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Successful adoptive chimeric antigen receptor (CAR) T-cell therapies against hematological malignancies require CAR-T expansion and durable persistence following infusion. Balancing increased CAR-T potency with safety, including severe cytokine-release syndrome (sCRS) and neurotoxicity, warrants inclusion of safety mechanisms to control in vivo CAR-T activity. Here, we describe a novel CAR-T cell platform that utilizes expression of the toll-like receptor (TLR) adaptor molecule, MyD88, and tumor-necrosis factor family member, CD40 (MC), tethered to the CAR molecule through an intentionally inefficient 2A linker system, providing a constitutive signal that drives CAR-T survival, proliferation, and antitumor activity against CD19+ and CD123+ hematological cancers. Robust activity of MC-enhanced CAR-T cells was associated with cachexia in animal models that corresponded with high levels of human cytokine production. However, toxicity could be successfully resolved by using the inducible caspase-9 (iC9) safety switch to reduce serum cytokines, by administration of a neutralizing antibody against TNF-α, or by selecting “low” cytokine-producing CD8+ T cells, without loss of antitumor activity. Interestingly, high basal activity was essential for in vivo CAR-T expansion. This study shows that co-opting novel signaling elements (i.e., MyD88 and CD40) and development of a unique CAR-T architecture can drive T-cell proliferation in vivo to enhance CAR-T therapies.

Grafting is widely used in the commercial production of cucurbits (Cucurbitaceae) and solanaceous (Solanaceae) vegetables, but seldom in the production of cruciferous vegetables such as cabbage (Brassica oleracea Capitata group). In our study, we developed a tube grafting method for cabbage using the ‘K-Y cross’ cabbage as the scion and ‘Tsuei Jin’ chinese kale (B. oleracea Alboglabra group) as the rootstock (K-Y/TJ), and then used the K-Y/TJ grafted seedlings to identify the best healing conditions. The examined healing conditions included temperature (15, 20, or 25 °C), relative humidity (RH; 75%, 85%, or 95%), and light intensity (high light intensity, 79 to 107 μmol·m–2·s–1; low light intensity, 38.6 to 58.8 μmol·m–2·s–1; or full darkness, 0 μmol·m–2·s–1). Considering all the healing conditions, the K-Y/TJ grafted seedlings healing at 20 °C, 95% RH, and high light intensity exhibited survival rates of up to 96.7% and overall superior seedling quality. ‘K-Y cross’ cabbages were then grafted onto chinese kale rootstocks, and the head traits of all grafted plants were comparable to those of nongrafted and/or self-grafted ‘K-Y cross’ plants. ‘K-Y cross’ plants grafted on ‘Jie Lan’ chinese kale rootstocks had greater ascorbic acid and total soluble solid (TSS) contents than nongrafted and self-grafted ‘K-Y cross’ plants. Overall, this research describes a successful tube grafting method and the optimal healing conditions for grafted cabbage seedlings, which can be used as a tool to improve head quality.

Objective: To investigate whether the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) is efficacy measure tool for interstitial Cystitis (IC) treatment with hydrodistention (HD) and bladder training (BT). Materials and methods: From January 2003 to March 2006, 108 consecutive IC patients were treated by HD and BT after HD. This study evaluated the efficacy of treatment with the specific questionnaire for IC, the ICSI and ICPI. Each patient filled out the questionnaire before HD and three months after HD and BT. The efficacy of the treatment was evaluated using the average scores of ICSI and ICPI. Results: The mean ± margin of error, (95% confidence interval) of total scores of ICSI and ICPI were 13.89 ± 2.95, (13.33–14.45) and 12.51 ± 2.50, (12.04–12.98) before HD, respectively, and were 2.70 ± 1.16, (2.44–2.95) and 1.99 ± 1.27, (1.71–2.26) (all p

Objective To investigate the anti-carcinogenic effect of metronomic Celecoxib (i.e., frequent administration in clinically available doses) against hepatocellular carcinoma (HCC) in the perspective of metastasis, spontaneous hepatocarcinogenesis, cancer invasion, proliferation, and stemness in vivo and in vitro. Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is known to cause anti-carcinogenic effects for HCC in suprapharmacological doses. However, the effects of metronomic Celecoxib treatment on HCC cells remain unclear. Methods The in vivo chemopreventive effect of metronomic Celecoxib (10mg/kg/d) was investigated by the syngeneic HCC implantation model and spontaneous hepatocarcinogenesis in HBV-transgenic(HBVtg) mice individually. HCC cell lines were treated by either suprapharmacological (100 μM) or metronomic (4 μM) Celecoxib therapy. Anti-carcinogenic effects were evaluated using cell invasion, cancer proliferation, angiogenesis, and phenotype of cancer stem/progenitor cells (CSPC). The molecular mechanism of metronomic Celecoxib on HCC was dissected using Luciferase assay. Results In vivo metronomic Celecoxib exerted its chemopreventive effect by significantly reducing tumor growth of implanted syngeneic HCC and spontaneous hepatocarcinogenesis in HBVtg mice. Unlike suprapharmacological dose, metronomic Celecoxib can only inhibit HCC cell invasion after a 7-day course of treatment via NF-κB/MMP9 dependent, COX2/PGE2 independent pathway. Metronomic Celecoxib also significantly suppressed HCC cell proliferation after a 7-day or 30-day culture. Besides, metronomic Celecoxib reduced CSPC phenotype by diminishing sphere formation, percentage of CD90+ population in sphere cells, and expression of CSPC markers. Conclusions Metronomic Celecoxib should be investigated clinically as a chemopreventive agent for selected high-risk HCC patients (e.g., HCC patients after curative treatments).

Introduction: This study compared the quantitative differences in immunohistochemical markers between uterine cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) and assessed the impact of these biomarkers on outcomes in patients treated with chemoradiotherapy (CRT).Method: This retrospective study included 118 patients (SCC in 76, AC in 42) who received definitive CRT. According to the International Federation of Gynecology and Obstetrics staging system, 14, 34, and 70 patients were classified as having stage IB3, II, and III disease, respectively. Baseline immunohistochemical biomarkers, including hypoxia, cell proliferation, cell adhesion, immunogenicity, inflammatory, and evasion of apoptosis biomarkers, were analyzed using tissue microarrays from biopsy specimens. The Mann-Whitney U test was carried out for quantitative analysis between SCC and AC. Cox regression analysis was used to examine the effects of the biomarkers and clinical parameters on treatment outcomes.Results: Using the H-scores of the biomarkers for SCC as a reference, increased expression of E-cadherin, calretinin, CAIX, and c-Myc and decreased levels of HIF-1α, VEGF, tumor necrosis factor-α, galectin-9, chemokine ligand 5, Bax, EGFR, and insulin-like growth factor 1 receptor were found in the patients with AC. A high E-cadherin (P = 0.002) and low Bax (P = 0.001) H-score were associated with inferior pelvic relapse-free survival. Conclusion: Cervical SCC exhibited strong expression of baseline immunohistochemical inflammatory, hypoxic, and angiogenesis biomarkers whereas the intensity of cell adhesion markers was more distinct in cervical AC. A high E-cadherin and a low Bax H-score were associated with a high rate of local relapse.

Background/aim The role of androgen receptor (AR) in hepatocellular carcinoma (HCC) development is controversial. Therefore, the translational value of targeting AR in HCC is unknown. Sorafenib, a multiple kinase inhibitor, is the standard therapy for patients with unresectable HCC. This study investigated sorafenib effect on AR in experimental models of HCC. Material and methods AR cDNA was introduced into HCC cells and in vitro cell growth and in vivo tumor growth were measured. Sphere cells, as well as epithelial cell adhesion molecule-positive (EpCAM+) and CD133+ cells were isolated from HCC cells with/without AR expression to observe in vitro/in vivo effects. Liver specific AR knockout in mouse models of spontaneous HCC (carcinogen-induced and hepatitis B virus-related HCC) was also implemented to examine gene expression. HCC cells/tumors were treated with sorafenib in order to determine effects on tumor growth and related gene expression. Result AR cDNA increased transactivation function, increased colony/sphere-forming activities, and enhanced tumorigenicity in HCC cells compared to their parental cells. Expression of the stemness marker EpCAM was also dramatically increased. In carcinogen-and HBV-induced HCC models, EpCAM+ cells were significantly reduced in AR-knockout mice compared to wild-type HCCs. In addition, AR reduced sorafenib-related signals, e.g. extracellular-regulated kinase, AKT serine/threonine kinase 1, and p38 mitogen-activated protein kinase, compared to that in parental cells. Regarding sorafenib cytotoxicity, AR-expressing cells were vulnerable to treatment. Moreover, the half maximal-inhibitory concentration (IC50) was drastically lowered in AR+/EpCAM+ compared to AR-/EpCAM- sphere cells. Strikingly, the IC50 in AR+/CD133+ vs. AR-/CD133+ cells were similar. Moreover, sorafenib robustly suppressed tumor growth in implanted AR+/EpCAM+ cells but not AR-/EpCAM- ones. Finally, bioinformatics analyses revealed EpCAM to be a prognostic biomarker in Asian and non-alcohol-consuming patients with HCC, suggesting suitability of a sorafenib regimen for such patients. Conclusion AR+/EpCAM+ may be a marker of responsiveness to sorafenib for patients with HCC. Prospective surveys associating AR/EpCAM expression with therapy outcomes are essential.

Aims. Liver cancer is a multietiological disease that has multiple factors contributing to the hepatocarcinogenic process, e.g., hepatitis viruses, carcinogens, male sex, or metabolic factors. Notably, emerging evidence reported that gut microbiota is crucial to the pathogenesis of hepatocellular carcinoma (HCC) via activation of innate immunity. However, the effect of time to gut microbiota exposure after birth is unknown. Using a germ-free animal housing environment, instead of antibiotics, we examined the effects of various time-to-exposure (TTE) to gut microbiota durations on HCC risk. Methods. HBV or carcinogen-mediated spontaneous HCC models were implemented in this study. The HCC incidence rates in mice either kept germ-free (GF; that is, with no exposure to gut microbiota) or exposed to gut microbiota after being moved to a specific pathogen-free (SPF) housing environment and with various time-to-exposure (TTE) durations, namely, 5 weeks after birth, 10 weeks after birth, or since conception (that is, 5-week TTE group, 10-week TTE group, and SPF group, respectively), were recorded. The mice were sacrificed at 30 or 40 weeks after birth, and macro-/microscopic observations and pathological diagnosis were performed. Results. The incidence of liver tumors among the male mice was higher than that among the female mice in the carcinogen-induced HCC mice sacrificed at 40 weeks after birth (with P=0.011, 0.035, 0.0003, and 0.012, respectively, in the GF group, 5-week TTE group, 10-week TTE group, and SPF group). Similarly, in the HBV-HCC model, the incidence of liver tumors among the male mice was significantly higher than that among the female mice (with P=0.013, 0.020, 0.012, and 0.002, respectively, in the GF group, 5-week TTE group, 10-week TTE group, and SPF group). These results suggest that gut microbiota exposure is irrelevant to the male sex preference of HCC. Surprisingly, when comparing carcinogen-induced HCC male mice in the 10-week TTE group (90%; n=10), 5-week TTE group (56%; n=9), and SPF group (30%; n=10) (P=0.020), we found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Similarly, when comparing HBV-HCC male mice in the 10-week TTE group (100%; n=11), 5-week TTE group (70%; n=10), and SPF group (33%; n=9) (P=0.080), we also found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Conclusions. Early (prepubertal) exposure to gut microbiome reduces the risk of HCC development, indicating a potentially important factor for cancer surveillance. Exploring the mechanisms by which such exposure affects HCC risk might lead to novel cancer vaccines.

We retrospectively reviewed the records of 142 patients with stage IB–IIIB cervical cancer who underwent 18F-FDG-PET/CT before external beam radiotherapy plus intracavitary brachytherapy and concurrent chemotherapy. The patients were divided into training and validation cohorts to confirm the reliability of predictors for recurrence. Kaplan–Meier analysis was performed and a Cox regression model was used to examine the effects of variables on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and pelvic relapse-free survival (PRFS). High gray-level run emphasis (HGRE) derived from gray-level run-length matrix most accurately and consistently predicted the presence of pelvic residual or recurrent tumors for both cohorts. In multivariate analysis, stages IIIA–IIIB (P = 0.001, hazard ratio [HR] = 4.07) and a low HGRE (P P = 0.001, HR = 2.86) and nonsquamous cell histology (P = 0.003, HR = 2.76) were prognostic factors for inferior PFS. The nonsquamous cell histology (P P = 0.001, HR = 4.69) were predictors for low PRFS. In cervical cancer patients receiving definitive chemoradiotherapy, pretreatment textural features on 18F-FDG-PET/CT can supplement the prognostic information.

Sphingosine‐1‐phosphate (S1P) is a bioactive lipid that exerts various pathophysiological functions through binding to its receptor family (S1PRs). Since first report of the breast cancer (BCA) promoting function by S1P production (through the function of sphingosine kinases) and S1P/S1PR signaling, their antagonists have never been successfully progress to clinics after three decades. Taking advantage of bioinformatics linking to gene expression to disease prognosis, we examined the impact of associated genes in BCA patients. We found high gene expressions involved in S1P anabolism suppressed disease progression of patients who are basal cell type BCA or receiving adjuvant therapy. In addition, S1PRs expression also suppressed disease progress of multiple categories of BCA patient progression. This result is contradictory to tumor promoter role of S1P/S1PRs which revealed in the literature. Further examination by directly adding S1P in BCA cells found a cell growth suppression function, which act via the expression of S1PR1. In conclusion, our study is the first evidence claiming a survival benefit function of S1P/S1PR signaling in BCA patients, which might explain the obstacle of relative antagonist apply in clinics.

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.

Background and Aims: Improving liver regeneration (LR) capacity and thereby liver function reserve is a critical bridging strategy for managing liver failure patients. Since estrogen signaling may participate in LR, our aim was to characterize the roles of ERα and ERβ in LR. Methods: LR capacity and estradiol levels following 2/3rd partial hepatectomy (PHx) were compared in ERα-KO or ERβ-KO vs. wildtype mice. The ERα- or ERβ-related transcriptome and interactome were analyzed from regenerating livers, and then bioinformatics was used for pathway discovery and analysis of interactome-transcriptome relationships. Human hepatic progenitors (HepRG cells) and mouse Hepa1-6 hepatocytes were used to elucidate molecular interactions and functions. Results: This paper demonstrated that estrogen signals orchestrate hepatic repopulation and differentiation via distinct transcriptome patterns governed by ERα or ERβ. Cell repopulation pathway was associated with the ERα-transcriptome, but cell differentiation and metabolic function were associated with the ERβ transcriptome. Mechanistic studies linking ERs interactomes and transcriptomes discovered that ERα-Chd1 interaction promoted cell growth by upregulating Ssxb6, Crygc, and Cst1; and, ERβ-Ube3a interaction facilitated hepatic progenitor cell differentiation to hepatocytes and cholangiocytes, specifically by upregulating Ifna5. Conclusions: ERα and ERβ orchestrate liver cell proliferation and differentiation respectively, thereby promoting LR.

Cholesterol affects cancer progression, and acetyl‐CoA is the primary cholesterogenesis substrate. The previous work has defined cholesterol bioflux via lipoprotein/receptor route is the gastric cancer (GCa) prognosis biosignature. The prognosis importance of acetyl‐CoA to cholesterogenesis (mevalonate pathway) in GCa is yet to be defined. Using Kaplan–Meier Plotter web‐based gene survival analyzer and The Cancer Genome Atlas (TCGA)‐database analyzed with DBdriver.v2 platform, we revealed acetyl‐CoA production and the mevalonate pathway are associated with GCa prognosis. We found mitochondrial‐derived acetyl‐CoA contributing enzymes (acyl‐coA synthetase super‐family 3; ACSS3) is the GCa progression confounder. Interestingly, it is not HMGCR (the committee enzyme of mevalonate pathway), but lower mevalonate pathway enzymes (e.g., MVK, LSS, DHCR14A1, SC4MOL, HSD17B7, SC5D) promote GCa patients 5‐years overall survival in a differential level. Advanced analyses found ACSS3 is prognosis biosignatures for multiple GCa disease conditions. This report uncovered a higher expression of ACSS3 in tumor comparing to normal parental lesions, which implicates a targeting value for GCa therapy. While knockdown ACSS3 could suppress growth and invasion of GCa cells, of which even more impactful under starvation condition. This is the first report, surprisingly, revealed ACSS3 as important cancer prognosis biomarker. Targeting ACSS3 could be a novel therapeutic strategy for cancer, in this case, GCa.

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 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.

Subclavian artery (SCA) perforation is a rare complication while performing SCA intervention. In our present report, a 73-year-old female, with stenosis of the left SCA and situs inversus, presented with exercise-induced left arm weakness. The SCA stenosis was treated with direct stenting with a balloon-expansible Express LD 10×25 mm stent. However, it caused iatrogenic SCA perforation and hemothorax. The perforation was sealed by endovascular repair with operator-modified Endurant II graft stent, which complicated with occlusion of left common carotid artery. And, the carotid artery was rescued by another stent. The graft stent, which was originally designed for abdominal aortic aneurysm, can be modified to suitable length and take as a rescue stent of large vessel with iatrogenic perforation. Due to strong radial force of graft stent, preservation of large side branches should been watched out.

Percutaneous transluminal coronary angioplasty with metal stent placement has become a well-developed treatment modality for coronary stenotic lesions. Although infection involving implanted stents is rare, it can, however, occur with high morbidity and mortality. We describe herein a case of an inserted coronary stent that was infected and complicated with recurrent stent thrombosis, pseudoaneurysm formation and severe sepsis. Despite repeated intervention and bypass surgery, the patient died from severe sepsis.

// Wei-Chun Chang 1, 2 , Shang-Fen Huang 1 , Yang-Ming Lee 2, 3 , Hsueh-Chou Lai 1, 2 , Bi-Hua Cheng 4 , Wei-Chung Cheng 1, 2 , Jason Yen-Ping Ho 1 , Long-Bin Jeng 1 , Wen-Lung Ma 1, 2, 5 1 Sex Hormone Research Center, Department of Obstetrics and Gynecology, Department of Gastroenterology, Research Center for Tumor Medical Science, and Organ Transplantation Center, China Medical University/Hospital, Taichung, Taiwan 2 Graduate Institute of Biomedical Sciences/Clinical Medical Science, School of Medicine, China Medical University, Taichung, Taiwan 3 Department of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua, Taiwan 4 Department of OBs& GYN, Chia-Yi Chang-Gong Memorial Hospital, Chia-Yi, Taiwan 5 Department of Nursing, Asia University, Taichung Taiwan Correspondence to: Wen-Lung Ma, email: maverick@mail.cmu.edu.tw Keywords: cholesterol, steroidogenesis, gastric cancer, CYP19A1 Received: March 24, 2016 Accepted: November 11, 2016 Published: November 23, 2016 ABSTRACT Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro . This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested.

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Providing memorable tourism experiences (MTEs) plays a crucial role in determining the competitiveness and sustainability of a destination for not only the business sector, but also the environment. Therefore, destination managers face a challenge in identifying, facilitating, and maintaining memorable tourism experiences among visitors. Although MTEs have been increasingly studied, research of the effects of MTEs on word-of-mouth and revisit behavior intentions is still at an early stage of development, particularly in the forest recreation context. The objectives of this study were twofold: To assess visitors&rsquo, MTEs in a selected forest recreation destination and to examine the effects of MTEs on word-of-mouth and revisit intentions. This study identified key memorable experiences of visitors in Xitou Nature Education Area (XNEA), Taiwan (R.O.C.), and examined the relevant relationships among MTEs and behavioral intentions. The results revealed that both refreshment and involvement experiences received the highest scores from the respondents, whereas perceived local culture received the lowest score. Refreshment, local culture, and involvement positively influenced the word-of-mouth intention of visitors. Additionally, hedonism, local culture, and involvement significantly positively influenced the revisit intention of visitors. This study provides additional insights into MTEs in nature-based tourism. The study results underline the importance of MTEs in forest recreation destinations that can encourage more word-of-mouth and revisit intentions of tourists.

Background/aim To determine the prognostic effects of immunohistochemical biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma of the uterine cervix. Materials and methods This study included 42 patients receiving definitive CRT. According to the International Federation of Gynecology and Obstetrics staging system, 13, 21, and 8 patients were classified as having stage IB2, II, and III disease, respectively. Baseline immunohistochemical biomarkers, including those for hypoxia, cell proliferation, cell adhesion, immunogenicity, and evasion of apoptosis, were analyzed using tissue microarrays from biopsy specimens. Results Myeloid cell leukemia-1 (MCL1) overexpression and the presence of pelvic lymph node metastasis were two prognostic factors for inferior cancer-specific survival. A higher H-score for c-MYC proto-oncogene, bHLH transcription factor (c-MYC) was associated with lower pelvic relapse-free survival. Conclusion For patients with adenocarcinoma of the uterine cervix requiring definitive CRT, treatment outcomes can be stratified by the immunohistochemical biomarkers MCL1 and c-MYC for cancer death and local failure, respectively.

Layout features become highly susceptible to lithography process fluctuations due to the widening subwavelength lithography gap. Problematic layout patterns incur poor printability even if they pass design rule checking. These hotspots should be detected and removed at early design phases to improve manufacturability. While existing studies mainly focus on hotspot detection and pattern classification, hotspot pattern library generation is rarely addressed in literature but crucial to the effectiveness and efficiency of hotspot detection. For an advanced process, in addition to yield-limiting patterns inherent from old processes and computation intensive lithography simulation, defect silicon images (SEM images) inspected from test wafers provide more realistic process-dependent hotspots. For facilitating hotspot pattern library generation, we raise a pattern matching problem of searching design layout patterns that may induce problematic SEM images. The key challenge is the various shape distortions between an SEM image and corresponding design layouts. Directly matching either feature points or shapes of both is thus not applicable. We observe that even with shape distortions, matched design layouts and the SEM image have similar density distribution. Therefore, in this paper, we propose an efficient multilevel pixilation framework to seek layout clips with similar density distribution from coarse- to finegranularities to an SEM image. The proposed framework possesses high parallelism. Our results show that the proposed method can effectively and efficiently identify matched layout pattern candidates.

We designed a deep learning model for assessingAll 142 patients with cervical cancer underwentIn 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.This is the first study to use deep learning model for assessing• This is the first study to use deep learning model for assessing

Background: Platinum-based therapy remains the cornerstone for cancer therapy; however, efficacy varies. The role of tumor macroenvironmental lipid entry via lipoprotein receptors has been reported. Yet, the roles and mechanism of low-density lipoprotein receptor (LDLR) in chemo-sensitivities are in large. Method: Patient study: Single cohort or public database cDNA microarray to associate LDLR expressions of epithelial ovarian carcinomas (EOCs) with disease prognosis. Laboratory study: In vitro and in vivo add-in/silencing LDLR were introduced to determines cisplatin sensitivity. Transcriptome-Lipidome Trans-omics and bioinformatic analyses to model molecular mechanism. Translation study: LDLR-lipidome was implemented to formulate efficacy boosting liposome. Findings: The LDLR expression is associate with platin-based chemotherapy patients prognosis. The LDLR abundance in EOC subtypes is associated with cisplatin sensitivity. Knocked-down or overexpressed LDLR in EOC could reversed the chemosensitivity pattern in vitro and in vivo. Trans-omics analyses elucidated the LDLR→LPC (Lyso-PhosphotidylCholine)→FAM83B (phospholipase-related)→FGFRs (cisplatin sensitivity and phospholipase-related) regulatory axis in cisplatin insensitivity. Implementing LPC-liposome encapsulated cisplatin facilitated DNA-adduct formation via lipid droplets (LDs) delivery. Bioinformatics analyses found that the LDL/R-route alters LD homeostasis, which is critical for therapeutic prognosis. Lastly, using LPCliposome could improve multiple cancer types of cisplatin insensitive cells. Interpretation: The LDL/R-route as tumor macroenvironmental lipid entry which impulses platinum insensitivity and disease outcome. The drug specific lipidome for liposome manufacture might be an efficienct pharmaceutics strategy for chemoagents. Funding Statement: This study was supported by Taiwan Ministry of Science and Technology (MOST104-2628-B-039-001-MY4; MOST106-2221-E-039-011-MY3); National Health Research Institute (NHRI-EX107-10705BI); and China Medical University/Hospital (CMU107-S-05; CMU107-TC-02; DMR-108-080; DMR-CELL-17014; DMR-CELL-1806; DMR-108-079). Declaration of Interests: All the authors in this work claimed no interests conflict. Ethics Approval Statement: Access to the tissue samples was approved by the Internal Review Board of China Medical University Hospital (DMR101-IRB2-276; and CMU105-REC3-122(CR1)). All the animal studies were performed under the supervision and guidelines of the China Medical University Animal Care and Use Committee (#CMOIACUC-2018-089).

Although plantar thermography can evaluate the immediate perfusion result after an endovascular therapy (EVT) has been performed, a relevant wound outcome study is still lacking. This study was to investigate whether angiosome-based plantar thermography could predict wound healing and freedom from major amputation after EVT in patients with critical limb ischemia (CLI)[1]. All 124 patients with CLI (Rutherford category 5 and 6) who underwent EVT from January 2017 to February 2019 were prospectively enrolled. All patients received thermography both before and after EVT. Both wound healing and freedom from major amputation at the 6-month follow-up period were recorded. There were 61 patients in the healing group and 63 patients in the non-healing group, whereas the major amputation total was 14 patients. The mean pre- and post-EVT temperature of the foot was significantly higher in the healing group than in the non-healing group (30.78 °C vs 29.42 °C, P = .015; and 32.34 °C vs 30.96 °C, P = .004, respectively). DIFF2 was significantly lower in the non-healing group (-1.38 vs -0.90, P = .009). DIFF1 and DIFF2 were significantly lower in the amputation group (-1.85 °C vs -1.11 °C, P = .026; and -1.82 °C vs -1.08 °C, P = .004). Multivariate analysis showed that DIFF2 stood out as an independent predictor for freedom from major amputation (hazard ratio 0.51, P = .045). Receiver operating characteristic curve analysis showed a DIFF2 cut-off value of -1.30 °C, which best predicts freedom from major amputation. Plantar thermography is associated with wound healing and helps predict freedom from major amputation in CLI patients undergoing EVT.

Endometrial stromal tumors are rare uterine tumors (

3D model construction techniques using RGB-D information have been gaining a great attention of the researchers around the world in recent decades. The RGB-D sensor, Microsoft Kinect is widely used in many research fields, such as in computer vision, computer graphics, and human computer interaction, due to its capacity of providing color and depth information. This paper presents our research finding on calibrating information from several Kinects in order to construct a 3D model of a human object and to render texture captured from RGB camera. We used multiple Kinect sensors, which are interconnected in a network. High bit rate streams captured at each Kinect are first sent to a centralized PC for the processing. This even can be extended to a remote PC in the Internet. Main contributions of this work include calibration of the multiple Kinects, properly aligning point clouds generated from multiple Kinects, and generation of the 3D shape of the human objects. Experimental results demonstrate that the proposed method provides a better 3D model of the human object being captured.

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.

Chicken anemia virus (CAV) is a severe threat to the chicken industry and causes heavy economic losses worldwide. In this study, we evaluated the immune response and protective efficacy provided by a subunit vaccine containing recombinant VP1 (rVP1) and pigeon interferon-γ (rPiIFN-γ). Results indicated that rPiIFN-γ enhanced humoral immunity elicited by rVP1 as early as 10 day after primary immunization and reach the high titer after secondary immunization. When compared to chickens immunized with rVP1, inactivated vaccine, chickens immunized with rVP1+rPiIFN-γ showed faster and higher levels (p

Purpose This study was carried out to assess the risk of gynecological malignancy in colorectal cancer survivors using a population-based retrospective cohort study. Method Using the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 37,176 patients with colorectal cancer diagnosed in 1998–2009, aged 20 years and above, without other cancer history. We also randomly selected 148,700 women without any cancer in the comparison cohort, frequency matched by age and diagnosis date. Incidences and hazards of breast, cervix, endometrial and ovarian cancers were evaluated by 201l. Results The overall incidence of the 4 types of gynecological cancer was 39.0% higher in colorectal cancer patients than in comparisons (2.99 vs. 2.14 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.46 (95% confidence interval (CI) = 1.31–1.62). Breast cancer accounted for most subsequent cancer. The multivariable Cox method measured HR was the highest for endometrial cancer (3.40, 95% CI = 2.59–4.47) for the colorectal cohort relative to comparisons, followed by ovarian cancer and breast cancer, except cervix cancer. The risk of gynecological malignancies was apparently elevated for colorectal cancer survivors Conclusions Follow-up measures are suggested for women with colorectal cancer for early detection and prevention of the subsequent gynecological malignancy.

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-&alpha, ) 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-&alpha, H score.

The present study re-assesses the characters of the Oriental genus Lobogonodes Bastelberger, 1909 based on all 8 species, including the newly described L. shiushioui sp. nov. and the distinct species L. dactylotypa Prout, 1940 stat. rev.. Three synapomorphic characters based on the male genitalia are proposed: the presence of a sclerotized subscaphium, the U-shaped connection between the juxta and anellus lobe and the saccus process pointed anteriorly. A new key to the species in this genus is provided.

Person identification (PID) is a key issue in many IoT applications. It has long been studied and achieved by technologies such as RFID and face/fingerprint/iris recognition. These approaches, however, have their limitations due to environmental constraints (such as lighting and obstacles) or require close contact to specific devices. Therefore, their recognition rates highly depend on use scenarios. To enable reliable and remote PID, in this work, we present EOY (Eye On You)1, a data fusion approach that combines two kinds of sensors, a 3D depth camera and wearable sensors embedded with inertial measurement unit (IMU). Since these two kinds of data share common features, we are able to fuse them to conduct PID. Further, the result can be transferred to a mobile platform (such as robot) since we have less constraints on devices. To realize EOY, we develop fusion algorithms to address practical challenges, such as asynchronous timing and coordinate calibration. The experimental evaluation shows that EOY can achieve the recognition rate of 95% and is very robust even in crowded areas.

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 training set and used to classify each slice set in the test set into the categories of with or without the 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. Funding Statement: This work was supported by grants from the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital (DMR-107-192, CRS-106-036, CRS106-039, CRS106-040, CRS106-041); Asia University (DMR-106-150); Academia Sinica Stroke Biosignature Project (BM10701010021); MOST Clinical Trial Consortium for Stroke (MOST 107-2321-B-039 -004-); Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the local institutional review board (certificate numbers CMUH102-REC2-74 and DMR99-IRB-010-1). Informed consent: This is a retrospective study for images’ analyses. The IRB also specifically waived the consent requirement.

Background:After living donor liver transplantation (LDLT), rising serum bilirubin levels commonly indicate insufficient numbers of hepatocytes are available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450 (CYP) 2A6 in humans (or cyp2a4 in rodents) can function as “bilirubin oxidase.” Functional hepatocytes contain abundant CYP2A6, which is considered a marker for hepatocyte function recovery. The aim of our study was to determine the impact of estradiol/estrogen receptor signaling on bilirubin levels during liver function recovery.Methods:We conducted a hospital-based cohort study of bilirubin levels after LDLT surgery in both liver graft donors and recipients, performed a transcriptome comparison of wild-type versus estrogen receptor (ER)α knockout mice and a bioinformatics analysis of transcriptome changes in their regenerating liver after two-third partial hepatectomy (PHx), and assayed in vitro expression of cytochrome (CYP2A6) in human hepatic progenitor cells (HepRG) treated with 17β-estradiol (E2).Results:The latency of bilirubin level reduction was shorter in women than in men, suggesting that a female factor promotes bilirubin recovery after liver transplantation surgery. In the PHx mouse model, the expression of the cyp2a4 gene was significantly lower in livers from the knockout ERα mice than in livers from their wild-type littermates; but the expression of other bilirubin metabolism–related genes were similar between these groups. Moreover, E2 or bilirubin treatments significantly promoted CYP2A6 expression in hepatocyte progenitor cells (HepRG cells). Sequence analysis revealed similar levels of aryl hydrocarbon receptor (AhR; bilirubin responsive nuclear receptor) and ESR1 binding to the promoter region of CYP2A6.Conclusions:This is the first report to demonstrate, on a molecular level, that E2/ERα signaling facilitates bilirubin metabolism in regenerating liver. Our findings contribute new knowledge to our understanding of why the latency of improved bilirubin metabolism and thereby liver function recovery is shorter in females than in males.

Histone deacetylase inhibitors (HDACi) are novel clinical anticancer drugs that inhibit HDAC gene expression and induce cell apoptosis in human cancers. Nevertheless, the detailed mechanism or the downstream HDAC targets by which HDACi mediates apoptosis in human breast cancer cells remains unclear. Here, we show that HDACi reduce tumorigenesis and induce intrinsic apoptosis of human breast cancer cells through the microRNA miR-125a-5p in vivo and in vitro. Intrinsic apoptosis was activated by the caspase 9/3 signaling pathway. In addition, HDACi mediated the expression of miR-125a-5p by activating RUNX3/p300/HDAC5 complex. Subsequently, miR-125a-5p silenced HDAC5 post-transcriptionally in the cells treated with HDACi. Thus, a regulatory loop may exist in human breast cancer cells involving miR-125a-5p and HDAC5 that is controlled by RUNX3 signaling. Silencing of miR-125a-5p and RUNX3 inhibited cancer progression and activated apoptosis, but silencing of HDAC5 had a converse effect. In conclusion, we demonstrate a possible new mechanism by which HDACi influence tumorigenesis and apoptosis via downregulation of miR-125a-5p expression. This study provides clinical implications in cancer chemotherapy using HDACi.

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.

Layout pattern classification, which groups similar layout clips into clusters, underlies a variety of design for manufacturability (DFM) applications such as hotspot library generation, hierarchical data storage, and yield optimization speedup. The key challenges of layout pattern classification are clip representation and clip clustering, while the mutually conflicting concerns are efficiency and solution quality (in terms of cluster count). In this paper, we present a fast and general layout pattern classification algorithm. Our simple but general clip representation captures both topology and density; we can handle not only rigid area match or edge displacement constraints but also variant edge tolerances and don't care regions. On the other hand, for achieving a small cluster count, our clip clustering is guided by the natural grouping structure of layout clips. Our experiments are conducted on 2016 CAD contest at ICCAD benchmark suite; our results show that our algorithm outperforms the reference solution and all contest winning teams, delivering the smallest cluster count, fastest runtime, and 100% validity. In addition to the good solution quality, the interplay between adopted simple and easily manipulated data structures and our algorithm makes it fast and viable to be incorporated into practical DFM flows.

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.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12872-017-0547-9) contains supplementary material, which is available to authorized users.

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.

Background Ovarian teratocarcinoma (OVTC) arises from germ cells and contains a high percentage of cancer stem/progenitor cells (CSPCs), which promote cancer development through their ability to self-renew. Androgen and androgen receptor (androgen/AR) signaling has been reported to participate in cancer stemness in some types of cancer; however, this phenomenon has never been studied in OVTC. Methods Ovarian teratocarcinoma cell line PA1 was manipulated to overexpress or knockdown AR by lentiviral deliver system. After analyzing of AR expression in PA1 cells, cell growth assay was assessed at every given time point. In order to determine ligand effect on AR actions, luciferase assay was performed to evaluate endogenous and exogenous AR function in PA1 cells. CD133 stem cell marker antibody was used to identify CSPCs in PA1 cells, and AR expression level in enriched CSPCs was determined. To assess AR effects on CD133 + population progression, stem cell functional assays (side population, sphere formation assay, CD133 expression) were used to analyze role of AR in PA1 CSPCs. In tissue specimen, immunohistochemistry staining was used to carry out AR and CD133 staining in normal and tumor tissue. Results We examined androgen/AR signaling in OVTC PA1 cells, a CSPCs-rich cell line, and found that AR, but not androgen, promoted cell growth. We also examined the effects of AR on CSPCs characteristics and found that AR expression was more abundant in CD133 + cells, a well-defined ovarian cancer stem/progenitor marker, than in CD133 − populations. Moreover, results of the sphere formation assay revealed that AR expression was required to maintain CSPCs populations. Interestingly, this AR-governed self-renewal capacity of CSPCs was only observed in CD133 + cells. In addition, we found that AR-mediated CSPCs enrichment was accompanied by down-regulation of p53 and p16. Finally, co-expression of AR and CD133 was more abundant in OVTC lesions than in normal ovarian tissue. Conclusion The results of this study suggest that AR itself might play a ligand-independent role in the development of OVTC.

Adenomyosis of the uterus is defined as the presence of endometrial tissue, including glands and stroma, situated at least 2.5 mm below the endometrial–myometrial junction and widely distributed within the myometrium layer of the uterus. There is no consensus on the appropriate treatment for symptomatic uterine adenomyosis in women who want to preserve their uterus, partly because adenomyosis is somewhat enigmatic in diagnosis and owing to its clinical significance. Hysterectomy, through either exploratory laparotomy or minimally invasive procedures, is a definite treatment for uterine adenomyosis, once the women have completed childbirth or do not require future fertility. However, many women with a uterine pathology still have a strong desire to preserve the uterus, for which conservative and uterine-sparing procedures are increasingly used, and with which fertility preservation or quality-of-life improvement can be achieved. Although medical management can be effective, similar to the management of uterine fibroids (myoma), its effect is often transient and rapid regrowth of adenomyosis and relapse of symptoms and signs always occur once the treatment is stopped. Therefore, other strategies should be selected. Conservative and uterine-sparing surgery might be one of the most familiar procedures of these uterine-sparing procedures. In this article, the latest knowledge and research evidence on uterine-sparing surgery for uterine adenomyosis are reviewed.

Endometrial cancer (EMC) is a sex steroid hormone-related female malignancy. Androgen and androgen receptor (androgen/AR) signals have been implicated in EMC progression. Cancer stem/progenitor cells (CSPCs) are suspected to link to chemoresistance in patients with EMC. In this study, we examined the androgen/AR roles in cisplatin resistance and CSPC population. We found AR expression increased naive EMC side population, CSPC population, cell migration, and epithelial–mesenchymal transition. Meanwhile, it decreased cisplatin cytotoxic effect on EMC cells. Collaterally, endogenous AR expressions in EMC cells were upregulated in the cisplatin-resisting state. Moreover, AR expression could further enhance CD133 expression, CSPC-related markers, and drug-resistance gene messenger RNA expression in EMC cells. Finally, the AR-associated gene expression might go through indirect regulation. This is the first report revealing AR function on EMC cells’ CSPC and cisplatin resistance.