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1.
Acta Cardiol Sin ; 39(3): 424-434, 2023 May.
Article in English | MEDLINE | ID: mdl-37229339

ABSTRACT

Background: There are limited reports on the treatment of complex calcified lesions using rotational atherectomy (RA) in octogenarians, particularly in high-risk patients. Objective: To evaluate procedural and clinical outcomes of RA in octogenarians. Methods: Consecutive RA patients from 2010 to 2018 were selected from our catheterization laboratory database, stratified into two groups (≥ or < 80 years old), and analyzed. Results: A total of 411 patients (269 males and 142 females) with a mean age of 73.8 ± 11.3 years were enrolled, of whom 153 were ≥ 80 years old and 258 were < 80 years old. Most of the patients displayed high-risk features. The baseline Syntax scores were high in both groups, and most lesions were heavily calcified (96.1% vs. 97.3%, p = 0.969, respectively). The use of hemodynamic support intra-aortic balloon pump was more frequent in the octogenarians (21.6% vs. 11.6%, p = 0.007), but the RA completion rate was similarly high (95.9% vs. 99.1%, p = 0.842). There was no difference in acute complications. The total/cardiovascular (CV) death rate within one year was higher in the octogenarians, along with higher major adverse cardiovascular event (MACE)/CV MACE rates in the first month. Cox regression analysis showed that age ≥ 80 years, acute coronary syndrome, ischemic cardiomyopathy/shock, multi-vessel disease and serum creatinine were all predictors of MACE, and that these factors plus peripheral artery disease were predictors of all-cause mortality in these patients. Conclusions: RA is feasible with a very high success rate in high-risk octogenarians with complex anatomies, and with equal safety and no increase in complications. The higher rates of all-cause death and MACE were attributed to an older age and other traditional risk factors.

2.
Acta Cardiol Sin ; 39(1): 97-108, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36685160

ABSTRACT

Peripheral artery disease (PAD) imposes a heavy burden of major adverse cardiovascular events that are associated with considerable mortality and morbidity, and major adverse limb events (e.g., thrombectomy, revascularization, amputation) that can substantially impact patients' daily functioning and quality of life. Global registry data have indicated that PAD is an underdiagnosed disease in Taiwan, and its associated risk factors remain inadequately controlled. This review discusses the burden of PAD in Taiwan, major guidelines on PAD management, and the latest clinical trial outcomes. Practical experience, opinions, and the latest trial data were integrated to derive a series of clinical algorithms - patient referral, PAD diagnosis, and the antithrombotic management of PAD. These algorithms can be adapted not only by physicians in Taiwan involved in the clinical management of patients with PAD but also by general practitioners in local clinics and regional hospital settings, with the ultimate aim of improving the totality of PAD patient care in Taiwan.

3.
J Interv Cardiol ; 2022: 7884401, 2022.
Article in English | MEDLINE | ID: mdl-35350479

ABSTRACT

Objective: Patients with advanced renal insufficiency are at high risk of coronary artery disease (CAD) and complex lesions. Treating complex calcified lesion with rotational atherectomy (RA) in these patients might be associated with higher risks and poorer outcomes. This study was set to evaluate features and outcomes of RA in these patients. Method: Consecutive patients who received coronary RA from April 2010 to April 2018 were queried from the Cath Lab database. The procedural details, angiography, and clinical information were reviewed in detail. Results: A total of 411 patients were enrolled and divided into Group A (baseline serum creatinine <5 mg/dl, n = 338) and Group B (baseline serum creatinine ≥ 5 mg/dl through ESRD, n = 73). Most patients had high-risk features (65.7% of acute coronary syndrome (ACS), 14.1% of ischemic cardiomyopathy, and 5.1% of cardiogenic shock). Group B patients were significantly younger (66.8 ± 11.4 vs. 75.2 ± 10.7 years, p < 0.001) and had more RCA and LCX but less LAD treated with RA. No difference was found in lesion location, vessel tortuosity, bifurcation lesions, chronic total occlusion, total lesion length, or total lesion numbers between the two groups. Less patients in Group B obtained completion of RA (95.9% vs 99.1%, p=0.037). There was no difference in the incidence of procedural complication or acute contrast-induced nephropathy. Group B patients had more deaths and MACE while in the hospital. The MACE and CV MACE were also higher in Group B patients at 180 days and one year, mostly due to TLR and TVR. Multivariate regression analysis showed that ACS, age, peripheral artery disease (PAD), advanced renal insufficiency, ischemic cardiomyopathy/shock, and high residual SYNTAX score were independent risk factors for in-hospital MACE, whereas ACS, advanced renal insufficiency, ischemic cardiomyopathy/shock, triple-vessel disease, and PAD independently predicted MACE at 6 months. Conclusions: Rotablation is feasible, safe, and could be carried out with very high success rate in very-high-risk patients with advanced renal dysfunction through ESRD without an increase in procedural complication.


Subject(s)
Atherectomy, Coronary , Kidney Failure, Chronic , Percutaneous Coronary Intervention , Vascular Calcification , Atherectomy, Coronary/adverse effects , Humans , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Vascular Calcification/therapy
4.
Int J Mol Sci ; 23(22)2022 Nov 12.
Article in English | MEDLINE | ID: mdl-36430445

ABSTRACT

Multicellular tumor spheroids and tumoroids are considered ideal in vitro models that reflect the features of the tumor microenvironment. Biomimetic components resembling the extracellular matrix form scaffolds to provide structure to 3-dimensional (3D) culture systems, supporting the growth of both spheroids and tumoroids. Although Matrigel has long been used to support 3D culture systems, batch variations, component complexity, and the use of components derived from tumors are complicating factors. To address these issues, we developed the ACD 3D culture system to provide better control and consistency. We evaluated spheroid and tumoroid formation using the ACD 3D culture system, including the assessment of cell viability and cancer marker expression. Under ACD 3D culture conditions, spheroids derived from cancer cell lines exhibited cancer stem cell characteristics, including a sphere-forming size and the expression of stem cell marker genes. The ACD 3D culture system was also able to support patient-derived primary cells and organoid cell cultures, displaying adequate cell growth, appropriate morphology, and resistance to oxaliplatin treatment. These spheroids could also be used for drug screening purposes. In conclusion, the ACD 3D culture system represents an efficient tool for basic cancer research and therapeutic development.


Subject(s)
Neoplasms , Spheroids, Cellular , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Cell Culture Techniques , Cell Line , Stem Cells/metabolism , Tumor Microenvironment
5.
Medicina (Kaunas) ; 58(7)2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35888594

ABSTRACT

Background and Objectives: The study assessed the effectiveness of a fracture liaison service (FLS) after 1 year of implementation in improving the outcomes of hip fracture surgery in older adult patients at Taipei Municipal Wanfang Hospital. Materials and Methods: The Wanfang hospital's FLS program was implemented using a multipronged programmatic strategy. The aims were to encourage the screening and treatment of osteoporosis and sarcopenia, to take a stratified care approach for patients with a high risk of poor postoperative outcomes, and to offer home visits for the assessment of environmental hazards of falling, and to improve the patient's adherence to osteoporosis treatment. The clinical data of 117 and 110 patients before and after FLS commencement, respectively, were collected from a local hip fracture registry; the data were analyzed to determine the outcomes 1 year after hip fracture surgery in terms of refracture, mortality, and activities of daily living. Results: The implementation of our FLS significantly increased the osteoporosis treatment rate after hip fracture surgery from 22.8% to 72.3%, significantly decreased the 1-year refracture rate from 11.8% to 4.9%, non-significantly decreased 1-year mortality from 17.9% to 11.8%, and improved functional outcomes 1 year after hip fracture surgery. Conclusions: Implementation of our FLS using the multipronged programmatic strategy effectively improved the outcomes and care quality after hip fracture surgery in the older adult population, offering a successful example as a valuable reference for establishing FLS to improve the outcomes in vulnerable older adults.


Subject(s)
Bone Density Conservation Agents , Hip Fractures , Osteoporosis , Osteoporotic Fractures , Activities of Daily Living , Aged , Bone Density Conservation Agents/therapeutic use , Hip Fractures/epidemiology , Hip Fractures/surgery , Hospitals, Municipal , Humans , Osteoporosis/drug therapy , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/prevention & control , Osteoporotic Fractures/surgery , Secondary Prevention
6.
Int J Mol Sci ; 22(14)2021 Jul 20.
Article in English | MEDLINE | ID: mdl-34299364

ABSTRACT

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to the nuclear receptor superfamily and can be activated through binding to its ligand androgens. Studies have reported an association between AR expression and EOC carcinogenesis, and AR is suggested to be involved in proliferation, migration/invasion, and stemness. In addition, alternative AR activating signals, including both ligand-dependent and ligand-independent, are involved in OVCA progression. Although some clinical trials have previously been conducted to evaluate the effects of anti-androgens in EOC, no significant results have been reported. In contrast, experimental studies evaluating the effects of anti-androgen or anti-AR reagents in AR-expressing EOC models have demonstrated positive results for suppressing disease progression. Since AR is involved in complex signaling pathways and may be expressed at various levels in OVCA, the aim of this article was to provide an overview of current studies and perspectives regarding the relevance of androgen/AR roles in OVCA.


Subject(s)
Androgens/metabolism , Ovarian Neoplasms/metabolism , Receptors, Androgen/metabolism , Signal Transduction/physiology , Carcinogenesis/metabolism , Female , Gene Expression Regulation, Neoplastic/physiology , Humans
7.
J Cell Mol Med ; 24(13): 7187-7200, 2020 07.
Article in English | MEDLINE | ID: mdl-32543783

ABSTRACT

This study aims to explore lipidic mechanism towards low-density lipoprotein receptor (LDLR)-mediated platinum chemotherapy resistance. By using the lipid profiling technology, LDLR knockdown was found to increase lysosomal lipids and decrease membranous lipid levels in EOC cells. LDLR knockdown also down-regulated ether-linked phosphatidylethanolamine (PE-O, lysosomes or peroxisomes) and up-regulated lysophosphatidylcholine [LPC, lipid droplet (LD)]. This implies that the manner of using Lands cycle (conversion of lysophospholipids) for LDs might affect cisplatin sensitivity. The bioinformatics analyses illustrated that LDLR-related lipid entry into LD, rather than an endogenous lipid resource (eg Kennedy pathway), controls the EOC prognosis of platinum chemotherapy patients. Moreover, LDLR knockdown increased the number of platinum-DNA adducts and reduced the LD platinum amount. By using a manufactured LPC-liposome-cisplatin (LLC) drug, the number of platinum-DNA adducts increased significantly in LLC-treated insensitive cells. Moreover, the cisplatin content in LDs increased upon LLC treatment. Furthermore, lipid profiles of 22 carcinoma cells with differential cisplatin sensitivity (9 sensitive vs 13 insensitive) were acquired. These profiles revealed low storage lipid levels in insensitive cells. This result recommends that LD lipidome might be a common pathway in multiple cancers for platinum sensitivity in EOC. Finally, LLC suppressed both cisplatin-insensitive human carcinoma cell training and testing sets. Thus, LDLR-platinum insensitivity can be due to a defective Lands cycle that hinders LPC production in LDs. Using lipidome assessment with the newly formulated LLC can be a promising cancer chemotherapy method.


Subject(s)
Cisplatin/therapeutic use , Lipid Droplets/metabolism , Lysophosphatidylcholines/metabolism , Animals , Cell Line, Tumor , Cisplatin/pharmacology , Female , Humans , Lipidomics , Liposomes , Mice, Nude , Models, Biological , Receptors, LDL/metabolism
8.
J Interv Cardiol ; 2020: 1894389, 2020.
Article in English | MEDLINE | ID: mdl-33223973

ABSTRACT

OBJECTIVE: Heavy calcifications remain formidable challenges to PCI, even for well-experienced operators. However, rotational atherectomy (RA)-induced coronary perforations (CPs) still could not be obviated. This study was to explore incidence and mechanisms of RA-induced CP in real-world practice. Knowing why CPs occur in RA should help operators avert such mishaps. METHOD: Patients who received coronary RA from April 2010 to December 2019 with keywords related to perforations were retrieved from database. The procedure details, angiography, and clinical information were reviewed in detail. RESULTS: A total of 479 RAs were performed with 11 perforations in 10 procedures among 9 patients documented. The incidence of RA-induced CP was 2.1%. The RA vessels were distributed in different territories, including first diagonal branch. Most CPs could be treated conservatively, but prolonged profound shock predisposed to poor outcome. CPs caused by rotawire tip occurred in 18.2% of cases, inappropriately sized burrs in 18.2% of cases, and rotawire damage with subsequent transection and perforation in another 18.2% of cases. A total of 5 (45.5%) perforations were caused by unintended and unnoticed bias cutting into noncalcified plaques (4, 36.4%) or through calcified vessel wall (1, 9.1%). The mechanisms for certain CPs were unique and illustrated in diagrams. CONCLUSION: CPs due to RA occur in certain percentage of patients. The mechanisms for CPs are diverse. Wire damage with subsequent transection could occur due to inappropriately repetitive burr stress on the wire body. A significant portion was due to unintended and unnoticed bias cutting into noncalcified plaque or through calcified vessel wall.


Subject(s)
Atherectomy, Coronary , Coronary Artery Disease , Coronary Vessels , Intraoperative Complications , Vascular Calcification/diagnosis , Vascular System Injuries , Aged , Atherectomy, Coronary/adverse effects , Atherectomy, Coronary/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Coronary Vessels/surgery , Female , Humans , Incidence , Intraoperative Complications/diagnosis , Intraoperative Complications/epidemiology , Male , Outcome and Process Assessment, Health Care , Taiwan/epidemiology , Vascular System Injuries/diagnosis , Vascular System Injuries/epidemiology , Vascular System Injuries/etiology
9.
J Formos Med Assoc ; 119(12): 1807-1816, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32107098

ABSTRACT

BACKGROUND: Sarcopenia, which is a common risk factor for falls and fractures, affects the functional outcome and mortality in geriatric populations. However, the prevalence of sarcopenia among geriatric Taiwanese patients with a hip fracture is unknown, nor is the effect of sarcopenia on the outcome of hip surgery. METHODS: From December 2017 to February 2019, geriatric patients who underwent surgery for a hip fracture were prospectively enrolled. Basic demographic data, responses to questionnaires for dementia screening and quality of life (QoL) and daily living activities (ADL) before the injury were analyzed to identify any association with sarcopenia. The QoL and ADL were monitored at six months after the operation to determine the difference between hip fracture patients with or without sarcopenia. RESULTS: Of 139 hip fracture patients, 70 (50.36%) were diagnosed with sarcopenia. Accounting for all confounding factors in the multivariate logistic regression, lower body mass index (BMI), male gender and a weaker handgrip are the risk factors that are most strongly associated with a diagnosis of sarcopenia in geriatric patients with a hip fracture. Hip fracture patients with sarcopenia also have poor ADL and a lower QoL than patients without sarcopenia before the injury and six months after the operation. CONCLUSION: A high prevalence of sarcopenia among geriatric hip fracture patients is associated with a poor mid-term outcome following hip surgery. Clinicians must recognize the risk of sarcopenia, especially for male hip fracture patients with a lower BMI and a weaker handgrip.


Subject(s)
Hip Fractures , Sarcopenia , Aged , Hand Strength , Hip Fractures/epidemiology , Hip Fractures/surgery , Humans , Male , Prevalence , Quality of Life , Sarcopenia/epidemiology
10.
Int J Mol Sci ; 21(11)2020 Jun 09.
Article in English | MEDLINE | ID: mdl-32527042

ABSTRACT

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Biomarkers, Tumor/genetics , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adult , Aged , Biomarkers, Tumor/metabolism , Chemoradiotherapy , Disease-Free Survival , Female , High-Throughput Nucleotide Sequencing , Humans , Middle Aged , Neoplasm Recurrence, Local/genetics , Prognosis , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/mortality
11.
Acta Cardiol Sin ; 36(5): 428-438, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32952352

ABSTRACT

BACKGROUND: The use of Complex and High-risk Coronary Interventions (CHIPs) has increased in recent years. Both rotational atherectomy (RA) and hemodynamic support are important parts of CHIPs. OBJECTIVES: This study aimed to retrospectively investigate the procedure results and clinical outcomes of intra-aortic balloon pump (IABP)-assisted RA in the contemporary drug-eluting stent era. METHODS: All consecutive patients who received RA under in-procedure IABP assistance from April 2010 to March 2018 were analyzed retrospectively. RESULTS: A total of 63 patients (77.7 ± 10.1 years, 69.8% male) were recruited, of whom 51 underwent RA with primary IABP assistance and 12 underwent bailout IABP. RA could be completed in 61 (96.8%) of the patients. Overall, vessel perforation, profound in-procedure shock, and ventricular arrhythmia occurred in 1.6%, 4.8% and 3.2% of the patients, respectively. The in-hospital, 30-day and 90-day major adverse cardiac event (MACE) rates were 22.2%, 27.4% and 36.1%, respectively, mostly driven by mortality. The MACE rates were significantly higher in the bail-out group in the hospital (50.0% vs. 15.7%, p = 0.018) at 30 days (58.3% vs. 20.0%, p = 0.013) and 90 days (66.7% vs. 28.6%, p = 0.020). CONCLUSIONS: Bail-out IABP was associated with increased MACEs, implying that the use of IABP should be implemented at the beginning of RA if a complex procedure is anticipated.

12.
J Cell Mol Med ; 23(11): 7417-7426, 2019 11.
Article in English | MEDLINE | ID: mdl-31557413

ABSTRACT

CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single-cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian-based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5-Fluorouracil (5-FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar-targeting compounds were tested, and the results showed that exemestane exhibited superior cancer-suppressing efficacy to other ARIs. In addition, exemestane down-regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5-FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose-dependent manner. Combining subminimal doses of 5-FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5-FU and exemestane for GCa therapy is recommended.


Subject(s)
Androstadienes/therapeutic use , Antineoplastic Agents/therapeutic use , Aromatase Inhibitors/therapeutic use , Stomach Neoplasms/drug therapy , Cell Proliferation/drug effects , Down-Regulation/drug effects , Drug Evaluation, Preclinical , Female , Fluorouracil/therapeutic use , Humans , Male , Middle Aged , Prognosis , Receptors, Estrogen/metabolism , Stomach Neoplasms/metabolism
13.
Eur Radiol ; 29(12): 6741-6749, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31134366

ABSTRACT

BACKGROUND: We designed a deep learning model for assessing 18F-FDG PET/CT for early prediction of local and distant failures for patients with locally advanced cervical cancer. METHODS: All 142 patients with cervical cancer underwent 18F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from a training set and used to classify each slice set in the test set into the categories of with or without local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result. RESULTS: In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively. CONCLUSION: This is the first study to use deep learning model for assessing 18F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. KEY POINTS: • This is the first study to use deep learning model for assessing 18 F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • All 142 patients with cervical cancer underwent 18 F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. • For local recurrence, all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.


Subject(s)
Chemoradiotherapy/methods , Deep Learning , Fluorodeoxyglucose F18 , Neoplasm Recurrence, Local/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Cervix Uteri/diagnostic imaging , Cervix Uteri/pathology , Cohort Studies , Female , Humans , Middle Aged , Prognosis , Radiopharmaceuticals , Recurrence , Retrospective Studies , Sensitivity and Specificity , Treatment Outcome , Uterine Cervical Neoplasms/pathology
14.
J Cell Mol Med ; 22(1): 46-56, 2018 01.
Article in English | MEDLINE | ID: mdl-28782227

ABSTRACT

The androgen receptor (AR) poly-glutamine polymorphism (AR-Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR-Qs and BaP in EMCA. During analysing patient AR-Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR-Q lengths (5-year OS of 61.3% in Q length <20 and 88% in Q length >23). And AhR is higher expressed in short AR-Q tumour compared to that in long AR-Q patient. In vitro study found androgen-response element (ARE) activity descends with AR-Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR-Q13 (but not AR-Q25, or -35) enhances BaP-induced dioxin-responsive element (DRE) activity. Lastly, AR-Q13 exerts higher colony-forming capacity than other AR-Qs, and knock-down AhR abolished AR-Q13-mediated colony numbers. This study demonstrated a possible interaction of gene (AR-Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large-scale epidemiology and public health survey on the interaction of environmental toxin and AR poly-Q in EMCA is suggested.


Subject(s)
Endometrial Neoplasms/genetics , Peptides/genetics , Receptors, Androgen/genetics , Receptors, Aryl Hydrocarbon/metabolism , Adult , Aged , Benzo(a)pyrene , Cell Line, Tumor , Cell Proliferation , Disease Progression , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Receptors, Androgen/metabolism , Tumor Stem Cell Assay
15.
J Interv Cardiol ; 31(4): 486-495, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29667231

ABSTRACT

OBJECTIVES: To evaluate the outcomes of rotational atherectomy for heavily-calcified side branches of coronary bifurcation lesions. BACKGROUND: Side-branch (SB) preservation is clinically important but technically challenging in heavily-calcified non-left main true bifurcation lesions. SB rotational atherectomy (SB RA) is sometimes mandatory but the clinical outcomes are not well studied. METHODS: We retrospectively studied the outcomes of patients who underwent RA at our institute for heavily calcified, balloon-uncrossable or-undilatable SB lesions over an approximately 5-year period (January 2011 to September 2016). RESULTS: Two hundred and forty-four patients underwent main vessel only RA (SB-MV + RA group) and another 48 patients underwent SB RA (SB + MV ± RA group) for 49 side branches. The demographic variables were comparable between the two groups. However, patients underwent SB RA experienced more SB perforations and greater acute contrast-induced nephropathy (CIN). Among the SB RA patients, 30 (62.5%) underwent RA for both SB and MV (SB + MV + RA subgroup), whereas the other 18 underwent SB only RA (SB + MV-RA subgroup). Patients in these two subgroups could be completed with similar procedural, fluoroscopic durations, and contrast doses. The long-term MACE rate of SB RA was 27.1% over a mean follow-up period of 25.1 months with no differences between the two subgroups. CONCLUSIONS: RA for SB preservation in complex and heavily-calcified bifurcation lesions was feasible with high success rate and quite favorable long-term outcomes in the drug-eluting stent (DES) era. Given the higher rates in SB perforation and acute CIN, we recommend that SB RA should be conducted by experienced operators.


Subject(s)
Atherectomy, Coronary , Coronary Artery Disease , Coronary Vessels , Long Term Adverse Effects , Vascular Calcification , Aged , Atherectomy, Coronary/adverse effects , Atherectomy, Coronary/methods , Atherectomy, Coronary/statistics & numerical data , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Coronary Artery Disease/surgery , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Coronary Vessels/surgery , Female , Humans , Long Term Adverse Effects/diagnosis , Long Term Adverse Effects/epidemiology , Male , Middle Aged , Retrospective Studies , Taiwan/epidemiology , Treatment Outcome , Vascular Calcification/diagnostic imaging , Vascular Calcification/pathology , Vascular Calcification/surgery
16.
Mol Ther ; 25(9): 2176-2188, 2017 09 06.
Article in English | MEDLINE | ID: mdl-28697888

ABSTRACT

Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors (CARs) is dependent on their specificity, survival, and in vivo expansion following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T cells can improve persistence and drive proliferation of antigen-specific CD4+ and CD8+ T cells following pathogen challenge or in graft-versus-host disease (GvHD) settings, suggesting that these costimulatory pathways may be co-opted to improve CAR-T cell persistence and function. Here, we present a novel strategy to activate TLR and CD40 signaling in human T cells using inducible MyD88/CD40 (iMC), which can be triggered in vivo via the synthetic dimerizing ligand, rimiducid, to provide potent costimulation to CAR-modified T cells. Importantly, the concurrent activation of iMC (with rimiducid) and CAR (by antigen recognition) is required for interleukin (IL)-2 production and robust CAR-T cell expansion and may provide a user-controlled mechanism to amplify CAR-T cell levels in vivo and augment anti-tumor efficacy.


Subject(s)
CD28 Antigens/metabolism , CD40 Antigens/metabolism , Receptors, Antigen, T-Cell/metabolism , Recombinant Fusion Proteins , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals , CD28 Antigens/genetics , CD40 Antigens/genetics , Cell Proliferation , Cell Survival , Cluster Analysis , Disease Models, Animal , Gene Expression Profiling , Humans , Immunotherapy, Adoptive/methods , Leukemia/genetics , Leukemia/immunology , Leukemia/metabolism , Leukemia/therapy , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Mice , Receptors, Antigen, T-Cell/genetics , Signal Transduction , T-Lymphocytes/drug effects , Toll-Like Receptors/metabolism , Xenograft Model Antitumor Assays
17.
Perfusion ; 33(2): 160-163, 2018 03.
Article in English | MEDLINE | ID: mdl-28825356

ABSTRACT

A 25-year-old previously healthy male presented to our emergency room with acute chest pain and ventricular arrhythmia-related cardiac arrest. ST elevation myocardial infarction was diagnosed and coronary angiography revealed diffuse critical narrowing from the proximal to the distal left anterior descending artery. Diffuse intramural hematoma was demonstrated on intravascular ultrasound. Two stents were placed to cover the whole dissection length and flow was successfully restored. Spontaneous coronary artery dissection can be a fatal event and could be mistaken for atherosclerotic plaque or coronary spasm rather than luminal compression on coronary angiography and intravascular imaging is helpful in this condition.


Subject(s)
Coronary Vessel Anomalies/complications , Heart Arrest/etiology , Myocardial Infarction/etiology , Vascular Diseases/congenital , Adult , Coronary Vessel Anomalies/pathology , Heart Arrest/pathology , Humans , Male , Myocardial Infarction/pathology , Vascular Diseases/complications , Vascular Diseases/pathology
18.
BMC Cardiovasc Disord ; 17(1): 115, 2017 05 08.
Article in English | MEDLINE | ID: mdl-28482853

ABSTRACT

BACKGROUND: Eosinophilic myocarditis encompasses a variety of etiologies and the prognosis varies. For patients with a hypersensitive response to medications, high-dose corticosteroids and discontinuation of culprit medications are the main treatments. CASE PRESENTATION: We reported a young man with biopsy-proven eosinophilic myocarditis which was possibly induced by Chinese herbal medicine. His heart failure and left ventricular hypertrophy improved soon after low-dose corticosteroid. CONCLUSION: Low-dose corticosteroid may be effective in selected patients with eosinophilic myocarditis. Early echocardiographic follow-up is mandatory for evaluation of the clinical response.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Drugs, Chinese Herbal/adverse effects , Eosinophilia/drug therapy , Myocarditis/drug therapy , Prednisolone/administration & dosage , Acute Disease , Adult , Biopsy , Echocardiography , Eosinophilia/chemically induced , Eosinophilia/diagnosis , Eosinophilia/immunology , Heart Failure/etiology , Humans , Hypertrophy, Left Ventricular/etiology , Male , Myocarditis/chemically induced , Myocarditis/diagnosis , Myocarditis/immunology , Remission Induction , Time Factors , Treatment Outcome
19.
Int Heart J ; 58(3): 447-450, 2017 May 31.
Article in English | MEDLINE | ID: mdl-28484121

ABSTRACT

With the increased use of intravascular catheters and devices, they have become the major non-malignant cause of superior vein cava (SVC) syndrome. We report a patient with liver cirrhosis who had received a peritoneovenous drainage catheter for refractory ascites, and then developed SVC syndrome because of concomitant occlusions of both the SVC and the drainage catheter. The patient regained patency of both the occluded vessel and the drainage catheter through percutaneous transluminal venoplasty, and there was dramatic improvement of clinical symptoms and good performance of the drainage catheter. Percutaneous intervention may be a feasible and effective therapy for SVC syndrome and intra-catheter thrombosis-related dysfunction.


Subject(s)
Catheters, Indwelling/adverse effects , Endovascular Procedures/methods , Liver Cirrhosis/complications , Superior Vena Cava Syndrome/surgery , Vena Cava, Superior/diagnostic imaging , Ascites/diagnosis , Ascites/therapy , Constriction, Pathologic/surgery , Drainage/instrumentation , Equipment Failure , Humans , Male , Middle Aged , Phlebography , Superior Vena Cava Syndrome/diagnosis , Superior Vena Cava Syndrome/etiology , Tomography, X-Ray Computed , Vena Cava, Superior/surgery
20.
J Cell Mol Med ; 20(6): 1076-85, 2016 06.
Article in English | MEDLINE | ID: mdl-26843513

ABSTRACT

Current knowledge regarding mechanisms of carcinogenesis in human beings centres around the accumulation of genetic instability, amplified cellular signalling, disturbed cellular energy metabolism and microenvironmental regulation governed by complicated cell-cell interactions. In this article, we provide an alternative view of cancer biology. We propose that cancer behaves as a systemic dictator that interacts with tissues throughout the body to control their metabolism and eventually homeostasis. The mechanism of development of this endocrine organ-like tumour (EOLT) tissue might be the driving force for cancer progression. Here, we review the literature that led to the development of this hypothesis. The EOLT phenotype can be defined as a tumour that alters systemic homeostasis. The literature indicates that the EOLT phenotype is present throughout cancer progression. The feedback mechanism that governs the interaction between tumours and various organs is unknown. We believe that investigating the mechanism of EOLT development may advance the current knowledge of regulation within the tumour macroenvironment and consequently lead to new diagnostic methods and therapy.


Subject(s)
Models, Biological , Neoplasms/metabolism , Animals , Energy Metabolism , Glucose/metabolism , Homeostasis , Humans , Microbiota , Mitochondria/metabolism , Neoplasms/genetics , Tumor Microenvironment
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