scholarly journals Aeromonas sobria Induced Sepsis Complicated with Necrotizing Fasciitis in a Child with Acute Lymphoblastic Leukemia

Reports ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 9
Author(s):  
Manuela Colosimo ◽  
Maria Concetta Galati ◽  
Umberto Riccelli ◽  
Simona Paola Tiburzi ◽  
Eulalia Galea ◽  
...  

Aeromonas species are gram negative and able to induce systemic diseases (i.e., gastrointestinal, respiratory, and cardiovascular, diseases, in addition to infection of brain and soft tissues). In this study, we describe the development of necrotizing fasciitis in a young immunocompromised girl, with a low response to drug treatment and who died after some months.

2015 ◽  
Vol 21 (4) ◽  
pp. 178-181
Author(s):  
Vincas Urbonas ◽  
Audronė Eidukaitė

Background. Currently available biomarkers are not specific and sensitive enough for early detection of bacterial infection in patients with cancer who have febrile neutropenia. The objective of this study was to assess diagnostic accuracy of interleukin-6 (IL-6), interleukin-8 (IL-8) and procalcitonin (PCT) in the identification of Gram-negative bacteremia at the beginning of a febrile episode in pediatric oncology patients with acute lymphoblastic leukemia (ALL). Methods. A total of 40 episodes of febrile neutropenia in 27 childhood cancer patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to the recommendations of manufacturers. Patients were classified into Gram-negative bacteremia (GNB) and fever of unknown origin (FUO) groups. Results. The median concentration of IL-6, IL-8 and PCT were higher in the GNB group compared to the FUO group (65.4  vs.  409.0  pg/ml, P  =  0.0025; 166.0  vs.  883.0  pg/ml, P  =  0.0002; 0.27  vs.  0.44  ng/ml, P = 0.0169, respectively). The areas under the curves (AUCs) for both IL-6 and IL-8 were 0.94 and 0.93, respectively, indicating that these cytokines discriminated patients with Gram-negative bacteremia with excellent accuracy, whereas PCT had lower diagnostic accuracy (AUC = 0.76). Conclusions. IL-6 and IL-8 evaluation might be used as an additional diagnostic tool for the prediction of Gram-negative bacteremia in pediatric patients with ALL during febrile neutropenia episodes.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2047-2047
Author(s):  
Somayeh Samadzadeh Tarighat ◽  
Fei Fei ◽  
Khuchtumur Bum-Erdene ◽  
Helen Blanchard ◽  
John Groffen ◽  
...  

Abstract Pre-B acute lymphoblastic leukemia (ALL) is one of the leading causes of cancer-related death, largely due to the high risk of relapse. Relapse often originates in the bone marrow microenvironment where stroma protects ALL cells against drug treatment. Galectin-3 (Gal3) is a carbohydrate-binding protein which recognizes cell surface receptors by binding LacNAc branches of N-glycans. We recently found that the stromal cells of the tumor microenvironment are the main source of Gal3 in ALL cells. In co-culture of ALL cells with supportive stroma (OP9), stroma-secreted Gal3 is actively internalized by ALL cells. Expression of Gal3 in ALL cells leads to significant protection of these cells against drug-induced apoptosis. The application and therapeutic benefits of targeting Gal3 and the lectin-mediated communication between the tumor microenvironment and leukemic cells in ALL treatment have not been explored. Here, we tested the hypothesis that Gal3 conveys important signals between the tumor microenvironment and ALL cells and that it represents a viable therapeutic target. We tested the preclinical activities of a first in class Gal3 inhibitor "KB1019.7" by studying its antileukemic effects on ALL cells in vitro. KB1019.7 is a novel carbohydrate-based compound with a micro Molar binding affinity for Gal3 as well as significant selectivity for Gal3 over Gal1. KB1019.7 acts by interfering with carbohydrate recognition activities of Gal3. Treatment of different ALL cells with KB1019.7 resulted in a dose-dependent reduction in cell viability. ALL cells which were cultured on a protective stroma (OP9) layer were plated alone or together with OP9 cells prior to drug treatment. The IC50 values (concentration of the inhibitor at which 50% cell death occurred) did not vary significantly among different ALL subgroups and were within mid micromolar range (average ~470 μM). The high tolerance of the cells to KB1019.7 may be explained by the fact that this compound is an optimized monovalent carbohydrate and not a classic Galectin inhibitor which are usually in the form of peptide or carbohydrate ligands. Gal3 is involved in several cellular activities including cell growth, cell differentiation and apoptosis. We evaluated the effects of KB1019.7 on modulating the biological functions of Gal3 in US7 (Ph-negative) and TXL2 (Ph-positive) B-cell leukemic cells. To this end, analysis of ALL cells exposed to 250 and 500 μM of KB1019.7 revealed a dose-dependent increase in the number of cells with 4N DNA content after 48 hours, suggesting that Gal3 inhibition may lead to accumulation of ALL cells in G2/M phase. More importantly, KB1019.7 had adverse effect on the acquired resistance to Vincristine in ALL cells. We treated US7 cells with vehicle control, KB1019.7 (500 μM), Vincristine (2.5 nM) or a combination of KB1019.7 and Vincristine in the presence of protective stroma (OP9) cells. Vincristine was chosen as the model for standard cytotoxic therapy in pre-B ALL. US7 cells developed resistance to Vincristine after continued exposure (~12 days) as evident by recovery and increase in cell viability observed after a time-dependent decline in cell number. Interestingly, introduction of KB1019.7 in combination with Vincristine effectively inhibited resistance to Vincristine and led to efficient cell death. Furthermore, KB1019.7 treatment promoted a significant downregulation in pERK1/2 protein levels which is often upregulated upon emergence of environmentally mediated drug resistance in ALL cells. Together our data demonstrate a role for Gal3 inhibition with KB1019.7 in inducing antileukemic responses in ALL cells including induction of cell death and cell cycle arrest. Furthermore, our results highlight the value of combining Gal3 inhibition with conventional chemotherapy as a tool to efficiently circumvent resistance to such therapies. Gal3 pro-tumor activities are documented in other hematologic malignancies and further studies to initiate and expand Gal3-targeted therapies in leukemia are highly warranted. Disclosures No relevant conflicts of interest to declare.


2001 ◽  
Vol 36 (6) ◽  
pp. 948-950 ◽  
Author(s):  
Tang-Her Jaing ◽  
Chen-Sheng Huang ◽  
Cheng-Hsun Chiu ◽  
Yhu-Chering Huang ◽  
Man-Shan Kong ◽  
...  

2020 ◽  
Author(s):  
Christopher R. M. Asquith ◽  
Louisa Temme ◽  
Tuomo Laitinen ◽  
Julie Pickett ◽  
Frank E. Kwarcinski ◽  
...  

AbstractThe development of a small library of 4-anilinoquinolines led to the identification of 7-iodo-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine 16 as a potent inhibitor of Protein Kinase Novel 3 (PKN3) with an IC50 of 1.3 μM in cells. Compound 16 presents a useful potential tool compound to study the biology of PKN3 including links to pancreatic and prostate cancer, along with T-cell acute lymphoblastic leukemia. These compounds may be useful tools to explore the therapeutic potential of PKN3 inhibition in prevention of a broad range of infectious and systemic diseases.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0258140
Author(s):  
Annie Luong ◽  
Fabio Cerignoli ◽  
Yama Abassi ◽  
Nora Heisterkamp ◽  
Hisham Abdel-Azim

The bone marrow is a frequent location of primary relapse after conventional cytotoxic drug treatment of human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Because stromal cells have a major role in promoting chemotherapy resistance, they should be included to more realistically model in vitro drug treatment. Here we validated a novel application of the xCELLigence system as a continuous co-culture to assess long-term effects of drug treatment on BCP-ALL cells. We found that bone marrow OP9 stromal cells adhere to the electrodes but are progressively displaced by dividing patient-derived BCP-ALL cells, resulting in reduction of impedance over time. Death of BCP-ALL cells due to drug treatment results in re-adherence of the stromal cells to the electrodes, increasing impedance. Importantly, vincristine inhibited proliferation of sensitive BCP-ALL cells in a dose-dependent manner, correlating with increased impedance. This system was able to discriminate sensitivity of two relapsed Philadelphia chromosome (Ph) positive ALLs to four different targeted kinase inhibitors. Moreover, differences in sensitivity of two CRLF2-drivenBCP-ALL cell lines to ruxolitinib were also seen. These results show that impedance can be used as a novel approach to monitor drug treatment and sensitivity of primary BCP-ALL cells in the presence of protective microenvironmental cells.


2012 ◽  
Vol 4 (1) ◽  
pp. 4 ◽  
Author(s):  
Paola Muggeo ◽  
Giampaolo Arcamone ◽  
Antonino Rizzo ◽  
Nicola Santoro

We report an uncommon ssevere soft-tissue infection of the thighs in a male child with acute lymphoblastic leukemia. Early and aggressive medical treatment and the conservative surgical approach were successful. Necrotizing fasciitis should be suspected in any soft-tissue infection until it can be definitely ruled out, since prompt deliver of medical and surgical intervention is essential.


2019 ◽  
Vol 36 (3) ◽  
pp. 265-269 ◽  
Author(s):  
Ayşe Gül Şahin ◽  
Ahmet Turan San ◽  
Selahattin Gürçay ◽  
Serhat Murat Alkan

Motil Aeromonas species are responsible for the formation of significant hemorrhagic septicemia in freshwater fish. Aeromonas are characteristic freshwater bacteria. They are often found in the ecosystem due to their being mobile. It is pathogenic in water, in various water creatures and in humans. In this study, it was determined that the bacterial strains obtained from Green terror (Andinoacara rivulatus) were Gram-negative, rod-shaped. VITEK-2 compact system is used for identification. Species have been identified as Aeromonas sobria. Aeromonas isolates were evaluated by 12 different antimicrobial agents in antimicrobial activity against the disk diffusion method. While cefquinome was found to be the most effective in the tested antimicrobials, the lowest sensitivity was determined against trimethoprim / sulphamethoxazole.


1992 ◽  
Vol 27 (5) ◽  
pp. 668-671 ◽  
Author(s):  
Brian W. Duncan ◽  
N.Scott Adzick ◽  
Alfred A. deLorimier ◽  
Michael T. Longaker ◽  
Linda D. Ferrell ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5366
Author(s):  
Paola Fernanda Ruiz-Aparicio ◽  
Gloria Inés Uribe ◽  
Adriana Linares-Ballesteros ◽  
Jean-Paul Vernot

Cell adhesion to stromal support and the associated intracellular signaling are central to drug resistance, therefore blocking both has been effective in increasing drug sensitization in leukemia. The stromal Ser/Thr protein kinase C (PKC) has been found to be important for conferring protection to leukemic cells. We aimed at elucidating the intracellular signals connected to cell adhesion and to stromal PKC. We found that NF-κB and Akt were up-regulated in mesenchymal stem cells (MSC) after binding of B-cell acute lymphoblastic leukemia (B-ALL) cells. Nevertheless, Akt inhibition did not induce B-ALL cell detachment. In spite of a clear activation of the NF-κB signaling pathway after B-ALL cell binding (up-regulation NF-κB1/2, and down-regulation of the IKBε and IKBα inhibitors) and an important reduction in cell adhesion after NF-κB inhibition, sensitization to the drug treatment was not observed. This was opposite to the PKC inhibitors Enzastaurin and HKPS, a novel chimeric peptide inhibitor, that were able to increase sensitization to dexamethasone, methotrexate, and vincristine. PLCγ1, Erk1/2, and CREB appear to be related to PKC signaling and PKC effect on drug sensitization since they were contra-regulated by HKPS when compared to dexamethasone-treated cells. Additionally, PKC inhibition by HKPS, but not by Enzastaurin, in MSC reduced the activity of three ABC transporters in leukemic cells treated with dexamethasone, a new indirect mechanism to increase sensitization to drug treatment in B-ALL cells. Our results show the validity of targeting the functional characteristic acquired and modulated during cell-to-cell interactions occurring in the leukemic niche.


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