scholarly journals CHK1 Inhibitors in Combination Chemotherapy: Thinking Beyond the Cell Cycle

2011 ◽  
Vol 11 (2) ◽  
pp. 133-140 ◽  
Author(s):  
P. Dent ◽  
Y. Tang ◽  
A. Yacoub ◽  
Y. Dai ◽  
P. B. Fisher ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Combination Chemotherapy

Systemic anti-cancer therapy

2019 ◽  
pp. 205-248
Keyword(s):  
Cell Cycle ◽  
Cancer Therapy ◽  
Combination Chemotherapy ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Agents ◽  
Treatment Modalities ◽  
Basic Principles ◽  
Routes Of Administration ◽  
Anti Cancer ◽  
Targeted Immunotherapy

In this chapter, cytotoxic chemotherapy is clearly defined as being distinct from targeted immunotherapy. The effect of chemotherapy on the cell cycle is summarized, as well as how different cytotoxic agents can be classified according to their action on the cell. The basic principles of combination chemotherapy regimes are laid out. The use of chemotherapy in curative, palliative, adjuvant, and neo-adjuvant settings is discussed, alongside how chemotherapy can be combined with other treatment modalities. Safe handling and the principles of administration of cytotoxic agents are covered here, as well as the differing routes of administration. There is a discussion of the differing challenges posed by using oral chemotherapy, and there is a section on recognizing and treating extravasation. The chapter concludes by introducing the main types of newer targeted therapies and how they differ in their action, both from each other and also from cytotoxic chemotherapy.

Molecular pathways and gene ontology categories in association with response to combination chemotherapy plus bevacizumab in inflammatory and locally advanced breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 509-509
Author(s):  
S. M. Swain ◽  
S. M. Steinberg ◽  
Z. Modrusan ◽  
V. Smith ◽  
F. de Sauvage ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Gene Ontology ◽  
Protein Kinase ◽  
Advanced Breast Cancer ◽  
Clinical Response ◽  
Combination Chemotherapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Molecular Pathways

509 Background: Inflammatory breast cancer (IBC) is an extremely aggressive subtype of locally advanced breast cancer (LABC) accounting for 1% to 6% of all breast cancers. The overall response rate to a combined modality therapy is 61.4%-83.5% and 15-year overall survival is 20%. Identification of Gene Ontology (GO) category or molecular pathway signature to distinguish subsets of patients with distinct clinical outcomes is imperative. Methods: 20 patients with IBC and 1 with LABC received one cycle of bevacizumab at 15mg/kg followed by six cycles of doxorubicin at 50mg/m2 and docetaxel at 75mg/m2 plus bevacizumab before surgery. Response to combination chemotherapy plus bevacizumab was measured with radiologic imaging modalities. Gene expression profiles from 20 tumor biopsies at baseline (1 with PD had inadequate biopsy) were measured with Agilent Whole Human Genome arrays and utilized to correlate with clinical response. Results: 14 (67%) of 21 patients (95% CI, 43%-85.4%) had a clinical partial response (PR), 5 had stable disease (SD) and 2 had progressive disease (PD). Of 103 molecular pathways, those of the stathmin and breast cancer resistance to antimicrotubule agents, and BTG family proteins and cell cycle regulation were significantly associated with response (PR versus SD+PD; P = .002 and .003). Members of the stathmin pathway are cyclin B1, cell division cycle 2, stathmin 1 (kinase interacting with leukemia-associated gene), and mitogen-activated protein kinase 13; BTG family members are retinoblastoma 1, CCR4-NOT transcription complex, subunit 7, and B-cell translocation gene 1. Sixteen of 965 GO classes were differentially expressed between patients with PR and PD plus SD (P < .005). Those include GO categories of transcription factor complex (14 genes; P = .00009), extracellular matrix (69 genes; P = .0006), and protein kinase activity (90 genes; P = .002). Tumor differentiation, ER, HER2/neu, and p53 were not associated with clinical response. Conclusions: Two pathways that regulate microtubule stability and cell cycle, and 16 GO categories are significantly associated with the response to the combination chemotherapy of docetaxel-doxorubicin plus bevacizumab. No significant financial relationships to disclose.

Maytansine-Induced Mitotic Arrest in Human Lymphoblasts

1977 ◽  
Vol 35 ◽  
pp. 460-461
Author(s):  
Tai-Te Chao ◽  
John Sullivan ◽  
Awtar Krishan
Keyword(s):  
Electron Microscopy ◽  
Cell Cycle ◽  
Transmission Electron Microscopy ◽  
Tubulin Polymerization ◽  
Vinca Alkaloids ◽  
Antimitotic Activity ◽  
Transmission Electron ◽  
Flow Microfluorometry ◽  
Brain Tubulin

Maytansine, a novel ansa macrolide (1), has potent anti-tumor and antimitotic activity (2, 3). It blocks cell cycle traverse in mitosis with resultant accumulation of metaphase cells (4). Inhibition of brain tubulin polymerization in vitro by maytansine has also been reported (3). The C-mitotic effect of this drug is similar to that of the well known Vinca- alkaloids, vinblastine and vincristine. This study was carried out to examine the effects of maytansine on the cell cycle traverse and the fine struc- I ture of human lymphoblasts.Log-phase cultures of CCRF-CEM human lymphoblasts were exposed to maytansine concentrations from 10-6 M to 10-10 M for 18 hrs. Aliquots of cells were removed for cell cycle analysis by flow microfluorometry (FMF) (5) and also processed for transmission electron microscopy (TEM). FMF analysis of cells treated with 10-8 M maytansine showed a reduction in the number of G1 cells and a corresponding build-up of cells with G2/M DNA content.

Fibronexus-Like Adhesion Sites are Present at the Invasive Zones of Human Epidermoid Carcinomas

1982 ◽  
Vol 40 ◽  
pp. 106-109
Author(s):  
Irwin I. Singer
Keyword(s):  
Cell Cycle ◽  
Serum Concentration ◽  
Substrate Binding ◽  
High Serum ◽  
Adhesion Sites ◽  
Substrate Adhesion ◽  
Focal Contacts ◽  
Adhesion Complex ◽  
Low Serum

Our previous results indicate that two types of fibronectin-cytoskeletal associations may be formed at the fibroblast surface: dorsal matrixbinding fibronexuses generated in high serum (5% FBS) cultures, and ventral substrate-adhering units formed in low serum (0.3% FBS) cultures. The substrate-adhering fibronexus consists of at least vinculin (VN) and actin in its cytoplasmic leg, and fibronectin (FN) as one of its major extracellular components. This substrate-adhesion complex is localized in focal contacts, the sites of closest substratum approach visualized with interference reflection microscopy, which appear to be the major points of cell-tosubstrate adhesion. In fibroblasts, the latter substrate-binding complex is characteristic of cultures that are arrested at the G1 phase of the cell cycle due to the low serum concentration in their medium. These arrested fibroblasts are very well spread, flattened, and immobile.

Immunocytochemical studies on the behavior of RuBisCO and LHCP II during the cell cycle of synchronized Euglena gracilis

1990 ◽  
Vol 48 (3) ◽  
pp. 662-663
Author(s):  
Tetsuaki Osafune ◽  
Shuji Sumida ◽  
Tomoko Ehara ◽  
Eiji Hase ◽  
Jerome A. Schiff
Keyword(s):  
Cell Cycle ◽  
Immunoelectron Microscopy ◽  
Growth Phase ◽  
Euglena Gracilis ◽  
Dark Period ◽  
Light Period ◽  
Carboxylase Activity ◽  
Immunocytochemical Studies ◽  
Lhcp Ii

Changes in the morphology of pyrenoid and the distribution of RuBisCO in the chloroplast of Euglena gracilis were followed by immunoelectron microscopy during the cell cycle in a light (14 h)- dark (10 h) synchronized culture under photoautotrophic conditions. The imrnunoreactive proteins wereconcentrated in the pyrenoid, and less densely distributed in the stroma during the light period (growth phase, Fig. 1-2), but the pyrenoid disappeared during the dark period (division phase), and RuBisCO was dispersed throughout the stroma. Toward the end of the division phase, the pyrenoid began to form in the center of the stroma, and RuBisCO is again concentrated in that pyrenoid region. From a comparison of photosynthetic CO2-fixation with the total carboxylase activity of RuBisCO extracted from Euglena cells in the growth phase, it is suggested that the carboxylase in the pyrenoid functions in CO2-fixation in photosynthesis.

Effect of Chrysanthemum flavonoids on growth and cell cycle regulators of gastric cancer cell

2010 ◽  
Vol 34 (8) ◽  
pp. S50-S50
Author(s):  
Xiaoyan Pan ◽  
Xinmei Zhou ◽  
Guangtao Xu ◽  
Lingfen Miao ◽  
Shuoru Zhu
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cell Cycle Regulators

Repair pathway choice for double-strand breaks

2020 ◽  
Vol 64 (5) ◽  
pp. 765-777 ◽  
Author(s):  
Yixi Xu ◽  
Dongyi Xu
Keyword(s):  
Cell Cycle ◽  
Double Strand Breaks ◽  
Homologous Region ◽  
Gene Repair ◽  
Repair Pathway ◽  
Dna Double Strand Breaks ◽  
Environmental Radiation ◽  
Strand Breaks ◽  
Dna End Resection ◽  
End Resection

Abstract Deoxyribonucleic acid (DNA) is at a constant risk of damage from endogenous substances, environmental radiation, and chemical stressors. DNA double-strand breaks (DSBs) pose a significant threat to genomic integrity and cell survival. There are two major pathways for DSB repair: nonhomologous end-joining (NHEJ) and homologous recombination (HR). The extent of DNA end resection, which determines the length of the 3′ single-stranded DNA (ssDNA) overhang, is the primary factor that determines whether repair is carried out via NHEJ or HR. NHEJ, which does not require a 3′ ssDNA tail, occurs throughout the cell cycle. 53BP1 and the cofactors PTIP or RIF1-shieldin protect the broken DNA end, inhibit long-range end resection and thus promote NHEJ. In contrast, HR mainly occurs during the S/G2 phase and requires DNA end processing to create a 3′ tail that can invade a homologous region, ensuring faithful gene repair. BRCA1 and the cofactors CtIP, EXO1, BLM/DNA2, and the MRE11–RAD50–NBS1 (MRN) complex promote DNA end resection and thus HR. DNA resection is influenced by the cell cycle, the chromatin environment, and the complexity of the DNA end break. Herein, we summarize the key factors involved in repair pathway selection for DSBs and discuss recent related publications.

Gut-enriched kruppel-like factor (GKLF) inhibits cellular proliferation by blocking the G1/S boundary of the cell cycle

2001 ◽  
Vol 120 (5) ◽  
pp. A103-A103
Author(s):  
X CHEN ◽  
D JOHNS ◽  
D GEIMAN ◽  
E MARBAN ◽  
V YANG
Keyword(s):  
Cell Cycle ◽  
Cellular Proliferation
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