China
Africa
Explore chapters and articles related to this topic
A Primary Culture System of Human Colon Carcinoma Cells and its Use in Evaluating Differentiation Therapy
Published in Leonard H. Augenlicht, Cell and Molecular Biology of Colon Cancer, 2019
Differentiation therapy for colon cancer could provide an alternative to chemotherapy and radiation therapy.1 In an attempt to determine the efficacy of this therapy, several investigators have studied the effects of differentiation agents on colon carcinoma cell lines.2-9 These studies clearly demonstrated that the differentiation agents dimethylformamide (DMF), dimethylsulfoxide (DMSO), and sodium butyrate could induce a number of morphological, antigenic, and functional changes in several human colon carcinoma cell lines. DMF, in particular, induced a loss of anchorage independent cell growth in vitro and decreased in vivo tumorigenicity in the nude mouse model.5
Neuroblastoma
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Immunotherapy is given along with differentiation therapy. Antibodies have been developed to target GD2, which is present on the surface of neuroblastoma cells, and targeted therapy against this receptor has been shown to have a significant effect on survival, with a 2-year EFS of 66% vs. 46% in the group that received standard therapy without immunotherapy. It is important to note that patients can have fairly significant systemic responses to the immunotherapy and should be monitored closely during infusion [26, 27].
Differentiation Induction in Acute Promyelocytic Leukemia
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Acute myeloid leukemia (AML) is a heterogeneous group of diseases typically associated with an aggressive course and generally a poor overall survival (OS). Despite advances in therapy over the past 20 years, long-term survival for patients with AML remains approximately 30% (1). Acute promyelocytic leukemia (APL) represents a distinctive subtype of AML. It accounts for approximately 10% to 15% of all patients with AML and is distinguished from other types by a younger median age (40 vs. 68 years), a unique genetic abnormality, the t(15;17) translocation and the formation of the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) fusion transcript, and most importantly, by the high cure rate achieved with differentiation therapy. Until the late 1980s and early 1990s, APL was considered the most fatal subtype of AML primarily because of a severe coagulopathy often leading to catastrophic hemorrhage early in the natural history of the disease or early in the course of treatment. The discovery that the leukemic promyelocytes from patients with APL were uniquely sensitive to all-trans retinoic acid (ATRA) and that the breakpoint on chromosome 17 that resulted in the development of an abnormal PML-RARα fusion product eventually led to the recognition that disruption of RARα gene product was the major cause of maturation arrest in APL (2,3). Currently, APL is associated with several variant chromosomal abnormalities leading to different gene rearrangements. PML-RARα is the product of t(15;17), NPM (nucleophosmin)-RARα is the product of t(5;17)(q35;q21), and is NuMA (nuclear matrix associated)-RARα the product of t(11;17)(q13;q21), all of which lead to a syndrome that is responsive to ATRA. PLZF (promyelocytic leukemia zinc finger)-RARα, the product of t(11;17)(q23; q21), is unresponsive to ATRA. Signal transducer and activator of transcription 5B (STAT5B) is the product of t(17;17)(q11;q21) (4). In addition to cytogenetic variants, molecular variant of the PML-RARα transcript such as bcr1, bcr2, and bcr3 have also been described (5). Advances in the understanding of APL have led to a new strategy in anti-leukemia therapy. Rather than relying on intensive chemotherapy, the treatment of APL focuses now on differentiation therapy to induce remission. Such a strategy results in long-term survival rates of more than 80% (6). This chapter will address the unique biology of APL, the role of ATRA in differentiation therapy and arsenic trioxide (ATO) in inducing apoptosis. Both agents contribute to the remarkable cure rates in APL. In addition, novel strategies such as FLT3 inhibitors, antiangiogenesis agents, monoclonal antibodies, differentiation agents, and histone deacetylase inhibitors will be described.
Securinine Induces Differentiation of Human Promyelocytic Leukemic HL-60 Cells through JNK-Mediated Signaling Pathway
Published in Nutrition and Cancer, 2022
Jeetesh Sharma, Ankita Pandey, Sapna Sharma, Aparna Dixit
Differentiation therapy, an alternative to standard chemotherapy, has shown remarkable improvement in the survival rate and prognosis of leukemia patients (3). It involves an external agent, natural or synthetic, a hormone or a cytokine, that irreversibly alters the cancer cell phenotype, thereby allowing them to differentiate like other normal cells in the body and undergo apoptosis (4). All-trans retinoic acid (ATRA), a vitamin A derivative, has been clinically successful as a potent inducer of acute promyelocytic leukemic (APL) cell differentiation (4, 5). ATRA treatment exhibited alterations in the morphology of cells, activation of nuclear receptors like RAR (types α, β, γ) and retinoid X receptors (RXR types α, β, γ) to induce apoptosis and regulation of cell cycle (5). However, like other chemotherapies, relapse, and resistance against ATRA in addition to other side effects, namely leukocytosis and differentiation syndrome, were observed, thus limiting its use against AML (6). Therefore, screening and identification of novel differentiating agents with minimal relapse rate and treatment resistance are desirable.
Heterogeneous Differentiation of Highly Proliferative Embryonal Carcinoma PCC4 Cells Induced by Curcumin: An In Vitro Study
Published in Nutrition and Cancer, 2021
Geetha Viswanathan, Lip Yong Chung, Usha K. Srinivas
Currently, the standard treatment option for GCT is chemotherapy in combination with etoposide, cisplatin, and bleomycin with or without surgical resection of the tumor. In addition, chemo-resistance is often a concern in GCT treatment. An alternative approach, referred to as differentiation therapy, employs a drug that reverses cell malignancy by inducing cell differentiation. A classic example of differentiation therapy is retinoic acid (RA) treatment for acute promyelocytic leukemia, an approach responsible for making this a curable form of cancer today (30). RA triggers differentiation of pluripotent cells to terminally differentiated and nonmalignant cells (31). However, RA treatment can cause retinoic acid syndrome in many patients, a syndrome characterized by symptoms that include fever, weight gain, respiratory distress, hypotension, and acute renal failure (32). Moreover, RA treatment is associated with developmental anomalies (33). Due to these potential severe side effects, the commonly used dosage of RA has been reduced from 45 to 25 mg/m2 per day (34); however, the dosage reduction reduces treatment efficacy.
The comparison of bone marrow kinetics between patients with acute myeloid leukemia and acute promyelocytic leukemia after induction chemotherapy
Published in Immunopharmacology and Immunotoxicology, 2020
Rafiye Ciftciler, Ibrahim C. Haznedaroglu, Osman Ozcebe, Salih Aksu, Nilgun Sayınalp, Hakan Goker, Haluk Demiroglu, Yahya Buyukasık
We investigated that neutrophil and platelet recovery times were statistically significantly longer in APL than AML patients after induction chemotherapy. Additionally, we compared the neutrophil and platelet recovery days of APL patients who received only AIDA and patients who received AIDA plus Ara-C regimen as induction chemotherapy. We showed that neutrophil and platelet recovery days were similar in patients who received only AIDA and in patients who received AIDA plus Ara-C regimen as induction chemotherapy. In subgroup analysis of APL patients, there was no significant difference in PRT and NRT. Although the mechanism of the results in this study was not fully understood, it can be thought that it is due to ATRA’s effect of differentiation of promyelocytes to mature neutrophils without bone marrow hypoplasia. Additionally, it may also be due to longer use of ATRA than cytotoxic chemotherapy agents in induction regimen. ATRA can selectively induce terminal differentiation of promyelocytic leukemic cells into normal granulocytes without causing bone marrow hypoplasia or exacerbation of the frequently occurring fatal hemorrhagic syndromes related with chemotherapy. Although development of rapid resistance to differentiation therapy is commonly observed, when combined with chemotherapy, this therapy can dramatically increase survival outcomes by improving the effectiveness of chemotherapy [8].