Association of gender-related tumor recurrence with a polymorphic variant of LMTK3 in stage II and III colon cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 454-454
Author(s):  
Wu Zhang ◽  
Armin Gerger ◽  
Melissa Janae Labonte ◽  
Dongyun Yang ◽  
Pierre Oliver Bohanes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Recurrence ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
In Vivo Studies

454 Background: Recent evidence suggests that Lemur Tyrosine Kinase 3 (LMTK3) activates estrogen receptor alpha (ERα) transcriptional activity in breast cancer. The mutant variants of two single nucleotide polymorphisms (SNPs) in LMTK3 (rs8108419 and rs9989661) were independently associated with reduced time to tumor recurrence (TTR), suggesting these SNPs were functionally significant. In colon cancer (CC), ERβ expression has been shown to be predominant with low levels of ERα also expressed. ERα stimulates cell proliferation, while ERβ negatively regulates the estrogen-dependent activity of ERα. Based on these previous findings, we hypothesized that LMTK3 rs808419 and rs9989661 may predict TTR in stage II and III CC. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 yrs (range 22–78 yrs)) with stage II (105 pts) or III (129 pts) CC at the University of Southern California. The median follow-up was 4.4 years. LMTK3 rs8108419 and rs9989661 were determined by PCR-RFLP. The primary endpoint of the study was TTR. This study was conducted adhering to the reporting recommendations for tumor marker prognostic studies (REMARK). Results: The minor allele of LMTK3 rs9989661 (C; frequency=30.5%) showed significantly longer median TTR (5.9 vs 12.2+ yrs; HR: 0.41, 95%CI: 0.15-1.18, log-rank p=0.086; univariate analysis) in female CC patients. After Cox proportional hazards model adjustment for stage and type of adjuvant chemotherapy, this result remained significant (HR: 0.25, 95%CI: 0.077-0.778, Wald test p=0.017). No significant association was found between TTR and LMTK3 rs9989661 in men and rs8108419 in both genders. Conclusions: This is the first report demonstrating LMTK3 rs9989661 associations with gender-related TTR in CC. We hypothesize that there is an ERα-dependent loop mechanism with higher estrogen levels in females exerting the effect on ERβ. Larger prospective trials are warranted to confirm these findings, and in vitro and in vivo studies are needed to identify the underlying biological mechanism.

Prediction of clinical outcome in stage II and III colon cancer by a common gene variant in AXIN2.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 387-387
Author(s):  
Joanna Szkandera ◽  
Gudrun Absenger ◽  
Melanie Weissmueller ◽  
Martin Pichler ◽  
Michael Stotz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Outcome ◽  
Cancer Progression ◽  
Tumor Recurrence ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Notch Pathway ◽  
Disease Free Survival ◽  
Cox Proportional Hazards Model ◽  
Stage Ii

387 Background: Recent evidence suggests that the Wnt and Notch signaling pathways are involved in colon cancer progression and tumor recurrence. There is substantial germline genetic variability in these pathways, including single nucleotide polymorphisms (SNPs). SNPs may alter transcription, translation or splicing, thereby causing inter-individual differences in a patient’s tumor recurrence capacity and chemoresistance. We hypothesized that SNPs analyzed in a comprehensive panel of Wnt and Notch pathway genes predict clinical outcome in patients with colon cancer. Methods: A total of 815 patients with stage II and III colon cancer treated at the Medical University of Graz were included in this retrospective study. FFPE tissue specimens from normal tissue adjacent to the tumor samples were available from 599 patients. 18 SNPs in Wnt and Notch pathway genes (SFRP, DKK2, DKK3, Axin2, APC, MYC, TCF7L2 and NOTCH-2) were determined by 5’-exonuclease assay (TaqMan). The primary endpoint of the study was disease-free survival (DFS). Results: The homozygous mutant variant of AXIN2 rs2240308 G>A was associated with a significantly increased median DFS (HR 0.638, 95% CI 0.432-0.942, p=0.024) in univariate analysis. Patients carrying at least one G allele in AXIN2 rs2240308 G>A showed a median DFS of 114 months. In contrast, patients with homozygous A/A showed a median DFS of 133 months. After Cox proportional hazards model adjustment for known prognostic markers this result remained significant (HR 0.671, 95% CI 0.453-0.992, p=0.046). Conclusions: To the best of our knowledge, this is the first study identifying a common genetic variant in AXIN2 as an independent prognostic marker in stage II and III colon cancer. Larger prospective trials are warranted to confirm these findings.

Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4001-4001 ◽  
Author(s):  
S. Tejpar ◽  
F. Bosman ◽  
M. Delorenzi ◽  
R. Fiocca ◽  
P. Yan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Multiple Testing ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Biological Effects ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Stage Iii

4001 Background: Patients with high MSI (MSI H) tumors are increasingly being recognized as a prognostic and predictive subgroup in colon cancer (COC). We investigated the incidence of MSI-H in stage II (n=395) and stage III (n=859) COC, its association with histopathological variables and its prognostic and predictive impact. Methods: The study accrued 3278 patients with Stage II and Stage III COC to receive post-operative 5-FU -LV with or without irinotecan (IRI). Paraffin tissue blocks of 1327/1405 available patients were successfully analyzed for MSI status using the NCI extended panel of 10 markers. MSI-H was defined as instability in ≥3 markers. Relapse Free Survival (RFS) and Overall Survival (OS, median follow up 68 months) were assessed. Results: MSI H was present in 22% (85) of Stage II and 12% (103)of Stage III colon cancer . MSI H status was significantly associated with age <60, higher T stage, higher grade, lower N stage and right sided tumor location. The table presents univariate RFS and OS hazard rates (with 95% confidence intervals) for prognostic and predictive impact per stage and arm, estimated by a survival regression analysis using Cox proportional hazards model and of selected P values by Wald tests. Conclusions: Microsatellite instability is a strong prognostic factor for RFS and OS when considering Stage II and Stage III COC. Subgroup analysis suggests a stronger effect in Stage II than in Stage III, but is limited by sample size and multiple testing. Taken together with differences in incidence between the stages, this may suggest stage specific biological effects of MSI. In contrast to previous reports (a) in Stage II the prognostic effect of MSI remained significant even in pts treated with 5FU (w/o IRI),(b) There is no evidence for an effect of the addition of IRI. [Table: see text] [Table: see text]

scholarly journals Aspirin administration might accelerate the subsidence of periprosthetic joint infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Ping Wei ◽  
Ju Chun Chien ◽  
Wei Hsin Hsiang ◽  
Shan Wei Yang ◽  
Chun Yu Chen
Keyword(s):  
Proportional Hazards Model ◽  
Joint Infection ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Treatment Modalities ◽  
Antibiofilm Activity ◽  
World Population ◽  
Current Standard

Abstract Since the past decade, aspirin, a popular anti-inflammatory drug, has been increasingly studied for its potential antimicrobial and antibiofilm activity with promising results, but studies were limited to in vitro and in vivo investigations. Moreover, evidence concerning the beneficial effects of aspirin on the treatment of biofilm-related infections in real-world population is limited. Thus, this study aimed to investigate whether aspirin could promote infection control for patients with periprosthetic joint infections (PJIs). A single-center database was searched. Regular aspirin exposure was defined as a prescription of aspirin for > 6 months before diagnosis of PJIs and consecutive use during the PJI treatment course at a dose ≧ 100 mg/day. General data, treatment modalities, and recurrence status were collected from medical records by an independent orthopedic surgeon. From January 01, 2010, to February 17, 2019, 88 patients who met the PJI criteria were identified and included in this study. Of these patients, 12 were taking aspirin regularly during the infectious events. In the Cox proportional hazards model, multivariate analysis revealed that the aspirin group demonstrated significant benefit via superior resolution of PJIs (HR 2.200; 95% CI 1.018–4.757; p = 0.045). In this study, aspirin is beneficial for infection resolution when combined with the current standard of PJI treatment and conventional antibiotics in the management of PJIs.

Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06

2006 ◽  
Vol 24 (13) ◽  
pp. 2059-2064 ◽  
Author(s):  
Barry C. Lembersky ◽  
H. Samuel Wieand ◽  
Nicholas J. Petrelli ◽  
Michael J. O'Connell ◽  
Linda H. Colangelo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Carcinoma Of The Colon ◽  
Primary Surgery ◽  
Stage Ii Colon Cancer

Purpose The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur (UFT) plus leucovorin (LV) with the efficacy of weekly intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS) and overall survival (OS) after primary surgery for colon carcinoma. Patients and Methods Between February 1997 and March 1999, 1,608 patients with stage II and III carcinoma of the colon were randomly assigned to receive either oral UFT+LV or intravenous FU+LV. Results Of the total patients, 47% had stage II colon cancer, and 53% had stage III colon cancer. Median follow-up time was 62.3 months. The estimated hazard ratio (HR) for OS of patients who received UFT+LV versus that of patients who received FU+LV was 1.014 (95% CI, 0.825 to 1.246). The estimated HR for DFS was 1.004 (95% CI, 0.847 to 1.190). Cox proportional hazards model analyses with regard to age (< 60 v ≥ 60 years), stage, or number of involved nodes (none v one to three v ≥ four nodes) revealed no interaction with OS or DFS. Toxicity was similar in the two groups. In the UFT+LV arm, 38.2% of patients experienced any grade 3 or 4 toxic event compared with 37.8% of patients in the FU+LV arm. Primary quality-of-life end points did not differ between the two regimens, although convenience of care analysis favored UFT+LV. Conclusion UFT+LV achieved similar DFS and OS when compared with an intravenous, weekly, bolus FU+LV regimen. The two regimens were equitoxic and generally well tolerated.

The effect of delay of adjuvant chemotherapy on survival in patients with resected stage II and III gastric cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15144-e15144
Author(s):  
Minkyu Jung ◽  
Hyoung Soon Park ◽  
Han Na Park ◽  
Seungtaek Lim ◽  
Ji Soo Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Hazards Model ◽  
Resected Stage

e15144 Background: Adjuvant chemotherapy improved survival in patients with gastric cancer. However, the association between the timing of adjuvant chemotherapy and survival has not been investigated. Methods: Patients with stage II and III gastric cancer who received adjuvant chemotherapy at Yonsei University Health System were included in this study. Time to adjuvant chemotherapy, relapse free survival (RFS), and overall survival (OS) were calculated from the day of surgery. RFS and OS were compared using log-rank test and multivariate analysis by the Cox proportional hazards model. Results: Among 675 patients, 226 patients (33.5%) began adjuvant chemotherapy within 1 month, 421 patients (60.1%) began adjuvant chemotherapy in 1 to 2 months, and 28 patients (4.1%) began adjuvant chemotherapy > 2 months after surgery. Intervals > 2 months between chemotherapy and surgery was associated with worse RFS and OS in both univariate analysis (RFS, p=0.039; OS, p=0.022, respectively) and a Cox proportional hazards model (RFS, hazard ratio [HR] =1.81, 95% confidential interval [CI] =1.05-3.12; OS, HR=1.96, 95% CI=1.11-3.47, respectively). Conclusions: Only 4.1% of patients initiated adjuvant chemotherapy >2 months after the date of curative surgery. Adjuvant chemotherapy delay > 2 months after surgical resection is associated with worse survival among patients with resected stage II and III gastric cancer.

scholarly journals In vitro and in vivo studies on stilbene analogs as potential treatment agents for colon cancer

2010 ◽  
Vol 45 (9) ◽  
pp. 3702-3708 ◽  
Author(s):  
Shiby Paul ◽  
Cassia S. Mizuno ◽  
Hong Jin Lee ◽  
Xi Zheng ◽  
Sarah Chajkowisk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
In Vivo Studies ◽  
Potential Treatment ◽  
Stilbene Analogs

scholarly journals Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5629
Author(s):  
Yusuke Sugino ◽  
Takeshi Sasaki ◽  
Manabu Kato ◽  
Satoru Masui ◽  
Kouhei Nishikawa ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Psoas Muscle ◽  
Hounsfield Unit ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cross Sectional

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study

2020 ◽  
Author(s):  
I Karaiskos ◽  
G L Daikos ◽  
A Gkoufa ◽  
G Adamis ◽  
A Stefos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Active Agent ◽  
Bloodstream Infections ◽  
National Registry ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Fatal Disease

Abstract Background Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. Objectives To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). Methods A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. Results One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. Conclusions Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma

2020 ◽  
pp. 1-7
Author(s):  
Volkan İzol ◽  
Mutlu Deger ◽  
Ender Ozden ◽  
Deniz Bolat ◽  
Burak Argun ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Upper Urinary Tract ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Recurrence Time ◽  
Tumor Biopsy ◽  
Group 2 ◽  
Group 1

<b><i>Objective:</i></b> The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). <b><i>Materials and Methods:</i></b> Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. <b><i>Results:</i></b> After exclusion, a total of 194 patients were analyzed: Group 1 <i>n</i> = 95 (49.0%) and Group 2 <i>n</i> = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12–250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3–144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (<i>p</i> = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (<i>p</i><b> =</b>0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (<i>p</i><b></b>&#x3c; 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65–5.41; <i>p</i> &#x3c; 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74–7.16; <i>p</i> &#x3c; 0.001) was found to be an independent prognostic factor for IRFS. <b><i>Conclusion:</i></b> Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.

Mucin O-glycosylating enzyme GALNT2 facilitates the malignant character of glioma by activating the EGFR/PI3K/Akt/mTOR axis

2019 ◽  
Vol 133 (10) ◽  
pp. 1167-1184 ◽  
Author(s):  
Zhongzheng Sun ◽  
Hao Xue ◽  
Yan Wei ◽  
Chaochao Wang ◽  
Rui Yu ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Glioma Cell ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
The Cancer Genome Atlas ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Expression Levels

AbstractN-Acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that regulates the initial step of mucin O-glycosylation, has been reported to play a role in influencing the malignancy of various cancers. However, the mechanism through which it influences gliomas is still unknown. In the current study, the Cox proportional hazards model was used to select genes. Data obtained from The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) of clinical specimens showed that increased GALNT2 expression levels were associated with an unfavorable prognosis and a higher tumor grade in human gliomas. Then, GALNT2 knockdown and overexpression were performed in glioma cell lines and verified by quantitative real-time PCR (qRT-PCR) and Western blotting. Functional assays demonstrated that GALNT2 was closely related to glioma cell proliferation, cycle transition, migration and invasion. Western blot analysis and lectin pull-down assays indicated that GALNT2 knockdown decreased the level of phosphorylated epidermal growth factor receptor (EGFR) and the expression of the Tn antigen on EGFR and affected the expression levels of p21, cyclin-dependent kinase 4 (CDK4), cyclinD1, matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) through the EGFR/PI3K/Akt/mTOR pathway. GALNT2 overexpression had the opposite effects. In vivo, the growth of orthotopic glioma xenografts in nude mice was distinctly inhibited by the expression of GALNT2 shRNA, and the tumors with GALNT2 shRNA exhibited less aggressiveness and reduced expression of Ki67 and MMP2. Overall, GALNT2 facilitates the malignant characteristics of glioma by influencing the O-glycosylation and phosphorylation of EGFR and the subsequent downstream PI3K/Akt/mTOR axis. Therefore, GALNT2 may serve as a novel biomarker and a potential target for future therapy of glioma.

Sign in / Sign up

Export Citation Format

Share Document