Stanozolol and the Treatment of Venous Ulceration — An Interim Report

1986 ◽  
Vol 1 (3) ◽  
pp. 197-203 ◽  
Author(s):  
G. T. Layer ◽  
M. C. Stacey ◽  
K. G. Burnand
Keyword(s):  
Rank Test ◽  
Inclusion Criteria ◽  
Double Blind ◽  
Venous Ulceration ◽  
Compression Bandaging ◽  
Venous Ulcers ◽  
Log Rank Test ◽  
Initial Area ◽  
Standard Regime

A report on an interim analysis of a large placebo-controlled double-blind randomized clinical trial evaluating the role of fibrinolytic enhancement in the management of venous ulceration is described. Seventy-five patients with venous ulcers have entered the trial and fulfilled the inclusion criteria. The ulcers were treated by a standard regime of compression bandaging combined with the oral administration of placebo or stanozolol (Stromba; Sterling Research Laboratories, Guildford). Treatment was continued until healing, and the healing times were compared between the two groups. Sixty-five per cent of ulcers treated with stanozolol have healed and 61.5 % on placebo. There was no overall difference in the healing times of patients treated with stanozolol or placebo. When the healing times were analysed after stratification into initial size, there was no difference between the ulcers of small (less than 2 cm2) or large (greater than 5 cm2) initial area, but for the ulcers between 2 and 5 cm2 there was a trend in favour of improved healing for those ulcers treated with stanozolol ( P = 0.13, log rank test).

Hand-foot syndrome (HFS) in patients treated with capecitabine (CAP) and the role of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8615-8615 ◽  
Author(s):  
V. Juneja ◽  
G. Black ◽  
J. Thornton ◽  
S. Russo ◽  
M. Johnson ◽  
...  
Keyword(s):  
Dihydropyrimidine Dehydrogenase ◽  
Rank Test ◽  
Toxicity Data ◽  
Log Rank Test ◽  
Hand Foot Syndrome ◽  
Median Cumulative Dose ◽  
Dose Modifications ◽  
Ecog Ps ◽  
Pharmacological Basis

8615 Background: HFS is the most common toxicity of CAP. Preclinical studies have shown that radiation (XRT) up-regulates TP, which may in turn increase efficacy of CAP. CAP is degraded by DPD, and a deficiency in this enzyme may increase toxicity of CAP. However, effect of XRT on frequency of HFS and association with TP and DPD has not been fully characterized. Methods: Toxicity data were collected from pts with LA pancreatic cancer enrolled in 3 clinical trials conducted at UAB between Apr 2001 and Jul 2005. Overall results of these trials have been reported elsewhere. Pts received XRT (50.4 Gy) with CAP (1,200–1,600 mg/m2 BID M-F) followed CAP (2,000 mg/m2 BID x 14 days). Pts were classified into 2 groups to evaluate HFS: CAP-XRT and CAP. Roche grading was used to assess HFS. Dose modifications were according to drug insert. Pts received prophylactic udder cream and pyridoxine. Tumor specimens were procured in 36 pts by EUS-FNA 1 wk pre- and 2 wks post XRT to evaluate TP and DPD. Age, race, sex, and PS were evaluated as prognostic factors. Results: Median duration of CAP was 6 wks (range: 3–6) for CAP-XRT and 2.5 cycles (range: 0–17) for CAP. Among 58 pts, 14 developed HFS (24%). CAP group had a higher incidence of HFS than CAP-XRT (17.2 % vs. 10.3 %; P = 0.12). Grade 2/3 HFS was observed in 15.5 % of CAP and 1.7 % of CAP-XRT (P = 0.0078). Median cumulative dose of CAP for first development of HFS was 235,000 mg/m2 in CAP-XRT group and 3,185,000 mg/m2 in CAP, with relative frequency of an event occurring in CAP-XRT vs. CAP of 0.59. HFS occurred at a median of 5 wks in CAP-XRT and 6 wks in CAP. Log-rank test showed neither age, sex, ECOG PS, or race was associated with development of HFS. There was no difference in tumor responses of pts with vs. without HFS. Mean tumor TP was higher among pts with vs. without HFS (275.77 vs. 215.29; P = 0.32). Mean tumor DPD was lower among pts with vs. without HFS (55.18 vs. 63.58; P = 0.49). Mean TP:DPD ratio was higher among pts with vs. without HFS (10.29 vs. 3.04; P = 0.31). Conclusions: This study suggests that incidence, severity, and time to occurrence of HFS with CAP-XRT < CAP, indicating no effect of XRT. No significant association of HFS with higher tumor TP or lower tumor DPD was found. Pharmacological basis for HFS with CAP needs to be explored. [Table: see text]

The role of serum carcinoembryonic antigen in predicting objective responses to chemotherapy and overall survival in patients with non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18084-e18084
Author(s):  
Hongbing Liu
Keyword(s):  
Protective Factor ◽  
Cox Regression ◽  
Rank Test ◽  
Small Cell Lung ◽  
Baseline Serum ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Serum Cea ◽  
Nsclc Patients

e18084 Background: Previous studies indicated the carcinoembryonic antigen (CEA) could predict the therapeutic objective response (OR) and overall survival (OS) of patients with cancers, including non-small cell lung cancer (NSCLC). However, the role it could play in evaluating therapeutic responses and OS in patients with NSCLC requires further elucidation. Herein, we investigated the potential role of CEA in predicting OR and OS in patients with NSCLC. Methods: 689 patients with NSCLC were enrolled between January 2000 and August 2011. The correlations between the CEA levels and OR or OS were examined via statistical analyses including the chi-squared test, logistical regression, paired-samples t-test, receiver operator characteristic curve, Kaplan-Meier survival analysis, log-rank test and Cox regression model. Results: The calculated cut-off for predicting an OR to chemotherapy in patients with NSCLC was a reduction of 5.28% in serum CEA. This value demonstrated a sensitivity of 61.3% and a specificity of 62.4%. Serum CEA levels significantly decreased after two cycles of chemotherapy in NSCLC patients (t = 2.196, P = 0.031). The Kaplan-Meier survival analysis indicated no significant correlation between baseline CEA and OS (log rank test =0.079). However, according to the Cox regression analysis the number of distant metastatic organs (=1 and ≥2) was the independent risk factor of the OS (P = 0.026; P =0.003), and the cycle numbers of chemotherapy was the protective factor for OS in patients with NSCLC (P=0.011).More importantly, baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes (P = 0.014; P = 0.017, respectively). Conclusions: Our study shows that baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes. While the baseline level of serum CEA was not a prognostic factor, the post-treatment reduction of serum CEA level can predict the OR in patients with NSCLC,. The number of chemotherapy cycles was the independent protective factor, while the numbers of distant metastatic organs was the independent risk factor for NSCLC patients’ OS.

Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 556-556 ◽  
Author(s):  
Takeru Wakatsuki ◽  
Eiji Shinozaki ◽  
Mitsukuni Suenaga ◽  
Izuma Nakayama ◽  
Tomohiro Matsushima ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adverse Events ◽  
Univariate Analysis ◽  
Rank Test ◽  
Multikinase Inhibitor ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Almost All ◽  
Therapy Target

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.

scholarly journals Overhydration and low serum prealbumin predict peritoneal dialysis-related peritonitis in continuous ambulatory peritoneal dialysis patients

2020 ◽  
Author(s):  
Quyen Dao Bui Quy ◽  
Tuan Pham Ngoc Huy ◽  
Loc Nguyen Duc ◽  
My Pham Van ◽  
Dung Nguyen Huu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Low Education ◽  
Curve Model ◽  
Independent Risk Factors ◽  
Low Serum

Abstract Background: In this study, we focused on the role of overhydration (OH) and low serum prealbumin concentration in predicting 3-year peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods: We measured serum prealbumin concentration and OH by body composition monitor on 278 CAPD patients (159 males and 119 females) with mean age of 46 years and the median peritoneal dialysis (PD) duration of 21 months. PD-related peritonitis was collected for 3 years. Results: After the 3-year follow-up, 44 patients diagnosed PD-related peritonitis (15.8%). Low education, serum albumin, prealbumin, high CRP-hs and OH were independent risk factors for predicting peritonitis during 36 months in CAPD patients. Based on the ROC curve model and Kaplan–Meier analysis, we realized that patients with low prealbumin and high OH were the independent predictors of 3-year peritonitis in CAPD patients (Prealbumin: AUC = 0.838, cut-off value = 32.5 mg/dL, Se= 90.9%, Sp = 32.9%; OH: AUC = 0.851, cut-off value = 1.33 L, Se = 79.5%, Sp = 85.5%; and Log-rank test p < 0.001, respectively). Conclusion: Overhydration and low serum prealbumin level were the independent predictors of PD-related peritonitis in CAPD patients.

Retrospective analysis of treatment effects and prognostic factors associated with overall survival in patients with resected adenocarcinoma of the pancreas.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 359-359
Author(s):  
Dai Chu Nguyen Luu ◽  
Xiaobai Li ◽  
Julia Ojcius ◽  
Peter Muscarella ◽  
Edwin Christopher Ellison ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Analysis ◽  
Pancreas Cancer ◽  
Tumor Grade ◽  
Positive Lymph Node ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Adenocarcinoma Of The Pancreas

359 Background: The role of adjuvant chemotherapy in pancreas cancer has been well established. The role of radiation therapy however remains controversial. The ESPAC-1 study showed a possible deleterious effect for radiation on survival of patients with resected pancreas cancer, although the study was limited by lack of compliance and quality control. Methods: We performed a retrospective analysis of patients who underwent curative resection of their cancer of the pancreas over the last 2 decades at the Ohio State University. 333 patients with adenocarcinoma of the pancreas were identified from our database and 148 subjects were found with complete treatment information available. Thirty patients had no treatment after resection. Log-rank test was used to compare the overall survival (OS) of two groups of patients: treated with chemotherapy (C, N=68) or fluoropyrimidine-based chemoradiation (CRT, N=50). Demographics of the CT and CRT groups were balanced. Patient characteristics including age, sex, tumor size, tumor location, tumor grade, nodal status, margins (R0 vs. R1) and number of hospitalizations within a six-month period of discharge from the hospital after surgery were compared across all groups. The effect of these variables on OS was assessed using log-rank test. Results: The mOS for C (21.5 months, 95% CI; 13.5, 24.6) and CRT (16.8 months, 95% CI; 13.9, 23.1) were similar. There was no statistically significant difference observed for C vs. CRT (p>0.8). Out of all the characteristic variables tested (N= 148), only the presence of at least one positive lymph node vs. none had a statistically significant negative effect on survival (mOS of 12.20 months vs. 23.10 months; p=0.0053). Conclusions: In patients with resected adenocarcinoma of the pancreas, the addition of radiation does not seem to add benefit. The presence of positive lymph nodes is an adverse prognostic factor on overall survival.

High expression of CD52 predicts poor prognosis of cytogenetic normal acute myeloid leukemia

2020 ◽  
Author(s):  
Ping Cai ◽  
Wenzhi Cai ◽  
Xiaoyu Xu ◽  
xiaofei Yang ◽  
yemin Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Leukemia Cell ◽  
Dna Demethylation ◽  
Rank Test ◽  
Log Rank Test ◽  
High Level ◽  
Acute Myeloid

Abstract Background: The prognosis of cytogenetic normal acute myeloid leukemia (CN-AML) varies. Finding new biomarkers affecting the prognosis of these patients may bring a new strategy for precise classification and treatment. CD52 play a significant role in chronic lymphocytic leukemia (CLL). However, the potential role of CD52 in CN-AML remains largely elusive. Methods: We analyzed the prognostic role of different expression levels of CD52 in 58 CN-AML from The Cancer Genome Atlas (TCGA) dataset and validate these results with 345 CN-AML patients from Gene Expression Omnibus (GEO) dataset. Results: CN-AML patients with high CD52 mRNA expression have a poorer prognosis compared to low CD52 expression ( event-free survival [EFS], P =0.056; overall survival [OS], P=0.043; log-rank test) and the results was verified by GSE12417 (OS, P=0.0197; log-rank test) and GSE71014 (OS, P=0.0197; log-rank test). Hematopoietic stem cell transplantation (HSCT) may improve prognosis of patients with CD52 high . Multivariate cox regression analysis show that the expression level of CD52 (HR=1.503; 95%CI:1.158-1.949 ; P=0.002) was a prognostic factor independent of age (HR=3.045; 95%CI:1.524-6.086; P=0.002) and FLT3 mutation status (HR=2.219; 95%CI:1.123-4.382; P=0.022). CD52 gene expression show a predictive effect on EFS (1-year survival- area under the curve [AUC]:0.685, 2-year survival-AUC:0.752) and OS (1-year survival-AUC: 0.717, 2-year survival-AUC:0.770). Besides, we also found that there is a significant negative correlation between CD52 mRNA expression and DNA methylation . CD52 DNA demethylation may responsible for the high level of CD52 mRNA. Functional enrichment analysis of differentially expressed genes in CD52 high and CD52 low suggests that leukemia cell adhesion-related pathways may be associated with poor prognosis in CD52 high patients . Conclusions: CD52 gene mRNA overexpression is an independent adverse prognostic factor for CN-AML, which could be reversed by HSCT. CD52 DNA demethylation may responsible for the high level of CD52 mRNA. The poor prognosis of patients with CD52 high may involves in leukemia cell adhesion-related pathways. Whether CD52 monoclonal antibodies play a role in high risk patients need further research.

RADT-27. EFFECTIVENESS ANALYSIS OF RADIOTHERAPY FOR INTRACRANIAL RECURRENT EPENDYMOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi47-vi47
Author(s):  
Qingjun Hu ◽  
Mingyao Lai ◽  
Juan Li ◽  
Linbo Cai
Keyword(s):  
Survival Time ◽  
Rank Test ◽  
Who Grade ◽  
Radiotherapy Group ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Recurrent Ependymoma ◽  
Grade Ii

Abstract OBJECTIVE There is no standard treatment for recurrent ependymoma. This study aimed to investigated the role of radiotherapy in recurrent ependymoma. METHODS Retrospective analysis was performed on 49 cases of recurrent ependymoma diagnosed in Guangdong Sanjiu Brain Hospital from January 2008 to July 2020. Overall survival (OS) was calculated by Kaplan-Meier method and tested by Log-rank test. P &lt; 0.05 was considered statistically significant. RESULTS The median age was 7 years (range:1-57 yrs). Nineteen patients were with ependymoma WHO grade II while 30 were with grade III, respectively. Recurrence treatment: 14 cases received re-surgery, 23 cases received radiotherapy, among them 16 cases received re-radiotherapy. To May, 2021, the median follow-up time was 35 months (range 3-153). Median PFS time was 17 months after initial diagnosis, median PFS time was 8 months after treatment to recurrence disease, Median OS time is 39 months, and median OS time is 20 months after recurrence. The median survival time for recurrence was 48 months vs. 11 months (P =0.001) in the radiotherapy group vs. non-radiotherapy group,res; Re-radiotherapy combined with chemotherapy vs reradiotherapy alone (0.194); RRT combined with anti-angiogenesis therapy vs. RRT alone (0.688). CONCLUSION Radiotherapy can prolong the survival time of recurrent ependymoma, and concurrent therapy as chemotherapy or anti-angiogenesis therapy with RT does not seem to improve the prognosis. Therefore, radiotherapy can be used as the main treatment for recurrent ependymoma.

scholarly journals Role of Bevacizumab in High-grade Meningiomas

2021 ◽  
Author(s):  
Xuexue Bai ◽  
xiangyu wang ◽  
Yiyao Cao
Keyword(s):  
Progression Free Survival ◽  
Rank Test ◽  
High Grade ◽  
Chi Square ◽  
Free Survival ◽  
Log Rank Test ◽  
Peritumoral Brain Edema ◽  
Chi Square Test

Abstract Background: To explore the role of bevacizumab (BV) in High-grade Meningiomas (HGMs) undergoing surgical treatment.Methods: Review the clinical data of 139 patients with HGMs and divide them into BV group and non- BV group according to whether they receive BV treatment. Then we compared the progression-free survival (PFS) and overall survival (OS) of the two groups.Results: The Chi-square test showed significant differences between the BV group and the non-BV group in terms of 12-month PFS (PFS-12), 36-month PFS (PFS-36), median PFS (M-PFS), 12-month OS (OS-12), 36-month OS (OS-36), and median OS (M-OS). However, there was no statistical difference between the BV group and the non-BV group in terms of 6-month PFS (PFS-6), 60-month PFS (PFS-60), and 60-month OS (OS-60). The log-rank test indicated significant differences in PFS and OS between the BV group and the non-BV group.Conclusion: The role of BV in patients with HGMs is to relieve the symptoms of peritumoral brain edema (PTBE) and prolong PFS and OS. However, whether increasing the dose of BV after surgery can improve the long-term PFS and OS of patients with HGMs needs further research.

Comparison of preoperative chemoradiation with radiation or chemotherapy alone in patients with non-metastatic, resectable retroperitoneal sarcoma

2021 ◽  
pp. 1-6
Author(s):  
Sung Jun Ma ◽  
Brian Yu ◽  
Lucas M. Serra ◽  
Austin J. Bartl ◽  
Oluwadamilola T. Oladeru ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Preoperative Chemoradiation ◽  
Retroperitoneal Sarcoma ◽  
Rank Test ◽  
Preoperative Radiation ◽  
Inclusion Criteria ◽  
Therapy Regimen ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
The Impact

Abstract Aim: Optimal preoperative therapy regimen in the treatment of resectable retroperitoneal sarcoma (RPS) remains unclear. This study compares the impact of preoperative radiation, chemoradiation and chemotherapy on overall survival (OS) in RPS patients. Materials and Methods: The National Cancer Database (NCDB) was queried for patients with non-metastatic, resectable RPS (2006–15). The primary endpoint was OS, evaluated by Kaplan–Meier method, log-rank test, Cox multivariable analysis and propensity score matching. Results: A total of 1,253 patients met the inclusion criteria, with 210 patients (17%) receiving chemoradiation, 850 patients (68%) receiving radiation and 193 patients (15%) receiving chemotherapy. On Cox multivariable analysis, when compared to preoperative chemoradiation, preoperative radiation was not associated with improved OS (hazards ratio [HR] 0·98, 95% CI 0·76–1·25, p = 0·84), while preoperative chemotherapy was associated with worse OS (HR 1·64, 95% CI 1·24–2·18, p < 0·001). Similar findings were observed in 199 and 128 matched pairs for preoperative radiation and chemotherapy, respectively, when compared to preoperative chemoradiation. Findings: Our study suggested an OS benefit in using preoperative chemoradiation compared to chemotherapy alone, but OS outcomes were comparable between preoperative chemoradiation and radiation alone.

Targeting Connective Tissue Growth Factor (CTGF) In Acute Lymphoblastic Leukemia Pre-Clinical Models: Anti-CTGF Monoclonal Antibody Attenuates Tumor Growth In Mouse Models of ALL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3257-3257
Author(s):  
Hongbo Lu ◽  
Venkata Lokesh Battula ◽  
Borys Korchin ◽  
Suzanne Spong ◽  
Martin Canizales ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Overall Survival ◽  
Tumor Growth ◽  
Statistical Significance ◽  
Leukemia Cell ◽  
Tissue Growth ◽  
Rank Test ◽  
Log Rank Test

Abstract Abstract 3257 Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of proteins involved in extracellular matrix production, tumor cell proliferation, adhesion, migration, and metastasis. In pancreatic cancer, CTGF derived from tumor cells is a critical regulator of tumor growth, and CTGF-specific antibody attenuates tumor growth and metastases in vivo (Cancer Res., 2006; 66(11):5816-27). Elevated CTGF levels have been detected in a number of malignancies, including in lymphoblasts from patients with acute lymphoblastic leukaemia (ALL), while no expression of CTGF was detected in normal peripheral blood mononuclear cells. Most importantly, recent studies with microarrays of B-ALL cells showed evidence of increased expression of CTGF, which was significantly associated with inferior outcome (Blood, 2007; 109(7):3080-3). In this study, we characterized mRNA expression and function of CTGF in ALL cell lines (Jurkat, REH, RS4;11, Nalm6) and in samples from primary ALL samples. RS4;11 and REH expressed high levels of CTGF mRNA (479.26±37.17 and 57.31±5.87 per 100 copies of ABL1, respectively), and CTGF secretion into culture supernatants was confirmed by immunoblotting with anti-CTGF antibody. In eleven primary pre-B-ALL patient samples, CTGF mRNA levels varied from 68.68±2.1 to 7030.2±170.47 per 100 copies of ABL1. In contrast, two T-ALL samples expressed very low levels of CTGF (4.7±0.19 and 5.2±0.12, respectively). To determine the functional role of CTGF in proliferation and survival of ALL cells, we utilized lentiviral shRNA to knock-down CTGF in RS4;11 cells. Cells stably infected with shRNA showed significant repression of CTGF levels (75.15%±0.98). Remarkably, CTGF knock down resulted in significant suppression of leukemia cell proliferation (by 57%) compared to control vector, but not in apoptosis induction. This data indicate that CTGF is critically involved in ALL cell proliferation. We next investigated the anti-leukemia efficacy of the fully human anti-CTGF monoclonal antibody FG-3019 (FibroGen, Inc.) using CTGF-expressing A20-luc/YFP leukemia cells in NOD/SCID/IL2 receptor gamma KO (NOG) mice. FG-3019 was administered intraperitoneally at 10 mg/kg/day twice a week starting on day 7 after leukemia cell injection. Compared to control human IgG, FG-3019 significantly inhibited leukemia growth as determined by bioluminescence imaging (38.3%±1.25) (Figure 1A) and significantly prolonged overall survival from 21 days to 31 days (p=0.01) (Figure 1B). In a subsequent in vivo experiment in NOD/Scid mice, xenografts derived from a primary CTGF-expressing ALL sample were treated with FG-3019 or control human IgG at 10 mg/kg/day twice a week starting at 7 days after cell injection. Similar to the cell line experiment, FG-3019 significantly prolonged the overall survival of animals otherwise dying from leukemia (median survival, control - 24 days, FG-3019- 31 days, p<0.01)(Figure 1C). Altogether, this data demonstrate that autocrine CTGF is highly expressed in pre B-ALL cell lines and primary ALL samples and represents a potential target for therapies blocking CTGF signaling. This is of particular importance given our recent findings of critical role of CTGF in the mesenchymal cells of the bone marrow microenvironment (Battula, ASH 2010). Mechanistic studies of the growth-promoting effects of CTGF in ALL are currently ongoing and will be presented. (A) Serial bioluminescence images of mice injected with A20-luc/YFP leukemia in groups receiving FG3019 or hIgG. Bioluminescence imaging results were averaged from the peak light-emitting exposure from each group and displayed as photons per second. Error bars represent the SEM of each group. (B) Overall survival of control (hIgG-treated) and FG3019-treated mice in the A20-luc/YFP leukemia murine model. Statistical significance was calculated using the log-rank test. (C) In the NOD/Scid mice xenograft model of ALL leukemia, the overall survival in two different groups was estimated by Kaplan-Meier method. Statistical significance was calculated using the log-rank test. Disclosures: Off Label Use: use of FG-3019 for treatment of ALL. Spong: FibroGen.Inc.: Employment.

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