier-associated adhesion was analyzed. Tumor metastasis was evaluated after intravenous injection of S. mutans in murine breast cancer hematogenous metastasis model. The results indicated that S. mutans invaded the ECs accompanied by inflammation and NF-κB activation. S. mutans exposure potentially disrupts endothelial integrity by decreasing vascular endothelial (VE)-cadherin expression. The migration and adhesion of tumor cells were enhanced in S. mutans-stimulated ECs. Furthermore, S. mutans-induced lung vascular inflammation promoted breast cancer cell metastasis to the lungs in vivo. The results indicate that oral bacteria promote tumor metastasis through vascular inflammation and the disruption of vascular barrier function. Improving oral hygiene in patients with cancer is of great significance in preventing postoperative pneumonia and tumor metastasis.


Breast Neoplasms , Streptococcus mutans , Humans , Mice , Animals , Female , Streptococcus mutans/physiology , Endothelial Cells/metabolism , Signal Transduction , Inflammation/metabolism , Breast Neoplasms/metabolism
11.
Sci Rep ; 12(1): 14050, 2022 08 18.
Article En | MEDLINE | ID: mdl-35982118

Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which is present in mouthwash, is effective against bacteria, fungi, and enveloped viruses. This study was conducted to explore the antiviral effect of CPC on SARS-CoV-2. There are few reports on the effect of CPC against wild-type SARS-CoV-2 at low concentrations such as 0.001%-0.005% (10-50 µg/mL). Interestingly, we found that low concentrations of CPC suppressed the infectivity of human isolated SARS-CoV-2 strains (Wuhan, Alpha, Beta, and Gamma) even in saliva. Furthermore, we demonstrated that CPC shows anti-SARS-CoV-2 effects without disrupting the virus envelope, using sucrose density analysis and electron microscopic examination. In conclusion, this study provided experimental evidence that CPC may inhibit SARS-CoV-2 infection even at lower concentrations.


COVID-19 Drug Treatment , Cetylpyridinium , Antiviral Agents/pharmacology , Cetylpyridinium/pharmacology , Humans , Mouthwashes/pharmacology , SARS-CoV-2
12.
BMC Musculoskelet Disord ; 23(1): 457, 2022 May 14.
Article En | MEDLINE | ID: mdl-35568855

BACKGROUND: Individuals with locomotive syndrome (LS) require nursing care services owing to problems with locomotion and the musculoskeletal system. Individuals with LS generally have a reduced walking speed compared with those without LS. However, differences in lower-limb kinematics and gait between individuals with and without LS are not fully understood. This study aimed to clarify the characteristics of the gait kinematics of individuals with LS using wearable sensors. METHODS: We assessed 125 participants (mean age 73.0 ± 6.7 years) who used a public health promotion facility. Based on the 25-question Geriatric Locomotive Function Scale (GLFS-25), these participants were grouped into the non-LS (GLFS-25 < 7), LS-stage 1 (GLFS-25 7-16), and LS-stage 2 (GLFS-25 ≥ 16) groups (larger GLFS-25 scores indicate worse locomotive ability). Spatiotemporal parameters and lower-limb kinematics during the 10-m walk test were analyzed by the "H-Gait system", which is a motion analysis system that was developed by the authors and is based on seven inertial sensors. The peak joint angles during the stance and swing phases, as well as the gait speed, cadence, and step length were compared among all groups. RESULTS: There were 69 participants in the non-LS group, 33 in the LS-stage 1 group, and 23 in the LS-stage 2 group. Compared with the non-LS group, the LS-stage 2 group showed significantly smaller peak angles of hip extension (9.5 ± 5.3° vs 4.2 ± 8.2°, P = 0.002), hip flexion (34.2 ± 8.8° vs 28.5 ± 9.5°, P = 0.026), and knee flexion (65.2 ± 18.7° vs 50.6 ± 18.5°, P = 0.005). The LS-stage 1 and LS-stage 2 groups had a significantly slower mean gait speed than the non-LS group (non-LS: 1.3 ± 0.2 m/s, LS-stage 1: 1.2 ± 0.2 m/s, LS-stage 2: 1.1 ± 0.2 m/s, P < 0.001). CONCLUSIONS: The LS-stage 2 group showed significantly different lower-limb kinematics compared with the non-LS group, including smaller peak angles of hip extension, hip flexion, and knee flexion. It would be useful to assess and improve these small peak joint angles during gait for individuals classified as LS-stage 2.


Gait , Wearable Electronic Devices , Aged , Biomechanical Phenomena , Humans , Locomotion , Syndrome , Walking Speed
13.
Ann Vasc Surg ; 79: 310-323, 2022 Feb.
Article En | MEDLINE | ID: mdl-34648855

BACKGROUND: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters. METHODS: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated. RESULTS: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow. CONCLUSIONS: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.


Aorta/physiopathology , Aortic Aneurysm/physiopathology , Aortic Dissection/physiopathology , Hemodynamics , Models, Cardiovascular , Patient-Specific Modeling , Aortic Dissection/diagnostic imaging , Aortic Dissection/therapy , Aorta/diagnostic imaging , Aortic Aneurysm/diagnostic imaging , Aortic Aneurysm/therapy , Aortography , Case-Control Studies , Clinical Decision-Making , Computed Tomography Angiography , Humans , Hydrodynamics , Numerical Analysis, Computer-Assisted , Prognosis
14.
Sensors (Basel) ; 21(8)2021 Apr 08.
Article En | MEDLINE | ID: mdl-33917951

Recently, treadmills equipped with a lower-body positive-pressure (LBPP) device have been developed to provide precise body weight support (BWS) during walking. Since lower limbs are covered in a waist-high chamber of an LBPP treadmill, a conventional motion analysis using an optical method is impossible to evaluate gait kinematics on LBPP. We have developed a wearable-sensor-based three-dimensional motion analysis system, H-Gait. The purpose of the present study was to investigate the effects of BWS by a LBPP treadmill on gait kinematics using an H-Gait system. Twenty-five healthy subjects walked at 2.5 km/h on a LBPP treadmill under the following three conditions: (1) 0%BWS, (2) 25%BWS and (3) 50%BWS conditions. Acceleration and angular velocity from seven wearable sensors were used to analyze lower limb kinematics during walking. BWS significantly decreased peak angles of hip adduction, knee adduction and ankle dorsiflexion. In particular, the peak knee adduction angle at the 50%BWS significantly decreased compared to at the 25%BWS (p = 0.012) or 0%BWS (p < 0.001). The present study showed that H-Gait system can detect the changes in gait kinematics in response to BWS by a LBPP treadmill and provided a useful clinical application of the H-Gait system to walking exercises.


Gait , Walking , Biomechanical Phenomena , Exercise Test , Humans , Knee Joint
15.
BMC Musculoskelet Disord ; 22(1): 46, 2021 Jan 08.
Article En | MEDLINE | ID: mdl-33419416

BACKGROUND: Hip osteoarthritis (OA) is a musculoskeletal condition that makes walking difficult due to pain induced by weight-bearing activities. Treadmills that support the body weight (BW) reduce the load on the lower limbs, and those equipped with a lower-body positive-pressure (LBPP) device, developed as a new method for unweighting, significantly reduce pain in patients with knee OA. However, the effects of unweighting on gait kinematics remain unclear in patients with hip OA. Therefore, we investigated the effects of unweighting on kinematics in patients with hip OA during walking on a treadmill equipped with an LBPP device. METHODS: A total of 15 women with hip OA and 15 age-matched female controls wore a three-dimensional (3-D) motion analysis system and walked at a self-selected speed on the LBPP treadmill. Data regarding self-reported hip pain using a numeric rating scale (NRS) in which the scores 0 and 10 represented no pain and the worst pain, respectively, under three different BW conditions (100, 75, and 50%) were collected. Moreover, 3-D peak joint angles during gait under each condition were calculated and compared. RESULTS: In the hip OA group, the NRS pain scores at 50 and 75% BW conditions significantly decreased compared with that at 100% BW condition (50%, P = 0.002; 75%, P = 0.026), and the peak hip extension angle decreased compared with that in the healthy controls (P = 0.044). In both groups, unweighting significantly decreased the peak hip (P < 0.001) and knee (P < 0.001) flexion angles and increased the peak ankle plantar flexion angle (P < 0.001) during walking. CONCLUSIONS: Unweighting by the LBPP treadmill decreased pain in the hip OA group but did not drastically alter the gait kinematics compared with that in the control group. Therefore, regarding the use of the LBPP treadmill for patients with hip OA, clinicians should consider the benefits of pain reduction rather than the kinematic changes.


Osteoarthritis, Hip , Osteoarthritis, Knee , Biomechanical Phenomena , Female , Gait , Humans , Knee Joint , Osteoarthritis, Hip/diagnosis , Osteoarthritis, Knee/diagnosis , Walking
16.
Cancer Res ; 80(14): 2996-3008, 2020 07 15.
Article En | MEDLINE | ID: mdl-32536602

Tumor endothelial cells (TEC) lining tumor blood vessels actively contribute to tumor progression and metastasis. In addition to tumor cells, TEC may develop drug resistance during cancer treatment, allowing the tumor cells to survive chemotherapy and metastasize. We previously reported that TECs resist paclitaxel treatment via upregulation of ABCB1. However, whether TEC phenotypes are altered by anticancer drugs remains to be clarified. Here, we show that ABCB1 expression increases after chemotherapy in urothelial carcinoma cases. The ratio of ABCB1-positive TEC before and after first-line chemotherapy in urothelial carcinoma tissues (n = 66) was analyzed by ABCB1 and CD31 immunostaining. In 42 cases (64%), this ratio increased after first-line chemotherapy. Chemotherapy elevated ABCB1 expression in endothelial cells by increasing tumor IL8 secretion. In clinical cases, ABCB1 expression in TEC correlated with IL8 expression in tumor cells after first-line chemotherapy, leading to poor prognosis. In vivo, the ABCB1 inhibitor combined with paclitaxel reduced tumor growth and metastasis compared with paclitaxel alone. Chemotherapy is suggested to cause inflammatory changes in tumors, inducing ABCB1 expression in TEC and conferring drug resistance. Overall, these findings indicate that TEC can survive during chemotherapy and provide a gateway for cancer metastasis. Targeting ABCB1 in TEC represents a novel strategy to overcome cancer drug resistance. SIGNIFICANCE: These findings show that inhibition of ABCB1 in tumor endothelial cells may improve clinical outcome, where ABCB1 expression contributes to drug resistance and metastasis following first-line chemotherapy.


Biomarkers, Tumor/metabolism , Drug Resistance, Neoplasm , Interleukin-8/metabolism , Neovascularization, Pathologic/pathology , Paclitaxel/pharmacology , Urinary Bladder Neoplasms/mortality , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Adult , Aged , Aged, 80 and over , Animals , Antineoplastic Agents/pharmacology , Apoptosis , Biomarkers, Tumor/genetics , Cell Proliferation , Drug Resistance, Multiple , Female , Gene Expression Regulation, Neoplastic , Humans , Induction Chemotherapy , Interleukin-8/genetics , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neovascularization, Pathologic/chemically induced , Prognosis , Survival Rate , Tumor Cells, Cultured , Urinary Bladder Neoplasms/blood supply , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Xenograft Model Antitumor Assays
17.
Sensors (Basel) ; 19(19)2019 Sep 28.
Article En | MEDLINE | ID: mdl-31569372

Overweight/obesity is a physical condition that affects daily activities, including walking. The main purpose of this study was to identify if there is a relationship between body mass index (BMI) and gait characteristics in young adults. 12 normal weight (NW) and 10 overweight/obese (OW) individuals walked at a self-selected speed along a 14 m indoor path. H-Gait system, combining seven inertial sensors (fixed on pelvis and lower limbs), was used to record gait data. Walking speed, spatio-temporal parameters and joint kinematics in 3D were analyzed. Differences between NW and OW and correlations between BMI and gait parameters were evaluated. Conventional spatio-temporal parameters did not show statistical differences between the two groups or correlations with the BMI. However, significant results were pointed out for the joint kinematics. OW showed greater hip joint angles in frontal and transverse planes, with respect to NW. In the transverse plane, OW showed a greater knee opening angle and a shorter length of knee and ankle trajectories. Correlations were found between BMI and kinematic parameters in the frontal and transverse planes. Despite some phenomena such as soft tissue artifact and kinematics cross-talk, which have to be more deeply assessed, current results show a relationship between BMI and gait characteristics in young adults that should be looked at in osteoarthritis prevention.


Body Mass Index , Gait/physiology , Monitoring, Physiologic/instrumentation , Overweight , Adult , Ankle Joint/physiology , Biomechanical Phenomena , Humans , Knee Joint/physiology , Male , Monitoring, Physiologic/methods , Overweight/physiopathology , Spatio-Temporal Analysis , Walking/physiology
18.
Biomed Mater Eng ; 30(3): 309-322, 2019.
Article En | MEDLINE | ID: mdl-31127751

The utilization of Asymmetric stent for recovering atherosclerotic diseases, particularly non-symmetric obstruction, is a quite challenging breakthrough treatment. In terms of eccentric plaque, the non-uniform stiffness of arterial layer causes the increasingly complex issues of vulnerability. This study investigated the vulnerability of the interaction between the Asymmetric stent and the surrounding arterial layer using structural transient dynamic analysis in ANSYS. Four combinations of stent deployment, i.e. the Sinusoidal stent expanded by the offset balloon, the Sinusoidal stent expanded by the ordinary cylindrical balloon, the Asymmetric stent expanded by the offset balloon, and the Asymmetric stent expanded by the ordinary cylindrical balloon, are generated for this comparative study. Multilayer material properties from recent in vitro experiments are adopted for the surrounding arterial layer, such as a fibrous cap, lipid core, diseased-healthy intima, and diseased-healthy media. In order to address plaque vulnerability, the Cauchy stresses and Hencky strains are used for stress measure because of convenience in comparison with the uniaxial/biaxial tension test data. The location-specific threshold value from the diseased human carotid artery is adopted for rupture criteria. The simulation indicated that as regards the eccentric plaque, the plaque vulnerability is caused by the plaque shape and components rather than caused by the geometrical structure of the stent or balloon expansion method. Nevertheless, the non-symmetric inflation of balloon, which leads against the plaque, contributed to an increase in the vulnerability of fibrous cap of fibroatheroma plaque.


Carotid Arteries/surgery , Plaque, Atherosclerotic/therapy , Stents , Carotid Arteries/pathology , Computer Simulation , Finite Element Analysis , Humans , Materials Testing , Models, Cardiovascular , Plaque, Atherosclerotic/pathology , Prosthesis Design , Stress, Mechanical
19.
Biomed Mater Eng ; 29(3): 299-317, 2018.
Article En | MEDLINE | ID: mdl-29578470

The selection of stent and balloon type is decisive in the stenting process. In the treatment of an eccentric plaque obstruction, a symmetric expansion from stent dilatation generates nonuniform stress distribution, which may aggravate fibrous cap prone to rupture. This paper developed a new stent design to treat eccentric plaque using structural transient dynamic analysis in ANSYS. A non-symmetric structural geometry of stent is generated to obtain reasonable stress distribution safe for the arterial layer surrounding the stent. To derive the novel structural geometry, a Sinusoidal stent type is modified by varying struts length and width, adding bridges, and varying curvature width of struts. An end ring of stent struts was also modified to eliminate dogboning phenomenon and to reduce the Ectropion angle. Two balloon types were used to deploy the stent, an ordinary cylindrical and offset balloon. Positive modification results were used to construct the final non-symmetric stent design, called an Asymmetric stent. Analyses of the deformation characteristics, changes in surface roughness and induced stresses within intact arterial layer were subsequently examined. Interaction between the stent and vessel wall was implemented by means of changes in surface roughness and stress distribution analyses. The Palmaz and the Sinusoidal stent were used for a comparative study. This study indicated that the Asymmetric stent types reduced the central radial recoiling and the dogboning phenomenon. In terms of changes in surface roughness and induced stresses, the Asymmetric stent has a comparable effect with that of the Sinusoidal stent. In addition, it could enhance the distribution of surface roughening as expanded by an offset balloon.


Carotid Artery Diseases/therapy , Plaque, Atherosclerotic/therapy , Stents , Carotid Arteries/pathology , Carotid Artery Diseases/pathology , Computer Simulation , Equipment Failure Analysis , Finite Element Analysis , Humans , Plaque, Atherosclerotic/pathology , Prosthesis Design , Stress, Mechanical , Surface Properties
20.
J Biomech ; 49(5): 684-690, 2016 Mar 21.
Article En | MEDLINE | ID: mdl-26947036

The objective of this work was to investigate the possibilities of using the wearable sensors-based H-Gait system in an actual clinical trial and proposes new gait parameters for characterizing OA gait. Seven H-Gait sensors, consisting of tri-axial inertial sensors, were attached to seven lower limb body segments (pelvis, both thighs, both shanks and both feet). The acceleration and angular velocity data measured were used to estimate three-dimensional kinematic parameters of patients during level walking. Three new parameters were proposed to assess the severity of OA based on the characteristics of these joint center trajectories in addition to conventional gait spatio-temporal parameters. The experiment was conducted on ten subjects with knee OA. The kinematic results obtained (hip, knee and ankle joint angles, joint trajectory in the horizontal and sagittal planes) were compared with those from a reference healthy (control) group. As a result, the angle between the right and left knee trajectories along with that of the ankle joint trajectories were almost twice as large (21.3° vs. 11.6° and 14.9° vs. 7.8°) compared to those of the healthy subjects. In conclusion, it was found that the ankle joints during stance abduct less to avoid adduction at the knee as the severity of OA increases and lead to more acute angles (less parallel) between the right and left knee/ankle joints in the horizontal plane. This method was capable to provide quantitative information about the gait of OA patients and has the advantage to allow for out-of-laboratory monitoring.


Gait , Monitoring, Physiologic/instrumentation , Osteoarthritis/physiopathology , Acceleration , Aged , Biomechanical Phenomena , Humans , Young Adult
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