scholarly journals Fosmanogepix (APX001) Is Effective in the Treatment of Immunocompromised Mice Infected with Invasive Pulmonary Scedosporiosis or Disseminated Fusariosis

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Sondus Alkhazraji ◽  
Teclegiorgis Gebremariam ◽  
Abdullah Alqarihi ◽  
Yiyou Gu ◽  
Zeinab Mamouei ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Fungal Infections ◽  
Treatment Options ◽  
High Dose ◽  
Minimum Effective Concentration ◽  
Immunosuppressed Patients ◽  
Immunocompromised Mice

ABSTRACT There are limited treatment options for immunosuppressed patients with lethal invasive fungal infections due to Fusarium and Scedosporium. Manogepix (MGX; APX001A) is a novel antifungal that targets the conserved Gwt1 enzyme required for localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. We evaluated the in vitro activity of MGX and the efficacy of the prodrug fosmanogepix (APX001) in immunosuppressed murine models of hematogenously disseminated fusariosis and pulmonary scedosporiosis. The MGX minimum effective concentration (MEC) for Scedosporium isolates was 0.03 μg/ml and ranged from 0.015 to 0.03 μg/ml for Fusarium isolates. In the scedosporiosis model, treatment of mice with 78 mg/kg and 104 mg/kg of body weight fosmanogepix, along with 1-aminobenzotriazole (ABT) to enhance the serum half-life of MGX, significantly increased median survival time versus placebo from 7 days to 13 and 11 days, respectively. Furthermore, administration of 104 mg/kg fosmanogepix resulted in an ∼2-log10 reduction in lung, kidney, or brain conidial equivalents/gram tissue (CE). Similarly, in the fusariosis model, 78 mg/kg and 104 mg/kg fosmanogepix plus ABT enhanced median survival time from 7 days to 12 and 10 days, respectively. A 2- to 3-log10 reduction in kidney and brain CE was observed. In both models, reduction in tissue fungal burden was corroborated with histopathological data, with target organs showing reduced or no abscesses in fosmanogepix-treated mice. Survival and tissue clearance were comparable to a clinically relevant high dose of liposomal amphotericin B (10 to 15 mg/kg). Our data support the continued development of fosmanogepix as a first-in-class treatment for infections caused by these rare molds.

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 Clinical Evaluation of an in Vitro Test for Radiosensitivity of Leukemic Lymphocytes

Blood ◽  
1962 ◽  
Vol 20 (4) ◽  
pp. 432-442 ◽  
Author(s):  
ROBERT SCHREK ◽  
STANLEY L. LEITHOLD ◽  
IRVING A. FRIEDMAN ◽  
WILLIAM R. BEST
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Leukocyte Count ◽  
In Vitro Test ◽  
X Rays ◽  
X Ray ◽  
Leukocyte Counts ◽  
Vitro Test

Abstract A recently developed slide-chamber method was used to test the radiosensitivity of blood lymphocytes from 80 patients with chronic lymphocytic or lymphosarcoma-cell leukemia. The objective of this study was to determine whether these in vitro tests on sensitivity to x-rays had any clinical significance. Two objective criteria were used to measure the clinical reactions of the leukemic patients. The first was the duration of survival of patients following the in vitro test. The second was the minimal leukocyte count of a patient following x-ray therapy; the minimal count was expressed as a percentage of the count before therapy. The in vitro radiosensitivity was measured by the 10 per cent survival time of lymphocytes irradiated with 1000 r. Blood lymphocytes from non-leukemic individuals were highly radiosensitive with indices of 1.1 to 2.2 days. In initial tests, the lymphocytes of 61 leukemic patients had the same high sensitivity to x-rays as lymphocytes from non-leukemic individuals. In contrast, the lymphocytes of 19 leukemic patients were radioresistant to irradiation with indices of 2.5 to 11 days. The 61 patients with radiosensitive lymphocytes had a median survival time of 22 months after the in vitro test. In contrast, the 19 patients with radioresistant lymphocytes had a median survival time of only 4 months. Clinical x-ray therapy caused a greater decline in leukocyte counts in patients with radiosensitive lymphocytes than in those with radioresistant cells. A significant index of 0.60 was obtained for the correlation of in vitro radiosensitivity of lymphocytes and the in vivo decrease in leukocyte counts of patients after x-ray therapy. It is concluded that an in vitro finding of radioresistant lymphocytes is correlated with a poor response of the leukocyte count to x-ray therapy and a short survival time of the patient.

Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid.

1986 ◽  
Vol 4 (5) ◽  
pp. 685-696 ◽  
Author(s):  
D Machover ◽  
E Goldschmidt ◽  
P Chollet ◽  
G Metzger ◽  
J Zittoun ◽  
...  
Keyword(s):  
Survival Time ◽  
Folinic Acid ◽  
Disease Progression ◽  
Median Time ◽  
Gastric Adenocarcinoma ◽  
Median Survival ◽  
Median Survival Time ◽  
Single Agent ◽  
High Dose ◽  
Gastric Adenocarcinomas

We report the results of an expanded trial of 5-fluorouracil (5-FU) combined with high-dose folinic acid for treatment of patients with advanced colorectal or advanced gastric adenocarcinoma. In each treatment course, the patients received both 5-FU (340 to 400 mg/m2/d by intravenous (IV) infusion for a period of 15 minutes) and folinic acid (200 mg/m2/d by IV bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete and partial response rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to 5-FU attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates greater than 10(-5) mol/L were achieved after a rapid single IV injection of 200 mg/m2 of folinic acid. Comparisons of our results with those reported in previous studies on 5-FU administered as a single agent suggest that, in advanced colorectal and gastric adenocarcinoma, folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly. Furthermore, some colorectal tumors that were previously resistant to 5-FU become sensitive to this drug. The survival of the patients who responded to therapy was markedly improved over that observed in reported series of untreated patients with advanced colorectal and gastric adenocarcinomas.

Population-Based Analysis of Secular Trends in Age at Death in Trisomy 18 Syndrome in Japan from 1975 to 2016

Neonatology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Maiko Suto ◽  
Tetsuya Isayama ◽  
Naho Morisaki
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Surgical Intervention ◽  
Patient Survival ◽  
Treatment Options ◽  
Vital Statistics ◽  
Trisomy 18 ◽  
Diagnostic Methods ◽  
Prenatal Diagnostic

<b><i>Introduction:</i></b> Despite changes in prenatal diagnostic methods and perceptions regarding the prognosis of and treatment options for patients with trisomy 18 syndrome, data on the secular changes in patient survival are limited. This study aimed to investigate the survival pattern for such patients. <b><i>Methods:</i></b> To investigate the general patient survival patterns, we used data from the vital statistics database of deaths in Japan from 1975 to 2016. We described demographic factors, such as sex, gestational age at delivery, and surgical history, for patients whose primary cause of death was trisomy 18 syndrome. <b><i>Results:</i></b> The proportions of deaths within 24 h of birth (4.0% in 1975–1980 to 21.9% in 2011–2016) and at age ≥1 year (8.9% in 1975–1980 to 17.7% in 2011–2016) increased. The median survival time was higher for females, infants born after 37 weeks of gestation, and those who received surgical intervention. The median survival time tripled among patients who received surgical intervention (61.5 days in 1995–2005 to 182.5 days in 2006–2016), and the proportion of such patients increased (from 3.8% in 1995 to 24.1% of the entire affected population in 2016). <b><i>Discussion/Conclusion:</i></b> In Japan, the median survival time of infants with trisomy 18 increased over time, and the proportion of death within 24 h and at ≥1 year increased. Greater acknowledgement of the possible benefits of surgical intervention likely led to the increased provision of interventions and contributed to the increased survival time.

scholarly journals Open reading frame Bm21 of Bombyx mori nucleopolyhedrovirus is not essential for virus replication in vitro, but its deletion extends the median survival time of infected larvae

2008 ◽  
Vol 89 (4) ◽  
pp. 922-930 ◽  
Author(s):  
Jinshan Huang ◽  
Bifang Hao ◽  
Fei Deng ◽  
Xiulian Sun ◽  
Hualin Wang ◽  
...  
Keyword(s):  
Survival Time ◽  
Bombyx Mori ◽  
Median Survival ◽  
Virus Replication ◽  
Median Survival Time ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Group I ◽  
Control Virus

In this report, the open reading frame 21 (Bm21) of Bombyx mori nucleopolyhedrovirus (BmNPV), one of the unique genes of group I NPVs, was characterized. Bm21 is predicted to encode a protein of 55.8 kDa and was found to contain imperfectly conserved leucine-rich repeats. 3′ Rapid amplification of cDNA ends (3′RACE) showed that the transcript of Bm21 was first detected from 6 h post-infection and that it also encompassed the complete Bm20. 5′RACE revealed three transcription initiation sites, one of which mapped to the baculovirus early transcription motifs CGTGC and CAGT. Transient-expression and superinfection assays indicated that BM21 localized in the nucleus of infected BmN cells. To study the function of BM21, a Bm21-null virus was constructed using bacmid technology. Viral one-step growth curve analyses showed that the Bm21-null virus had similar budded virus production kinetics to those of the parental virus. Bioassay analyses showed that the median lethal concentration (LC50) of the Bm21-null virus was similar to that of the control virus; however, the median survival time (ST50) of the knockout virus was significantly longer than the control virus. These results indicate that BM21 is not essential for virus replication in vitro, but that deletion of the gene delays the killing of the infected larvae.

scholarly journals ET-8 Integrated diagnostic approach to predict prognosis for malignant gliomas

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi5-vi5
Author(s):  
Masataka Isoda ◽  
Kensuke Tateishi ◽  
Jo Sasame ◽  
Takahiro Hayashi ◽  
Youhei Miyake ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Drug Screening ◽  
Median Survival Time ◽  
Drug Sensitivity ◽  
Chemotherapeutic Agents ◽  
Who Grade ◽  
Response To Chemotherapy ◽  
Mgmt Promoter

Abstract Previous studies indicated that MGMT promoter methylation status with IDH and TERT promotor mutation are major prognostic factors in glioma. In addition to these molecular features, we have been assessing drug sensitivity against several chemotherapeutic agents, including temozolomide (TMZ). Here, we examined if this combined information could strongly predict drug sensitivity and the prognosis in glioma patients. One hundred and twenty-five IDH wild-type gliomas (WHO grade III and grade IV) were included in this study and retrospectively analyzed. Among them, we focused on 37 patients with partial surgical resection and biopsy to assess radiological difference on MRI. The primary cultured tumor cells were exposed with several compounds for 72 hours, then ATP based cell viability assay was performed. The favorable radiological therapeutic effect was found in 6 out of 8 (75%) with MGMT promoter methylated cases, while unfavorable in 23 of 29 (79.3%) with MGMT promoter unmethylated cases (p=0.008). The drug screening assay demonstrated that 7 of 10 cases with favorable TMZ sensitivity in vitro showed response on MRI, whereas 22 of 27 (81.5%) cases with TMZ resistance in vitro indicated tumor progression (p=0.006). Of note, all 5 cases with sensitive to TMZ and methylated MGMT promoter demonstrated favorable radiological response (p=0.002). These 5 cases tended to survive longer (median survival time, 697 days) as compared to others (median survival time, 391 days, p=0.13). These data indicate that integrated approach with genomic assessment and drug screening test may predict therapeutic response to chemotherapy and contribute selecting optimal therapy in glioma patients.

scholarly journals Deuterium depletion inhibits lung cancer cell growth and migration in vitro and results in severalfold increase of median survival time of non-small cell lung cancer patients receiving conventional therapy

2021 ◽  
Vol 9 (2) ◽  
pp. 12-19
Author(s):  
Somlyai G ◽  
Kovács BZs ◽  
Somlyai I ◽  
Papp A ◽  
Nagy LI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Cancer Cell ◽  
Median Survival ◽  
Median Survival Time ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 84% of all lung cancer diagnoses. In advanced NSCLC, including adenocarcinoma and squamous cell carcinoma, median survival time (MST) rarely exceeds 10-12 months. Reduced deuterium (D) concentration in water of tissue culture media and in drinking water for humans has shown a strong anticancer effect in previous investigations. In the present study, 1 parts per million (ppm) decrease of D-concentration every 8 hours resulted in reduced growth rate of the A459 lung cancer cell line in vitro, and the cell migration was also dose-dependently reduced. Retrospective study of 183 NSCLC patients consuming commercially available deuterium-depleted water (DDW) revealed a severalfold increase of MST, which was 149 months for 19 patients and 40 months for 110 patients, who started DDW-consumption at early or advanced stage, respectively. Interestingly, MST showed a significant difference by gender (107 months in females and 41.2 months in males). Application of DDW in combination with surgery plus other conventional therapies (68 patients) gave 149 months MST, while for DDW combined with chemotherapy only (48 patients) MST was 43.7 months. The present results support earlier data that integration of D-depletion to conventional therapies increases the efficacy of therapy, reduces relapse rate and increases MST.

Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma

2006 ◽  
Vol 24 (10) ◽  
pp. 1561-1567 ◽  
Author(s):  
William G. Richards ◽  
Lambros Zellos ◽  
Raphael Bueno ◽  
Michael T. Jaklitsch ◽  
Pasi A. Jänne ◽  
...  
Keyword(s):  
Relative Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Sodium Thiosulfate ◽  
Postoperative Mortality ◽  
Maximum Tolerated Dose ◽  
Rank Test ◽  
High Dose ◽  
Epithelial Tumors

Purpose To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). Patients and Methods Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42°C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. Results Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. Conclusion Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.

Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated.

1996 ◽  
Vol 14 (7) ◽  
pp. 2167-2173 ◽  
Author(s):  
J Bladé ◽  
J F San Miguel ◽  
M Fontanillas ◽  
A Alcalá ◽  
J Maldonado ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
L 62

PURPOSE To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.

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.

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