EXTH-28. MOLECULAR CHARACTERIZATION OF HUMAN GLIOMAS AND IDENTIFICATION OF NEOPLASMS RESPONSIBLE FOR NEW BIOPHARMACEUTICALS OBTAINED FROM ANIMAL VENOM: A TRANSLATIONAL APPROACH

Abstract Gliomas correspond to approximately 80% of primary malignant brain tumors in adults. Associate histopathological classification to the identification of the molecular profile of these tumors is a great strategy to predict the tumor’s behavior and its responsiveness to the treatments. Studies have shown the potential of using biopharmaceuticals against cancer. Our research group has recently found two main subfractions isolated from Phoneutria nigriventer spider venom (PnV) (called SF1 and SF11) that can act decreasing the number of migrating cells during transwell assay. Therefore, the present study aimed to characterize, as regards molecular identity, the responsiveness of glioma samples collected from patients to the molecules purified from the PnV, in order to improve diagnostic and prognostic predictions, as well as contribute to the development of new drugs. After consent of the patients, samples of the tumors clinically diagnosed as glioma were collected during the surgical procedure to cultivation, that were performed until 10 passages to establish a lineage before use. To analyze its responsiveness to PnV in a migration assay, cultured human glioblastoma (1-JA63) cells were treated with PnV-isolated (HPLC) subfractions (SF1 and SF11 at 1 µg/ml) for 12 and 48 h (control stayed in IMDM) in a transwell system. SFs (mainly SF1) treatment induced a significant reduction in the number of migrating cells after 48 hours of exposure, in comparison to the control (untreated). Ongoing trials continue the establishment of another tumor samples of gliomas and migration tests with PnV subfractions will be carried out, to compare their effects in relation to other degrees of the disease also correlating the tumor response to the drug with the molecular profile. The results will contribute to the development of a potential individualized therapy also adding information about the correlation between the molecular identity of the tumor and its prognosis.

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Identification and Characterization of Multiple Myeloma Stem Cell-Like Cells

Cancers ◽

10.3390/cancers13143523 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3523

Author(s):

Wancheng Guo ◽

Haiqin Wang ◽

Peng Chen ◽

Xiaokai Shen ◽

Boxin Zhang ◽

...

Keyword(s):

Multiple Myeloma ◽

Drug Resistance ◽

Stem Cell ◽

New Drugs ◽

Cell Therapies ◽

High Relapse Rate ◽

High Incidence ◽

Poorly Differentiated ◽

Identification And Characterization

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.

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Antiangiogenic potential of Jatropha curcas latex in the chick chorioallantoic membrane model

Scientia Medica ◽

10.15448/1980-6108.2019.1.32157 ◽

2019 ◽

Vol 29 (1) ◽

pp. 32157

Author(s):

Luciane Madureira Almeida ◽

Elisa Flávia Luiz Cardoso Bailão ◽

Illana Reis Pereira ◽

Fabrício Alves Ferreira ◽

Patrícia Lima D'Abadia ◽

...

Keyword(s):

Thermal Stability ◽

Jatropha Curcas ◽

Physicochemical Characterization ◽

Chorioallantoic Membrane ◽

Angiogenesis Inhibitor ◽

Negative Control ◽

New Drugs ◽

Membrane Model ◽

Chick Chorioallantoic Membrane

AIMS: To perform a physicochemical and phytochemical characterization of Jatropha curcas latex and to investigate its antiangiogenic potential. METHODS: We performed an initial physicochemical characterization of J. curcas latex using thermal gravimetric analyses and Fourier Transform Infrared spectroscopy. After that, phenols, tannins and flavonoids were quantified. Finally, the potential of J. curcas latex to inhibit angiogenesis was evaluated using the chick chorioallantoic membrane model. Five groups of 20 fertilized chicken eggs each had the chorioallantoic membrane exposed to the following solutions: (1) water, negative control; (2) dexamethasone, angiogenesis inhibitor; (3) Regederm®, positive control; (4) 25% J. curcas latex diluted in water; (5) 50% J. curcas latex diluted in water; and (6) J. curcas crude latex. Analysis of the newly-formed vascular net was made through captured images and quantification of the number of pixels. Histological analyses were performed to evaluate the inflammation, neovascularization, and hyperemia parameters. The results were statically analyzed with a significance level set at p ˂0.05.RESULTS: Physicochemical characterization showed that J. curcas latex presented a low amount of cis-1.4-polyisoprene, which reduced its elasticity and thermal stability. Phytochemical analyses of J. curcas latex identified a substantial amount of phenols, tannins, and flavonoids (51.9%, 11.8%, and 0.07% respectively). Using a chick chorioallantoic membrane assay, we demonstrated the antiangiogenic potential of J. curcas latex. The latex induced a decrease in the vascularization of the membranes when compared with neutral and positive controls (water and Regederm®). However, when compared with the negative control (dexamethasone), higher J. curcas latex concentrations showed no significant differences.CONCLUSIONS: J. curcas latex showed low thermal stability, and consisted of phenols, tannins, and flavonoids, but little or no rubber. Moreover, this latex demonstrated a significant antiangiogenic activity on a chick chorioallantoic membrane model. The combination of antimutagenic, cytotoxic, antioxidant and antiangiogenic properties makes J. curcas latex a potential target for the development of new drugs.

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Characterization of the mechanisms involved in the early specification and migration of Prox1-expressing lymphatic endothelial cells

Developmental Biology ◽

10.1016/j.ydbio.2011.05.636 ◽

2011 ◽

Vol 356 (1) ◽

pp. 171

Author(s):

Ying Yang ◽

Kimberle Shen ◽

Sathish Srinivasan ◽

Amira Masri ◽

Joshua Scallan ◽

...

Keyword(s):

Endothelial Cells ◽

Lymphatic Endothelial Cells ◽

And Migration

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Environ-Economic Synthesis and Characterization of Some New 1,2,4-Triazole Derivatives as Organic Fluorescent Materials and Potent Fungicidal Agents

Organic Chemistry International ◽

10.1155/2013/659107 ◽

2013 ◽

Vol 2013 ◽

pp. 1-19 ◽

Cited By ~ 5

Author(s):

Harshita Sachdeva ◽

Rekha Saroj ◽

Sarita Khaturia ◽

Diksha Dwivedi

Keyword(s):

Aromatic Aldehydes ◽

New Drugs ◽

Fluorescence Study ◽

One Pot ◽

Triazole Derivatives ◽

Fluorescent Materials ◽

Cyclocondensation Reaction ◽

Practical Tool ◽

High Yields

A multicomponent one-pot clean cyclocondensation reaction of 4-chloro-2-nitro aniline/amino acids and aromatic aldehydes/indole-2,3-diones with thiosemicarbazide in water yielding triazole/spiro indole-triazole derivatives in high yields and shorter reaction time and displaying excellent florescent property is reported. The developed MCR may provide a valuable practical tool for the synthesis of new drugs containing the title core fragment. All the newly synthesized compounds have been characterized by IR, 1HNMR, 13CNMR, and fluorescence study and also been screened for antimicrobial activity.

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A systematic characterization of intrinsically formed microglia-like cells during retinal organoid differentiation.

10.1101/2021.12.30.474511 ◽

2022 ◽

Author(s):

Katarina Bartalska ◽

Verena Hübschmann ◽

Medina Korkut-Demirbaş ◽

Ryan John Abat Cubero ◽

Alessandro Venturino ◽

...

Keyword(s):

Protein Composition ◽

Human Microglia ◽

Development Organization ◽

Cellular Environment ◽

Preferential Localization ◽

Circuit Development ◽

And Migration ◽

Induced Pluripotent ◽

Insight Into

Brain organoids differentiated from human induced pluripotent stem cells provide a unique opportunity to investigate the development, organization and connectivity of neurons in a complex cellular environment. However, organoids usually lack microglia, brain-resident immune cells which are both present in the early human embryonic brain and participate in neuronal circuit development. Here, we find that microglia innately develop in unguided retinal organoid differentiation between week 3 and 4 in 2.5D culture and appear later in floating, non-pigmented, 3D-cystic compartments. We enriched for cystic structures using a low-dosed BMP4 application and performed mass spectrometry, thus defining the protein composition of microglia-containing compartments. We found that cystic compartments expressed both mesenchymal and epithelial markers with microglia enriched in the mesenchymal region. Interestingly, microglia-like cells started to express the border-associated macrophage marker CD163. The preferential localization of human microglia to a mesenchymal compartment provides insight into the behavior and migration of microglia. The model will ultimately allow detailed study of these enigmatic cells and how they enter and distribute within the human brain.

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Gene expression profiling after LINC00472 overexpression in an NSCLC cell line

Cancer Biomarkers ◽

10.3233/cbm-210242 ◽

2021 ◽

pp. 1-14

Author(s):

Danbi Seo ◽

Jungwook Roh ◽

Yeonsoo Chae ◽

Wanyeon Kim

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Tumor Suppressors ◽

Enrichment Analysis ◽

Nsclc Cell Line ◽

Sequencing Analysis ◽

Genetic Characteristics ◽

Migration Assay ◽

Non Coding Rna ◽

And Migration

Lung cancer accounts for a large proportion of cancer-related deaths worldwide. Personalized therapeutic medicine based on the genetic characteristics of non-small cell lung cancer (NSCLC) is a promising field, and discovering clinically applicable biomarkers of NSCLC is required. LINC00472 is a long non-coding RNA and has been recently suggested to be a biomarker of NSCLC, but little is known of its mechanism in NSCLC. Thus, the current study was performed to document changes in gene expression after LINC00472 overexpression in NSCLC cells. As a result of cell viability and migration assay, LINC00472 downregulated cell survival, proliferation, and motility. Transcriptome sequencing analysis showed 3,782 genes expression were changed in LINC00472 overexpressing cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed most genes were associated with intracellular metabolism. The PPP1R12B, RGS5, RBM5, RBL2, LDLR and PTPRM genes were upregulated by LINC00472 overexpression and these genes functioned as tumor suppressors in several cancers. In contrast, SPSB1, PCNA, CD24, CDK5, CDC25A, and EIF4EBP1 were downregulated by LINC00472, and they functioned as oncogenes in various cancers. Consequently, the function of LINC00472 in tumorigenesis might be related to changes in the expressions of other oncogenes and tumor suppressors.

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miR-208a-3p promotes NSCLC proliferation and migration by suppressing lncRNA-MEG3 expression

10.21203/rs.3.rs-877755/v1 ◽

2021 ◽

Author(s):

Linfei Yang ◽

Qian Li ◽

Hai Zhong ◽

Liang Ye ◽

Surong Fang ◽

...

Keyword(s):

Protein Extraction ◽

Underlying Mechanism ◽

In Vitro Assays ◽

Cell Viability Assay ◽

Migration Assay ◽

Normal Tissues ◽

Viability Assay ◽

And Migration ◽

Proliferation And Migration

Abstract Background The disordered expression of maternally expressed gene 3 (MEG3) has been observed in non-small-cell lung cancer (NSCLC). However, the molecular mechanism accounting for this abnormal expression is not fully understood. Methods MEG3 expression was detected by qRT-PCR in 51 cases of NSCLC and adjacent normal tissues. Then, the relationship between MEG3 and miR-208a-3p was assessed in vitro by cell viability assay, cell migration assay, protein extraction and western blot analysis. Resoults We observed that MEG3 expression was decreased in NSCLC tissues. And MEG3 expression was negatively related to lymph node metastasis and differentiation. Moreover, MEG3 expression is regulated by miR-208a-3p expression by overexpression and knockout experiments. Furthermore, we focused on the underlying mechanism of MEG3 downregulation. We found that the overexpression of miR-208a-3p reduced the level of MEG3 expression based on computational predictions and in vitro assays. Using CCK-8 and transwell migration assays, we found that the overexpression of miR-208a-3p can increased proliferation and apoptosis in NSCLC cells. Moreover, the depletion of MEG3 rescued the proliferation and migration induced by miR-208a-3p knockdown. Conclusion Taken together, the results of this study reveal that miR-208a-3p promotes NSCLC tumorigenesis by negatively regulating MEG3 expression and functions as an oncogenic miRNA in NSCLC.

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The Characterization of Stratigraphic Play in Middle Baong Sand for Hydrocarbon Prospecting in Offshore North Sumatera Basin

10.29118/ipa21-g-138 ◽

2021 ◽

Author(s):

A. Nurhasan

Keyword(s):

Depositional Environment ◽

Hydrocarbon Exploration ◽

Ratio Distribution ◽

Basin Floor ◽

Distinct Character ◽

Net To Gross ◽

And Migration ◽

Sand Bodies ◽

Malacca Strait

Pertamina EP is operating a small block in Offshore North Sumatera Basin where a couple of the fields are producing gas and condensate from the Belumai Carbonate. However, the wells production is depleting and several delineation wells are unable to find additional reserves, it is important to find a new play within the block. Few discoveries in the Middle Baong Sand (MBS) reservoir suggested a promising stratigraphic play to be explored, but it requires more detailed characterization of the reservoir extent. The Malacca strait-sourced MBS consists of several deposited sand packages during a mega sequence. The term MBS might represent a deltaic environment from a transgressive system tract of some marine shore bar or a basin floor fan. Each system has a distinct character (thickness, net to gross ratio, distribution) that must be evaluated before proposing an exploration well. The depositional environment and reservoir distribution are interpreted and modeled using regional 2D seismic and high-quality 3D seismic. Paleo-bathymetric interpretation from well samples shows a good correlation with the palinspastic reconstruction. The result shows that the Pertamia EP working area is located in the shore bar depositional environment. Seismic attributes are used to delineate reservoir distribution within the working block and well logs are used to constrain prospective sand bodies and water zones identification. Furthermore, source rock maturation and migration path and hydrocarbon occurrence from the discovery wells have been evaluated for hydrocarbon prospecting and risking. This study suggests a promising lead for hydrocarbon exploration in the study area and opens up a new opportunity for an underexplored play.

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P06.01 Pediatric non-pontine diffuse midline glioma H3K27M mutant: a monoinstitutional experience

Neuro-Oncology ◽

10.1093/neuonc/noab180.079 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii24-ii24

Author(s):

E Schiavello ◽

V Biassoni ◽

L De Cecco ◽

E Pecori ◽

S Filippo ◽

...

Keyword(s):

Liquid Biopsy ◽

P53 Mutation ◽

New Drugs ◽

Molecular Profile ◽

Histopathological Diagnosis ◽

Diffuse Astrocytoma ◽

Number Of Patients ◽

Pathological Evaluation ◽

Diffuse Midline Glioma ◽

Astrocytoma Grade

Abstract BACKGROUND The new entity “diffuse-midline-glioma H3K27M-mutant”(DMG) was defined in the 2016 WHO classification. This tumor subtype, regardless of histological features, is associated with an aggressive clinical behavior and poor prognosis, sharing the same outcome as DIPG. MATERIAL AND METHODS We report our experience from 2016 to 2018 in treating patients with radiotherapy and concomitant Nimotuzumab/Vinorelbine, as already published for DIPG’s patients (DOI10.1007/s11060-014-1428-z). All patients’ parents provided written informed consent for treatment. RESULTS Patients were 9: 7/9 females, median age at diagnosis 13 years (range 1–26); 8 with localized disease, 1 with spinal fluid (CSF) dissemination. Five patients had thalamic disease (1 bithalamic), 2 ponto-cerebellar (one with 2 lesions), 1 pineal gland and one with disseminated CSF disease at diagnosis. 3/9 were biopsed in thalamus, the others had partial resection. Central neuropathological review with confirmed histopathological diagnosis of DMG mutated was necessary for inclusion. At the first pathological evaluation tumors had been classified according to the fourth edition of the WHO 2007 as glioblastoma (n=4), anaplastic astrocytoma grade III (n=1), diffuse astrocytoma grade II (n=1), and 1 glial tumor with oligodendroglial features; 2 patients already had DMG at the first pathological evaluation. Immunohistochemical analysis revealed p53 mutation in 3 patients. All 9 patients were evaluated on serial plasma samples with NGS targeted panel (Pan-Cancer) and 6/9 presented p53 mutation in at least one of the samples. 8/9 expressed MAP2K1 gain of function at liquid biopsy. The small number of patients did not allow correlations with the prognosis. Two patients completed the scheduled 2 years of treatment: one had a local relapse at 37 months after diagnosis, the other is alive without evidence of progression at 30 months. With a median follow up of 14.4 months, PFS and OS were 33% and 77% at 1 year; OS was 22% at 2 years, with 2 patients long survivors at 36 and 40 months after diagnosis. CONCLUSION The molecular and phenotypic pattern of DMG allows to include patients in clinical trials/registry shared with patients suffering from DIPG. Our knowledge is still limited about this entity; new insights into molecular profile should help us to study new drugs directed against the effects of the H3K27M mutations and to define new diagnostic/prognostic approach as liquid biopsy able to correlate treatments and prognosis

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Anti-Stress, Glial- and Neuro-Differentiation Potential of Resveratrol: Characterization by Cellular, Biochemical and Imaging Assays

Nutrients ◽

10.3390/nu12030671 ◽

2020 ◽

Vol 12 (3) ◽

pp. 671

Author(s):

Sajal Afzal ◽

Sukant Garg ◽

Divya Adiga ◽

Yoshiyuki Ishida ◽

Keiji Terao ◽

...

Keyword(s):

Oxidative Dna Damage ◽

Specific Protein ◽

New Drugs ◽

Protein Markers ◽

Human Neuroblastoma ◽

Differentiation Potential ◽

Daily Lives ◽

Rat Glioma ◽

Age Related

Environmental stress, exhaustive industrialization and the use of chemicals in our daily lives contribute to increasing incidence of cancer and other pathologies. Although the cancer treatment has revolutionized in last 2–3 decades, shortcomings such as (i) extremely high cost of treatment, (ii) poor availability of drugs, (iii) severe side effects and (iv) emergence of drug resistance have prioritized the need of developing alternate natural, economic and welfare (NEW) therapeutics reagents. Identification and characterization of such anti-stress NEW drugs that not only limit the growth of cancer cells but also reprogram them to perform their specific functions are highly desired. We recruited rat glioma- and human neuroblastoma-based assays to explore such activities of resveratrol, a naturally occurring stilbenoid. We demonstrate that nontoxic doses of resveratrol protect cells against a variety of stresses that are largely involved in age-related brain pathologies. These included oxidative, DNA damage, metal toxicity, heat, hypoxia, and protein aggregation stresses. Furthermore, it caused differentiation of cells to functional astrocytes and neurons as characterized by the upregulation of their specific protein markers. These findings endorse multiple bioactivities of resveratrol and encourage them to be tested for their benefits in animal models and humans.

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