scholarly journals In vivo radioprotective effects of recombinant human granulocyte colony- stimulating factor in lethally irradiated mice

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 638-645 ◽  
Author(s):  
FM Uckun ◽  
L Souza ◽  
KG Waddick ◽  
M Wick ◽  
CW Song
Keyword(s):  
Survival Rate ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Conclusive Evidence ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Treatment Regimens ◽  
Stimulating Factor

Abstract The purpose of this study was to investigate the in vivo radioprotective effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the effects of increasing doses of rhG-CSF on survival of mice receiving 700 cGy (LD100/30) single dose total body irradiation (TBI). While 1 microgram/kg to 100 micrograms/kg doses of rhG-CSF were not radioprotective, a dose-dependent radioprotection was observed at 200 micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four different rhG-CSF treatment regimens side by side for their radioprotective effects in LD100/30 irradiated mice. One hundred percent of control mice receiving phosphate buffered saline died within 21 days after TBI with a median survival of 14 days. The median survival was prolonged to 20 days and the actuarial 60-day survival rate was increased to 27% when mice received 2,000 micrograms/kg rhG- CSF 24 hours before TBI (P = .0002; Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24 days and the actuarial 60-day survival rate was increased to 33%, when mice were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was administered in two divided doses of 1,000 micrograms/kg given 24 hours before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen prolonged the median survival time of LD100/30 irradiated mice to more than 60 days and increased the actuarial 60-day survival rate to 62% (P = .0001; Mantel-Peto-Cox). By comparison, no survival advantage was observed when mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects were observed when mice were irradiated with 650 cGy (LD80/30). The presented findings provide conclusive evidence that rhG-CSF has significant in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.

In vivo radioprotective effects of recombinant human granulocyte colony- stimulating factor in lethally irradiated mice

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 638-645 ◽  
Author(s):  
FM Uckun ◽  
L Souza ◽  
KG Waddick ◽  
M Wick ◽  
CW Song
Keyword(s):  
Survival Rate ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Conclusive Evidence ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Treatment Regimens ◽  
Stimulating Factor

The purpose of this study was to investigate the in vivo radioprotective effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the effects of increasing doses of rhG-CSF on survival of mice receiving 700 cGy (LD100/30) single dose total body irradiation (TBI). While 1 microgram/kg to 100 micrograms/kg doses of rhG-CSF were not radioprotective, a dose-dependent radioprotection was observed at 200 micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four different rhG-CSF treatment regimens side by side for their radioprotective effects in LD100/30 irradiated mice. One hundred percent of control mice receiving phosphate buffered saline died within 21 days after TBI with a median survival of 14 days. The median survival was prolonged to 20 days and the actuarial 60-day survival rate was increased to 27% when mice received 2,000 micrograms/kg rhG- CSF 24 hours before TBI (P = .0002; Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24 days and the actuarial 60-day survival rate was increased to 33%, when mice were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was administered in two divided doses of 1,000 micrograms/kg given 24 hours before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen prolonged the median survival time of LD100/30 irradiated mice to more than 60 days and increased the actuarial 60-day survival rate to 62% (P = .0001; Mantel-Peto-Cox). By comparison, no survival advantage was observed when mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects were observed when mice were irradiated with 650 cGy (LD80/30). The presented findings provide conclusive evidence that rhG-CSF has significant in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.

Doxorubicin and dose-escalated cyclophosphamide with granulocyte colony-stimulating factor for the treatment of hormone-resistant prostate cancer.

1996 ◽  
Vol 14 (5) ◽  
pp. 1617-1625 ◽  
Author(s):  
E J Small ◽  
S Srinivas ◽  
B Egan ◽  
A McMillan ◽  
T P Rearden
Keyword(s):  
Prostate Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Fixed Dose ◽  
Survival Duration ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
The Impact ◽  
Stimulating Factor

PURPOSE The goals of this study were to define the efficacy and toxicity of doxorubicin and dose-escalated cyclophosphamide (Cy) along with granulocyte colony-stimulating factor (G-CSF) in the treatment of hormone-refractory prostate cancer (HRPC), to determine the maximal-tolerated dose (MTD) of Cy in this regimen, and to evaluate the impact of prior pelvic irradiation (XRT) on MTD and toxicity. PATIENTS AND METHODS Thirty-five patients were treated every 21 days with fixed-dose doxorubicin (40 mg/m2) and Cy 800 to 2,000 mg/m2 (in a cohort dose-escalation schema) along with G-CSF. RESULTS Five of 15 patients (33%) with measurable disease obtained an objective response. Sixteen of 35 patients (46%) had a greater than 50% decrease in prostate-specific antigen (PSA) level (95% confidence interval [CI], 28.8% to 63.4%). Ten of 35 patients (28.6%) had a greater than 75% decrease in PSA level. The median survival time was 11 months. The median survival duration of patients with a greater than 50% decrease in PSA level was 23 months, versus a median survival time of 7 months in patients without a PSA response (P = .02). Although 33% of cycles were associated with grade 4 neutropenia, febrile neutropenia occurred in only 7.8% of all cycles. Thrombocytopenia and anemia were rare. Nonhematologic toxicity was minimal. Patients who had received prior pelvic XRT had a lower Cy MTD, but their hematologic toxicity was not appreciably different. CONCLUSION This is a well-tolerated, active regimen for the treatment of HRPC. Toxicity was not different in patients with prior pelvic XRT, although these patients had a lower MTD.

scholarly journals Survival after surgery among patients with cholangiocarcinoma in Northeast Thailand according to anatomical and morphological classification

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chaiwat Tawarungruang ◽  
Narong Khuntikeo ◽  
Nittaya Chamadol ◽  
Vallop Laopaiboon ◽  
Jaruwan Thuanman ◽  
...  
Keyword(s):  
Survival Rate ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Cox Regression ◽  
Survival Rates ◽  
Care Program ◽  
Tumor Location ◽  
Northeast Thailand ◽  
Curative Surgery

Abstract Background Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0–3.6), with median survival time of 17.8 months (95% CI: 15.4–20.2), and 5-year survival rate of 24.6% (95% CI: 20.7–28.6). The longest median survival time was 21.8 months (95% CI: 16.3–27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8–46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9–63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4–58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01–2.09; P = 0.013) compared to ICCA+ID patients. Conclusions Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

scholarly journals A comparison of hematopoiesis in normal and splenectomized mice treated with granulocyte colony-stimulating factor

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 563-569 ◽  
Author(s):  
G Molineux ◽  
Z Pojda ◽  
TM Dexter
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extramedullary Hematopoiesis ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Response Data ◽  
Hematopoietic Precursor ◽  
Stimulating Factor

Abstract Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induces leukocytosis in vivo in both intact and splenectomized mice. Full dose response data showed a plateau in this effect at doses over 500 micrograms rhG-CSF/kg body weight/d in intact mice. The effect is magnified in splenectomized mice, where leukocyte numbers reach 100 x 10(6) mL after 4 days' treatment at 250 micrograms/kg/d. Further hematopoietic precursor populations are also affected in both marrow and the spleen; in general, marrow parameters were depressed, while splenic populations were enlarged. In splenectomized mice, both blood- borne stem cells were enhanced, and foci of extramedullary hematopoiesis were enlarged in addition to the effects seen in intact mice. In the marrow of splenectomized and intact mice treated with a high dose of G-CSF, erythroid suppression in the marrow was confirmed with radioactive iron. Our studies confirm and extend previous work on the mode of action of G-CSF, and indicate that side effects of high dose G-CSF therapy might include erythroid suppression in the bone marrow.

scholarly journals Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy—a preclinical study using a syngeneic breast cancer model

2020 ◽  
Author(s):  
Patrycja Guzik ◽  
Klaudia Siwowska ◽  
Hsin-Yu Fang ◽  
Susan Cohrs ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Tumor Cells ◽  
Median Survival ◽  
Breast Tumor ◽  
Median Survival Time ◽  
Therapy Outcome ◽  
Minor Effect

Abstract Purpose It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [177Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy. Methods In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [177Lu]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [177Lu]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 × 200 μg; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment. Results [177Lu]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [177Lu]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [177Lu]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls. Conclusion Application of [177Lu]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.

scholarly journals Interleukin-6 and the Granulocyte Colony-Stimulating Factor Receptor Are Major Independent Regulators of Granulopoiesis In Vivo But Are Not Required for Lineage Commitment or Terminal Differentiation

Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2583-2590 ◽  
Author(s):  
Fulu Liu ◽  
Jennifer Poursine-Laurent ◽  
Huai Yang Wu ◽  
Daniel C. Link
Keyword(s):  
Interleukin 6 ◽  
Terminal Differentiation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Normal Numbers ◽  
Stimulating Factor ◽  
Deficient Mice ◽  
Additional Loss

Multiple hematopoietic cytokines can stimulate granulopoiesis; however, their relative importance in vivo and mechanisms of action remain unclear. We recently reported that granulocyte colony-stimulating factor receptor (G-CSFR)-deficient mice have a severe quantitative defect in granulopoiesis despite which phenotypically normal neutrophils were still detected. These results confirmed a role for the G-CSFR as a major regulator of granulopoiesis in vivo, but also indicated that G-CSFR independent mechanisms of granulopoiesis must exist. To explore the role of interleukin-6 (IL-6) in granulopoiesis, we generated IL-6 × G-CSFR doubly deficient mice. The additional loss of IL-6 significantly worsened the neutropenia present in young adult G-CSFR–deficient mice; moreover, exogenous IL-6 stimulated granulopoiesis in vivo in the absence of G-CSFR signals. Near normal numbers of myeloid progenitors were detected in the bone marrow of IL-6 × G-CSFR–deficient mice and their ability to terminally differentiate into mature neutrophils was observed. These results indicate that IL-6 is an independent regulator of granulopoiesis in vivo and show that neither G-CSFR or IL-6 signals are required for the commitment of multipotential progenitors to the myeloid lineage or for their terminal differentiation.

scholarly journals In Vivo Administration of Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination

2019 ◽  
Author(s):  
Shigetaka Shimodaira ◽  
Ryu Yanagisawa ◽  
Terutsugu Koya ◽  
Koichi Hirabayashi ◽  
Yumiko Higuchi ◽  
...  
Keyword(s):  
Low Dose ◽  
Immune Monitoring ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Functional Activities ◽  
Pulsed Dc ◽  
Dc Vaccines ◽  
Stimulating Factor ◽  
Autologous Monocyte

Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.

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