Proliferation and production of hemopoietic cells in two stages of disease: Preleukemia and overt leukemia

Dormer, Peter G.; Hegemann, F; Brinkmann, W

doi:10.1007/bf01469046

Cited by 27 publications

(6 citation statements)

References 17 publications

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“…Turnover of hematopoetic cells in the bone marrow is particularly rapid and often exceeds that of the leukemic cells (Clarkson et al, 1967; Dormer et al, 1976). Epithelial cells in the mucosa of the gastrointestinal tract (Boyes et al, 1971; Lipkin, 1973) or epidermal skin and hair follicle cells are also characterized by rapid proliferation (Hoogduijn et al, 2006).…”

Section: Targeted Therapy Cell Proliferation Rate and Chemotherapymentioning

confidence: 99%

Impaired DNA damage response — An Achilles' heel sensitizing cancer to chemotherapy and radiotherapy

Darzynkiewicz

Traganos

Wlodkowic

2009

European Journal of Pharmacology

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Despite the progress in targeting particular molecular abnormalities specific to different cancers (targeted therapy), chemo-and radiotherapies are still the most effective of all anticancer modalities. Induction of DNA damage and inhibition of cell proliferation are the objects of most chemotherapeutic agents and radiation. Their effectiveness was initially thought to be due to the high rate of proliferation of cancer cells. However, normal cell proliferation rate in some tissues often exceeds that of curable tumors. Most tumors have impaired DNA damage response (DDR) and the evidence is forthcoming that this confers sensitivity to chemo-or radiotherapy. DDR is a complex set of events which elicits a plethora of molecular interactions engaging signaling pathways designed to: (a) halt cell cycle progression and division to prevent transfer of DNA damage to progeny cells; (b) increase the accessibility of the damaged sites to the DNA repair machinery; (c) engage DNA repair mechanisms and (d) activate the apoptotic pathway when DNA cannot be successfully repaired. A defective DDR makes cancer cells unable to effectively stop cell cycle progression, engage in DNA repair and/or trigger the apoptotic program when treated with DNA damaging drugs. With continued exposure to the drug, such cells accumulate DNA damage which leads to their reproductive death that may have features of cell senescence. Cancers with nonfunctional BRCA1 and BRCA2 are particularly sensitive to combined treatment with DNA damaging drugs and inhibitors of poly(ADP-ribose) polymerase. Antitumor strategies are being designed to treat cancers having particular defects in their DDR, concurrent with protecting normal cells.

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Section: Targeted Therapy Cell Proliferation Rate and Chemotherapymentioning

confidence: 99%

Impaired DNA damage response — An Achilles' heel sensitizing cancer to chemotherapy and radiotherapy

Darzynkiewicz

Traganos

Wlodkowic

2009

European Journal of Pharmacology

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“…Traditional chemotherapies act on rapidly dividing cells, which unfortunately also include some of the normal cells in the body. In fact, in many organs, normal cells proliferate at the same rate or even more rapidly than tumour cells [254], such as hematopoietic cells in the bone marrow [255,256], and epithelial cells in the mucosa of the gastrointestinal tract [257], skin and hair follicles [258]. This poses a problem in terms of adverse effects when treating cancer.…”

Section: Effect Of Targeting Wee1 and Chk1/2 On Normal Cellsmentioning

confidence: 99%

Synthetic retinoid CD437 induces apoptosis and acts synergistically with TRAIL receptor-2 agonist in malignant melanoma

Magnussen

Rosnes

Shahzidi

et al. 2012

Biochemical and Biophysical Research Communications

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Background: Malignant melanoma has an increasing incidence rate and the metastatic disease is notoriously resistant to standard chemotherapy. Loss of cell cycle checkpoints is frequently found in many cancer types and makes the cells reliant on compensatory mechanisms to control progression. This feature may be exploited in therapy, and kinases involved in checkpoint regulation, such as Wee1 and Chk1/2, have thus become attractive therapeutic targets. Methods: In the present study we combined a Wee1 inhibitor (MK1775) with Chk1/2 inhibitor (AZD7762) in malignant melanoma cell lines grown in vitro (2D and 3D cultures) and in xenografts models. Results: Our in vitro studies showed that combined inhibition of Wee1 and Chk1/2 synergistically decreased viability and increased apoptosis (cleavage of caspase 3 and PARP), which may be explained by accumulation of DNA-damage (increased expression of γ-H2A.X)-and premature mitosis of S-phase cells. Compared to either inhibitor used as single agents, combined treatment reduced spheroid growth and led to greater tumour growth inhibition in melanoma xenografts. Conclusions: These data provide a rationale for further evaluation of the combination of Wee1 and Chk1/2 inhibitors in malignant melanoma.

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“…The available data, so far, re veal a low 3HTDR-LI and an increased fraction of cells in Gi associated with a prolonged DNA synthesis [3][4][5][6]17].…”

Section: Discussionmentioning

confidence: 99%

Biological Significance of Nonlymphocytic Oligoblastic Leukemia

Sánchez-Fayos¹,

Outeiriño²,

Calabuig³

et al. 1984

Acta Haematol

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Kinetic studies of marrow dividing granulocytic precursors (mitotic index and flash labeling index with ³H-TDR) were carried out in 11 patients with oligoblastic leukemia (OBL). The results were compared with similar data from cases of conventional acute non-lymphocytic leukemia (ANLL). The cytokinetic results were as follows: MI (%) in OBL, mean = 0.75; MI (%) in ANLL, mean = 0.66; p > 0.7; LI (%) in OBL, mean= 15.0; LI (%) in ANLL, mean= 15.4, p > 0.7. The lack of cytokinetic differences between these two groups of patients stands in favor of the hypothesis that OBL might represent a special type of smoldering leukemia with a ‘plateau’ of blast cell accumulation established at a subleukemic level.

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Proliferation and production of hemopoietic cells in two stages of disease: Preleukemia and overt leukemia

Cited by 27 publications

References 17 publications

Impaired DNA damage response — An Achilles' heel sensitizing cancer to chemotherapy and radiotherapy

Impaired DNA damage response — An Achilles' heel sensitizing cancer to chemotherapy and radiotherapy

Synthetic retinoid CD437 induces apoptosis and acts synergistically with TRAIL receptor-2 agonist in malignant melanoma

Biological Significance of Nonlymphocytic Oligoblastic Leukemia

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