Allogeneic Committed Hematopoietic Progenitors Are Protective Against Radiation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4871-4871
Author(s):  
Benny J. Chen ◽  
Divino Deoliveira ◽  
Nelson J. Chao
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Bone Marrow Failure ◽  
Stem Cell Marker ◽  
Whole Body ◽  
Control Group ◽  
Hematopoietic Progenitors ◽  
Post Irradiation ◽  
Histocompatibility Complex

Abstract Whole-body irradiation may lead to bone marrow failure and death. It was previously reported that congenic myeloerythroid-restricted progenitors are able to radioprotect lethally irradiated animals. However, this approach will not be practical because syngeneic/congenic donors are rarely available in humans. To solve this problem, we investigated whether allogeneic committed progenitors are also radioprotective. Hematopoietic committed progenitors were isolated by FACS based on the presence of early progenitor marker CD244 and the absence of stem cell marker CD150 (CD244+CD150−). BALB/c mice (H2d) were lethally irradiated with 8.5 Gy. Within 4 hours of irradiation, the irradiated mice were infused with 5x105 sorted hematopoietic progenitors from major histocompatibility complex mistmatched C57BL/6 donors (H2b). As shown in the Figure B, all the mice in the radiation control group died within 15 days post irradiation (median survival time: 13 days). Infusion of hematopoietic committed progenitors significantly prolonged the survival of the lethally irradiated mice (P=0.0018, median survival time: 28 days). These results are similar to the results obtained from congenic hematopoietic progenitors using 1x105 cells (Figure A, P<0.0001, median survival time: 10 days vs. 28 days). These data suggest that allogeneic hematopoietic committed progenitor cells are also able to mediate radioprotective effects. Similar to the congenic hematopoietic committed progenitors, allogeneic progenitors may also exert radioprotective effects by jumpstarting hematologic recovery post irradiation. These cells may be stockpiled and used as “off-the-shelf” products for radiation injury and other applications. Figure Figure

scholarly journals Treatment of Established Graft-Versus-Host Disease in Dogs by Antithymocyte Serum or Prednisone

Blood ◽  
1973 ◽  
Vol 42 (4) ◽  
pp. 601-609 ◽  
Author(s):  
R. Storb ◽  
H. J. Kolb ◽  
T. C. Graham ◽  
H. Kolb ◽  
P. L. Weiden ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Immunosuppressive Agent ◽  
Whole Body ◽  
Graft Versus Host ◽  
Group 3 ◽  
Group 2 ◽  
Long Term Survivors

Abstract Marrow grafts after 1200 R of whole-body irradiation were carried out between pairs of unrelated dogs of different breeds that were incompatible for dog histocompatibility antigens. Three groups of recipients were studied. Recipients in all groups were treated with the immunosuppressive agent methotrexate (MTX), 0.4 mg/kg, on days 1, 3, 6, and 11, and then once weekly until day 102 after grafting. Dogs in group 1 were given MTX only. Thirty of 35 recipients died between 11 and 51 days and five survived more than 102 days. Median survival time was 20 days. Dogs in group 2 were treated with rabbit antidog antithymocyte serum (ATS) when graft-versus-host (GVH) disease became established. Eight of ten recipients died between 19 and 76 days and two survived more than 102 days. Median survival time was 45 days. Dogs in group 3 were treated with daily injections of prednisone when GVH disease became apparent. Seven of nine recipients died between 11 and 34 days and two survived more than 102 days. Median survival time was 24 days. It was concluded that established GVH disease in dogs with histoincompatible marrow grafts can be favorably influenced by ATS with significant (p < 0.01) prolongation of survival. However, there was no evidence that treatment with ATS increased the fraction of long-term survivors in this histoincompatible setting. Prednisone was ineffective and did not prolong survival (p > 0.1).

Validation of IPSS criteria in more than 1,600 MDS patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7079-7079 ◽  
Author(s):  
F. Quddus ◽  
A. Ahmed ◽  
S. Naqvi ◽  
K. Hasan ◽  
M. Mumtaz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Survival Time ◽  
Median Survival ◽  
Scoring System ◽  
Median Survival Time ◽  
Bone Marrow Failure ◽  
Prognostic Indicators ◽  
International Prognostic Scoring System ◽  
P Value ◽  
Survival Difference

7079 Myelodysplastic syndromes (MDS) are a diverse group of clonal stem cell disorders characterized by bone marrow failure, dysmyelopoiesis and peripheral cytopenias and affecting predominantly an elderly population. The International Prognostic Scoring System (IPSS) incorporates the number of peripheral cytopenias, percentage of bone marrow blasts and chromosomal abnormalities and assigns a score to predict survival and risk of disease progression to AML. Using the extensive MDS database at the University of Massachusetts we analyzed survival time in relation to IPSS scoring and also its various individual components, i.e. blast percentage, number of cell lines involved and the number of karyotype abnormalities in 1,200+ patients. The overall median survival time in 1,424 MDS patients as a group was 2.9 years. IPSS low group had the longest median survival time of 7.5 years with IPSS Int-1 3.6 years. There was minimal difference in the median survival time between IPSS Int-2 and IPSS high risk group 1.2 and 1.1 years respectively. These results were significant for a P value of <0.0001. The median survival time for blasts <5% was 5.3 years and blast 5–10% was 1.7 years. Interestingly, there was minimal survival difference between median survival time for blasts 11–20% and blasts >20% showing 1.2 years and 1.3 years respectively. Again, these results were significant for a P value of <0.0001. The median survival time for the number of cytopenias involved was also calculated with 0, 1, 2 and 3 numbers of cytopenias showing 6.4 years, 4.4 years, 2.6 years and 1.8 years respectively, with P value of <0.0001. The median survival time for normal karyotype versus one or two karyotype abnormality was 4.9 years, 2.6 years and 2.4 years respectively. Three or more karyotype abnormalities showed a median survival time of 0.8 years. The P value was again significant (<0.0001). Our results not only validate the prognostic value of IPSS scoring system as a whole but also its various individual prognostic indicators. No significant financial relationships to disclose.

scholarly journals Elevated Serum Uric Acid is Associated With Poor Survival in Advanced HCC Patients and Febuxostat Improves Prognosis in HCC Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Le Wu ◽  
Wenlong Yang ◽  
Yu Zhang ◽  
Xiaoyue Du ◽  
Nan Jin ◽  
...  
Keyword(s):  
Uric Acid ◽  
Survival Time ◽  
Serum Uric Acid ◽  
Median Survival ◽  
Median Survival Time ◽  
Elevated Serum ◽  
Acid Group ◽  
Control Group ◽  
Poor Survival ◽  
Advanced Hcc

Objective: Serum uric acid is associated with tumor progression and hepatocarcinogenesis. Here, we aimed to determine whether serum uric acid is related to the survival time of patients with hepatocellular carcinoma (HCC) and whether the inhibition of uric acid production affects the progression and survival of rats with HCC.Methods: The follow-up data of 288 patients with advanced HCC were analyzed. Ten purine metabolites in serum and liver samples of diethylnitrosamine (DEN)-induced HCC rats were quantitatively determined by an established UPLC-MS/MS method. On this basis, febuxostat, a specific inhibitor of xanthine oxidase (XOD), was used to interfere with HCC rats.Results: The serum uric acid level of HCC patients was significantly negatively correlated with survival days (r = -0.155). The median survival time was 133.5 days in the high uric acid group (&gt;360 μmol/L, n = 80) and 176.0 days in the normal serum uric acid group (&lt;360 μmol/L, n = 208, p = 0.0013). The levels of hypoxanthine, guanine, and uric acid; XOD activity; and xanthine dehydrogenase mRNA expression in the serum or liver samples of HCC rats were significantly upregulated compared with those in the control group. After febuxostat intervention in DEN-induced HCC rats, the number of atypical cells and inflammatory cells decreased significantly; the serum alpha fetoprotein level and Fisher’s ratio tended to return to normal; the median survival time increased from 36 to 96 days (p = 0.08). In addition, serum malondialdehyde, superoxide dismutase, and glutathione activity nearly returned to the level of the healthy control group.Conclusion: The elevation of serum uric acid implies a risk of poor survival in advanced HCC patients and Febuxostat can reduce the generation of reactive oxygen species, thereby playing a role in delaying the progression of liver cancer.

scholarly journals Rapamycin Promote the Inhibition Rate of Proliferation on SHI-1 Cells and Enhance the Efficacy of Chemotherapy in Npg Leukemia Mice

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5217-5217
Author(s):  
Jing Xu ◽  
Zhenjiang Li ◽  
Jifu Zheng ◽  
Qiong Wu ◽  
Qingming Wang ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Peripheral Blood ◽  
Median Survival Time ◽  
Combined Treatment ◽  
Leukemia Cell Line ◽  
Control Group ◽  
Inhibition Rate ◽  
Chemotherapy Group

Abstract Acute myeloid leukemia (AML) is a malignant hematologic disease. The remission rate of traditional chemotherapy is about 70-80%. In order to improve the efficacy of chemotherapy, some new drug which could enhance the efficacy of chemotherapy should be explored. Rapamycin is an immunosuppressive agent which can regulate cell proliferation, autophagy and other activities by inhibiting mTOR signal pathway. The studies of rapamycin as an anti-leukemia agent were limited. We had successfully establish a leukemia model in NPG mice with systemic leukemia infiltration using the human acute monocytic leukemia cell line SHI-1 cells. So in this study, the rapamycin and/or chemotherapy were used to treat the SHI-1 cells in vitro and NPG leukemia mice to investigate the efficacy of rapamycin in the treatment of AML. Rapamycin alone could effectively inhibit the proliferation of SHI-1 cells in vitro, and the inhibition rate were 35.4% which lower than the inhibition rate chemotherapy group (49.9%) using cytarabine and adriamycin. The combination with rapamycin and chemotherapy could significantly enhanced the inhibition rate to 60.3% (P<0.05) (Fig A). At day 19 after SHI-1 were inoculated to the NPG mice from tail vein, nearly 1% CD45 and CD33 positive cells were found in the peripheral blood. Then the NPG mice were divided to 4 groups to receive treatment. Control group without any treatment, rapamycin group were intraperitoneally injected with rapamycin (10mg/kg) every day for 5 days, chemotherapy group were intraperitoneally injected with cytarabine (100mg/kg for 5 days) and adriamycin (1mg/kg every other day for 3 times), combined group were treated with rapamycin, cytarabine and adriamycin. At the first day after treatment, one NPG mice were sacrificed randomly in four groups. The weight of the spleen in control group, rapamycin group, chemotherapy group and combination group were 78.6 mg, 48.9 mg, 16.1 mg, 11.7 mg respectively (Fig B). The ratio of human CD33 and CD45 positive cells in peripheral blood, bone marrow and spleen of NPG mice were 20.2%, 23.2% and 16.8% in control group, 2.02%, 2.68% and 3.31% in rapamycin group, 13.6%, 14.2% and 5.50% in chemotherapy group, 0.31%, 2.49% and 1.22% in combined group respectively (Fig C). Histopathological results showed that the degree of leukemia infiltration in the organs of NPG in the rapamycin group, chemotherapy group, and the combined group was significantly less than that of the control group. The median survival time of NPG mice in control group was 30.5 days. The treatment of rapamycin or chemotherapy could significantly prolong the media survival time of NPG mice to 35.0 and 34.0 days (P<0.05). When combined rapamycin with chemotherapy, the life time of NPG mice were significantly extended to 39 days (P<0.05) (Fig D). When NPG mice were died, more neoplasms were grow in the organs such as kidney, liver, stomach, mesenteric, mediastinum, bladder, spine, skin and neck in the NPG mice of control group, the treatment of rapamycin, chemotherapy and combined treatment would significantly decrease the counts of infiltrative organ with leukemia cells (Fig E). Altogether, our studies verified that rapamycin could inhibit the growth of SHI-1 cells and enhance the efficacy of chemotherapy in vitro. In NPG leukemia mice, the treatment of rapamycin alone could gain the efficacy as in chemotherapy group, when combined with chemotherapy, rapamycin had synergistic effect to significantly enhance the efficacy of chemotherapy to prolong the median survival time and decrease the degree of leukemia infiltration in NPG mice. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals CTNI-30. THERAPEUTIC EFFECTS OF RADIOTHERAPY WITH CONCOMITANT AND ADJUVANT TEMOZOLOMIDE VERSUS RADIOTHERAPY WITH CONCOMITANT TEMOZOLOMIDE ALONE IN CHILDREN WITH DIPG: A SINGLE-CENTER EXPERIENCE WITH 82 CASES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii49-ii49
Author(s):  
Mingyao Lai ◽  
Juan Li ◽  
Qingjun Hu ◽  
Jiangfen Zhou ◽  
Shaoqun Li ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Disease Recurrence ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Hematological Toxicity ◽  
Therapeutic Effects ◽  
Single Center Experience ◽  
Adjuvant Temozolomide ◽  
Temozolomide Chemotherapy

Abstract OBJECTIVE To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy with concomitant temozolomide alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of temozolomide in the treatment of pediatric DIPG. METHODS The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and December 30, 2019 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant temozolomide chemotherapy, and (3) with or without adjuvant temozolomide chemotherapy. RESULTS A total of 82 pediatric patients were eligible for the study, with a median age of 7 years (range 2–16 years). The median follow-up was 8.6 months (range 2–28 months) and the median survival time was 9.4 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant temozolomide was 9.8 months, longer than 7.5 months of the other 16 patients treated with radiotherapy with concomitant temozolomide alone, with statistical differences (P=0.010). Moreover, bevacizumab and nimotuzumab didn’t bring survival benefits to patients with disease recurrence or progression. Hematological toxicity (Grade IV) was not found. CONCLUSION Radiotherapy with concomitant and adjuvant temozolomide prolongs the survival time of children with DIPG.

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 Culex quinquefasciatus (Diptera: Culicidae) survivorship following the ingestion of bird blood infected with Haemoproteus sp. parasites

2021 ◽  
Author(s):  
Dayvion R. Adams ◽  
Andrew J. Golnar ◽  
Sarah A. Hamer ◽  
Michel A. Slotman ◽  
Gabriel L. Hamer
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Culex Quinquefasciatus ◽  
Median Survival Time ◽  
Bird Species ◽  
Protozoan Parasite ◽  
Cardinalis Cardinalis ◽  
Vector Borne ◽  
And Behavior ◽  
Negative Controls

AbstractArthropod vectors are frequently exposed to a diverse assemblage of parasites, but the consequence of these infections on their biology and behavior are poorly understood. We experimentally evaluated whether the ingestion of a common protozoan parasite of avian hosts (Haemoproteus spp.; Haemosporida: Haemoproteidae) impacted the survivorship of Culex quinquefasciatus (Say) (Diptera: Culicidae). Blood was collected from wild northern cardinals (Cardinalis cardinalis) in College Station, Texas, and screened for the presence of Haemoproteus spp. parasites using microscopic and molecular methods. Experimental groups of Cx. quinquefasciatus mosquitoes were offered Haemoproteus-positive cardinal blood through an artificial feeding apparatus, while control groups received Haemoproteus-negative cardinal blood or domestic canary (Serinus canaria domestica) blood. Culex quinquefasciatus mosquitoes exposed to Haemoproteus infected cardinal blood survived significantly fewer days than mosquitoes that ingested Haemoproteus-negative cardinal blood. The survival of mosquitoes fed on positive cardinal blood had a median survival time of 18 days post-exposure and the survival of mosquitoes fed on negative cardinal blood exceeded 50% across the 30 day observation period. Additionally, mosquitoes that fed on canary controls survived significantly fewer days than cardinal negative controls, with canary control mosquitoes having a median survival time of 17 days. This study further supports prior observations that Haemoproteus parasites can be pathogenic to bird-biting mosquitoes, and suggests that Haemoproteus parasites may indirectly suppress the transmission of co-circulating vector-borne pathogens by modulating vector survivorship. Our results also suggest that even in the absence of parasite infection, bloodmeals from different bird species can influence mosquito survivorship.

scholarly journals 3217 Catatonia, Delirium and Coma: Implications for Mortality

2019 ◽  
Vol 3 (s1) ◽  
pp. 37-37
Author(s):  
Jo Ellen Wilson ◽  
Sarasota Mihalko ◽  
Stephan Heckers ◽  
Pratik P. Pandharipande ◽  
Timothy D. Girard ◽  
...  
Keyword(s):  
Survival Time ◽  
Critically Ill ◽  
Median Survival ◽  
Critically Ill Patients ◽  
Median Survival Time ◽  
Rating Scale ◽  
Brain Dysfunction ◽  
Survival Times ◽  
Dsm 5 ◽  
Acute Brain Dysfunction

OBJECTIVES/SPECIFIC AIMS: Delirium, a form of acute brain dysfunction, characterized by changes in attention and alertness, is a known independent predictor of mortality in the Intensive Care Unit (ICU). We sought to understand whether catatonia, a more recently recognized form of acute brain dysfunction, is associated with increased 30-day mortality in critically ill older adults. METHODS/STUDY POPULATION: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Coma, was defined as a Richmond Agitation Scale score of −4 or −5. We used the Cox Proportional Hazards model predicting 30-day mortality after adjusting for delirium, coma and catatonia status. RESULTS/ANTICIPATED RESULTS: We enrolled 335 medical, surgical or trauma critically ill patients with 1103 matched delirium and catatonia assessments. Median age was 58 years (IQR: 48 - 67). Main indications for admission to the ICU included: airway disease or protection (32%; N=100) or sepsis and/or shock (25%; N=79. In the unadjusted analysis, regardless of the presence of catatonia, non-delirious individuals have the highest median survival times, while delirious patients have the lowest median survival time. Comparing the absence and presence of catatonia, the presence of catatonia worsens survival (Figure 1). In a time-dependent Cox model, comparing non-delirious individuals, holding catatonia status constant, delirious individuals have 1.72 times the hazards of death (IQR: 1.321, 2.231) while those with coma have 5.48 times the hazards of death (IQR: 4.298, 6.984). For DSM-5 catatonia scores, a 1-unit increase in the score is associated with 1.18 times the hazards of in-hospital mortality. Comparing two individuals with the same delirium status, an individual with a DSM-5 catatonia score of 0 (no catatonia) will have 1.178 times the hazard of death (IQR: 1.086, 1.278), while an individual with a score of 3 catatonia items (catatonia) present will have 1.63 times the hazard of death. DISCUSSION/SIGNIFICANCE OF IMPACT: Non-delirious individuals have the highest median survival times, while those who are comatose have the lowest median survival times after a critical illness, holding catatonia status constant. Comparing the absence and presence of catatonia, the presence of catatonia seems to worsen survival. Those individual who are both comatose and catatonic have the lowest median survival time.

MEDIAN SURVIVAL TIME

The Lancet ◽  
1982 ◽  
Vol 319 (8280) ◽  
pp. 1076
Author(s):  
P.M. Stell
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time
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