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Добірка наукової літератури з теми "ONCOTHERAPEUTICS"

Автор: Grafiati

Опубліковано: 11 вересня 2023

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Статті в журналах з теми "ONCOTHERAPEUTICS"

Raja, Junaid, and David C. Madoff. "Oncopharmacology in Interventional Radiology." Seminars in Interventional Radiology 39, no. 04 (August 2022): 411–15. http://dx.doi.org/10.1055/s-0042-1758076.

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AbstractThe broad scope of malignancies treated in interventional oncology is mirrored by the breadth of oncotherapeutics, drugs used to treat cancer. Many of these treatments are administered endovascularly, though a group of therapies can be delivered percutaneously. Perhaps the best taxonomy of oncotherapeutics is based on their biological inactivity or activity and the mechanism by which they interact with treated and targeted tissues. As the fields of interventional oncology and oncotherapeutics continue to grow and expand, this framework may provide a more organized approach in helping distinguish and select the best therapy for patients.

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Ladd, Joseph. "Advancements in oncotherapeutics drive positive outcomes in cancer." Pharmacy Today 23, no. 7 (July 2017): 24–25. http://dx.doi.org/10.1016/j.ptdy.2017.06.019.

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Dailey, Kaitlin M., JuliAnne E. Allgood, Paige R. Johnson, Mackenzie A. Ostlie, Kambri C. Schaner, Benjamin D. Brooks, and Amanda E. Brooks. "The next frontier of oncotherapy: accomplishing clinical translation of oncolytic bacteria through genetic engineering." Future Microbiology 16, no. 5 (March 2021): 341–68. http://dx.doi.org/10.2217/fmb-2020-0245.

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The development of a ‘smart’ drug capable of distinguishing tumor from host cells has been sought for centuries, but the microenvironment of solid tumors continues to confound therapeutics. Solid tumors present several challenges for current oncotherapeutics, including aberrant vascularization, hypoxia, necrosis, abnormally high pH and local immune suppression. While traditional chemotherapeutics are limited by such an environment, oncolytic microbes are drawn to it – having an innate ability to selectively infect, colonize and eradicate solid tumors. Development of an oncolytic species would represent a shift in the cancer therapeutic paradigm, with ramifications reaching from the medical into the socio-economic. Modern genetic engineering techniques could be implemented to customize ‘Frankenstein’ bacteria with advantageous characteristics from several species.

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Kansara, Samarth, Vijay Pandey, Peter E. Lobie, Gautam Sethi, Manoj Garg, and Amit Kumar Pandey. "Mechanistic Involvement of Long Non-Coding RNAs in Oncotherapeutics Resistance in Triple-Negative Breast Cancer." Cells 9, no. 6 (June 21, 2020): 1511. http://dx.doi.org/10.3390/cells9061511.

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Triple-negative breast cancer (TNBC) is one of the most lethal forms of breast cancer (BC), with a significant disease burden worldwide. Chemoresistance and lack of targeted therapeutics are major hindrances to effective treatments in the clinic and are crucial causes of a worse prognosis and high rate of relapse/recurrence in patients diagnosed with TNBC. In the last decade, long non-coding RNAs (lncRNAs) have been found to perform a pivotal role in most cellular functions. The aberrant functional expression of lncRNAs plays an ever-increasing role in the progression of diverse malignancies, including TNBC. Therefore, lncRNAs have been recently studied as predictors and modifiers of chemoresistance. Our review discusses the potential involvement of lncRNAs in drug-resistant mechanisms commonly found in TNBC and highlights various therapeutic strategies to target lncRNAs in this malignancy.

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Raftopoulou, Christina, Fani-Marlen Roumelioti, Eleni Dragona, Stefanie Gimelli, Frédérique Sloan-Béna, Vasilis Gorgoulis, Stylianos E. Antonarakis, and Sarantis Gagos. "Karyotypic Flexibility of the Complex Cancer Genome and the Role of Polyploidization in Maintenance of Structural Integrity of Cancer Chromosomes." Cancers 12, no. 3 (March 5, 2020): 591. http://dx.doi.org/10.3390/cancers12030591.

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Ongoing chromosomal instability in neoplasia (CIN) generates intratumor genomic heterogeneity and limits the efficiency of oncotherapeutics. Neoplastic human cells utilizing the alternative lengthening of telomeres (ALT)-pathway, display extensive structural and numerical CIN. To unravel patterns of genome evolution driven by oncogene-replication stress, telomere dysfunction, or genotoxic therapeutic interventions, we examined by comparative genomic hybridization five karyotypically-diverse outcomes of the ALT osteosarcoma cell line U2-OS. These results demonstrate a high tendency of the complex cancer genome to perpetuate specific genomic imbalances despite the karyotypic evolution, indicating an ongoing process of genome dosage maintenance. Molecular karyotyping in four ALT human cell lines showed that mitotic cells with low levels of random structural CIN display frequent evidence of whole genome doubling (WGD), suggesting that WGD may protect clonal chromosome aberrations from hypermutation. We tested this longstanding hypothesis in ALT cells exposed to gamma irradiation or to inducible DNA replication stress under overexpression of p21. Single-cell cytogenomic analyses revealed that although polyploidization promotes genomic heterogeneity, it also protects the complex cancer genome and hence confers genotoxic therapy resistance by generating identical extra copies of driver chromosomal aberrations, which can be spared in the process of tumor evolution if they undergo unstable or unfit rearrangements.

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Adeniji, Emmanuel A., Fisayo A. Olotu, and Mahmoud E. S. Soliman. "Exploring the Lapse in Druggability: Sequence Analysis, Structural Dynamics and Binding Site Characterization of K-RasG12C Variant, a Feasible Oncotherapeutics Target." Anti-Cancer Agents in Medicinal Chemistry 18, no. 11 (January 28, 2019): 1540–50. http://dx.doi.org/10.2174/1871520618666180718110231.

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Background: The difficulty in druggability of K-Ras variant has presented a challenge in the treatment of cancer diseases associated with its dysfunctionality. Despite the identification of different binding sites, limited information exists in the literature about their characteristics. Therefore, identification, crossvalidation and characterization of its druggable sites would aid the design of chemical compounds that will arrest its dysfunctionality related oncogenesis. Objective: This study entails the identification, cross-validation and characterization of K-Ras G12C variant’s binding sites for potential druggability, coupled with the elucidation of alterations in 3D conformations and dynamics. Method: Molecular dynamics simulation was carried out on the inactive, the active and the hyperactive K-RasG12Cvariant using the amber software package. The SiteMap software was employed in identifying and characterizing the druggable binding sites while the validation of the binding sites was carried out with the SiteHound and MetaPocket servers. Results: Four druggable binding sites were identified, validated and characterized based on physicochemical attributes such as size, volume, degree of enclosure or exposure, degree of contact, hydrophobic/hydrophilic character, hydrophobic/hydrophilic balance and hydrogen-bonding features. Conformational studies also revealed that the K-Ras variant exhibited notable structural instability, increased flexibility and a strongly anticorrelated movement compared to the inactive and active wildtype forms. Conclusion: The attributes of the characterized druggable sites will be useful in designing site-specific K-Ras inhibitors for the treatment of K-Ras variant associated cancer diseases.

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Lantier, Louis, Agathe Poupee-Beauge, Louis Lantier, Céline Ducournau, Anne Di Tommaso, Stéphanie Germon, Nathalie Moiré, Gordon Lee, Antoine Touze, and Isabelle Dimier-Poisson. "846 Neospora caninum – an immunotherapeutic protozoan against solid cancers." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A899. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0846.

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BackgroundImmunotherapy induces, provides, and/or reactivates anti-tumor immune responses. Some microorganisms also can initiate response that lyzes infected tumor and/or stimulates systemic immunity. Attenuated viruses or bacteria are well studied as oncotherapeutics, but not protozoa except Toxoplasma gondii.1 We assessed the effect on tumors of other protozoa that were naturally non-pathogenic to humans. Thus, we discovered the ability to use Neospora caninum (Nc) in a manner and form that demonstrated a synergistic array of pertinent immunotherapeutic characteristics against solid cancers. Our first Article on Neospora as Onco-immunotherapeutic is currently under revision after review by the JITC. We report on the most recent data notably from Nc engineered to secrete human IL-15 within the tumor.MethodsIn vitro, the immunostimulatory properties of Nc strains wildtype and engineered to secrete human IL-15 were studied. In vivo experiments of treatment with of Nc tachyzoites2 administered locally (intra and peri tumoral) or remotely (subcutaneous) in a murine thymoma EG7 tumor and in human Merkel cell carcinoma (MCC).ResultsWe demonstrated that the treatment of thymoma EG7 by Nc strongly inhibited tumor development. Analysis of immune responses and interactions between Nc and tumor cells showed that Nc had the ability to lyze infected cancer cells, reactivated immune competence within the Tumor Microenvironment (TME), and activated the systemic immune system by promoting the recruitment of immune cells to the site of tumor. We also established in a NOD/SCID mouse model that Nc was able to induce a strong regression of human MCC. Recently, to further enhance oncotherapeutic effect, we engineered an Nc strain to secrete human IL-15 (cross reactive with mouse cells), associated with alpha subunit of IL-15 receptor, increasing its stability.3 This strain induced proliferation of human PBMCs and their secretion of IFN-γ. In the EG7 model, human IL-15 secreting Nc showed greater protection against tumor development, confirming enhancement of immunotherapy by engineering Nc to deliver/secrete IL-15.ConclusionsThese results highlight Neospora caninum as a potentially extremely efficient, and non-toxic anti-cancer agent, capable of being engineered to express at its surface or to secrete bio-drugs, like human IL-15 cytokine. Our work has identified the broad clinical possibilities of using N. caninum as an oncolytic protozoan in human medicine capable of vectoring molecular therapy, overcoming TME defenses.ReferencesFox BA, Butler KL, Guevara RB, Bzik DJ. Cancer therapy in a microbial bottle: Uncorking the novel biology of the protozoan Toxoplasma gondii. PLoS Pathog 2017;13(9):e1006523. https://doi.org/10.1371/journal.ppat.1006523Bjerkas I, Jenkins MC, Dubey JP. Identification and characterization of Neospora caninum tachyzoite antigens useful for diagnosis of neosporosis. Clin Diagn Lab Immunol 1994;1(2):214-221.Article for publication in the Journal of Immunotherapy of Cancer, under revision on September 20, 2020.

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AbdRabou, Mervat Ahmed, Ahmed B. M. Mehany, Islam M. Farrag, Amany Belal, Othman F. Abdelzaher, Abdou El-Sharkawy, Asmaa M. Abd El-Azez, Salah M. EL-Sharkawy, and Manal H. Al Badawi. "Therapeutic Effect of Murine Bone Marrow-Derived Mesenchymal Stromal/Stem Cells and Human Placental Extract on Testicular Toxicity Resulting from Doxorubicin in Rats." BioMed Research International 2021 (August 6, 2021): 1–13. http://dx.doi.org/10.1155/2021/9979670.

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Oncotherapeutics like doxorubicin can affect male gonads; as a result, it leads to infertility. This work was conducted to demonstrate the toxic effects of doxorubicin on testes of male albino rats. Fifty male albino rats aged 5-7 weeks were used in this study. The animals were randomly separated into 5 sets (each set containing ten rats). Group I received saline (i.p.) for 4 weeks. Group II was given doxorubicin (DOX), 5 mg/kg BW (i.p.) once/week for 4 weeks. Groups III and IV were treated in the same way as the DOX group, left for one week without medication, and then injected with mesenchymal stromal cells (MSCs) or human placental extract (HPE) therapy in a single dose of 5 × 10 6 in 200 ml PRP/week or 40 μl placental extract for 4 weeks via the caudal vein. Group V rats were treated in the same way as the DOX group also, left for one week without medication, and then injected with MSC+HPE. A significant decrease in serum testosterone, FSH, and LH levels was observed in rats treated with DOX compared to the control group. A significant elevation was recorded in rats treated with DOX+MSC or DOX+HPE when compared with the DOX group only. Rats that were given MSC+HPE after DOX intoxication showed a significant increase in hormone levels when compared to rats treated with either MSC or HPE. Light and electron microscopic examinations revealed that DOX intoxication initiated degenerative and necrotic changes in seminiferous tubules associated with partial or complete cessation of spermatogenesis. These effects were reversed by the effect of MSC or HPE. Coadministration of MSC and HPE even showed further improvement. Finally, we can say that doxorubicin has a deleterious impact on rat testes; however, therapeutic effects can be induced through MSC and/or HPE administration.

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Chhajed, Santosh Subhash, Pramodkumar P. Gupta, Sanjay Kshirsagar, Sakshi Tomar, Debarshi Kar Mahapatra, and Raji Sundararajan. "N-(2-(1H-benzo[d]imidazol-2-yl)Phenyl)-2- (Substituted-styryl)Aniline as Anti-proliferative Agents: Rejuvenating the Importance of Low Molecular Weight Ligands in Oncotherapeutics." Indian Journal of Pharmaceutical Education and Research 54, no. 2 (March 3, 2020): 432–39. http://dx.doi.org/10.5530/ijper.54.2.49.

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Dailey, Kaitlin M., Krysten Vance, Kyle McAndrews, Reed I. Jacobson, Jandro Delgado, Paige R. Johnson, Taylor M. Woolery, et al. "Abstract PO-037: Development of an RGD CRISPR-modified Clostridium novyi NT spores as an intravenous oncotherapy." Cancer Research 81, no. 22_Supplement (November 15, 2021): PO—037—PO—037. http://dx.doi.org/10.1158/1538-7445.panca21-po-037.

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Abstract The efficacy of current oncotherapeutics is largely limited by an inability to access avascular tissues, which is in part responsible for forty years of stagnant pancreatic cancer statistics where the median survival remains a mere six months. Oncolytic bacteria such as Clostridium novyi-NT overcome this challenge with its ultrasensitive, innate affinity for hypoxic/necrotic areas found at the center of solid tumors and their metastases. While preclinical and clinical data from intratumoral injections of C. novyi-NT are promising, many tumors are inaccessible to such injections. Preclinical trials of analogous IV injections have uncovered other obstacles such as rapid clearance of C. novyi-NT by the immune system independent of septic complications. To mitigate rapid clearance, CRISPR/Cas9n was used to genetically modify a non-toxic form of C. novyi-NT to express a tumor targeting RGD peptide on the spore surface. Through this novel, first of its kind, methodology, spores with stronger affinity to a surface coated with the targeted binding partner of RGD, aVb3 integrin, have been generated. Importantly, there was no statistically significant difference in the genetically modified spore’s capacity for sporulation or germination when compared to unmodified C. novyi-NT spores, nor was a difference in lytic capacity observed, suggesting no relevant off-target effects from genomic modification. Biodistribution and efficacy of non-toxic RGD-modified spores was evaluated in an immunocompetent, syngeneic, pancreatic cancer murine model. Ongoing efforts to characterize the biodistribution and efficacy of the intravenously injected RGD-modified C. novyi-NT include the application of multiplex immunofluorescence, laser microdissection, and live, whole animal imaging. Supported as a pilot project by funds from NIH COBRE grant 1P20GM109024, Doctoral Dissertation Funds to KMD from NDSU, and by discretionary funds from investigators at UNMC. Citation Format: Kaitlin M. Dailey, Krysten Vance, Kyle McAndrews, Reed I. Jacobson, Jandro Delgado, Paige R. Johnson, Taylor M. Woolery, Megan Orr, Jiha Kim, Sanku Mallik, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks. Development of an RGD CRISPR-modified Clostridium novyi NT spores as an intravenous oncotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-037.

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Дисертації з теми "ONCOTHERAPEUTICS"

KAR, ROHAN. "STUDYING THE MIR-24 EXPRESSION PROFILE IN BREAST CARCINOMAS AND SYNTHESIS OF LIPOSOMES AS NANOVEHICLES FOR SIRNA BASED FUTURE ONCOTHERAPEUTICS." Thesis, 2016. http://dspace.dtu.ac.in:8080/jspui/handle/repository/14998.

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Breast cancer related mortalities are currently on the rise and hence the need for model therapeutics to improve survival and quality of life in patients is a prime necessity. Much of the prognosis and tumour behaviour in patients are controlled by the cancer stem cells, which ultimately leads to chemotherapeutic resistance and disease recurrence. MiRNA are short non-coding RNAs with potential roles in carcinogenesis and mRNA silencing. miRNA-24 could be a probable regulator of epithelial to mesenchymal transition (EMT) mediated via Klf-8 and Notch-1. However, the exact mechanism for miR-24, Klf-8 and Notch-1 mediated EMT remains obscure. EMT is a hallmark of highly metastatic and devastating tumours and reversing the process of EMT could be a potent strategy towards developing favouring therapeutics in high-grade breast carcinomas. However, it is necessary to optimally deliver miRNA inhibitors such as siRNAs (small interfering RNAs) to the afflicted cells in order to reverse or limit the process of EMT. Liposomes and alginate-chitosan gels could be potential candidates owing to their nano dimensions and the probability of using these nano particles for combinatorial therapy remains an august possibility. Nevertheless, further experiments shall be needed first to establish a concrete mechanism and then to synthesize an optimal vector for siRNA trafficking. Dual targeting of tumour cells could then be possible with two tier liposome-alginate nanostructures Under the scope of this thesis, an attempt has been made to identify and delve one such probable EMT modulating miRNA, miR-24 in breast cancer. In addition to this liposomes and gels have been fabricated, which could in future serve as potential candidates of two tier architecture for drug delivery in breast cancers.

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Частини книг з теми "ONCOTHERAPEUTICS"

Patel, Alkeshkumar. "Drug Repurposing in Oncotherapeutics." In Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.92302.

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Repurposing or repositioning means validating and application of previously approved drugs in the treatment of another disease that might be relevant or irrelevant to existing use in disease based on the principle of polypharmacology. Repurposed drugs are already well documented for pharmacokinetic, pharmacodynamic, drug interaction, and toxicity parameters. In 1962, thalidomide treatment in pregnant women led to phocomelia in their newborn but while repurposed based on anti-angiogenesis property, it showed efficacy in hematologic malignancies like multiple myeloma. The repurposing is becoming an essential tool in the anti-cancer drug development due to existing drugs are not effective, high cost of treatment, therapy may degrade the quality of life, improvement of survival after treatment is not guaranteed, relapse may occur, and drug resistance may develop due to tumor heterogeneity. Repurposing can be addressed well with the help of literature-based discovery, high throughput technology, bioinformatics multi-omics approaches, side effects, and phenotypes. Many regulatory bodies like EML, NIH, and FDA promote repurposing programs that support the identification of alternative uses of existing medicines. Cancer becomes the major health issue, and the need to discover promising anti-cancer drugs through repurposing remains very high due to decline in FDA approval since 1990, huge expenses incurred in the drug development and prediction of dangerous future burden.

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Rashid, Nowsheeba, Rouf Ahmad Bhat, Nighat Mushtaq, and Ifra Ashraf. "Exploitation of revered potent medicinal mushroom Ganoderma lucidum with particular accent on oncotherapeutics." In Medicinal and Aromatic Plants, 397–431. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-819590-1.00015-x.

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