免疫不全のゼブラフィッシュで移植されたヒトの癌と治療反応を視覚化
Chuan Yan1, Dalton C Brunson2, Qin Tang2
1Molecular Pathology Unit, Massachusetts General Hospital Research Institute, Charlestown, MA 02129, USA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02139, USA.
Cell
|April 30, 2019
まとめ
人間の癌の異種移植を ダイナミックに視覚化するために 光学的に明確なゼブラフィッシュモデルを開発しました このモデルは,細胞循環停止とアポトーシスを追跡することによって,ラブドミオサルコマの組み合わせ治療の有効性を明らかにしました.
科学分野:
- 比較免疫学
- 癌の生物学
- ゼブラフィッシュのモデル
背景:
- Xenograftモデルは,がん薬の臨床前有効性評価に不可欠です.
- 異種移植における単細胞フェノタイプを直接視覚化することは依然として困難である.
研究 の 目的:
- 人間の癌のダイナミックな単細胞視覚化のための光学的に明確なゼブラフィッシュ異種移植モデルを開発する.
- リブドミオサルコムの併用療法の臨床前有効性を評価する.
主な方法:
- 異種移植のために適応性やNKの免疫細胞が欠けているゼブラフィッシュのprkdc-/- を利用した.
- ダイナミックイメージングのために,光変換細胞系統追跡とFUCCI細胞サイクルレポーターを使用した.
- オラパリブ (PARP阻害剤) とテモゾロミド (DNA破壊剤) の併用療法
主要な成果:
- 37°Cでヒトの様々な癌を移植し,単細胞の可視化が可能になりました.
- ヒトのラブドミオサルコマにおける移転性および増殖性細胞状態を特定した.
- アポトーシスの前のG2段階でのラブドミオサルコマ細胞を止めることが実証されています.
- 患者からの異種移植を成功させました
結論:
- 開発されたゼブラフィッシュモデルは,がん異種移植のダイナミックな単細胞解像度を提供します.
- オラパリブとテモゾロミドの併用は,ラブドミオサルコマに対する臨床前有効性を示しています.
- このモデルは様々な癌の 個別化治療の開発を容易にする.
関連する概念動画
02:49Cancer Therapies
9.9K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
9.9K
02:57Targeted Cancer Therapies
8.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.7K
01:25Immunodeficiency Diseases
2.0K
Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
There are three main causes of immunodeficiency...
2.0K
00:59Gene Therapy
27.4K
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
27.4K
01:26Group Therapy
403
Group therapy is a sociocultural approach to psychological treatment, where individuals with shared psychological challenges come together under the guidance of a mental health professional. This therapeutic modality offers unique opportunities for individuals to connect, share, and grow within the context of a supportive group. By fostering mutual understanding and collaboration, group therapy can address a range of psychological concerns effectively, often complementing or surpassing the...
403
01:29Psychodynamic Therapy
544
Psychodynamic therapies emphasize the exploration of unconscious processes and early childhood experiences as fundamental contributors to psychological difficulties. These therapies, deeply rooted in Freud's psychoanalytic theory, aim to uncover and resolve unconscious conflicts, granting individuals insights that promote emotional and behavioral healing. Contemporary psychodynamic approaches have evolved, integrating a broader range of influences and methodologies while still valuing the...
544