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#32619922   2020/06/20 To Up

Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India.

There are few comprehensive studies from Asia on clinicopathologic features of mismatch repair (MMR)-deficient endometrial carcinomas, including rarely from our country. One hundred and four cases of endometrial carcinomas were tested for four MMR proteins by immunohistochemistry. Among 50 MMR-deficient (MMRd) tumors(48%), age-range was 27-68 years(median = 53) and tumor size(n = 34) varied from 1.2-10 cm(average = 4.6). Lower uterine segment(LUS) was involved in 21/31 cases(67.7%). Histopathologically, all cases were endometrioid adenocarcinomas(EMACs), of FIGO grade 2(low-grade)(18 cases) and 3(high-grade)(32 cases), displaying de-differentiated, undifferentiated and lymphoepithelioma(LE)-like patterns, in 24 cases(48%). Tumor infiltration ≥ half of myometrium was seen in 30/44 cases (68.1%); lymphovascular emboli in 19/43 cases(44.1%); and lymph node metastasis in 7/22(31.8%) cases. Uncommonly, clear cell component(n = 2) and focal neuroendocrine differentiation (n = 2) were observed. Immunohistochemically, tumor cells showed paired loss of MLH1 and PMS2 in 33(66%) and MSH2 and MSH6 in 14(28%) cases, along with loss of MSH2 and PMS2, in two and a single case, respectively. Nine patients(18%) were treated for another cancer and 9/33(27.2%) disclosed familial history of cancer. MSH2 was the most frequently lost MMR protein in those cases. Additionally, tumor cells displayed ER positivity in 41/50 cases(82%), PR in 38/41cases(92.6%) and wild-type p53 staining in 24/28 cases(85.7%). Tumor with LE-pattern showed PDLI immunoexpression. Certain clinicopathologic features suggestive for MMRd associated ECs, such as relatively large-sized tumors, involving LUS; especially high-grade, infiltrative EMACs, with undifferentiated/de-differentiated, and LE-like patterns; showing deep muscle invasion, frequent PR immunoexpression and invariably, wild-type p53 immunostaining can be useful in screening cases of Lynch syndrome. This constitutes the first report on these tumors from our country.
Bharat Rekhi, Santosh Menon, Kedar K Deodhar, Jaya Ghosh, Supriya Chopra, Amita Maheshwari

1609 related Products with: Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India.

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#32619809   2020/06/14 To Up

Combined TLR4 and TLR9 agonists induce distinct phenotypic changes in innate immunity in vitro and in vivo.

Toll-like receptor (TLR)4 and TLR9 agonists, MPL and CpG, are used as adjuvants in vaccines and have been investigated for their combined potential. However, how these two combined agonists regulate transcriptional changes in innate immune cells and cells at the site of vaccination has not been thoroughly investigated. Here, we utilized transcriptomics to investigate how CpG, MPL, and CpG + MPL impact gene expression in dendritic cells (DC) in vitro. Principal component analysis of transcriptional changes after single and combined treatment indicated that CpG, MPL, and CpG + MPL caused distinct gene signatures. CpG + MPL induced antiviral gene expression and activated the interferon regulatory factor pathway. In vitro changes were associated with lower in vivo morbidity upon viral challenge, elevated systemic cytokine protein production, local cytokine mRNA expression, and increased migratory monocyte derived DC populations in the draining lymph node following vaccination with CpG + MPL. This report suggests that CpG + MPL enhances transcription of antiviral and inflammatory genes and increases DC migration.
Anna T Lampe, Bhanwar Lal Puniya, Angela K Pannier, Tomás Helikar, Deborah M Brown

2116 related Products with: Combined TLR4 and TLR9 agonists induce distinct phenotypic changes in innate immunity in vitro and in vivo.

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#32619439   2020/06/30 To Up

Immunophenotypic and Pathologic Heterogeneity of Unclassified Renal Cell Carcinoma: A Study of 300 Cases.

Renal cell carcinoma, unclassified (RCC-U), is a heterogenous group of tumors that do not fit in any recognized histologic types. Immunohistochemical studies are frequently used to characterize these tumors. Herein, we sought to investigate the immunophenotypes of 300 cases of RCC-U. The cases were morphologically classified into three groups: oncocytoma/chromophobe renal cell carcinoma-like -Group 1; clear cell renal cell carcinoma-like - Group 2; and others (i.e., papillary renal cell carcinoma-like/collecting duct-like/pure sarcomatoid) - Group 3. Male-to-female ratio was 1.4. Most cases (168, 66%) were Group 1. Group 3 was associated with larger tumor size, advanced stage, and frequent lymph node metastases. The most commonly used immunohistochemical stains were CK7 (n=270; 89.5%), vimentin (n=186, 82%), CD10 (n=181; 59.9%), and AMACR (n=162; 54%). Pancytokeratin (79/101; 78.2%) and PAX8 (54/61; 88.5%) were diffusely positive in most cases, followed by AMACR (69/117; 59%). CD117 was positive in 53/118 cases (45%). RCC-U is a morphologically and immunophenotypically heterogenous group of tumors, comprehensive work-up is needed before rendering the diagnosis.
Mahmut Akgul, Liang Cheng

2782 related Products with: Immunophenotypic and Pathologic Heterogeneity of Unclassified Renal Cell Carcinoma: A Study of 300 Cases.



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#32619422   2020/06/30 To Up

Poor hive thermoregulation produces an Allee effect and leads to colony collapse.

In recent years the honey bee industry has been experiencing increased loss of hives. The accumulation of multiple stressors on a hive potentially drives hive loss in various ways, including winter loss and colony collapse disorder. One of these stressors is the breakdown of thermoregulation inside the hive. For pupae to develop correctly into healthy adult bees, the temperature within the hive must be regulated by the hive bees to within a narrow range that ensures optimal development. Suboptimal development in adults affects their brain and flight muscles so bees becomes inefficient foragers with shorter life spans. We model the effect of thermoregulation on hive health using a system of delay differential equations that show that thermoregulatory stress has the capacity to drive colony loss in the model via a saddle-node bifurcation with an associated Allee effect.
Zeaiter Zeaiter, Mary R Myerscough

2843 related Products with: Poor hive thermoregulation produces an Allee effect and leads to colony collapse.

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#32619381   2020/07/03 To Up

Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?

The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. Treatment plans ( = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.
Kai Joachim Borm, Cristoforo Simonetto, Pavel Kundrát, Markus Eidemüller, Markus Oechsner, Mathias Düsberg, Stephanie Elisabeth Combs

2631 related Products with: Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?



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#32619179   2020/07/03 To Up

Serum Carboxypeptidase N 1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer.

The incidence and mortality of breast cancer are increasing annually. Breast cancer seriously threatens women's health and quality of life. We aimed to measure the clinical value of CPN1, a new serum marker of breast cancer and to evaluate the efficacy of CPN1 in combination with CA15-3.
Ranliang Cui, Chaomin Wang, Qi Zhao, Yichao Wang, Yueguo Li

2494 related Products with: Serum Carboxypeptidase N 1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer.

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#32619080   2020/07/03 To Up

Soybean AP1 homologs control flowering time and plant height.

Flowering time and plant height are key agronomic traits that directly affect soybean (Glycine max) yield. APETALA1 (AP1) functions as a class A gene in the ABCE model for floral organ development, helping to specify carpel, stamen, petal, and sepal identities. There are four AP1 homologs in soybean, all of which are mainly expressed in the shoot apex. Here, we used CRISPR-Cas9 technology to generate a homozygous quadruple mutant, gmap1, with loss-of-function mutations in all four GmAP1 genes. Under short-day (SD) conditions, the gmap1 quadruple mutant exhibited delayed flowering, changes in flower morphology, and increased node number and internode length, resulting in plants that were taller than the wild type. Conversely, overexpression of GmAP1a resulted in early flowering and reduced plant height compared to the wild type under SD conditions. The gmap1 mutant and the overexpression lines also exhibited altered expression of several genes related to flowering and GA metabolism, thereby providing insight into the role of GmAP1 in the regulatory networks controlling flowering time and plant height in soybean. Increased node number is the trait with the most promise for enhancing soybean pod number and grain yield. Therefore, the mutant alleles of the four AP1 homologs described here will be invaluable for molecular breeding of improved soybean yield. This article is protected by copyright. All rights reserved.
Liyu Chen, Haiyang Nan, Lingping Kong, Lin Yue, Hui Yang, Qingsong Zhao, Chao Fang, Haiyang Li, Qun Cheng, Sijia Lu, Fanjiang Kong, Baohui Liu, Lidong Dong

1847 related Products with: Soybean AP1 homologs control flowering time and plant height.

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#32618845   2020/06/28 To Up

Recent developments in head and neck melanoma.

To provide an overview of recently published articles covering melanoma management of the head and neck region.
Neal Deot, Amar Suryadevara

2097 related Products with: Recent developments in head and neck melanoma.



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#32618346   2020/07/03 To Up

Vascular Endothelial Growth Factor Receptor-3 Expression Predicts Sentinel Node Status in Primary Cutaneous Melanoma.

This study analysed the expression of vascular endothelial growth factor-A (VEGF), VEGFR-2, and VEGFR-3 in primary cutaneous melanomas with positive and negative sentinel node status (SLN) (a total of 58 specimens divided into 2 groups of 29 for each status). A quantification score was developed for protein expression, by considering the percentage of SLN+ tumour cells (0: 0%, 1: up to 1%, 2: 2-10%, 3: 11-50%, and 4: > 50%) in relation to the intensity of staining (0: negative, 1: low, 2: medium, 3: strong). Tumoural VEGFR-3 expression (mean ± standard deviation) in SLN+ tumours (9.62 ± 3.09) was significantly stronger than in SLN- tumours (6.13 ± 3.87; p < 0.001). A binary logistic regression model proved VEGFR-3 expression and tumour thickness to be significant independent predictors of SLN. These data provide evidence that VEGFR-3 expression may play a critical role in the pathogenesis of malignant melanoma and that its investigation may help to improve the selection of patients with primary cutaneous melanoma for sentinel node biopsy.
Ferdinand Toberer, Holger A Haenssle, Martin Laimer, Monika Heinzel-Gutenbrunner, Alexander Enk, Wolfgang Hartschuh, Peter Helmbold, Heinz Kutzner

1066 related Products with: Vascular Endothelial Growth Factor Receptor-3 Expression Predicts Sentinel Node Status in Primary Cutaneous Melanoma.

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#32618195   2020/07/03 To Up

Liquid chromatography mass spectrometry-based nontargeted metabolomics predicts prognosis of hepatocellular carcinoma after curative resection.

Assessment and prediction of prognostic risk in patients with hepatocellular carcinoma (HCC) would greatly benefit the optimal treatment selection. Here, we aimed to identify the critical metabolites associated with the outcomes and develop a risk score to assess the prognosis of HCC patients after curative resection. A total of 78 serum samples of HCC patients were analyzed by liquid chromatography-mass spectrometry (LC-MS) to characterize the metabolic profiling. A novel network-based feature selection method (NFSM) was developed to define the critical metabolites with the most discriminant capacity to outcomes. The metabolites defined by NFSM was further reduced by Cox regression analysis to generate a prognostic metabolite panel-phenylalanine and choline. Furthermore, univariate and multivariate Cox regression analyses were applied to combine the metabolite panel with the presence of satellite nodes to generate a global prognostic index (GPI) score for overall survival assessment. Compared with the current clinical classification systems including Barcelona-Clinic Liver Cancer (BCLC) stage, Tumor-Node-Metastasis (TNM) stage and Albumin-Bilirubin (ALBI) grade, the GPI score presented comparable performance according to the time-dependent receiver operating characteristics curves and was validated in an independent cohort, which suggested metabolomics could serve as a helpful tool to stratify the HCC prognostic risk after operation.
Qingqing Wang, Benzhe Su, Liwei Dong, Tianyi Jiang, Yexiong Tan, Xin Lu, Xinyu Liu, Xiaohui Lin, Guowang Xu

1080 related Products with: Liquid chromatography mass spectrometry-based nontargeted metabolomics predicts prognosis of hepatocellular carcinoma after curative resection.



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