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Статті в журналах з теми "COMBINATORIAL THERAPY"

Автор: Grafiati

Опубліковано: 11 вересня 2023

Оновлено: 16 січня 2024

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1

Stritzker, J., and A. A. Szalay. "Single-agent combinatorial cancer therapy." Proceedings of the National Academy of Sciences 110, no. 21 (May 10, 2013): 8325–26. http://dx.doi.org/10.1073/pnas.1305832110.

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2

Baust, J. G. "Cryoablation: An Emergent Combinatorial Therapy." Cryobiology 92 (February 2020): 272. http://dx.doi.org/10.1016/j.cryobiol.2019.11.010.

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3

Koh, Yoon Woo. "Combinatorial Targeted Therapy in Thyroid Cancer." Korean Journal of Otorhinolaryngology-Head and Neck Surgery 53, no. 4 (2010): 203. http://dx.doi.org/10.3342/kjorl-hns.2010.53.4.203.

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4

Mittra, Arjun, and Debu Tripathy. "Looking ahead to rational combinatorial therapy." Community Oncology 9, no. 2 (February 2012): 40–41. http://dx.doi.org/10.1016/j.cmonc.2012.02.002.

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5

Sabbatino, Francesco, Yangyang Wang, Ravin Poudel, Matteo Ligorio, Elvira Favoino, Xinhui Wang, Jennifer Wargo, Soldano Ferrone, Keith D. Lillemoe, and Cristina R. Ferrone. "Novel combinatorial therapy for pancreatic adenocarcinoma." Journal of the American College of Surgeons 217, no. 3 (September 2013): S137. http://dx.doi.org/10.1016/j.jamcollsurg.2013.07.319.

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6

Anitha, A., S. Maya, Amal J. Sivaram, U. Mony, and R. Jayakumar. "Combinatorial nanomedicines for colon cancer therapy." Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 8, no. 1 (June 10, 2015): 151–59. http://dx.doi.org/10.1002/wnan.1353.

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7

Vojvodic, Sladjana, Gabor Katona, and Miroslav Sarac. "Combinatorial pharmacogenomic test for successful antidepressant treatment of a major depressive disorder." Medical review 74, no. 3-4 (2021): 117–22. http://dx.doi.org/10.2298/mpns2104117v.

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Анотація:

Introduction. The combinatorial pharmacogenomic test has shown the potential to predict antidepressant response, tolerability, selection, and dosage in the treatment of a major depressive disorder. A case of successful management of antidepressant therapy adjustment is reported by using the combinatorial pharmacogenomic test. Case Report. A 53-year old man, severely disabled due to a rare genetic disease, Usher syndrome type 3, was treated with numerous antidepressants. However, episodes of major depression recurred, along with frequent suicidal thoughts. A combinatorial pharmacogenomic test was considered to design a potentially effective antidepressant therapy. Conclusion. According to the results of the combinatorial pharmacogenomic test, the patient constantly received inadequate antidepressant therapy, which did not lead to an improvement of depression due to moderate gene-drug interaction. The patient was prescribed nortriptyline, which proved to be one of the few most adequate according to the test. He showed improvement with subjectively more tolerable depression without suicidal thoughts and episodes of major depression. This case showed that the combinatorial pharmacogenomic testing may contribute to better selection of antidepressant therapy.

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8

Sabei, Fahad Y., Olena Taratula, Hassan A. Albarqi, Adel M. Al-Fatease, Abraham S. Moses, Ananiya A. Demessie, Youngrong Park, et al. "A targeted combinatorial therapy for Ewing's sarcoma." Nanomedicine: Nanotechnology, Biology and Medicine 37 (October 2021): 102446. http://dx.doi.org/10.1016/j.nano.2021.102446.

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9

Kwong, L. N., and M. A. Davies. "Targeted therapy for melanoma: rational combinatorial approaches." Oncogene 33, no. 1 (February 18, 2013): 1–9. http://dx.doi.org/10.1038/onc.2013.34.

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10

Mukerjee, A., A. P. Ranjan, and J. K. Vishwanatha. "Combinatorial Nanoparticles for Cancer Diagnosis and Therapy." Current Medicinal Chemistry 19, no. 22 (June 1, 2012): 3714–21. http://dx.doi.org/10.2174/092986712801661176.

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11

Bhatia, Karanpreet, Bhumika, and Asmita Das. "Combinatorial drug therapy in cancer - New insights." Life Sciences 258 (October 2020): 118134. http://dx.doi.org/10.1016/j.lfs.2020.118134.

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12

Beik, Jaber, Maziar Khateri, Zohreh Khosravi, S. Kamran Kamrava, Siavash Kooranifar, Habib Ghaznavi, and Ali Shakeri-Zadeh. "Gold nanoparticles in combinatorial cancer therapy strategies." Coordination Chemistry Reviews 387 (May 2019): 299–324. http://dx.doi.org/10.1016/j.ccr.2019.02.025.

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13

Kushwah, Atar Singh, Rajnikant Mishra, Ashwin Kumar Shukla, and Monisha Banerjee. "Combinatorial therapy of Cynodon dactylon and Metformin with Cisplatin in cervical cancer." Journal of Scientific Research 66, no. 04 (2022): 35–41. http://dx.doi.org/10.37398/jsr.2022.660406.

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Cisplatin based chemoradiation (CRT) is the standard treatment for cervical cancer, which controls tumor growth and improves the overall survival of patients. However, patients undergoing chemo-radiation show widespread toxicities which may be either early or late. There is a constant effort to improve cancer therapy and overcome current challenges in cervical cancer by developing a combinatorial drug therapy using phytocompounds. In the present study, we review the combinatorial therapy of Cynodon dactylon and metformin with cisplatin as an alternative therapy for cervical cancer. During frequent exposures to chemotherapy, patients develop resistance to cisplatin, leading to cytotoxicity and recurrence. The conjugate of biologically active moieties of natural products along with cisplatin will probably lead to development of a new therapy with improved drug efficacy and reduced toxicity. Therefore, Cynodon dactylon (Doob) is a natural source of antioxidants and metformin which is an antidiabetic and has anticancerous properties too. The combinatorial regimen of Cynodon dactylon and metformin along with cisplatin may increase the drug efficacy and reduce cisplatin-related toxicity. However, widespread research is required in this field for the mainstream application of this combinatorial therapy.

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14

Liu, Tingting, Bo Jin, Jun Chen, Hui Wang, Shuiyu Lin, Jun Dang, and Guang Li. "Comparative risk of serious and fatal treatment-related adverse events caused by 19 immune checkpoint inhibitors used in cancer treatment: a network meta-analysis." Therapeutic Advances in Medical Oncology 12 (January 2020): 175883592094092. http://dx.doi.org/10.1177/1758835920940927.

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Background: This network meta-analysis assessed the comparative risk of grade 3–5 and grade 5 treatment-related adverse events (TRAEs) for immune checkpoint inhibitors (ICIs), either alone or in combination with other modalities, for cancer treatment. Methods: PubMed, Embase, Cochrane Library, Web of Science, and recent predominant oncology congresses were searched for relevant phase II and phase III randomized controlled trials (RCTs). As outcomes, grade 3–5, and grade 5 TRAE outcomes were reported as odds ratios and 95% confidence intervals. Results: In 67 RCTs involving 36,422 patients and 19 ICIs, the incidence of grade 3–5 and grade 5 TRAEs was 17.9% and 0.8% with ICI monotherapy and 46.3% and 1.4%, respectively, with combinatorial therapy. Pneumonitis was the most common cause of grade 5 TRAEs following either monotherapy (16.3%) or combinatorial therapy (11.4%). Regarding grade 3–5 TRAEs, atezolizumab + chemotherapy (CT) and antiangiogenic therapy (AT) (atezolizumab + CAT), pembrolizumab + CT, ipilimumab + CT, and atezolizumab + CT were more toxic than any ICI monotherapy, pembrolizumab or nivolumab + radiotherapy (RT), and ICIs dual therapy (durvalumab + tremelimumab and nivolumab + ipilimumab). Tremelimumab, ipilimumab, durvalumab, and pembrolizumab were, however, associated with higher grade 5 TRAEs than combinatorial treatments. Atezolizumab + CAT was the most toxic and nivolumab + RT was the least toxic of combinatorial treatments; among monotherapies, tremelimumab and avelumab were the most and least toxic, respectively. The toxicity ranking changed with type of grade 3–5 TRAEs. Conclusions: Compared with combinatorial therapy, ICI monotherapy caused lower grade 3–5 TRAEs, but some monotherapies resulted in a higher incidence of fatal TRAEs. Atezolizumab + CAT and nivolumab + RT were the most and least toxic of combinatorial treatments, respectively, and tremelimumab and avelumab were the most and least toxic of the monotherapies, respectively.

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15

Singh, P., A. Uzgare, I. Litvinov, S. R. Denmeade, and J. T. Isaacs. "Combinatorial androgen receptor targeted therapy for prostate cancer." Endocrine-Related Cancer 13, no. 3 (September 2006): 653–66. http://dx.doi.org/10.1677/erc.1.00797.

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Prostatic carcinogenesis is associated with changes in the androgen receptor (AR) axis converting it from a paracrine dependence upon stromal signaling to an autocrine-initiated signaling for proliferation and survival of prostatic cancer cells. This malignant conversion is due to gain of function changes in which the AR activates novel genomic (i.e. transcriptional) and non-genomic signaling pathways, which are not present in normal prostate epithelial cells. During further progression, additional molecular changes occur which allow these unique malignancy-dependent AR signaling pathways to be activated even in the low androgen ligand environment present following androgen ablation therapy. These signaling pathways are the result of partnering the AR with a series of other genomic (e.g. transcriptional co-activators) or non-genomic (e.g. steroid receptor co-activator (Src) kinase) signaling molecules. Thus, a combinatorial androgen receptor targeted therapy (termed CART therapy) inhibiting several points in the AR signaling cascade is needed to prevent the approximately 30,000 US males per year dying subsequent to failure of standard androgen ablation therapy. To develop such CART therapy, a series of agents targeted at specific points in the AR cascade should be used in combination with standard androgen ablative therapy to define the fewest number of agents needed to produce the maximal therapeutic anti-prostate cancer effect. As an initial approach for developing such CART therapy, a variety of new agents could be combined with luteinizing hormone-releasing hormone analogs. These include: (1) 5α-reductase inhibitors to inhibit the conversion of testosterone to the more potent androgen, dihydrotestosterone; (2) geldanamycin analogs to downregulate AR protein in prostate cancer cells, (3) ‘bulky’ steroid analogs, which can bind to AR and prevent its partnering with other co-activators/signaling molecules, and (4) small molecule kinase inhibitors to inhibit MEK, which is activated as part of the malignant AR signaling cascade.

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16

Vivero-Escoto, Juan L. "Multifunctional Polysilsesquioxane Nanoparticles for Combinatorial Therapy of Cancer." Video Proceedings of Advanced Materials 1, no. 1 (November 1, 2020): 2020–0829. http://dx.doi.org/10.5185/vpoam.2020.0829.

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17

Kanda, Akio, Satoru Ebihara, Hiroyasu Yasuda, Ohrui Takashi, Takahiko Sasaki, and Hidetada Sasaki. "A Combinatorial Therapy for Pneumonia in Elderly People." Journal of the American Geriatrics Society 52, no. 5 (May 2004): 846–47. http://dx.doi.org/10.1111/j.1532-5415.2004.52230_5.x.

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18

Jernberg-Wiklund, Helena, and Kenneth Nilsson. "Toward a rational combinaTORial therapy for multiple myeloma." Blood 104, no. 13 (December 15, 2004): 3845–46. http://dx.doi.org/10.1182/blood-2004-09-3648.

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19

Gálvez-Gastélum, F. J., J. J. Garcia-Bañuelos, C. Beas-Zárate, A. Segura-Flores, H. González, V. Chaparro-Huerta, A. Salazar-Montes, et al. "Combinatorial gene therapy induces regression of hepatic encephalopathy." Gene Therapy 18, no. 1 (August 12, 2010): 88–94. http://dx.doi.org/10.1038/gt.2010.107.

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20

Pang, Kaifang, Ying-Wooi Wan, William T. Choi, Lawrence A. Donehower, Jingchun Sun, Dhruv Pant, and Zhandong Liu. "Combinatorial therapy discovery using mixed integer linear programming." Bioinformatics 30, no. 10 (January 24, 2014): 1456–63. http://dx.doi.org/10.1093/bioinformatics/btu046.

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21

León-Buitimea, Angel, Cesar R. Garza-Cárdenas, María Fernanda Román-García, César Agustín Ramírez-Díaz, Martha Ulloa-Ramírez, and José Rubén Morones-Ramírez. "Nanomaterials-Based Combinatorial Therapy as a Strategy to Combat Antibiotic Resistance." Antibiotics 11, no. 6 (June 12, 2022): 794. http://dx.doi.org/10.3390/antibiotics11060794.

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Since the discovery of antibiotics, humanity has been able to cope with the battle against bacterial infections. However, the inappropriate use of antibiotics, the lack of innovation in therapeutic agents, and other factors have allowed the emergence of new bacterial strains resistant to multiple antibiotic treatments, causing a crisis in the health sector. Furthermore, the World Health Organization has listed a series of pathogens (ESKAPE group) that have acquired new and varied resistance to different antibiotics families. Therefore, the scientific community has prioritized designing and developing novel treatments to combat these ESKAPE pathogens and other emergent multidrug-resistant bacteria. One of the solutions is the use of combinatorial therapies. Combinatorial therapies seek to enhance the effects of individual treatments at lower doses, bringing the advantage of being, in most cases, much less harmful to patients. Among the new developments in combinatorial therapies, nanomaterials have gained significant interest. Some of the most promising nanotherapeutics include polymers, inorganic nanoparticles, and antimicrobial peptides due to their bactericidal and nanocarrier properties. Therefore, this review focuses on discussing the state-of-the-art of the most significant advances and concludes with a perspective on the future developments of nanotherapeutic combinatorial treatments that target bacterial infections.

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22

Wang, Bin, Jin Huang, Shanshan Li, Zhanyu Pan, Yongming Guo, Yinli Yang, Ling Li, et al. "The Combinatorial Effect of Cisplatin and Moxibustion on Tumor Growth Inhibition with Special Reference to Modulation of the Immune Microenvironment in Lewis Lung Cancer Mice." Evidence-Based Complementary and Alternative Medicine 2020 (December 29, 2020): 1–14. http://dx.doi.org/10.1155/2020/3170803.

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Objective. As a first-line treatment for non-small cell lung cancer (NSCLC), the efficacy of chemotherapy is still unsatisfactory. Moxibustion has been shown to improve the side effects of radiotherapy and chemotherapy and regulate immune function. This study aimed to explore the antitumor effects and potential mechanisms of combinatorial cisplatin and moxibustion treatment for NSCLC by targeting the tumor microenvironment. Methods. Lewis lung cancer (LLC)-bearing mice were induced and treated with cisplatin or/and moxibustion at ST36 (Zusanli), and the growth, weight, and area of the tumor were evaluated. The numbers of various T cell subsets and myeloid cells in the tumor were assessed by flow cytometry, and the gene expression of related markers and cytokines was detected with real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the tumor vascular structure was investigated using CD31 and α-smooth muscle actin (α-SMA) immunofluorescence staining. The expression of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) was detected by immunohistochemical staining. Results. Both cisplatin and moxibustion inhibited LLC tumor growth and reduced both the tumor area and weight, with the combinatorial therapy showing superior outcomes. Moxibustion upregulated the infiltration of CD4+ T cells and Th1 cells in the tumor, and the combinatorial therapy increased the proportion of CD8+ cytotoxic T cells (CTLs), CD4+T cells, Th1, Th9 cells, and M1 macrophages, as well as the expression of Cd69, Ifng, and Cd86 mRNA. The combinatorial therapy improved vascular normalization by increasing both the microvessel density (MVD) and pericyte coverage (α-SMA area density) and inhibiting the expression of the VEGF. Conclusions. Combinatorial cisplatin and moxibustion treatment inhibited the LLC tumor growth by mechanisms related to the improvement of the tumor immune microenvironment and vascular normalization, providing an effective combinatorial therapy beneficial for patients with NSCLC.

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23

Seo, Hyun Ah, Sokviseth Moeng, Seokmin Sim, Hyo Jeong Kuh, Soo Young Choi, and Jong Kook Park. "MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies." Cells 9, no. 1 (December 20, 2019): 29. http://dx.doi.org/10.3390/cells9010029.

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

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24

Jiang, Kai, Di Zhao, Rui Ye, Xinlong Liu, Chao Gao, Yuanyuan Guo, Chuan Zhang, Jian Zeng, Shi Wang, and Jie Song. "Transdermal delivery of poly-hyaluronic acid-based spherical nucleic acids for chemogene therapy." Nanoscale 14, no. 5 (2022): 1834–46. http://dx.doi.org/10.1039/d1nr06353g.

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25

Kumari, Smita, Dia Advani, Sudhanshu Sharma, Rashmi K. Ambasta, and Pravir Kumar. "Combinatorial therapy in tumor microenvironment: Where do we stand?" Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1876, no. 2 (December 2021): 188585. http://dx.doi.org/10.1016/j.bbcan.2021.188585.

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26

Hao, Yang, Chih Kit Chung, Zhenfeng Yu, Ruben V. Huis in ‘t Veld, Ferry A. Ossendorp, Peter ten Dijke, and Luis J. Cruz. "Combinatorial Therapeutic Approaches with Nanomaterial-Based Photodynamic Cancer Therapy." Pharmaceutics 14, no. 1 (January 4, 2022): 120. http://dx.doi.org/10.3390/pharmaceutics14010120.

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Photodynamic therapy (PDT), in which a light source is used in combination with a photosensitizer to induce local cell death, has shown great promise in therapeutically targeting primary tumors with negligible toxicity and minimal invasiveness. However, numerous studies have shown that noninvasive PDT alone is not sufficient to completely ablate tumors in deep tissues, due to its inherent shortcomings. Therefore, depending on the characteristics and type of tumor, PDT can be combined with surgery, radiotherapy, immunomodulators, chemotherapy, and/or targeted therapy, preferably in a patient-tailored manner. Nanoparticles are attractive delivery vehicles that can overcome the shortcomings of traditional photosensitizers, as well as enable the codelivery of multiple therapeutic drugs in a spatiotemporally controlled manner. Nanotechnology-based combination strategies have provided inspiration to improve the anticancer effects of PDT. Here, we briefly introduce the mechanism of PDT and summarize the photosensitizers that have been tested preclinically for various cancer types and clinically approved for cancer treatment. Moreover, we discuss the current challenges facing the combination of PDT and multiple cancer treatment options, and we highlight the opportunities of nanoparticle-based PDT in cancer therapies.

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27

Cortese, Barbara, Stefania D’Amone, Mariangela Testini, Patrizia Ratano, and Ilaria Elena Palamà. "Hybrid Clustered Nanoparticles for Chemo-Antibacterial Combinatorial Cancer Therapy." Cancers 11, no. 9 (September 10, 2019): 1338. http://dx.doi.org/10.3390/cancers11091338.

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Background: A great number of therapeutic limitations, such as chemoresistance, high dosage, and long treatments, are still present in cancer therapy, and are often followed by side effects such as infections, which represent the primary cause of death among patients. Methods: We report pH- and enzymatic-responsive hybrid clustered nanoparticles (HC-NPs), composed of a PCL polymeric core loaded with an anticancer drug, such as Imatinib Mesylate (IM), and coated with biodegradable multilayers embedded with antibacterial and anticancer baby-ship silver NPs, as well as a monoclonal antibody for specific targeting of cancer cells conjugated on the surface. Results: The HC-NPs presented an onion-like structure that serially responded to endogenous stimuli. After internalization into targeted cancer cells, the clustered nanoparticles were able to break up, thanks to intracellular proteases which degraded the biodegradable multilayers and allowed the release of the baby-ship NPs and the IM loaded within the pH-sensible polymer present inside the mothership core. In vitro studies validated the efficiency of HC-NPs in human chronic leukemic cells. This cellular model allowed us to demonstrate specificity and molecular targeting sensitivity, achieved by using a combinatorial approach inside a single nano-platform, instead of free administrations. The combinatory effect of chemotherapic drug and AgNPs in one single nanosystem showed an improved cell death efficacy. In addition, HC-NPs showed a good antibacterial capacity on Gram-negative and Gram-positive bacteria. Conclusions: This study shows an important combinatorial anticancer and antimicrobial effect in vitro.

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28

Singh, Abhay Kumar, Baidyanath Chakravarty, and Koel Chaudhury. "Nanoparticle-Assisted Combinatorial Therapy for Effective Treatment of Endometriosis." Journal of Biomedical Nanotechnology 11, no. 5 (May 1, 2015): 789–804. http://dx.doi.org/10.1166/jbn.2015.2020.

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29

Matthews, Ruth C., and James P. Burnie. "Recombinant antibodies: a natural partner in combinatorial antifungal therapy." Vaccine 22, no. 7 (February 2004): 865–71. http://dx.doi.org/10.1016/j.vaccine.2003.11.032.

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30

Shanavas, Asifkhan, Nishant K. Jain, Navneet Kaur, Dinesh Thummuri, Maruthi Prasanna, Rajendra Prasad, Vegi Ganga Modi Naidu, Dhirendra Bahadur, and Rohit Srivastava. "Polymeric Core–Shell Combinatorial Nanomedicine for Synergistic Anticancer Therapy." ACS Omega 4, no. 22 (November 11, 2019): 19614–22. http://dx.doi.org/10.1021/acsomega.9b02167.

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31

Gálvez-Gastélum, Francisco J., Aida A. Segura-Flores, María D. Senties-Gomez, Jose F. Muñoz-Valle, and Juan S. Armendáriz-Borunda. "Combinatorial gene therapy renders increased survival in cirrhotic rats." Journal of Biomedical Science 17, no. 1 (2010): 42. http://dx.doi.org/10.1186/1423-0127-17-42.

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32

Li, V. W., R. A. Ball, N. Vasan, and W. W. Li. "Antiangiogenic therapy for squamous cell carcinoma using combinatorial agents." Journal of Clinical Oncology 23, no. 16_suppl (June 2005): 3032. http://dx.doi.org/10.1200/jco.2005.23.16_suppl.3032.

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33

Barbosa, Silvia, Antonio Topete, Manuel Alatorre-Meda, Eva M. Villar-Alvarez, Alberto Pardo, Carmen Alvarez-Lorenzo, Angel Concheiro, Pablo Taboada, and Víctor Mosquera. "Targeted Combinatorial Therapy Using Gold Nanostars as Theranostic Platforms." Journal of Physical Chemistry C 118, no. 45 (October 31, 2014): 26313–23. http://dx.doi.org/10.1021/jp505979e.

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34

Takaichi, Shohei, Jennifer L. Tomlinson, Mincheng Yu, Amro M. Abdelrahman, Nathan W. Werneburg, Gregory J. Gores, and Rory L. Smoot. "Effect of AXL on cholangiocarcinoma survival and sensitivity to cytotoxic chemotherapy." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 591. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.591.

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591 Background: Cholangiocarcinoma (CCA) is a lethal disease with limited therapeutic options. We have demonstrated the interaction of Src-family kinase LCK with AXL, a TAM receptor tyrosine kinase (RTK), by phosphoproteomic analysis in CCA ( J Hepatol 2022). AXL is reported to act as a mechanism of acquired drug resistance in solid cancers. However, the role of AXL in CCA remains to be elucidated. Here, we investigated the significance of AXL expression as a potential therapeutic target in CCA. Methods: We first evaluated the expression levels of AXL in CCA and the associations with patient outcome using publicly available data from The Cancer Genome Atlas (TCGA). Next, to evaluate whether AXL inactivation sensitizes CCA cells to gemcitabine and cisplatin (GemCis) therapy as a standard therapy. AXL downregulation was achieved via siRNA approach and the selective inhibitor bemcentinib. We examined 50% inhibitory concentration (IC50) value of HuCCT1, a well characterized CCA cell line, on GemCis therapy with and without AXL knockdown using CellTiter-Glo cell viability assay. Then we assessed the efficacy of the combinatorial therapy of GemCis and bemcentinib utilizing Calcusyn software. Finally, apoptosis was evaluated by Annexin V assay. In vivo efficacy was assessed using a SB-1 (murine CCA cell line) and syngeneic murine model of CCA in C57Bl/6J mice treated with vehicle, GemCis, bemcentinib, and the combination of GemCis and bemcentinib. Results: In the TCGA cohorts, AXL is significantly expressed in CCA (P < 0.01), and disease-free survival and overall survival in low AXL expression group are significantly longer than those in high AXL expression group (P = 0.04, 0.01). In in vitro study, IC50 value of GemCis was decreased from 685nM to 129nM after AXL knockdown. Synergy effect was observed with the value of CI = 0.17 and Fa = 0.50 in the combinatorial therapy. The combinatorial therapy caused significantly increased apoptosis compared to GemCis or bemcentinib alone (P < 0.01, P < 0.01). In in vivo study, the combinatorial therapy significantly suppressed the tumor growth compared to GemCis or bemcentinib alone (P = 0.04, 0.01). Conclusions: Targeting AXL sensitizes CCA cell lines and preclinical models to standard of care GemCis combinatorial therapy. Our study suggests that the addition of AXL targeted therapy to cytotoxic chemotherapy can increase the response in CCA patients and is a promising combination.

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Ahmad, Touqeer, Rizwana Sarwar, Ayesha Iqbal, Uzma Bashir, Umar Farooq, Sobia Ahsan Halim, Ajmal Khan, and Ahmed Al-Harrasi. "Recent advances in combinatorial cancer therapy via multifunctionalized gold nanoparticles." Nanomedicine 15, no. 12 (May 2020): 1221–37. http://dx.doi.org/10.2217/nnm-2020-0051.

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The diverse behavior of nanogold in the therapeutic field is related to its unique size and shape. Nanogold offers improvements in modern diagnostic and therapeutic implications, increases disease specificity and targeted drug delivery, and is relatively economical compared with other chemotherapeutic protocols. The diagnosis of cancer and photothermal therapy improve drastically with the implementation of nanotechnology. Different types of nanoparticles, that is, gold silica nanoshells, nanorods and nanospheres of diverse shapes and geometries, are used widely in the photothermal therapy of cancerous cells and nodules. Numerous reviews have been published on the therapeutic applications of gold nanoparticles, but studies on combinatorial applications of nanogold in cancer therapy are limited. This review focuses on the combinatorial cancer therapy using optical properties of nanogold with different shapes and geometries, and their therapeutic applications in cancer diagnosis, photothermal therapy, cancer imaging and targeted drug delivery.

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Bao, Xuhui, Stephen T. Keir, Smita K. Nair, Ira Pastan, Darell D. Bigner, and Vidyalakshmi Chandramohan. "A combinatorial immunotherapy for malignant brain tumors: D2C7 immunotoxin and immune checkpoint inhibitors." Journal of Clinical Oncology 35, no. 7_suppl (March 1, 2017): 102. http://dx.doi.org/10.1200/jco.2017.35.7_suppl.102.

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102 Background: Immunotoxins can induce direct and rapid cytotoxicity by targeting specific tumor antigens. D2C7 is a unique recombinant immunotoxin targeting EGFRwt/EGFRvIII, two frequently overexpressed proteins on gliomas, and is currently being tested in a phase I/II clinical trial (NCT02303678) for recurrent malignant gliomas. Immunotoxins have also been shown to induce a secondary antitumor immune response via stimulation of cytotoxic T lymphocytes (CTLs). Immune checkpoint inhibitors, which have successfully treated several advanced tumors by promoting the antitumor function of CTLs, may further enhance this immunotoxin-induced antitumor response. Thus, we hypothesize that combining D2C7 with immune checkpoint inhibitors will promote long-term tumor regression due to primary cytotoxicity and enhanced anti-tumor immunity. Methods: We developed a CT2A-mD2C7 mouse glioma cell line with robust in vitro cytotoxicity of D2C7 (IC50= 0.47 ng/mL). In vivo anti-tumor efficacy was evaluated by intratumoral injection of D2C7 combined with intraperitoneal injection of anti-CTLA4 or anti-PD1 antibodies in single-side and bilateral subcutaneous (SC) CT2A-mD2C7 glioma models in C57BL/6 immunocompetent mice. Results: In the single-side model, D2C7 monotherapy and combinatorial therapy showed a significant tumor growth delay (P < 0.01). Complete regression ( ≥ 40%) was only observed in combinatorial therapy groups. All cured mice rejected the rechallenging of CT2A parental cells in the contralateral flank and the subsequent rechallenging of CT2A-mD2C7 cells in the brain. In the bilateral model, the larger right tumors were treated with D2C7/anti-CTLA4/anti-PD1 monotherapy or D2C7+anti-CTLA4/PD1 combinatorial therapy, while the left tumors were untreated by D2C7. In the groups where the right tumors were treated with monotherapy or combinatorial therapy, the left untreated tumors also grew much slower. Furthermore, the combinatorial therapy led to the most significantly delayed growth of the left untreated tumors (P < 0.05). Conclusions: Immune checkpoint inhibitors can enhance D2C7-induced anti-tumor immunity to achieve a synergistic long-term tumor regression.

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Egorova, Anna, Ivan Pyankov, Marianna Maretina, Vladislav Baranov, and Anton Kiselev. "Peptide Nanoparticle-Mediated Combinatorial Delivery of Cancer-Related siRNAs for Synergistic Anti-Proliferative Activity in Triple Negative Breast Cancer Cells." Pharmaceuticals 14, no. 10 (September 23, 2021): 957. http://dx.doi.org/10.3390/ph14100957.

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Triple negative breast cancer (TNBC) is one of the deadliest types of cancer for women of different age groups. Frequently this cancer does not respond to conservative treatment. Combinatorial RNAi can be suggested as an advanced approach to TNBC therapy. Due to the fact that TNBC cells overexpress chemokine receptor 4 we used modular L1 peptide-based nanoparticles modified with CXCR4 ligand for combinatorial delivery of siRNAs suppressing major transduction pathways. TNBC cell line MDA-MB-231 was used as a cellular model. Genes encoding the AQP3, CDC20, and COL4A2 proteins responsible for proliferative activity in TNBC cells were selected as RNAi targets. The siRNA binding ability of the carrier was studied at different charge ratios. The silencing specificity was demonstrated for all siRNAs studied. Alamar Blue proliferation assay has shown significant reduction in the anti-proliferative activity after combinatorial siRNA transfection compared to single siRNA delivery.The most significant synergistic effect has been demonstrated for combinatorial transfection of anti-COL4A2and anti-CDC20 siRNAs what resulted in 1.5–2 fold inhibition of proliferation and migration of TNBC cells. Based on our findings, we have concluded that combinatorial treatment by CXCR4-ligand modified L1-polyplexes formed with AQP3, CDC20, and COL4A2 siRNAs effectively inhibits proliferation of TNBC cells and can be suggested as useful tool for RNAi-mediated cancer therapy.

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Venkatesh, Yarra, Kumari Shanti Kiran, Sk Sheriff Shah, Amrita Chaudhuri, Satyahari Dey, and N. D. Pradeep Singh. "One- and two-photon responsive sulfur dioxide (SO2) donors: a combinatorial drug delivery for improved antibiotic therapy." Organic & Biomolecular Chemistry 17, no. 10 (2019): 2640–45. http://dx.doi.org/10.1039/c9ob00090a.

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Xu, Pei-Yao, Xiang Zheng, Ranjith Kumar Kankala, Shi-Bin Wang, and Ai-Zheng Chen. "Advances in Indocyanine Green-Based Codelivery Nanoplatforms for Combinatorial Therapy." ACS Biomaterials Science & Engineering 7, no. 3 (February 4, 2021): 939–62. http://dx.doi.org/10.1021/acsbiomaterials.0c01644.

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Cortese, Barbara, Stefania D’Amone, and Ilaria Palamà. "Wool-Like Hollow Polymeric Nanoparticles for CML Chemo-Combinatorial Therapy." Pharmaceutics 10, no. 2 (April 18, 2018): 52. http://dx.doi.org/10.3390/pharmaceutics10020052.

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Jehan, Shah, Jiaxin Huang, Umar Farooq, Irum Basheer, and Wenhu Zhou. "Combinatorial effect of thymoquinone with chemo agents for tumor therapy." Phytomedicine 98 (April 2022): 153936. http://dx.doi.org/10.1016/j.phymed.2022.153936.

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Makarova, K. S., Yu V. Gumenetskaya, V. A. Biryukov, I. A. Strikanova, T. A. Kireeva, O. G. Lepilina, O. B. Karyakin, S. A. Ivanov, and A. D. Kaprin. "Combinatorial radiation therapy for prostate cancer with seminal vesicle invasion." Cancer Urology 17, no. 4 (February 10, 2022): 94–99. http://dx.doi.org/10.17650/1726-9776-2021-17-4-94-99.

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Background. It seems advisable to investigate the feasibility of radiation therapy combined with hormone therapy to treat locally advanced prostate cancer. Combination of two ways to deliver ionizing radiation doses enables us to elevate a total tumor dose and to reduce radiation exposure to critical organs. However, the feasibility of combinatorial radiation therapy (CRT) in prostate cancer patients with seminal vesicle invasion remains insufficiently investigated. The number of studies focusing on this problem is still extremely small.Objective of this study is to evaluate the efficacy and toxicity of radiation therapy combined with hormone therapy for prostate cancer with seminal vesicle invasion.Materials and methods. From April 2016 to April 2020, 52 patients with prostate cancer (cT3bN0) received CRT at the clinic of the A.F. Tsyb Medical Radiological Research Center. The median patient follow-up was 29.7 months (from 11.9 to 58.4 months). The mean age of patients was 65.7 years. The initial mean level of PSA was 28.7 ng/ml. Fifty (96.2 %) patients were given radiation therapy together with hormone therapy.Results. The tolerability of CRT appeared satisfactory. Grade I acute radiation-induced reactions of the urinary tract occurred in 13 (25 %) patients; grade II ones - in 2 (3.8 %) patients. Grade I acute radiation-induced reactions of the gastrointestinal tract occurred in 11 (21.5 %) patients; grade II ones - in 1 (1.9 %) patient. Grade I late complications of the urinary tract were noted in 4 (7.7 %) patients; grade II ones - in 2 (3.8 %) patients. Grade I late complications of the gastrointestinal tract were noted in 2 (3.8 %) patients; grade II ones - in 3 (5.8 %) patients.The three-year cancer-specific survival rate was 97 %; the overall survival rate was 83 %. Eight (15.4 %) patients showed prostate cancer progression. Five (9.6 %) patients experienced cancer recurrence in the form of distant bone metastases. In 1 (1.9 %) patient, disease recurrence was associated with involvement of regional lymphatic collectors and distant inguinal lymph node metastases. Local recurrence was noted in 1 (1.9 %) patient. One (1.9 %) patient developed loco-regional recurrence with distant metastasis to bones. The three-year recurrence-free survival rate was 75.6 %.Conclusion. Our study demonstrates that CRT is highly effective in prostate cancer (cT3bN0) treatment while having an acceptable level of complications.

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Reardon, David A., Mark R. Gilbert, Wolfgang Wick, and Linda Liau. "Immunotherapy for neuro-oncology: the critical rationale for combinatorial therapy." Neuro-Oncology 17, suppl 7 (October 29, 2015): vii32—vii40. http://dx.doi.org/10.1093/neuonc/nov178.

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Al-Lazikani, Bissan, Udai Banerji, and Paul Workman. "Combinatorial drug therapy for cancer in the post-genomic era." Nature Biotechnology 30, no. 7 (July 2012): 679–92. http://dx.doi.org/10.1038/nbt.2284.

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Koh, J. T., Z. Zhao, Z. Wang, I. S. Lewis, P. H. Krebsbach, and R. T. Franceschi. "Combinatorial Gene Therapy with BMP2/7 Enhances Cranial Bone Regeneration." Journal of Dental Research 87, no. 9 (September 2008): 845–49. http://dx.doi.org/10.1177/154405910808700906.

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BMP2/7 heterodimer expression by adenovirus can stimulate bone formation at subcutaneous sites. In the present study, we evaluate whether this approach will also promote healing of cranial defects. Adenovirus expressing BMP2 or BMP7 (AdBMP2, AdBMP7) was titrated to yield equivalent BMP protein levels after transduction into murine BLK cells. Analysis of conditioned medium showed that BMP2/7 heterodimers have enhanced ability to stimulate alkaline phosphatase and Smad 1,5,8 phosphorylation relative to equivalent amounts of BMP2 or BMP7 homodimers. To measure bone regeneration, we implanted virally transduced BLK cells into critical-sized calvarial defects generated in C57BL6 mice. AdBMP2/7-transduced cells were more effective in healing cranial defects than were cells individually transduced with AdBMP2 or BMP7. Dramatic increases in bone volume fraction, as measured by microCT, as well as fusion of regenerated bone with the defect margins were noted. Thus, the use of gene therapy to express heterodimeric BMPs is a promising potential therapy for healing craniofacial bones.

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Kokaia, Merab. "Combinatorial gene therapy for epilepsy: simultaneous NPY and Y2 overexpression." Neuropeptides 55 (February 2016): 4–5. http://dx.doi.org/10.1016/j.npep.2015.11.010.

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Sullivan, Ryan J., and Keith T. Flaherty. "New Strategies in Melanoma: Entering the Era of Combinatorial Therapy." Clinical Cancer Research 21, no. 11 (May 31, 2015): 2424–35. http://dx.doi.org/10.1158/1078-0432.ccr-14-1650.

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Fedorov, B. S., M. A. Fadeev, A. B. Eremeev, N. P. Konovalova, G. N. Bogdanov, L. V. Tatyanenko, T. E. Sashenkova, and D. V. Mishchenko. "Hydroxamic acids: synthesis and adjuvant activity in combinatorial anticancer therapy." Russian Chemical Bulletin 65, no. 3 (March 2016): 801–5. http://dx.doi.org/10.1007/s11172-016-1377-0.

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Rauschenbach, Laurèl, Anja Wieland, Roman Reinartz, Sied Kebir, Andreas Till, Marvin Darkwah Oppong, Celia Dobersalske, et al. "Drug repositioning of antiretroviral ritonavir for combinatorial therapy in glioblastoma." European Journal of Cancer 140 (November 2020): 130–39. http://dx.doi.org/10.1016/j.ejca.2020.09.017.

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Singh, Amit, Meghna Talekar, Thanh-Huyen Tran, Abishek Samanta, Ravi Sundaram, and Mansoor Amiji. "Combinatorial approach in the design of multifunctional polymeric nano-delivery systems for cancer therapy." J. Mater. Chem. B 2, no. 46 (2014): 8069–84. http://dx.doi.org/10.1039/c4tb01083c.

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