Therapeutic effect of p65 AS-ODN, a subset of NF-κB, on pancreatic cancer

核因子-κB(NF-κB)是细胞分裂和生存的关键调节因子,参与肿瘤发生、增殖、转移等多方面的调控环节,在胰腺癌的发生、发展过程中发挥着重要作用.     

Therapeutic effect of p65 AS-ODN, a subset of NF-κB, on pancreatic cancer

核因子-κB(NF-κB)是细胞分裂和生存的关键调节因子,参与肿瘤发生、增殖、转移等多方面的调控环节,在胰腺癌的发生、发展过程中发挥着重要作用.     

Role of FDG-PET/CT in evaluating surgical outcomes of operable breast cancer – Usefulness for malignant grade of triple-negative breast cancer

BackgroundThe aim of this study was to evaluate the significance of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers.MethodsOf 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined.ResultsReceiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUV_max) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUV_max ≤ 3.8 and 91.6% for patients with a tumor of SUV_max > 3.8 (p < 0.001). High value of SUV_max was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUV_max (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUV_max ≤ 8.6 and 42.9% for patients with a tumor of SUV_max > 8.6 (p = 0.002), and high SUV_max was the only significant independent prognostic factor (p = 0.047).ConclusionFDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype.     

Is sarcopenia a missed factor in the management of patients with metastatic breast cancer?

BackgroundSarcopenia has emerged as an important parameter to predict outcomes and treatment toxicity. However, limited data are available to assess sarcopenia prevalence in metastatic breast cancer and to evaluate its management.MethodsThe SCAN study was a cross-sectional multicenter French study that aimed to estimate sarcopenia prevalence in a real-life sample of metastatic cancer patients. Sarcopenia was identified by low muscle mass (estimated from the skeletal muscle index at the third lumbar, via computed tomography) and low muscle strength (defined by handgrip strength). Three populations were distinguished based on EWGSOP criteria: a sarcopenic group with low muscle mass AND strength, a pre-sarcopenic group with low muscle mass OR strength and a normal group with high muscle mass AND strength.ResultsAmong 766 included patients, 139 patients with breast cancer and median age of 61.2 years (29.9–97.8 years) were evaluable; 29.5% were sarcopenic and 41.0% were pre-sarcopenic. Sarcopenic patients were older (P < 0.01), had a worse PS-score (P < 0.05), and a higher number of metastatic sites (P < 0.01), the majority being hepatic and bone. A moderate agreement between the oncologist's diagnosis and sarcopenia evaluation by muscle mass and strength was recognized (Cohen's kappa = 0.45). No associations were found between sarcopenia and adverse event occurrence in the 12 patients for whom these were reported. Sarcopenic patients were underdiagnosed and nutritional care and physical activity were less proposed.ConclusionIt is necessary to evaluate sarcopenia due to its impact on patient prognosis, and its utility in guiding patient management in metastatic breast cancer.     

Aberrant expression of laminin γ2 correlates with poor prognosis and promotes invasion in extrahepatic cholangiocarcinoma

Background

To investigate the potential role of laminin γ2 and its correlation with prognosis in patients with extrahepatic cholangiocarcinoma (CCA).

Materials and methods

Laminin γ2 expression was evaluated by immunohistochemistry in 72 extrahepatic CCA patients after surgical resection. Knockdown of laminin γ2 was achieved via small interfering RNA transfection in the extrahepatic CCA cell line QBC939.

Results

Thirty-six of 72 extrahepatic CCAs (50%) stained positive for laminin γ2 in two types of patterns: stromal staining (28/72, 39%) and cytoplasmic staining (24/72, 33%). All 16 paracancerous tissue samples showed negative staining. Both stromal and cytoplasmic laminin γ2 expressions correlated with lymph node metastasis. Kaplan-Meier analysis showed that aberrant expression of laminin γ2 correlated with poor overall survival and early recurrence. Cox regression analysis further demonstrated that laminin γ2 expression was a significant independent predictor of poor overall survival and early recurrence. Immunofluorescence staining revealed cytoplasmic expression of laminin γ2 in QBC939 cells. Knockdown of laminin γ2 significantly reduced QBC939 cell invasion and migration.

Conclusions

Aberrant expression of laminin γ2 correlates with poor prognosis and promotes invasion in extrahepatic CCA.     

High expression of karyopherin-α2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy

Background

Conventional clinicopathologic risk factors have failed to accurately predict the prognosis of patients with bladder cancer (BC).

Objective

To evaluate karyopherin-α2 (KPNA2) expression as a progression marker in patients with non–muscle-invasive BC (NMIBC) treated by conservative methods and as a prognostic marker in patients with invasive BC undergoing radical cystectomy (RC).

Design, setting, and participants

Two different tissue microarrays were constructed, one with 234 primary Ta/T1 tumours from patients treated by transurethral resection of the bladder and one with 377 tumours from RC patients.

Intervention

KPNA2 expression based on immunohistochemistry.

Measurements

Risk of progression of Ta/T1 patients to muscle-invasive BC was estimated in clinical follow-up to progression or a minimum of 53 mo. Risk of recurrent disease and death following RC was estimated in clinical follow-up of a minimum of 24 mo in patients alive.

Results and limitations

A high KPNA2 expression in Ta/T1 patients was significantly correlated with a higher risk of progression that was independent of conventional risk factors in multivariate analysis. In patients undergoing RC, a high KPNA2 expression was an independent predictor of poor prognosis. A high KPNA2 expression was correlated with a higher risk of visceral metastasis rather than lymphatic spread.

Conclusions

KPNA2 expression is a marker for progression of NMIBC and a prognostic marker in patients undergoing RC.     

Is conservative surgery a good option for patients with “triple negative” breast cancer?

BackgroundTriple negative breast cancers (negative estrogen receptor, progestagen receptor and no overexpression of HER2) seems to be more aggressive than other breast carcinoma subtypes. Therefore, it is necessary to analyze if a more aggressive surgical treatment should be offered to this subgroup of patients.Patients and methodsThe Castellon Cancer Registry Database (C.Valenciana, Spain) was used to identify eligible breast cancer patients. Female patients who were diagnosed and/or treated from January 2000 to December 2008 with primary, invasive, unilateral breast cancer at our hospital were included. A total of 410 patients make up the study population. Kaplan–Meier curves and log-rank tests were used to estimate 5-year local recurrence functions and to compare them across strata. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals to fit the effect of conservative surgery and other independent variables on local recurrence.ResultsMedian follow-up time was 60 months (1–127 months). A total of 21 patients (5%) presented a local recurrence during follow-up. There was a 9% difference in terms of local recurrence between conservative and non-conservative techniques for triple negative patients, whereas such difference was only 1% for no triple negative patients. On univariate analysis for local recurrence, only tumor size and lymph node metastasis were statistically associated with local recurrence. All other variables (type of surgery, triple negative status, molecular classification, tumor grade, age, adjuvant treatments, and total number of analyzed lymph nodes) were not statistically significant. On multivariate analysis, independent prognostic factors were breast conservative surgery (HR 4.62 95%CI 1.12–16.82), number of positive lymph nodes (HR 1.07 95%CI 1.01–1.17) and millimetre tumor size (HR 1.02 95%CI 1.01–1.06). In contrast, triple negative status trended to be a risk factor but without statistical significance (HR 1.59 95%CI 0.42–8.04).ConclusionsIt was not possible to find statistically significant differences between conservative and non-conservative surgery for triple negative breast cancer. However, a trend was observed for higher recurrence rates after breast conservative surgery for this group of patients. Prospective clinical trials are needed to confirm this observation.     

Depth of tumor invasion in locally advanced rectal cancer correlates with patients’ prognosis: The usefulness of elastic stain for its measurement

Purpose The relationship between the prognosis and the extent of colorectal carcinoma (CRC) is still unclear. As a simple parameter of the local invasion of CRC, we assessed the extent of tumor invasion beyond the outer border of the muscularis propria (MP). Methods We examined 147 cases of CRC using a slight modification of the procedure established by the Japanese Society for Cancer of the Colon and Rectum. For the statistical analysis, the patients were divided into two groups, namely, a “shallow” group and a “deep” group, using a specific cut-off value (COV). A multivariate analysis to identify independent prognostic factors was performed. Results Significant differences in the 5-year survival rate were observed between the “shallow” and “deep” groups in 39 cases of rectal carcinoma (COV 4 mm; 72.4% vs. 30.0%, hazard ratio = 3.204), but not observed in 147 cases of CRC. In addition, the outcome for patients with “deep” cancer in the lower rectum was markedly worse than that for patients with “shallow” cancer (COV 4 mm; 81.8% vs. 12.5%, hazard ratio = 5.371). Conclusions The depth of tumor invasion beyond the MP is thus considered to be an important prognostic factor for patients with T3/T4 rectal carcinoma, especially in the lower rectum. A careful follow-up is required for the patients with rectal carcinoma that has invaded more than 4 mm beyond the MP.     

Effect of NF-κB modulated PTH expression on hypocalcemia in acute pancreatitis

低钙血症是重症急性胰腺炎(SAP)的重要并发症之一,与疾病的严重程度和预后密切相关,其产生和发展的确切机制未明.     

Effect of NF-κB modulated PTH expression on hypocalcemia in acute pancreatitis

低钙血症是重症急性胰腺炎(SAP)的重要并发症之一,与疾病的严重程度和预后密切相关,其产生和发展的确切机制未明.     

Circulating osteoprotegerin and receptor activator of NF-κB ligand system in patients with β-thalassemia major

Osteoporosis represents an important cause of morbidity in patients with β-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-κB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age ± SEM, 24.26 ± 1.29 years; range, 13–41 years) and females (n = 31; age, 24.59 ± 0.95 years; range, 12–34 years) with β-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 ± 0.12 vs. 3.25 ± 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 ± 0.03 vs. 0.295 ± 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = −0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = −0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in β-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.     

Weekly nab-paclitaxel is safe and effective in ≥65 years old patients with metastatic breast cancer: a post-hoc analysis

Purpose

This post-hoc analysis of 2 studies investigated the safety and efficacy of weekly and every-3-week (q3w) nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in older patients with metastatic breast cancer (MBC) compared with q3w solvent-based paclitaxel and docetaxel.

Results

Patients ≥65 years (median: 69) were analyzed. In phase 2 (n = 52), overall response rates (ORR) for weekly nab-paclitaxel were 60–64% vs 22% for q3w nab-paclitaxel and 32% for docetaxel. In phase 3 (n = 62), ORRs were 27% for q3w nab-paclitaxel and 19% for solvent-based paclitaxel. In phase 2, median progression-free survival (PFS) was 18.9 months for 150 mg/m² weekly nab-paclitaxel vs 8.5–13.8 months for all other regimens. In phase 3, median PFS for q3w nab-paclitaxel and solvent-based paclitaxel were 5.6 months and 3.5 months, respectively. Weekly nab-paclitaxel resulted in less serious adverse events compared with all other regimens.

Conclusions

Weekly nab-paclitaxel was safe and more efficacious compared with the q3w schedule and with solvent-based taxanes in older patients with MBC.