scholarly journals EFFICACY OF GRANULOCYTE COLONY-STIMULATING FACTOR AND ENTEROSORPTION IN MELPHALAN-INDUCED BONE MARROW SUPPRESSION IN GUERIN CARCINOMA GRAFTED RATS

Author(s):  
O. O. Shevchuk ◽  
I. M. Todor ◽  
N. Yu. Lukianova ◽  
N. K. Rodionova ◽  
V. G. Nikolaev ◽  
...  

Background. Side effects of antineoplastic agents (especially leukopenia and neutropenia) could be the main limiting factors for efficient treatment. Objective. The research is aimed at the study of myeloprotective capability of biosimilars of granulocyte colony stimulating factor (G-CSF) and granular carbon oral adsorbent C2 in melphalan-induced bone marrow suppression in Guerin carcinoma-grafted rats. Methods. Melphalan at the dose of 5.5 mg/kg was used to promote bone marrow suppression in the Guerin carcinoma grafted rats. To fight myelosuppression, we used filgrastim and its analogue, designed and produced by IEPOR, a recombinant granulocyte colony-stimulating factor (r-GCSF). Carbon granulated enterosorbent C2 was used for enteral sorption therapy (bulk density γ=0.18 g/cm3, diameter of granules 0.15-0.25 mm, BET pore surface – 2162 m2/g). All rats were sacrificed on the 17th day after carcinoma cells inoculation or on the 8th day after Melphalan injection. Results. Alkylating cytostatic agent caused severe leukopenia (by 95.7%), neutropenia (by 73.9%), and thrombocytopenia (by 84.9%) in the experimental rats. Mortality rate was 57%. Filgrastim and enterosorption with carbon oral adsorbent C2 increased the studied indices, but the most prominent results were observed when combination of both factors was used. Studied means did not affect the anti-tumor efficacy of Melphalan alone and in combination. Conclusions. Our results are perspective for further investigation of the efficacy of the combination of carbon oral adsorbents and hematopoietic cytokines in cases of ameliorate anti-cancer chemotherapy side effects, and its implementation into clinics.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4111-4111
Author(s):  
Guangsheng He ◽  
Xiang Zhang ◽  
Wu Depei ◽  
Aining Sun ◽  
Zhengming Jin ◽  
...  

Abstract Abstract 4111 Objective Biphenotypic acute leukemia (BAL) involves both myeloid and lymphoid cells, and there is lack of uniformity in treatment at present. Optimal approach for therapy of BAL is unknown, and BAL usually becomes refractory to conventional chemotherapy. It was found that CAG regimen [low-dose cytosine arabinoside (Ara-C) plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor (G-CSF)] is effective for both myeloid leukemia and refractory acute lymphoblastic leukemia. To explore the efficiency of CAG regimen for refractory BAL, 12 BAL patients who were failed to daunorubicin/mitoxantrone, cytosine arabinoside, vincristine, prednisone (D/MAOP) regimen, were treated by CAG. 8 were males and 4 was female, with ages ranging from 20 to 43 years (median=34 years). Immunophenotype of B lymphoid lineage/myeloid lineage showed in 8 patients, and T lymphoid lineage/myeloid lineage showed in 4 patients. The patients whose blast cells did not decrease 50% after induction regimen with lymphoid and/or myeloid drugs were defined as refractory cases. Methods 12 refractory BAL patients were treated by CAG regimen (cytosine arabinoside 10 mg/m2 subcutaneously every 12 hours, day 1-14; aclarubicin 5-7 mg/m2 intravenously daily, day 1-8; and concurrent use of granulocyte colony-stimulating factor 200μg·m-2·d-1 subcutaneously) from November 2002 to April 2009. The efficacy of the regimen was evaluated by response rate, and the side-effects was also measured. Results The major chemotherapy toxicity was bone marrow depression, mainly showing as pancytopenia. Median duration of absolute neutrophil count (ANC)<0.50×109/L and of platelet (PLT) count<20×109/L was 13 (range, 1-17) days and 1 day (range, 0-5 days), respectively. Median transfusion of red cells and PLT was 4 (range, 1.5-12) U and 20 (range, 0-40) U, respectively. Besides bone marrow depression, other side-effects such as infection, bleeding, nausea and vomiting also occurred during therapy. According to chemotherapy toxicity assessment of WHO, there were 7 patients confronting infection, among whom only 2 patient occurred III-‡W infection. No serious nausea vomiting or hepatic function damage happened. Disclosures: No relevant conflicts of interest to declare.


2000 ◽  
Vol 18 (4) ◽  
pp. 435-440 ◽  
Author(s):  
Roger Harris ◽  
Gavin Marx ◽  
Mark Gillett ◽  
Adrian Kark ◽  
Shalini Arunanthy

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Yasuhiro Yamada ◽  
Yoshiaki Ikuta ◽  
Kisato Nosaka ◽  
Nobutomo Miyanari ◽  
Naoko Hayashi ◽  
...  

Accidental cisplatin overdose has been occurring with an increasing frequency due to expanding usage of the agent. However, the optimal strategy to treat such patients remains to be established. Here, we report a case of large cisplatin overdose, successfully managed by plasma exchange, intravenous hydration, granulocyte colony-stimulating factor (G-CSF) administration, and other supportive care. A 67-year-old man with esophageal carcinoma received a large cisplatin overdose of 240 , when he received adjuvant therapy following subtotal esophagectomy. On day 4, he experienced frank cisplatin toxicities and emergency plasma exchange was initiated. With 7 cycles of plasma exchange, the cisplatin concentration decreased from 2,350 to 110 ng/mL. Severe bone marrow suppression with high fever ensued on day 10, which was successfully treated with G-CSF and antibiotics. Despite moderate hearing sense reduction, he recovered without significant complications. Immediate plasma exchange with hydration and other care was efficacious in quickly lowering cisplatin concentrations.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Wen-Ching Tzaan ◽  
Hsien-Chih Chen

Intervertebral disc (IVD) degeneration is a multifactorial process that is influenced by contributions from genetic predisposition, the aging phenomenon, lifestyle conditions, biomechanical loading and activities, and other health factors (such as diabetes). Attempts to decelerate disc degeneration using various techniques have been reported. However, to date, there has been no proven technique effective for broad clinical application. Granulocyte colony-stimulating factor (GCSF) is a growth factor cytokine that has been shown to enhance the availability of circulating hematopoietic stem cells to the brain and heart as well as their capacity for mobilization of mesenchymal bone marrow stem cells. GCSF also exerts significant increases in circulating neutrophils as well as potent anti-inflammatory effects. In our study, we hypothesize that GCSF can induce bone marrow stem cells differentiation and mobilization to regenerate the degenerated IVD. We found that GCSF had no contribution in disc regeneration or maintenance; however, there were cell proliferation within end plates. The effects of GCSF treatment on end plates might deserve further investigation.


Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4711-4719 ◽  
Author(s):  
Kyle J. Eash ◽  
Jacquelyn M. Means ◽  
Douglas W. White ◽  
Daniel C. Link

Abstract The number of neutrophils in the blood is tightly regulated to ensure adequate protection against microbial pathogens while minimizing damage to host tissue. Neutrophil homeostasis in the blood is achieved through a balance of neutrophil production, release from the bone marrow, and clearance from the circulation. Accumulating evidence suggests that signaling by CXCL12, through its major receptor CXCR4, plays a key role in maintaining neutrophil homeostasis. Herein, we generated mice with a myeloid lineage–restricted deletion of CXCR4 to define the mechanisms by which CXCR4 signals regulate this process. We show that CXCR4 negatively regulates neutrophil release from the bone marrow in a cell-autonomous fashion. However, CXCR4 is dispensable for neutrophil clearance from the circulation. Neutrophil mobilization responses to granulocyte colony-stimulating factor (G-CSF), CXCL2, or Listeria monocytogenes infection are absent or impaired, suggesting that disruption of CXCR4 signaling may be a common step mediating neutrophil release. Collectively, these data suggest that CXCR4 signaling maintains neutrophil homeostasis in the blood under both basal and stress granulopoiesis conditions primarily by regulating neutrophil release from the bone marrow.


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