Ge, Fangfang: Unveiling Multi-Faceted Insights in Cancer Therapeutics : From Immunomodulation to Predictive Signatures. - Bonn, 2023. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-73380
@phdthesis{handle:20.500.11811/11159,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-73380,
author = {{Fangfang Ge}},
title = {Unveiling Multi-Faceted Insights in Cancer Therapeutics : From Immunomodulation to Predictive Signatures},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2023,
month = dec,

note = {Continual and dedicated endeavors are actively underway to advance the field of cancer immunotherapy, with a specific focus on enhancing the efficacy and applicability of various methodologies. One prominent avenue of research involves the ongoing refinement of cytokine-induced killer (CIK) cell therapy, a promising immunotherapeutic approach. CIK cells cytotoxicity against a variety of tumor target cells, potentially synergistic with surgery, chemotherapy, and radiotherapy. In the realm of addressing hematological malignancies and liver cancer, an enduring endeavor persists to uncover novel therapeutic modalities with the intent of attaining enhanced clinical outcomes. This pursuit is driven by the aspiration to curtail instances of recurrence and to efficaciously manage cases post-recurrence. Our research comprises two distinct components. The first pertains to the assessment of both the efficacy and underlying mechanisms associated with the combination of Cytokine-Induced Killer (CIK) cells and anti-tumor agents encompassing HSP90 inhibitors (namely, 17-DMAG and Ganetespib) as well as non-anti-tumor agents (such as meticrane) for the treatment of hematological malignancies and liver cancer. The second facet of our study involves the elucidation of non-coding RNA (long non-coding RNA, or lncRNA) profiles within the context of cancer. The primary objectives encompass prognostic prediction and the identification of potential therapeutic targets inherent to these intricate molecular signatures. In our publication, our results revealed that CIK cytotoxicity in Burkitt’s lymphoma (BL) cells was augmented in combination with HSP90 inhibitors and we provide evidence that CIK cells combination with HSP90 inhibitors, target BL cells via the Fas–FasL axis rather than the NKG2D pathway. We also evaluated the antitumor properties of the diuretic drug mericrane against hematological malignancies and liver cancer, and its synergistic effect when combined with CIK cells and epigenetic drugs for cancer therapy. Meticrane exhibited notable anti-cancer properties in the contexts of both liver cancer and leukemia. Moreover, its application in conjunction with epigenetic agents displayed an inclination towards additive or synergistic interactions, thereby presenting a promising avenue for therapeutic enhancement against both liver cancer and Hematological malignancies. However, it is noteworthy that no synergistic effect was observed when combined with Cytokine-Induced Killer (CIK) cells, as opposed to the independent utilization of CIK cells and meticrane in addressing Hematological malignancies and liver cancer. We utilized bioinformatic analysis to discern lncRNAs with plausible associations to the survival outcomes of cancer patients. Through this rigorous approach, we successfully identified a subset of lncRNAs that exhibit significant prognostic relevance within the context of cancer patients.
Collectively, the integrated approach involving the concurrent administration of Cytokine-Induced Killer (CIK) cells and HSP90 inhibitors presents a promising avenue for conferring tangible clinical advantages to individuals afflicted with Burkitt's lymphoma (BL). Furthermore, meticrane has demonstrated pronounced anti-cancer efficacy, and its conjunction with epigenetic agents has unveiled an inclination towards additive or synergistic responses in the treatment of liver cancer and leukemia. In addition, our research has contributed to the identification of long non-coding RNAs (lncRNAs) closely linked to prognostic considerations, thereby facilitating their potential deployment as predictive tools and therapeutic targets. This multifaceted exploration enriches our comprehension of cancer biology and broadens the horizons of therapeutic strategies.},

url = {https://hdl.handle.net/20.500.11811/11159}
}

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