scholarly journals Quantitative Proteomics of Potato Leaves Infected with Phytophthora infestans Provides Insights into Coordinated and Altered Protein Expression during Early and Late Disease Stages

2019 ◽  
Vol 20 (1) ◽  
pp. 136 ◽  
Author(s):  
Chunfang Xiao ◽  
Jianhua Gao ◽  
Yuanxue Zhang ◽  
Zhen Wang ◽  
Denghong Zhang ◽  
...  
Keyword(s):  
Phytophthora Infestans ◽  
Protein Modification ◽  
Foliar Application ◽  
Early Stage ◽  
Expression Patterns ◽  
Cellular Protein ◽  
Disease Stage ◽  
Post Inoculation ◽  
Disease Stages ◽  
Sarpo Mira

In order to get a better understanding of protein association during Solanum tuberosum (cv. Sarpo Mira)–Phytophthora infestans incompatible interaction, we investigated the proteome dynamics of cv. Sarpo Mira, after foliar application of zoospore suspension from P. infestans isolate, at three key time-points: zero hours post inoculation (hpi) (Control), 48 hpi (EI), and 120 hpi (LI); divided into early and late disease stages by the tandem mass tagging (TMT) method. A total of 1229 differentially-expressed proteins (DEPs) were identified in cv. Sarpo Mira in a pairwise comparison of the two disease stages, including commonly shared DEPs, specific DEPs in early and late disease stages, respectively. Over 80% of the changes in protein abundance were up-regulated in the early stages of infection, whereas more DEPs (61%) were down-regulated in the later disease stage. Expression patterns, functional category, and enrichment tests highlighted significant coordination and enrichment of cell wall-associated defense response proteins during the early stage of infection. The late stage was characterized by a cellular protein modification process, membrane protein complex formation, and cell death induction. These results, together with phenotypic observations, provide further insight into the molecular mechanism of P. infestans resistance in potatos.

scholarly journals A Cysteine Protease Gene Is Expressed Early in Resistant Potato Interactions with Phytophthora infestans

1999 ◽  
Vol 12 (12) ◽  
pp. 1114-1119 ◽  
Author(s):  
Anna O. Avrova ◽  
Helen E. Stewart ◽  
Walter De Jong ◽  
Jacqueline Heilbronn ◽  
Gary D. Lyon ◽  
...  
Keyword(s):  
Phytophthora Infestans ◽  
Cysteine Protease ◽  
Early Stage ◽  
Cathepsin K ◽  
Field Resistance ◽  
Amino Acid Sequences ◽  
Ribonuclease Protection Assay ◽  
Post Inoculation ◽  
Protease Gene ◽  
Ribonuclease Protection

A potato cysteine protease (cyp) cDNA expressed at an early stage of an incompatible interaction with Phytophthora infestans was isolated. Both the nucleotide and deduced amino acid sequences are highly homologous to those of a tomato cysteine protease, CYP1. Striking protein similarity to all known cathepsins in animals, particularly cathepsin K, was also observed. However, unlike cathepsins, a granulin binding domain is located near the carboxyl terminus of the putative CYP protein. In animals, granulins bind to receptors in the plasma membrane and signal cell growth and division. A ribonuclease protection assay demonstrated that the cyp gene is tightly regulated and is induced 15 h post inoculation with P. infestans in potato leaves either with high field resistance or in which a resistance (R) gene is activated. We conclude that a common signaling pathway is activated in each form of resistance.

Differential Expression of Metastasis-Associated Genes in Papilla of Vater and Pancreatic Cancer Correlates With Disease Stage

2001 ◽  
Vol 19 (9) ◽  
pp. 2422-2432 ◽  
Author(s):  
Helmut Friess ◽  
Xiao-Zhong Guo ◽  
Adrien A. Tempia-Caliera ◽  
Akira Fukuda ◽  
Marcus E. Martignoni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
In Situ Hybridization ◽  
Early Stage ◽  
Expression Patterns ◽  
Tumor Biology ◽  
Disease Stage ◽  
Papilla Of Vater ◽  
Advanced Tumor ◽  
Tumor Stages

PURPOSE: Papilla of Vater cancer has a much better prognosis than pancreatic cancer. It is not known whether this is the result of differences in the tumor biology of the two malignancies. Because metastasis formation is a critical step in tumor progression and a negative prognostic factor, we compared the expression of nm23-H1 and KAI1, two metastasis-suppressing genes, in papilla of Vater cancer and pancreatic cancer. PATIENTS AND METHODS: Analysis was performed in nine normal human papilla of Vater samples, 27 papilla of Vater cancers, 16 normal pancreatic samples, and 29 pancreatic cancers. Expression of nm23-H1 and KAI1 was analyzed by Northern blot analysis and in situ hybridization. In addition, immunohistochemistry was performed to localize the respective proteins. RESULTS: There was no difference in nm23-H1 and KAI1 mRNA expression levels in normal versus cancerous papilla of Vater samples. In contrast, nm23-H1 and KAI1 RNA expression was upregulated in early tumor stages of pancreatic cancer and reduced in advanced tumor stages. When expression of nm23-H1 and KAI1 RNA was analyzed by use of in situ hybridization, normal epithelial cells of the papilla of Vater exhibited mRNA staining intensity similar to that of papilla of Vater cancer cells. Similar levels of nm23-H1 and KAI1 immunoreactivity also were observed in these samples. In contrast, early stage pancreatic cancer samples exhibited stronger nm23-H1 and KAI1 immunoreactivity than normal controls. Furthermore, early pancreatic cancer stages exhibited higher KAI1 and nm23-H1 immunostaining than advanced tumor stages. CONCLUSION: Differences in the expression patterns of the two tumor suppressor genes nm23-H1 and KAI1 may contribute to the different prognoses of papilla of Vater cancer and pancreatic cancer. Our findings support the hypothesis that biologic differences rather than earlier diagnosis influence the different outcomes of these two tumor entities.

Evaluating if darbepoetin alfa efficacy and safety in patients with chemotherapy-induced anemia is affected by the disease stage of the patient

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18568-18568
Author(s):  
L. S. Schwartzberg ◽  
J. Glaspy ◽  
D. Tomita ◽  
T. Lillie
Keyword(s):  
Clinical Trials ◽  
Darbepoetin Alfa ◽  
Early Stage ◽  
Tnm Classification ◽  
The Other ◽  
Disease Stage ◽  
Evidence Based ◽  
Efficacy And Safety ◽  
Evidence Based Guidelines ◽  
Disease Stages

18568 Background: Cancer patients (pts) often develop chemotherapy-induced anemia (CIA), resulting in increased transfusion incidence and fatigue. Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent that can reduce the incidence of transfusions, increase hemoglobin (Hb) levels to a range of 11 to 13 g/dL (as recommended by evidence-based guidelines), and decrease fatigue in pts with CIA. The 74-hour half-life of DA allows it to be effectively administered weekly (QW), every 2 weeks (Q2W), or every 3 weeks (Q3W). DA treatment can also be synchronized with chemotherapy (Glaspy et al., 2005). Here we examined if the efficacy and safety of DA for treating CIA is affected by the disease stage of the pt. Methods: Eight clinical trials (including single-arm, active-controlled, and placebo-controlled studies) were analyzed that described the administration of DA QW (2 studies), Q2W (3 studies), or Q3W (3 studies) to pts with CIA. Tumor-Nodes-Metastases (TNM) classification was used to define disease stage of I, II, III, or IV. A clinically meaningful endpoint evaluated was the proportion of pts achieving a target Hb of ≥ 11 g/dL. Other endpoints included incidence of transfusions, change in FACT-F score at end of study from baseline, and incidence of adverse events. Results: A high percentage of pts in all disease stages achieved a target Hb of ≥ 11 g/dL in response to DA treatment (see Table ). Early stage pts were seen to benefit at least as much as later stage pts. A similar trend was seen for the other efficacy and safety endpoints (data will be presented). Conclusions: The present analysis suggests that DA administered QW, Q2W, or Q3W can effectively correct anemia when administered to pts in either early or late disease stages. The potential to synchronize DA treatment and chemotherapy regardless of disease stage may increase pt convenience by reducing the number of clinic visits. [Table: see text] [Table: see text]

scholarly journals Outcomes in patients with lacrimal gland carcinoma treated with definitive radiotherapy or eye-sparing surgery followed by adjuvant radiotherapy

2020 ◽  
Author(s):  
Yun-Hsuan Lin ◽  
ShihMing Huang ◽  
Wing-Keen Yap ◽  
Ju-Wen Yang ◽  
Ling Yeung ◽  
...  
Keyword(s):  
Lacrimal Gland ◽  
Distant Metastasis ◽  
Adjuvant Radiotherapy ◽  
Early Stage ◽  
Treatment Strategies ◽  
Disease Stage ◽  
Excision Biopsy ◽  
Free Survival ◽  
Gland Carcinoma ◽  
Disease Stages

Abstract Background The optimal treatment for lacrimal gland cancer remains unclear. Eye-preserving surgery, as opposed to exenteration, followed by adjuvant radiotherapy (RT), has recently been reported to deliver satisfying outcomes, but evidence is sparse. The aim of the present study was to evaluate outcomes in patients with lacrimal gland cancer treated at two tertiary medical centers.Methods We retrospectively examined data from patients with lacrimal gland cancer who had received eye-preserving surgical treatment followed by adjuvant RT with or without chemotherapy, or (if the tumor was inoperable) excision biopsy with definitive RT with or without chemotherapy. Baseline clinical and pathological characteristics were considered. Outcomes of interest included post-treatment complications, overall survival (OS), locoregional progression-free survival (LPFS), and distant metastasis-free survival (DMFS).Results Eighteen patients were included. Two-year OS, LPFS, and DMFS rates were 69.0%, 76.7%, and 71.4%, respectively. Patients with early-stage (T1–T2) lacrimal gland cancer had significantly better outcomes than those with advanced-stage disease (T3–T4). Two-year OS, LPFS, and DMFS rates were each 100% in patients with disease stages T1–T2, and 37.5%, 50%, and 37.5%, respectively, in those with disease stages T3–T4 (P<0.05). Orbital complications were well tolerated.Conclusions Eye-sparing surgery with adjuvant RT can achieve satisfying results in patients with T1–T2 lacrimal gland carcinoma. Disease stage T3 and above was associated with poor outcomes even with post-operative RT, likely due to distant metastasis. Adding neoadjuvant chemotherapy or adjuvant chemotherapy to current treatment strategies might be a suitable choice for this group of patients.

scholarly journals Prolonged detection of complete viral genomes demonstrated by SARS-CoV-2 sequencing of serial respiratory specimens

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255691
Author(s):  
Neta S. Zuckerman ◽  
Efrat Bucris ◽  
Oran Erster ◽  
Michal Mandelboim ◽  
Amos Adler ◽  
...  
Keyword(s):  
Early Stage ◽  
Disease Stage ◽  
N Gene ◽  
Viral Gene ◽  
Late Time ◽  
Positive Real ◽  
Gene Target ◽  
Viral Genomes ◽  
Next Generation Sequencing Ngs ◽  
Disease Stages

Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is clinically essential, and is required also to monitor confirmed cases aiming to prevent further spread. Positive real-time PCR results at late time points following initial diagnosis may be clinically misleading as this methodology cannot account for the infection capabilities and the existence of whole genome sequences. In this study, 47 serial respiratory samples were tested by Allplex-nCoV test (Seegene), a triplex of three assays targeting the SARS-CoV-2 RdRP, E and N genes and subsequently assessed by next generation sequencing (NGS). COVID19 patients were tested at an early stage of the disease, when all these viral gene targets were positive, and at an advanced stage, when only the N gene target was positive in the Allplex-nCoV test. The corresponding NGS results showed the presence of complete viral genome copies at both early and advanced stages of the disease, although the total number of mapped sequences was lower in samples from advanced disease stages. We conclude that reduced viral transmission at this late disease stage may result from the low quantities of complete viral sequences and not solely from transcription favoring the N gene.

scholarly journals Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thomas J. Wilkinson ◽  
Daniel G. D. Nixon ◽  
Jared Palmer ◽  
Courtney J. Lightfoot ◽  
Alice C. Smith
Keyword(s):  
Kidney Disease ◽  
Early Stage ◽  
Symptom Burden ◽  
Final Analysis ◽  
Physical Symptoms ◽  
Disease Trajectory ◽  
High Prevalence ◽  
Comparative Group ◽  
The Difference ◽  
Disease Stages

Abstract Background Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population. Methods Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom. Results In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was ‘feeling tired’; and 4) being female independently increased the likelihood of reporting more symptoms. Conclusions Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue. Trial registration The study was registered prospectively as ISRCTN11596292.

scholarly journals Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

2021 ◽  
Author(s):  
Fabiola De Marchi ◽  
◽  
Claudia Carrarini ◽  
Antonio De Martino ◽  
Luca Diamanti ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Time Course ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Multisystem Disorder ◽  
Behavioral Impairment ◽  
Behavioral Impairments ◽  
Als Patients ◽  
Disease Stages ◽  
Lateral Sclerosis

Abstract Background and aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. Conclusions To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8517-8517
Author(s):  
Davina Gale ◽  
Katrin Heider ◽  
Malcolm Perry ◽  
Giovanni Marsico ◽  
Andrea Ruiz-Valdepeñas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Sequencing ◽  
Early Stage ◽  
Post Treatment ◽  
Disease Stage ◽  
Analytical Sensitivity ◽  
Disease Relapse ◽  
Clinical Progression ◽  
Liquid Biopsies ◽  
Early Stage Disease

8517 Background: Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence. Conclusive evidence for utility of ctDNA in early-stage non-small cell lung cancer (NSCLC) is awaited. Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. Methods: We analysed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating tumour DNA (LUCID) study, with disease stage I (49%), II (28%) and III (23%). 62% were adenocarcinomas. Plasma was collected before and after treatment, and at 3, 6 and 9 months after surgery (N = 69) or chemoradiotherapy (N = 19). Additional plasma was collected at disease relapse for 17 patients. Median follow-up was 3 years, and 40 patients progressed or died of any cause. We employed the RaDaR™ assay, a highly sensitive personalized assay using deep sequencing of up to 48 tumor-specific variants. Variants identified by tumor exome analysis were tested by deep sequencing of tumor tissue and buffy coat DNA to verify somatic mutations and exclude clonal hematopoiesis. The RaDaR assay demonstrated 90% sensitivity at 0.001% MAF in analytical validation studies. Results: ctDNA was detected in 26% of samples, at median MAF of 0.047% (range: 0.0007% to > 2%), and prior to treatment in 87%, 77% and 24% for disease stage III, II and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse, with Hazard Ratio of 20.7 (CI: 7.7-55.5, p-value < 0.0001). All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all 8 patients that relapsed within 300 days of treatment. Across 27 patients whose disease progressed during the study, ctDNA was detected at any timepoint post-treatment in 17 cases, with a median lead time of 203 days, and up to 741 days prior to clinical progression. ctDNA was detected post-treatment, in 13 of the 15 patients that progressed and had ctDNA detected prior to treatment. Conclusions: Our results support an emerging paradigm shift, by demonstrating that liquid biopsies can reliably detect recurrence of NSCLC at a preclinical stage, many months before clinical progression, thereby offering the opportunity for earlier therapeutic intervention. Clinical trial information: NCT04153526.

Stem-like tumor cells and proinflammatory cytokines in the ascitic fluid of ovarian cancer patients

2021 ◽  
Vol 66 (5) ◽  
pp. 297-303
Author(s):  
S. O. Gening ◽  
T. V. Abakumova ◽  
I. I. Antoneeva ◽  
A. A. Rizvanov ◽  
T. P. Gening ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Blood Serum ◽  
Tumor Cells ◽  
Ascitic Fluid ◽  
Early Stage ◽  
Abdominal Cavity ◽  
Disease Stage ◽  
Cell Populations ◽  
Benign Ovarian Tumors ◽  
Number Of Cells

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination.

Development of extracellular vesicles-based classifier for detection of early-stage bladder, ovarian, and pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3048-3048
Author(s):  
Juan Pablo Hinestrosa ◽  
Razelle Kurzrock ◽  
Jean Lewis ◽  
Nick Schork ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Confidence Interval ◽  
Extracellular Vesicles ◽  
Metastatic Disease ◽  
Cancer Detection ◽  
Early Stage ◽  
Expression Patterns ◽  
Stepwise Logistic Regression ◽  
Liquid Biopsies ◽  
Cancer Early Detection

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.

Sign in / Sign up

Export Citation Format

Share Document