scholarly journals PFKFB3: A Potential Key to Ocular Angiogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zi-Yi Zhou ◽  
Lin Wang ◽  
Yu-Sheng Wang ◽  
Guo-Rui Dou
Keyword(s):  
Cell Metabolism ◽  
Current Treatment ◽  
Potential Treatment ◽  
Ocular Angiogenesis ◽  
Pathological Angiogenesis ◽  
Novel Treatment ◽  
Promising Target ◽  
Long Time ◽  
New Evidence ◽  
Endothelial Cell Metabolism

The current treatment for ocular pathological angiogenesis mainly focuses on anti-VEGF signals. This treatment has been confirmed as effective despite the unfavorable side effects and unsatisfactory efficiency. Recently, endothelial cell metabolism, especially glycolysis, has been attracting attention as a potential treatment by an increasing number of researchers. Emerging evidence has shown that regulation of endothelial glycolysis can influence vessel sprouting. This new evidence has raised the potential for novel treatment targets that have been overlooked for a long time. In this review, we discuss the process of endothelial glycolysis as a promising target and consider regulation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as treatment for ocular pathological angiogenesis.

scholarly journals Unique Genomic Landscape of High-Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms

2020 ◽  
pp. 972-987
Author(s):  
Ramez N. Eskander ◽  
Julia Elvin ◽  
Laurie Gay ◽  
Jeffrey S. Ross ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Current Treatment ◽  
High Grade ◽  
Novel Treatment ◽  
Sample Average ◽  
Genomic Landscape ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Sample Range ◽  
Novel Treatment Strategies

PURPOSE High-grade neuroendocrine cervical cancer (HGNECC) is an uncommon malignancy with limited therapeutic options; treatment is patterned after the histologically similar small-cell lung cancer (SCLC). To better understand HGNECC biology, we report its genomic landscape. PATIENTS AND METHODS Ninety-seven patients with HGNECC underwent comprehensive genomic profiling (182-315 genes). These results were subsequently compared with a cohort of 1,800 SCLCs. RESULTS The median age of patients with HGNECC was 40.5 years; 83 patients (85.6%) harbored high-risk human papillomavirus (HPV). Overall, 294 genomic alterations (GAs) were identified (median, 2 GAs/sample; average, 3.0 GAs/sample, range, 0-25 GAs/sample) in 109 distinct genes. The most frequently altered genes were PIK3CA (19.6% of cohort), MYC (15.5%), TP53 (15.5%), and PTEN (14.4%). RB1 GAs occurred in 4% versus 32% of HPV-positive versus HPV-negative tumors ( P < .0001). GAs in HGNECC involved the following pathways: PI3K/AKT/mTOR (41.2%); RAS/MEK (11.3%); homologous recombination (9.3%); and ERBB (7.2%). Two tumors (2.1%) had high tumor mutational burden (TMB; both with MSH2 alterations); 16 (16.5%) had intermediate TMB. Seventy-one patients (73%) had ≥ 1 alteration that was theoretically druggable. Comparing HGNECC with SCLC, significant differences in TMB, microsatellite instability, HPV-positive status, and in PIK3CA, MYC, PTEN, TP53, ARID1A, and RB1 alteration rates were found. CONCLUSION This large cohort of patients with HGNECC demonstrated a genomic landscape distinct from SCLC, calling into question the biologic and therapeutic relevance of the histologic similarities between the entities. Furthermore, 73% of HGNECC tumors had potentially actionable alterations, suggesting novel treatment strategies for this aggressive malignancy.

scholarly journals Laminar Shear Stress Inhibits Endothelial Cell Metabolism via KLF2-Mediated Repression of PFKFB3

2015 ◽  
Vol 35 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Anuradha Doddaballapur ◽  
Katharina M. Michalik ◽  
Yosif Manavski ◽  
Tina Lucas ◽  
Riekelt H. Houtkooper ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Cell Metabolism ◽  
Laminar Shear Stress ◽  
Laminar Shear ◽  
Endothelial Cell Metabolism

scholarly journals Expression of the oncofetal ED-B–containing fibronectin isoform in hematologic tumors enables ED-B–targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients

Blood ◽  
2009 ◽  
Vol 113 (10) ◽  
pp. 2265-2274 ◽  
Author(s):  
Stefanie Sauer ◽  
Paola A. Erba ◽  
Mario Petrini ◽  
Andreas Menrad ◽  
Leonardo Giovannoni ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Hodgkin Lymphoma ◽  
Hematologic Malignancies ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Bone Marrow Biopsies ◽  
Normal Tissues ◽  
Non Hodgkin Lymphoma ◽  
Promising Target

Abstract Current treatment of hematologic malignancies involves rather unspecific chemotherapy, frequently resulting in severe adverse events. Thus, modern clinical research focuses on compounds able to discriminate malignant from normal tissues. Being expressed in newly formed blood vessels of solid cancers but not in normal mature tissues, the extradomain B of fibronectin (ED-B FN) is a promising target for selective cancer therapies. Using immunohistology with a new epitope retrieval technique for paraffin-embedded tissues, ED-B FN expression was found in biopsies from more than 200 Hodgkin and non-Hodgkin lymphoma patients of nearly all entities, and in patients with myeloproliferative diseases. ED-B FN expression was nearly absent in normal lymph nodes (n = 10) and bone marrow biopsies (n = 9). The extent of vascular ED-B FN expression in lymphoma tissues was positively correlated with grade of malignancy. ED-B FN expression was enhanced in lymph nodes with severe lymphadenopathy and in some hyperplastic tonsils. The in vivo accessibility of ED-B FN was confirmed in 3 lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with 131I-labeled L19 small immunoprotein (131I-L19SIP). In 2 relapsed Hodgkin lymphoma patients131I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.

scholarly journals MiR-144 overexpression as a promising therapeutic strategy to overcome glioblastoma cell invasiveness and resistance to chemotherapy

2019 ◽  
Vol 28 (16) ◽  
pp. 2738-2751 ◽  
Author(s):  
Ana M S Cardoso ◽  
Madalena Sousa ◽  
Catarina M Morais ◽  
Liliana R Oancea-Castillo ◽  
Anne Régnier-Vigouroux ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Cell Metabolism ◽  
Combined Therapy ◽  
Treatment Options ◽  
Primary Brain Tumor ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Current Standard ◽  
Aberrant Expression ◽  
Post Surgery

Abstract Glioblastoma (GB) is the most aggressive and common form of primary brain tumor, characterized by fast proliferation, high invasion, and resistance to current standard treatment. The average survival rate post-diagnosis is only of 14.6 months, despite the aggressive standard post-surgery treatment approaches of radiotherapy concomitant with chemotherapy with temozolomide. Altered cell metabolism has been identified as an emerging cancer hallmark, including in GB, thus offering a new target for cancer therapies. On the other hand, abnormal expression levels of miRNAs, key regulators of multiple molecular pathways, have been correlated with pathological manifestations of cancer, such as chemoresistance, proliferation, and resistance to apoptosis. In this work, we hypothesized that gene therapy based on modulation of a miRNA with aberrant expression in GB and predicted to target crucial metabolic enzymes might impair tumor cell metabolism. We found that the increase of miR-144 levels, shown to be downregulated in U87 and DBTRG human GB cell lines, as well as in GB tumor samples, promoted the downregulation of mRNA of enzymes involved in bioenergetic pathways, with consequent alterations in cell metabolism, impairment of migratory capacity, and sensitization of DBTRG cells to a chemotherapeutic drug, the dichloroacetate (DCA). Taken together, our findings provide evidence that the miR-144 plus DCA combined therapy holds promise to overcome GB-acquired chemoresistance, therefore deserving to be explored toward its potential application as a complementary therapeutic approach to the current treatment options for this type of brain tumor.

The importance and cost-effectiveness of the MenB vaccine within healthcare services

2020 ◽  
Vol 26 (5) ◽  
pp. 153-155
Author(s):  
Gemma Harris
Keyword(s):  
Cost Effectiveness ◽  
Survival Rates ◽  
Healthcare Services ◽  
Current Treatment ◽  
Meningococcal Meningitis ◽  
Common Causes ◽  
The Cost ◽  
New Evidence

Gemma Harris looks at new evidence that survival rates of meningococcal B – one of the most common causes of meningococcal meningitis – are increasing, and discusses what needs to be done to improve this further and the cost-effectiveness of current treatment for the NHS.

scholarly journals A Sphingolipid Inhibitor Induces a Cytokinesis Arrest and Blocks Stage Differentiation in Giardia lamblia

2007 ◽  
Vol 52 (2) ◽  
pp. 563-569 ◽  
Author(s):  
Sabrina Sonda ◽  
Saša Štefanić ◽  
Adrian B. Hehl
Keyword(s):  
Giardia Lamblia ◽  
Cell Metabolism ◽  
Microscopic Analysis ◽  
Dependent Manner ◽  
Promising Target ◽  
Proliferation And Differentiation ◽  
Parasite Stage ◽  
Specific Stage ◽  
Parasite Replication

ABSTRACT Sphingolipid biosynthesis pathways have recently emerged as a promising target for therapeutic intervention against pathogens, including parasites. A key step in the synthesis of complex sphingolipids is the glucosylation of ceramide, mediated by glucosylceramide (GlcCer) synthase, whose activity can be inhibited by PPMP (1-phenyl-2-palmitoylamino-3-morpholino-1-propanol). In this study, we investigated whether PPMP inhibits the proliferation and differentiation of the pathogenic parasite Giardia lamblia, the major cause of parasite-induced diarrhea worldwide. PPMP was found to block in vitro parasite replication in a dose-dependent manner, with a 50% inhibitory concentration of 3.5 μM. The inhibition of parasite replication was irreversible at 10 μM PPMP, a concentration that did not affect mammalian cell metabolism. Importantly, PPMP inhibited the completion of cell division at a specific stage in late cytokinesis. Microscopic analysis of cells incubated with PPMP revealed the aberrant accumulation of cellular membranes belonging to the endoplasmic reticulum network in the caudal area of the parasites. Finally, PPMP induced a 90% reduction in G. lamblia differentiation into cysts, the parasite stage responsible for the transmission of the disease. These results show that PPMP is a powerful inhibitor of G. lamblia in vitro and that as-yet-uncharacterized sphingolipid biosynthetic pathways are potential targets for the development of anti-G. lamblia agents.

ENMET: Endothelial Cell Metabolism Mathematical Model

2009 ◽  
Author(s):  
Gianni Orsi ◽  
Carmelo De Maria ◽  
Federico Vozzi ◽  
Mariangela Guzzardi ◽  
Arti Ahluwalia ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Endothelial Cell ◽  
Cell Metabolism ◽  
Endothelial Cell Metabolism
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