Metastasis is a life-threatening feature of cancer and is primarily responsible for cancer patient mortality. Cross talk between tumor cells and endothelium is important for tumor progression and ...metastasis. However, very little is known about the mechanisms by which endothelial cells (ECs) that are close to tumor cells, respond to the tumor cells during tumor progression and metastasis. In this study, we exploited the use of EC-specific signal transducer activator of transcription 3 (STAT3) knockout mice to investigate the role of STAT3 in ECs in tumor progression and metastasis. We found that the loss of STAT3 in ECs did not affect primary Lewis lung carcinoma (LLC) tumor growth, but it reduced in vivo LLC metastasis in experimental and spontaneous metastasis models. Mechanistically, STAT3 activation upregulated cell adhesion molecule expression, including E-selectin and P-selectin, in murine endothelial MS-1 cells treated with tumor cell-conditioned media in vitro and in pre-metastatic lungs of tumor-bearing mice in vivo. We also found that both E-selectin and P-selectin were, at least in part, responsible for STAT3-induced adhesion and invasion of LLC cells through an EC monolayer. However, tumor cell-conditioned media from B16F10 melanoma cells did not activate STAT3 in MS-1 cells. As a result, EC STAT3 knockout did not affect B16F10 melanoma cell metastasis. In addition, various human cancer cells activated STAT3 in human ECs (HUVECs), resulting in increased cell adhesion molecule expression. Collectively, our findings demonstrate that STAT3 activation in ECs promotes tumor metastasis through the induction of cell adhesion molecules, demonstrating a role for ECs in response to tumor cells during tumor metastasis.
A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) ...vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002).
Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group.
9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate.
The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia.
NCT00543543; NCT00943722.
Background
The impact of chemotherapy‐associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. ...The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres.
Methods
PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords ‘chemotherapy’, ‘liver resection’, ‘outcome’ and ‘colorectal metastases’ to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals.
Results
A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo–Clavien grade III–V; OR 1·73, 95 per cent c.i. 1·02 to 2·95; P = 0·043). Severe steatosis was associated with decreased liver surgery‐specific complications (OR 0·52, 95 per cent c.i. 0·27 to 1·00; P = 0·049), whereas steatohepatitis was linked to an increase in these complications (OR 2·08, 1·18 to 3·66; P = 0·012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2·22, 1·48 to 3·34; P = 0·001) and liver surgery‐specific complications (OR 3·35, 2·11 to 5·32; P < 0·001). Finally, oxaliplatin treatment was linked to severe SD (OR 2·74, 1·67 to 4·49; P < 0·001).
Conclusion
An increase in postoperative major morbidity and liver surgery‐specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD.
Increased complications in severe sinusoidal dilatation and steatohepatitis
Background
Few studies investigated the optimal timing for tracheostomy and its influence on the clinical outcomes in critically ill pediatric patients. This study evaluated the differences in ...clinical outcomes between early and late tracheostomy in pediatric intensive care unit (ICU) patients.
Methods
We assessed 111 pediatric patients. Patients who underwent a tracheostomy within 14 days of mechanical ventilation (MV) were assigned to the early tracheostomy group, whereas those who underwent tracheostomy after 14 days of MV were included in the late tracheostomy group. Clinical outcomes, including mortality, duration of MV, length of ICU and hospital stays, and incidence of ventilator‐associated pneumonia (VAP) were compared between the groups.
Results
Of the 111 pediatric patients, 61 and 50 were included in the early and late tracheostomy groups, respectively. Total MV duration and the length of ICU and hospital stay were significantly longer in the late tracheostomy group than in the early tracheostomy group (all P < 0.01). The VAP rate per 1000 ventilator days before tracheostomy was 2.6 and 3.8 in the early and late tracheostomy groups, respectively. There were no significant differences in mortality rate between the groups. No severe complications were associated with tracheostomy itself.
Conclusions
Tracheostomy performed within 14 days after the initiation of MV was associated with reduced duration of MV and length of ICU and hospital stay. Although there was no effect on mortality rate, children may benefit from early tracheostomy without severe complications.
To evaluate the efficacy and safety of the combination of oxaliplatin and S-1 (OS) in treating metastatic colorectal cancer.
Eligible patients were those with measurable lesions, no previous history ...of chemotherapy (except adjuvant chemotherapy), an age of 18–70 years, and an Eastern Cooperative Oncology Group performance status of zero to two. Oxaliplatin 130 mg/m2 was administered i.v. on day 1, and S-1 40 mg/m2 b.i.d. was administered orally on days 1–14, every 3 weeks.
Forty-eight patients (median age, 56 years) were enrolled: 23 had colon cancer, seven rectosigmoid colon cancer; and 18 rectal cancer. Of the 48 patients, 31 were diagnosed with metastatic cancer and 17 had relapsed cancer after surgery, with adjuvant chemotherapy or chemoradiotherapy. In total, 413 cycles were administered (median 6 per patient; range 2–24). Toxicity was evaluated in 48 patient and response in 46. Major toxic effects were grade 3/4 thrombocytopenia (13%) and neutropenia (10%). The overall response rate was 54% 95% confidence interval (CI) 40% to 68%. The median time to progression and median survival time were 8.5 (95% CI 6.2–10.9) months and 27.2 (95% CI 20.3–34.0) months, respectively.
These data indicate that the OS regimen is effective and well tolerated in patients with advanced colorectal cancer.
Abstract
The AMoRE collaboration is preparing for the second phase of
the experiment, AMoRE-II, which will exploit a 100 kg of
100
Mo
isotopes to search for neutrinoless double beta decay from the
...isotope. Most of the
100
Mo isotopes will be contained in the
lithium molybdate (Li
2
MoO
4
) crystals, which will act as
absorbers of cryogenic calorimeters coupled to MMC (metallic
magnetic calorimeter) sensors. The detector array will have a total
mass of approximately 200 kg with hundreds of detector
modules. Hence, considerable effort has been taken to optimize the
lithium molybdate crystal detector in terms of the detector
performance and preparation procedure to build many detector modules
in a reasonable schedule without compromising the detector
performance. We found some critical experimental conditions to
improve the energy resolution in a series of test experiments. In
this paper, we discuss the effect of surface treatment and thermal
link connection in improving the energy resolution from 14–15 keV
to below 7 keV at 2.615 MeV,
208
Tl gamma line, which is near
the Q-value of the decay of
100
Mo, 3.034MeV. We also report
the high discrimination power for the separation of alpha particles
using the simultaneous scintillation light detection with a test
performed in the cryogen-free dilution refrigerator.
Background
Onychopapilloma is a benign tumour of the nail bed and distal matrix and commonly presents as longitudinal erythronychia, longitudinal leukonychia or longitudinal melanonychia. Because ...onychopapilloma is rare, its clinical characteristics and dermoscopic findings have not been well investigated in Asia.
Objectives
This study aimed to investigate the clinical characteristics and dermoscopic and pathologic findings of onychopapilloma in Korea.
Methods
We retrospectively reviewed the medical records and clinical/dermoscopic photographs of 39 patients diagnosed with onychopapilloma in the Pusan National University Hospitals (Busan and Yangsan) for 11 years (2010–2021).
Results
Among 39 patients, 23 (59.0%) were men, and 16 (41.0%) were women. The mean age was 46.1 (16–77) years. All lesions were single, and most of them were located on the fingers (92.3%), especially the thumb (66.7%). The most common clinical feature was longitudinal erythronychia (56.4%), and the most common dermoscopic finding was distal subungual hyperkeratosis (100%). We found two new dermoscopic features: macrolunula and trailing lunula along the longitudinal band. Among 18 patients who underwent surgical excision, only 6 (33.3%) showed typical acanthosis and papillomatosis on the nail bed.
Conclusions
We found that Asian onychopapilloma has similar clinicodermoscopic findings to the Caucasian one, that is to say, longitudinal erythronychia and distal subungual hyperkeratosis were the most common nail change and dermoscopic finding, respectively. We propose two new dermoscopic features of onychopapilloma: macrolunula and trailing lunula along the longitudinal band.
Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including ...the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.
Despite optimal pharmacotherapy and cognitive-behavioral treatments, a proportion of patients with obsessive-compulsive disorder (OCD) remain refractory to treatment. Neurosurgical ablative or ...nondestructive stimulation procedures to treat these refractory patients have been investigated. However, despite the potential benefits of these surgical procedures, patients show significant surgery-related complications. This preliminary study investigated the use of bilateral thermal capsulotomy for patients with treatment-refractory OCD using magnetic resonance-guided focused ultrasound (MRgFUS) as a novel, minimally invasive, non-cranium-opening surgical technique. Between February and May 2013, four patients with medically refractory OCD were treated with MRgFUS to ablate the anterior limb of the internal capsule. Patients underwent comprehensive neuropsychological evaluations and imaging at baseline, 1 week, 1 month and 6 months following treatment. Outcomes were measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A), and treatment-related adverse events were evaluated. The results showed gradual improvements in Y-BOCS scores (a mean improvement of 33%) over the 6-month follow-up period, and all patients showed almost immediate and sustained improvements in depression (a mean reduction of 61.1%) and anxiety (a mean reduction of 69.4%). No patients demonstrated any side effects (physical or neuropsychological) in relation to the procedure. In addition, there were no significant differences found in the comprehensive neuropsychological test scores between the baseline and 6-month time points. This study demonstrates that bilateral thermal capsulotomy with MRgFUS can be used without inducing side effects to treat patients with medically refractory OCD. If larger trials validate the safety, effectiveness and long-term durability of this new approach, this procedure could considerably change the clinical management of treatment-refractory OCD.
Aim To investigate magnetic resonance imaging (MRI) findings that could be used to differentiate intramedullary spinal ependymoma from astrocytoma, and to determine predictors for this ...differentiation. Materials and methods MRI images of 43 consecutive patients with pathologically proven intramedullary spinal ependymoma ( n = 24) and astrocytoma ( n = 19) were comparatively evaluated with regard to size, location, margin, signal intensity, contrast enhancement, presence of syringohydromyelia, tumoural cyst, non-tumoural cyst, and haemorrhage. MRI findings and demographic data were compared between the two tumour groups using univariate and multivariate logistic regression analyses. Results In patients with ependymoma, older age and a larger solid component were more often observed than in astrocytoma. Central location, presence of enhancement, diffuse enhancement, syringohydromyelia, haemorrhage, and cap sign were more frequently observed in ependymoma. However, multivariate analysis revealed that syringohydromyelia was the only variable able to independently differentiate ependymoma from astrocytoma, with an odds ratio of 62.9 (95% CI: 4.38–903.22; p = 0.002). Conclusion Among the various findings, the presence of syringohydromyelia is the main factor distinguishing ependymoma from astrocytoma.
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