Surrogate role of kinetic of perioperative circulating cancer cells (CTCs) in patients with liver metastases (M) of colorectal cancer (CRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21086-e21086
Author(s):  
Lucia Teijeira ◽  
Antonio Viudez ◽  
Maria L Antelo ◽  
Antonio Tarifa ◽  
Cruz Zazpe ◽  
...  
Keyword(s):  
Pathological Response ◽  
The Other ◽  
Kinetic Behavior ◽  
Wild Type ◽  
Cellsearch System ◽  
Future Studies ◽  
Circulating Cancer Cells ◽  
Kras Status

e21086 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before/just performed and 3 months after radical liver surgery (LS) in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. Methods: 7.5 ml of blood were drawn in CellSave tubes. CTCs were isolated and enumerated before/just perfomed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex®/Immunicon Corp.) Results: From February 2009 to December 2011, 35 pts were included. Median age was 61 (45-77); 53.7 % men. Kras status: 66.7% wild-type and 33.3% mutated; 48.6% with synchronous disease. Fong-Criteria (FC) distribution: 31.4% pts with 1 FC, 37.1% pts with 2 FC and 31.4% pts with 3 FC, of whom 60% received neoadjuvant (90% fluoropirimidines-based; 33.3% cetuximab-based; 38% bevacizumab-based) and 77.1% adjuvant treatment. PR and SD were observed in 60% and 40% of pts, respectively. In 70.7% of cases, limited LS were done (68.3% R0, median metastases resected:3) Of the 17 pts analysed, pCR were observed in 2 (12%) with 7 other pts (41%) with major pathological response. With a median of follow-up of 20 months (media 21.3; 95% CI:17.3-41.4) progression disease occurred in 13 pts (55.6% with liver progression), and 5 pts died. Median CTCs was 1 before (0-2: 76%; ≥3: 24%) and just performed surgery (0-2: 65%; ³3: 35%) and 0 in the 3 months determination (0-2: 94.1%; ³3: 5.9%). In the presurgery analysis, DFS was 15 months for the CTCs ≥3 group and 33 months for <3 CTCs (HR: 0.95; 95% CI:0.34-2.64) while in the postsurgery analysis, DFS was 13 months in CTCs ≥3 group and 33 months for <3 CTCs (HR: 1.11; 95% CI:0.37-3.29) CTCs ≥3 group after surgery, OS was 33 months, not having reached in the other groups. Conclusions: There is a marked difference in DFS in favor of pts with CTCs levels 0-2 before and just performed surgery. Our study shows a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.

Role of presurgery circulating cancer cells (CTCs) as a potential pronostic factor in patients (pts) with liver surgery (LS) of colorectal cancer (CRC) metastases (M).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 518-518
Author(s):  
Lucia Teijeira ◽  
Antonio Viúdez ◽  
Maria L. Antelo ◽  
Antonio Tarifa ◽  
Cruz Zazpe ◽  
...  
Keyword(s):  
Independent Predictor ◽  
Primary Tumour ◽  
Neoadjuvant Treatment ◽  
Wild Type ◽  
Cellsearch System ◽  
Future Studies ◽  
Circulating Cancer Cells ◽  
Kras Status

518 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before, just performed and 3 months after radical LS in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. Methods: 7.5 ml of blood were drawn in CellSave tubes. CTCs were enumerated before, just performed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex/Immunicon Corp.) Results: From February 2009 to August 2011, 30 pts with LS of CRC M were included. Median age was 59 (45-75); 63.3 % men. Kras status: 63.2% wild-type and 36.8% mutated; 46.7% with synchronous disease. Fong-Criteria (FC) distribution: 30% pts with 1 FC, 36.7% pts with 2 FC and 33.3% pts with 3 FC, of whom 56.7% received neoadjuvant (76.4% fluoropirimidines-based; 29% cetuximab-based; 47% bevacizumab-based) and 73.3% adjuvant treatment. PR and SD were observed in 68.8% and 31.3% of pts, respectively (100% DCR). In 83% of cases, limited LS were done (79.3% R0, median M resected: 2), 20% of pts with synchronous surgery of primary tumour. Of the 15 pts analysed, pCR were observed in 2 (13.3%) with 6 other pts (40%) with major pathological response. With a median of follow-up of 21 months, progression disease occurred in 9 pts (55.6% with liver progression), and 4 pts died. Median CTCs was 0 before (0-2: 85%; ≥3: 14.8%), just performed (0-2: 78%; ≥3: 21%) and 3 months after surgery (0-2: 94.1%; ≥3: 5.9%). DFS for pts with pre-surgery CTCs ≥3 was 10 months, and not reached for 0-2 CTCs group. OS has not been achieved in any CTCs group. In the multivariate analysis, with FC and pre-surgery CTCs, pre-surgery CTCs ≥3 tends to be an independent predictor of outcome (HR: 2.83; CI:0.53-15). Conclusions: Independently of neoadjuvant treatment, pre-surgery CTCs levels ≥3 could be a surrogate of short DFS in pts with LS of CRC M. Our study shown a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.

scholarly journals Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis

2006 ◽  
Vol 203 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Tetsuya Honda ◽  
Eri Segi-Nishida ◽  
Yoshiki Miyachi ◽  
Shuh Narumiya
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
The Other ◽  
Receptor Subtype ◽  
Significant Suppression ◽  
Wild Type ◽  
Collagen Induced Arthritis

Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP−/−) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP−/− mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.

scholarly journals Cystic renal diseases: role of ultrasound. Part II, genetic cystic renal diseases

2020 ◽  
Author(s):  
Adnan Kabaalioglu ◽  
Nesrin Gunduz ◽  
Ayse Keven ◽  
Emel Durmaz ◽  
Mine Aslan ◽  
...  
Keyword(s):  
Renal Cysts ◽  
The Other ◽  
Renal Diseases ◽  
Intravenous Contrast ◽  
Pictorial Essay ◽  
The Subject ◽  
Key Features

Kidney cysts are quite common in adults. Though small simple renal cysts in an adult over 30-40 years of age are not too unusual, however, if the same cysts are seen in a child, and especially if there are additional findings, then several diagnostic possibilities may come to mind. The role of ultrasound, together with the help of intravenous contrast agents and Doppler mode, are very critical in describing the morphologic features and follow-up of the complex or multiple and bilateral renal cysts. These sonographic signs are occasionally specific for diagnosis, but in many cases sonographic clues should be evaluated together with the other genetic and clinical data to reach diagnosis.The first part of this pictorial essay included the introduction into the subject and the classification of non-genetic cystic renal diseases. The key features for the non-genetic cystic renal diseases are illustrated. In the second part, eye-catching features of genetic cystic renal diseases are demonstrated.

scholarly journals Glucomannan-Mediated Attachment of Rhizobium leguminosarum to Pea Root Hairs Is Required for Competitive Nodule Infection

2008 ◽  
Vol 190 (13) ◽  
pp. 4706-4715 ◽  
Author(s):  
Alan Williams ◽  
Adam Wilkinson ◽  
Martin Krehenbrink ◽  
Daniela M. Russo ◽  
Angeles Zorreguieta ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Rhizobium Leguminosarum ◽  
Root Hairs ◽  
The Other ◽  
Plant Interactions ◽  
Wild Type ◽  
Polysaccharide Synthesis ◽  
Surface Polysaccharides

ABSTRACT The Rhizobium leguminosarum biovar viciae genome contains several genes predicted to determine surface polysaccharides. Mutants predicted to affect the initial steps of polysaccharide synthesis were identified and characterized. In addition to the known cellulose (cel) and acidic exopolysaccharide (EPS) (pss) genes, we mutated three other loci; one of these loci (gmsA) determines glucomannan synthesis and one (gelA) determines a gel-forming polysaccharide, but the role of the other locus (an exoY-like gene) was not identified. Mutants were tested for attachment and biofilm formation in vitro and on root hairs; the mutant lacking the EPS was defective for both of these characteristics, but mutation of gelA or the exoY-like gene had no effect on either type of attachment. The cellulose (celA) mutant attached and formed normal biofilms in vitro, but it did not form a biofilm on root hairs, although attachment did occur. The cellulose-dependent biofilm on root hairs appears not to be critical for nodulation, because the celA mutant competed with the wild-type for nodule infection. The glucomannan (gmsA) mutant attached and formed normal biofilms in vitro, but it was defective for attachment and biofilm formation on root hairs. Although this mutant formed nodules on peas, it was very strongly outcompeted by the wild type in mixed inoculations, showing that glucomannan is critical for competitive nodulation. The polysaccharide synthesis genes around gmsA are highly conserved among other rhizobia and agrobacteria but are absent from closely related bacteria (such as Brucella spp.) that are not normally plant associated, suggesting that these genes may play a wide role in bacterium-plant interactions.

Life Events and Mania

1987 ◽  
Vol 150 (2) ◽  
pp. 235-240 ◽  
Author(s):  
A. Ambelas
Keyword(s):  
Life Events ◽  
Manic Episode ◽  
The Other ◽  
Manic Patients ◽  
Group Comparisons

Fifty patients in their first manic episode were compared retrospectively with groups of (a) manic patients in other than first admissions and (b) acute surgical cases. They were then followed up for 3–8 years. First manic admissions were linked to life events far more frequently – 66%vs20% and 8% respectively for the other groups. Within-group comparisons showed patients with life events were much younger. The link between life events and manic episodes appeared immediate and selective, a view further supported by the findings of the follow-up. Later episodes precipitated by life events seem to require smaller amounts of stress. The possible role of life events in relation to mania is discussed.

Exosomes as novel prognostic biomarker in potentially resectable colorectal cancer liver metastatic (CCLM) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3558-3558
Author(s):  
Ina Valeria Zurlo ◽  
Mariantonietta Di Salvatore ◽  
Donatella Lucchetti ◽  
Filomena Colella ◽  
Claudio Ricciardi Tenore ◽  
...  
Keyword(s):  
Liver Surgery ◽  
Scoring Systems ◽  
Aggressive Approach ◽  
Post Surgery ◽  
Mutational Status ◽  
Kras Status ◽  
The One ◽  
Major Hepatectomies

3558 Background: Target therapies and new surgical strategies deeply modify the history of CCLM patients (pts). Several prognostic scoring systems have been developed but no one is able to identify pts who should be excluded from a potentially useless surgery. Currently research is committed in identifying early biomarkers able to discern pts who could benefit from an aggressive approach. Exosomes are arising as promising biomarkers in cancer. The aim of this pivotal study was to analyze the association among exosome levels during CCLM-pts treatment, clinical outcomes and the KRAS status. Methods: We enrolled 22 pts with CCLM candidate to preoperative chemotherapy (pCT) and subsequent liver surgery. A blood sample was collected before pCT, after surgery, monthly during follow-up and at progression (PD). Exosomes were isolated by ultracentrifugation and characterized by standard methods. Exosomes concentration was assessed by Bradford assay. We adopted ddPCR™ KRAS G12/G13 Screening Kit to evaluate the KRAS status in exosomal DNA (e-DNA). Results: 22 CCLM pts received pCT and underwent liver surgery: 5 major hepatectomies and 17 multiple liver resections. Changes in exosomes plasma levels were found to correlate with each treatment step,resulting reduced after pCT and surgery and increased at PD, respectively (p = 0.0026). Pts with higher baseline exosome levels experimented shorter PFS than those with lower levels (p = 0.0033 HR 0.2). No association was found between exosome levels after liver surgery and disease free interval nor overall survival. KRAS status on e-DNA was evaluated on 10 pts in baseline, in pCT, after surgery, and in PD samples. In 8 out of 10 pts e-DNA displayed the same mutational status than the one detected on tumor DNA. Changes in e-DNA KRAS copies were found statistically significant in pCT vs surgery and pCT vs PD (p = 0.039; p = 0.04). Conclusions: Our study suggests a prognostic role of exosome levels in CCLM pts. Moreover, we showed that KRAS mutational status could be monitored during the post-surgery follow up by analyzing e-DNA. Overall, our data confirm the potential role of exosomes in liquid biopsy tool to monitor molecular changes during the treatment of CCLM pts.

Abstract 16603: Appropriate Timing of Pacemaker Implantation in Patients With Wild-Type and Variant Amyloidogenic Transthyretin Cardiac Amyloidosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yusei Kawahara ◽  
Miwa Ito ◽  
Tadashi Hoshiyama ◽  
Hisanori Kanazawa ◽  
Kenichi Tsujita
Keyword(s):  
Cardiac Amyloidosis ◽  
Pacemaker Implantation ◽  
The Other ◽  
Cardiac Conduction ◽  
Wild Type ◽  
Conduction Disorders ◽  
Other Hand ◽  
Conduction Disorder ◽  
Second Degree

Background and Objectives: It has been shown that cardiac conduction disorders can be seen in patients with wild-type amyloidogenic transthyretin (ATTRwt) and variant ATTR (ATTRv) cardiac amyloidosis. However, its appropriate timing of pacemaker implantation has not been clarified yet. Methods and Results: The consecutive 100 patients with ATTRwt cardiac amyloidosis who diagnosed by myocardium biopsy and/or technetium-99m-pyrophosphate scintigraphy and 62 patients with ATTRv cardiac amyloidosis who diagnosed by means of genetic screening were included in this study. In patients with ATTRwt cardiac amyloidosis, 21 patients have normal conduction at the time of diagnosis. However, conduction disorder had seen in only 5 patient (first degree atrioventricular block (AVB); 4 patients, complete AVB; 1 patients) and only one patient underwent cardiac implantable electric device (CIED) implantation during follow-up period. On the other hand, in patients with ATTRv cardiac amyloidosis, 36 patients have normal conduction at the time of diagnosis. However, conduction disorder had seen in 13 patient (first degree AVB; 8 patients, second degree AVB; 3 patients, trifascicular block; 1 patients, complete AVB; 1 patients) (5/21 vs 13/36, p=0.335) and 6 patients underwent CIED implantation during follow-up period (1/21 vs 6/36, p=0.186). Furthermore, in ATTRwt cardiac amyloidosis, 10 patients (first degree AVB; 2 patients, second degree AVB; 1 patient, trifascicular block; 7 patients) had underwent CIED implantation because of cardiac conduction disorders and/or prevention of sudden cardiac death. However, only 4 patients with trifascicular block progressed to complete AVB.On the other hand, In ATTRv cardiac amyloidosis, 14 patients (first degree AVB; 2 patients, second degree AVB; 4 patient, trifascicular block; 8 patients) had underwent CIED implantation for same reason. However, only 3 patients with trifascicular block progressed to complete AVB. Conclusions: Patients with ATTRv cardiac amyloidosis were more likely to progress conduction disorders than those with ATTRwt cardiac amyloidosis. However, prophylactic pacemaker implantation might had not need in both ATTRwt and ATTRv patients with first or second degree AVB.

scholarly journals Construction and Characterization of a Derivative of Neisseria gonorrhoeae Strain MS11 Devoid of AllopaGenes

2012 ◽  
Vol 194 (23) ◽  
pp. 6468-6478 ◽  
Author(s):  
Adriana LeVan ◽  
Lindsey I. Zimmerman ◽  
Amanda C. Mahle ◽  
Karen V. Swanson ◽  
Philip DeShong ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
The Other ◽  
Flow Cytometry Analysis ◽  
Wild Type ◽  
Homogeneous Population ◽  
Host Cell Interactions ◽  
Strain Ms11 ◽  
Adherence Ability

ABSTRACTTo better understand the role of Opa in gonococcal infections, we created and characterized a derivative of MS11 (MS11Δopa) that had the coding sequence for all 11 Opa proteins deleted. The MS11Δopa bacterium lost the ability to bind to purified lipooligosaccharide (LOS). While nonpiliated MS11Δopa and nonpiliated Opa-expressing MS11 cells grew at the same rate, nonpiliated MS11Δopa cells rarely formed clumps of more than four bacteria when grown in broth with vigorous shaking. Using flow cytometry analysis, we demonstrated that MS11Δopa produced a homogeneous population of bacteria that failed to bind monoclonal antibody (MAb) 4B12, a MAb specific for Opa. Opa-expressing MS11 cells consisted of two predominant populations, where ∼85% bound MAb 4B12 to a significant level and the other population bound little if any MAb. Approximately 90% of bacteria isolated from a phenotypically Opa-negative colony (a colony that does not refract light) failed to bind MAb 4B12; the remaining 10% bound MAb to various degrees. Piliated MS11Δopa cells formed dispersed microcolonies on ME180 cells which were visually distinct from those of piliated Opa-expressing MS11 cells. When Opa expression was reintroduced into MS11Δopa, the adherence ability of the strain recovered to wild-type levels. These data indicate that Opa contributes to both bacterium-bacterium and bacterium-host cell interactions.

scholarly journals Central Nervous System–Targeted Complement Inhibition Mediates Neuroprotection after Closed Head Injury in Transgenic Mice

2003 ◽  
Vol 23 (9) ◽  
pp. 1070-1074 ◽  
Author(s):  
Mario Rancan ◽  
Maria C. Morganti-Kossmann ◽  
Scott R. Barnum ◽  
Silvia Saft ◽  
Oliver I. Schmidt ◽  
...  
Keyword(s):  
Head Injury ◽  
Transgenic Mice ◽  
Closed Head Injury ◽  
Wild Type ◽  
Complement Inhibition ◽  
Future Studies ◽  
Closed Head ◽  
Targeted Expression ◽  
The Complement System

The role of intracerebral complement activation after traumatic brain injury remains unclear. In this study, the authors demonstrate that transgenic mice with astrocyte-targeted expression of the soluble complement inhibitor sCrry have a significantly reduced neurologic impairment and improved blood–brain barrier function after closed head injury compared with wild-type C57BL/6 littermates. This work further implicates the complement system as a participant in secondary progression of brain damage after head trauma and provides a strong rationale for future studies of posttraumatic pharmacologic complement inhibition.

scholarly journals SarA Is a Repressor of hla (α-Hemolysin) Transcription in Staphylococcus aureus: Its Apparent Role as an Activator of hla in the Prototype Strain NCTC 8325 Depends on Reduced Expression of sarS

2006 ◽  
Vol 188 (24) ◽  
pp. 8526-8533 ◽  
Author(s):  
Jan Oscarsson ◽  
Anna Kanth ◽  
Karin Tegmark-Wisell ◽  
Staffan Arvidson
Keyword(s):  
Staphylococcus Aureus ◽  
Northern Blot Analysis ◽  
Prototype Strain ◽  
Relative Increase ◽  
The Other ◽  
Wild Type ◽  
Triple Mutant ◽  
Strain Nctc ◽  
Repressor Activity

ABSTRACT In most Staphylococcus aureus strains, inactivation of sarA increases hla transcription, indicating that sarA is a repressor. However, in S. aureus NCTC 8325 and its derivatives, used for most studies of hla regulation, inactivation of sarA resulted in decreased hla transcription. The disparate phenotype of strain NCTC 8325 seems to be associated with its rsbU mutation, which leads to σB deficiency. This has now been verified by the demonstration that sarA repressed hla transcription in an rsbU + derivative of strain 8325-4 (SH1000). That sarA could act as a repressor of hla in an 8325-4 background was confirmed by the observation that inactivation of sarA in an agr sarS rot triple mutant dramatically increased hla transcription to wild-type levels. However, the apparent role of sarA as an activator of hla in 8325-4 was not a result of the rsbU mutation alone, as inactivation of sarA in another rsbU mutant, strain V8, led to increased hla transcription. Northern blot analysis revealed much higher levels of sarS mRNA in strain V8 than in 8325-4, which was likely due to the mutation in the sarS activator, tcaR, in 8325-4, which was not found in strain V8. On the other hand, the relative increase in sarS transcription upon the inactivation of sarA was 15-fold higher in 8325-4 than in strain V8. Because of this, inactivation of sarA in 8325-4 means a net increase in repressor activity, whereas in strain V8, inactivation of sarA means a net decrease in repressor activity and, therefore, enhanced hla transcription.

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