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Ahmed M. Abu El-Asrar Ajmal Ahmad Eef Allegaert Mohammad Mairaj Siddiquei Priscilla W. Gikandi Gert De Hertogh 《Ocular immunology and inflammation》2020,28(4):575-588
ABSTRACT
Purpose
To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163+ M2 macrophages in proliferative diabetic retinopathy (PDR). 相似文献4.
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Shingo Hashimoto Masaki Katsurada Rie Muramatsu Kumiko Asai Kenichiro Tanaka Kensuke Hayashi Yoshiaki Kibe Koichiro Nakajima Yukiko Hattori Hiromitsu Iwata Jun-etsu Mizoe Hiroyuki Ogino Yuta Shibamoto 《Practical radiation oncology》2019,9(2):e149-e155
Purpose
Suppression of respiratory movement of the liver would be desirable for high-precision radiation therapy for liver tumors. We aimed to investigate the effect of our original device-free compressed shell fixation method and breathing instruction on suppression of respiratory movement. The characteristics of liver motion based on the movement of a fiducial marker were also analyzed.Methods and Materials
First, respiratory amplitudes of the liver with the device-free compressed shell were analyzed from the data of 146 patients. The effect of this shell fixing method on liver movement was evaluated. Second, as another cohort study with 166 patients, interfractional internal motion of the liver for patients fixed in the shell was calculated using the fiducial marker coordinate data of images for position setting before daily irradiation. Third, in another 12 patients, intrafractional internal motion was calculated from the fiducial marker coordinate data using x-ray images before and after irradiation.Results
The median respiratory movement without the shell, after fixing with the shell, and after instructing on the breathing method with the shell was 14.2 (interquartile range, 10.7-19.8), 11.5 (8.6-17.5), and 10.4 mm (7.3-15.8), respectively. Systematic and random errors of interfractional internal motion were all ≤2 mm in the left-right and anteroposterior directions and 3.7 and 3.0 mm, respectively, in the craniocaudal direction. Systematic and random errors of intrafractional internal motion were all ≤1.3 mm in the left-right and anteroposterior directions and 0.8 and 2.4 mm, respectively, in the craniocaudal direction.Conclusions
The device-free compressed shell fixation method was effective in suppressing the respiratory movement of the liver. Irradiation position matching using the fiducial marker can correct the interfractional internal motion on each day, which would contribute to the reduction of the margin to be given around the target. 相似文献6.
Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11. 相似文献
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Dominique Trudel Luminita-Mihaela Avarvarei Michèle Orain Stéphane Turcotte Marie Plante Jean Grégoire Reinhild Kappelhoff David P. Labbé Dimcho Bachvarov Bernard Têtu Christopher M. Overall Isabelle Bairati 《Pathology, research and practice》2019,215(6):152369
Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
8.
Joobin Sattar Adi Kartolo Wilma M. Hopman Joshua Matthew Lakoff Tara Baetz 《Journal of Geriatric Oncology》2019,10(3):411-414
ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted. 相似文献
9.
Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
10.
Sania Amr Magdy Garas Dina N. K. Boulos Doa’a A. Saleh Irene A. Jillson Christopher A. Loffredo 《Journal of substance use》2019,24(3):341-345
Background: Egyptian street youth use substances including tobacco, illicit drugs, and pharmaceutical drugs. To understand the circumstances, including adverse childhood experiences, that place adolescents at risk for engaging in substance use, we conducted in-depth interviews among a sample of Egyptian street children. Methods: From youth residing at or attending Caritas, a non-profit organization, which provides shelter and education to street youth, seven girls and twelve boys, aged 12–18 years, participated in open-ended, in-depth interviews. Results: Eight out of the 19 participants reported family history (early exposure) to substance use; and seven of them were initiated by either a family member (sibling), friend or coworker. Most of the participants reported a history of conflict with or abuse (verbal or physical) by their parents or siblings, or stressful situations at home; they used substance(s) to alleviate their stress. Few attended school, and some were forced to work and help their family. Conclusions: Among Egyptian youth, adverse childhood experiences, such as poverty, child abuse, and family substance use, challenge somewhat susceptible youths and lead them to the path of substance use and addiction. Prevention intervention should be multifaceted, culturally adaptable, and primarily targeting the social environment during childhood. 相似文献