scholarly journals Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Huan-he Ni ◽  
Lin Zhang ◽  
He Huang ◽  
Shu-qin Dai ◽  
Jiang Li
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Cox Proportional Hazards ◽  
Tumour Cells ◽  
Rank Test ◽  
Independent Factor

Abstract Background Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC). Methods Specimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson’s or Spearman’s chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls. Results We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR− MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II–IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037). Conclusion Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

scholarly journals Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

2020 ◽  
Author(s):  
Huan-he Ni ◽  
Lin Zhang ◽  
He Huang ◽  
Shu-qin Dai ◽  
Jiang Li
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Cox Proportional Hazards ◽  
Tumour Cells ◽  
Rank Test ◽  
Independent Factor

Abstract Background: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).Methods: Paraffin tumour specimens from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's or Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.Results: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR- MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P= 0.010) and OS (HR = 5.140, P= 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).Conclusion: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

scholarly journals Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

2020 ◽  
Author(s):  
Huan-he Ni ◽  
Lin Zhang ◽  
He Huang ◽  
Shu-qin Dai ◽  
Jiang Li
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Cox Proportional Hazards ◽  
Tumour Cells ◽  
Rank Test ◽  
Independent Factor

Abstract Background: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).Methods: Specimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's or Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.Results: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR- MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P= 0.010) and OS (HR = 5.140, P= 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).Conclusion: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

scholarly journals Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

2020 ◽  
Author(s):  
Huanhe Ni ◽  
Lin Zhang ◽  
Hong-xia Chen ◽  
Shu-qin Dai ◽  
Jiang Li
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Cox Model ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Cox Proportional Hazards ◽  
Tumour Cells ◽  
Rank Test ◽  
Independent Factor ◽  
Chi Square

Abstract Background: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).Methods: Paraffin tumour specimens from 197 CC patients were collected. The expression of METTL3 and CD33 was measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's and Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses.Results: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stages. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. The Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P= 0.010) and OS (HR = 5.140, P= 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).Conclusion: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

Pharmacogenetics of Tamoxifen Biotransformation Is Associated With Clinical Outcomes of Efficacy and Hot Flashes

2005 ◽  
Vol 23 (36) ◽  
pp. 9312-9318 ◽  
Author(s):  
Matthew P. Goetz ◽  
James M. Rae ◽  
Vera J. Suman ◽  
Stephanie L. Safgren ◽  
Matthew M. Ames ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Hot Flashes ◽  
Disease Free Survival ◽  
Metabolic Activation ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Buccal Cells ◽  
Cancer Trial ◽  
Adjuvant Breast Cancer

Purpose Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown. Methods We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial. The relationship between genotype and disease outcome was determined using the log-rank test and Cox proportional hazards modeling. Results Paraffin blocks were obtained from 223 of 256 eligible patients, and buccal cells were obtained from 17 living women. CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women. The concordance rate between buccal and tumor genotype was 100%. Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele. In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (hazard ratio [HR], 1.85; P = .176) and DFS (HR, 1.86; P = .089). The CYP3A5*3 variant was not associated with any of these clinical outcomes. Conclusion In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.

Validation of CA-125 concentration nadir within the normal range following primary treatment as a predictor of survival for epithelial ovarian cancer (EOC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16007-16007
Author(s):  
A. Prat ◽  
J. Del Campo ◽  
S. Peralta ◽  
S. Cedres ◽  
A. Perez ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Model ◽  
Primary Treatment ◽  
Cox Proportional Hazards ◽  
University Hospital ◽  
Stage Iii ◽  
Ca 125 ◽  
Rank Test ◽  
Normal Range

16007 Background: Recent studies suggest that the CA-125 nadir within the normal range after surgery and chemotherapy treatment is a predictor of survival (Crawford, ASCO 2004; Crawford, Ann Oncol 2005) and relapse (Markman, J Clin Oncol 2006). In order to validate these previous findings, we have conducted a retrospective analysis of patients (pts) treated in our institution for EOC. Methods: Between March 1, 1997, and October 30, 2005, all pts treated for EOC at Vall d'Hebron University Hospital were identified from the tumor registry database and screened retrospectively for their standard prognostic factors (age at diagnosis (=65 vs. >65), stage (III-IV vs. IC-II), and suboptimal vs. optimal cytorreduction). Inclusion criteria: an elevated CA-125 at time of diagnosis (>35 U/mL); primary treatment (PT) that consisted in surgery and intravenous carboplatin/paclitaxel for a maximum of 6–9 cycles; complete clinical and radiological response to initial treatment with normalization of CA-125 (=35 U/mL); and disease status at the time of last follow-up. Standard Kaplan-Meier methods were used to plot the progression-free survival (PFS) of members of each of the nadir groups. The relative contribution of the different potential correlates of prognosis was assessed by the Cox proportional hazards method. Results: 123 pts were identified: 64 Group A (=10 U/mL), 42 Group B (11–20 U/mL), 17 Group C (21–35 U/mL). Median age: 56. Stage IC 25%, II 13%, III 52%, IV 10%. Median follow-up 39.2 months (m). Median PFS was 69.7 m, 27.7 m, and 15.8 m for A, B and C, respectively (p< .0001, log-rank test). The Cox model showed a highly-significant impact on PFS in relation to CA-125 nadir levels, residual tumor after surgery and stage. Hazard ratios (HR) for PFS (95% CI) of B vs. A, C vs. B, and C vs. A were 1.98 (p= .034), 2.35 (p= .02), and 4.67 (p< .001), respectively. HR for PFS (95% CI) of suboptimal vs. optimal cytorreduction and stage III-IV vs. IC-II were 1.84 (p= .058) and 3.2 (p= .002), respectively. Conclusions: The CA-125 nadir in the normal range following PT for EOC is a reproducible predictor of PFS in stage IC-IV. Prospective studies of maintenance-consolidation therapies or different approaches in selected pts based on CA-125 nadir seem warranted. No significant financial relationships to disclose.

scholarly journals Study Of The Association Of Tumor Deposits With Tumour-infiltrating Lymphocytes And Prognosis In Gastric Cancer Patients

2021 ◽  
Author(s):  
Xinyue Li ◽  
Jing Yang
Keyword(s):  
Gastric Cancer ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cancer Specific Survival ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Abstract Background: To investigate the relationship between tumour deposits(TDs) with the clinicopathological characteristics,prognosis of gastric cancer and tumour-infiltrating lymphocytes( TILs）.Methods: The pathological findings of 369 patients with gastric cancer were retrospectively analysed to observe the expression of TDs, and the levels of stromal TILs . The relationships between TDs status, clinicopathological characteristics, and TILs infiltration level were compared using the chi-square test, and rank data were tested using the rank sum test. Kaplan-Meier was used for survival analysis, and the log-rank test was used to determine the differences in survival curves between groups. The prognostic value of TDs was assessed using multivariate Cox proportional hazards regression analysis.Results: TDs were significantly associated with sex, Lymphovascular invasion, Perineural invasion, pathological TNM stage, and clinical stage (all P<0.05). TILs levels were lower in TDs(+) group and higher in TDs(-) group. TDs(+) group had poor Disease-free survival, cancer-specific survival , and overall survival as compared with TDs(-) groups.Conclusions: TDs is negatively correlated with TILs , and TDs+ was an Independent predictors of the prognosis of gastric cancer.

A tertiary cancer center experience with yttrium-90 radioembolization in hepatocellular carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 443-443
Author(s):  
Kerry Schaffer ◽  
Marcus Smith Noel ◽  
Aram F. Hezel ◽  
Alan W. Katz ◽  
Ashwani Sharma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Model ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Bridge To Transplant ◽  
Kaplan Meier ◽  
Pugh Class

443 Background: Local-regional radioembolization with Yitrium-90 (Y-90) has become standard practice for patients with hepatocellular carcinoma (HCC) either as a bridge to transplant, or for local disease control. Outcomes data in the United States are limited and here we review our institutional experience with Y-90 radioembolization. Methods: We retrospectively reviewed charts from 70 patients with HCC who were treated with Y-90 from May 2010- January 2014. Clinical variables including Child-Pugh class and CLIP score were extracted from patient records. The Cox proportional hazards model was used to determine prognostic factors, and Kaplan-Meier curves were used to determine PFS and OS. Results: Median age was 61 (range 43-82), 79% Caucasian, 84% male, and 79% Child-Pugh class A. Median progression free survival (PFS) was 8.4 months (95% CI 6-10.7) and overall survival (OS) was 14.2 months (95% CI 9.7-21). Overall survival significantly differed by Child -Pugh score (p= 0.009), CLIP score (p=0.003), and presence of portal vein thrombosis (PVT) (p=0.0384), based on the log-rank test comparing Kaplan-Meier curves. Using univariate Cox proportional hazards models, both elevated baseline AFP, measured on a log scale (HR 1.79, 95% CI 1.32-2.43, p=0.0002) and post Y-90 treatment with sorafenib (HR=2.30, 95% CI 1.07-4.95, p=0.03) were associated with worse mortality. Elevated AFP (HR 2.45, 95% CI 1.73-3.47, p<0.0001) and Child-Pugh score of B (HR 4.83, 95% CI 2.23-10.43, p<0.0001) were associated with worse mortality in a multivariate Cox model adjusting for age and ethnicity. Furthermore, AFP values were significantly higher in the 10 patients who died within 4 months of Y-90 (p=0.001), and significantly lower in 7 patients who eventually received a liver transplant (p=0.0002). Conclusions: In patients undergoing treatment with Y-90 radioembolization, Child-Pugh class, CLIP score, presence of PVT, baseline AFP, and sorafenib post Y-90 were significantly associated with overall survival. Median PFS and OS data in this institutional cohort are encouraging. Further prospective studies on Y-90 treatment for HCC are warranted.

Is neoadjuvant (neoadj) treatment necessary prior to liver resection in patients with resectable liver metastases (mets) from colorectal carcinoma (CRC) treated with post-resection hepatic arterial infusion (HAI) plus systemic (SYS) chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14503-14503 ◽  
Author(s):  
N. E. Kemeny ◽  
M. Capanu ◽  
F. Huitzil-Melendez ◽  
D. Haviland ◽  
Y. Fong ◽  
...  
Keyword(s):  
Liver Resection ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Hepatic Arterial Infusion ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Test Results ◽  
Cox Proportional Hazards Models ◽  
Resection Margin Status ◽  
Improvement In Survival

14503 Background: Neoadjuvant therapy in patients (pts) with resectable liver mets has been reported to be associated with improved survival. We evaluated the clinical benefit of neoadj therapy in our pts receiving HAI + SYS after liver resection. Methods: In 4 studies of HAI + SYS after resection of CRC mets, data on neoadj, age, gender, clinical risk score (CRS), number of mets, primary site, resection margin status, presence of synchronous primary and/or bilobar disease were analyzed. Univariate and multivariate Cox proportional hazards models were used to examine differences in overall survival, hepatic or extrahepatic disease-free survival (DFS) between pts who received vs pts who did not receive neoadj. Differences among subgroups were compared using the log-rank test. Results: 234 pts from 4 post-liver resection trials using HAI + SYS were included. Each trial used HAI floxuridine/dexamethasone, with differing SYS regimens: FU/LV (n = 74); CPT11 (n = 98); FOLFOX (n = 31); and FOLFOX or FOLFIRI, ± bevacizumab (n = 31). Neoadj was given to 28% of the pts. Median followup was 4.6 years. No differences in terms of survival, hepatic or extrahepatic DFS were noted between pts who did or did not receive neoadj. Multivariate analyses showed no survival advantage for pts who received neoadj (Y vs N) (HR 0.997, 95% CI, 0.56–1.78). No subsets of pts were identified that showed an improvement in survival from neoadj (table), including pts who responded to neoadj prior to liver resection. Conclusions: Our results do not appear to support the use of neoadj in pts with resectable liver mets from CRC, if they are to be treated with postoperative HAI and SYS chemotherapy. [Table: see text] No significant financial relationships to disclose.

Inhibition of glioblastoma and enhancement of survival via the use of mibefradil in conjunction with radiosurgery

2013 ◽  
Vol 118 (4) ◽  
pp. 830-837 ◽  
Author(s):  
Jason P. Sheehan ◽  
Zhiyuan Xu ◽  
Britney Popp ◽  
Leigh Kowalski ◽  
David Schlesinger
Keyword(s):  
Tumor Volume ◽  
Proportional Hazards ◽  
Chemotherapeutic Agents ◽  
Cox Proportional Hazards ◽  
In Vitro Assays ◽  
Rank Test ◽  
Group 4 ◽  
Group 2

Object The survival of patients with high-grade gliomas remains unfavorable. Mibefradil, a T-type calcium channel inhibitor capable of synchronizing dividing cells at the G1 phase, has demonstrated potential benefit in conjunction with chemotherapeutic agents for gliomas in in vitro studies. In vivo study of mibefradil and radiosurgery is lacking. The authors used an intracranial C6 glioma model in rats to study tumor response to mibefradil and radiosurgery. Methods Two weeks after implantation of C6 cells into the animals, each rat underwent MRI every 2 weeks thereafter for 8 weeks. After tumor was confirmed on MRI, the rats were randomly assigned to one of the experimental groups. Tumor volumes were measured on MR images. Experimental Group 1 received 30 mg/kg of mibefradil intraperitoneally 3 times a day for 1 week starting on postoperative day (POD) 15; Group 2 received 8 Gy of cranial radiation via radiosurgery delivered on POD 15; Group 3 underwent radiosurgery on POD 15, followed by 1 week of mibefradil; and Group 4 received mibefradil on POD 15 for 1 week, followed by radiosurgery sometime from POD 15 to POD 22. Twenty-seven glioma-bearing rats were analyzed. Survival was compared between groups using Kaplan-Meier methodology. Results Median survival in Groups 1, 2, 3, and 4 was 35, 31, 43, and 52 days, respectively (p = 0.036, log-rank test). Two animals in Group 4 survived to POD 60, which is twice the expected survival of untreated animals in this model. Analysis of variance and a post hoc test indicated no tumor volume differences on PODs 15 and 29. However, significant volume differences were found on POD 43; mean tumor volumes for Groups 1, 2, 3, and 4 were 250, 266, 167, and 34 mm3, respectively (p = 0.046, ANOVA). A Cox proportional hazards regression test showed survival was associated with tumor volume on POD 29 (p = 0.001) rather than on POD 15 (p = 0.162). In vitro assays demonstrated an appreciable and dose-dependent increase in apoptosis between 2- and 7-μM concentrations of mibefradil. Conclusions Mibefradil response is schedule dependent and enhances survival and reduces glioblastoma when combined with ionizing radiation.

Decreased survival in cervical cancer patients with thromboembolic events

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16034-16034
Author(s):  
G. M. Jacobson ◽  
M. Goodheart ◽  
B. Smith ◽  
J. Lammli
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Gynecologic Oncology ◽  
Retrospective Chart Review ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
P Value ◽  
Thromboembolic Events ◽  
The University

16034 Background: We have previously reported on the incidence of thromboembolic events (TE) in cervical cancer patients treated with definitive chemoradiation.Patients with TE seemed to have decreased survival compared to those without TE. We reviewed a larger cohort to compare the survival of cervical cancer patients with and without TE. Materials and Methods: We performed a retrospective chart review of cervical cancer patients diagnosed and treated at the University for Iowa from January 1997 until December 2003. Data sources included the University of Iowa Tumor Registry, the Gynecologic Oncology Tumor Data Base, and the relevant ICD-9 codes to identify cervical carcinoma and types of TE in both inpatients and outpatients. Statistical analysis included the Pearson chi-squared test for categorical variable, and the two-sample t-test for continuous factors. Log-rank tests were used for survival analysis along with the generation of Kaplan-Meier survival curves. Multivariate analysis was performed with Cox proportional hazards regression. All tests are two sided and carried out at the 5% level of significance. Results: Three hundred and fifty nine (359) patients were treated with surgery or chemoradiation; thirty-six patients (10%) developed TE. There were significant associations between thromboembolic status and pelvic irradiation (p=0.0493), chemotherapy (p=0.0118), and stage (p=0.0197). Survival could not be estimated for patients not experiencing a thromboembolism; survival did not drop below 50% by the end of follow-up. Median survival time for patients with thromboembolism was 4.5 years. According to log-rank test, this difference was significant (p-value<0.0001). Conclusion: The incidence of thromboembolic events in this cohort of cervical cancer patients was 10%. TE was associated with a significant decrease in survival. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document