Dietary β-carotene,cigarette smoking,and lung cancer in men

A cohort of 5,080 men living in a retirement community in California (United States) and initially free from lung cancer were followed from June 1981 to December 1989. At recruitment, each study participant completed a mailed questionnaire which requested information on the subject's medical history, use of cigarettes, and usual consumption frequencies during the preceding 12 months of 44 vegetable and fruit items. Men who had never smoked had the highest mean daily intake of -carotene (8,505 g), followed by past smokers (7,761 g) and then by current smokers (6,178 g). -Carotene intake of the subject's wife was correlated significantly with that of the husband in the 4,018 spouse pairs (r=0.46; P=0.0001). Among men with similar smoking habits, dietary -carotene intake significantly decreased with the spouse's smoking habit: never, past, and current smokers (P=0.004; test for linear trend). During 31,477 person-years of follow-up, 125 incident cases of lung cancer were observed among the cohort of 5,080 men. Age-adjusted relative risks for lung cancer were below unity (i.e., demonstrating a reduced risk) for higher relative to lower consumption of -carotene, of all vegetables and fruits, and of yellow vegetables alone. However, these relative risks approached or crossed the null value when adjusted for personal smoking.This study was supported by US Public Health Service grants CA-17054 and CA-32197 from the National Cancer Institute.     

Caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous tissues and chronic non-atrophic gastritis

Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidin-peroxidase(SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage(P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased(P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia(P<0.01).Caveolin-1 expression correlated positively with E-cadherin(r=0.41,P<0.05).Caveolin-1(r= 0.36,P<0.05) and E-cadherin(r= 0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion: These results suggested that dysregulated expressions of caveolin‐1, E‐cadherin and β‐catenin correlated with the development of gastric cancer and its biological behavior.     

Expression of E-cadherin, β-catenin and topoisomerase IIα in leiomyosarcomas

Introduction  

The expression of E-cadherin, β-catenin and topoisomerase II has been associated with clinical outcome of several cancers including sarcomas. We aimed to evaluate the expression of these markers in leiomyosarcomas (LMS).     

Association of serum α-tocopherol, β-carotene,and retinol with liver cancer incidence and chronic liver disease mortality

Background:

Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, β-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers.

Methods:

Baseline and 3-year follow-up serum were available from 29 046 and 22 805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models.

Results:

Higher β-carotene and retinol levels were associated with less liver cancer (β-carotene: 0.35, 0.22–0.55, P-trend <0.0001; retinol: 0.58, 0.39–0.85, P-trend=0.0009) and CLD mortality (β-carotene: 0.47, 0.30–0.75, P-trend=0.001; retinol: 0.55, 0.38–0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40–0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64–1.74, P-trend=0.77). Participants with higher levels of β-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels.

Conclusions:

Our findings suggest that higher concentrations of β-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.     

Altered expression of β-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma

The aim of the study was to evaluate the immunoexpression of E-cadherin, β-catenin, and Ki-67, as well as the promoter methylation of E-cadherin gene in epithelial ovarian cancer (EOC), as well as to find a possible relationship between the immunoexpression and hypermethylation. Promoter methylation was studied using methylation-specific PCR in 86 malignant cases, 14 low malignant potential (LMP) tumors and 19 benign cystadenomas. Immunohistochemical expression was carried out in 64 malignant cases, 8 LMP tumors, and 11 benign cystadenomas. Immunoexpression of E-cadherin was reduced in EOC, while 100 % expression was seen in LMP tumors and benign cystadenomas. An interesting observation was the nuclear expression of E-cadherin in a high percentage of cancers, which showed a positive correlation with Ki-67. Β-Catenin expression showed heterogeneous localization with increased nuclear localization, which was significantly higher in cases that did not express E-cadherin. Promoter methylation of E-cadherin was 36, 14, and 11 % in EOC, LMP tumors, and benign cystadenomas, respectively. Our results suggest that reduced expression of E-cadherin is associated with promoter methylation of E-cadherin gene, in addition to providing evidence for the aberrant nuclear localization of E-cadherin in EOC.     

The expressions and significance of α-, β-catenins and cyclin D1 in breast cancers

Objective  To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods  High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in the 60 cases of breast cancer tissues. Results  Abnormal immunoreactivities of α-and β-catenins were observed in 37 (61.7%) and 42 (70%) cases of breast cancer tissues, respectively. There were 28 cases (46.7%) who showed cyclin D1 overexpression. The abnormal expression rates of α-and β-catenins in infiltrating lobular carcinoma (ILC) were significantly higher than those in infiltrating ductal carcinoma (IDC) (P < 0.05), but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer (P > 0.05). The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer (P < 0.05), but not with histological type and the extent of differentiation (P > 0.05). Cyclin D1 overexpression was observed in 57.1% (24/42) of these cases that showed abnormal staining of β-catenin, but only observed in 22.2% (4/18) of these cases with normal membranous staining of β-catenin. There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 (r _s = 0.321, P < 0.05). Conclusion  The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer. The abnormal expressions of α-and β-catenins are not a key factor in malignant cell metastasis in breast cancer, but may also involve in the progress.     

Location, location, location: FoxM1 mediates β-catenin nuclear translocation and promotes glioma tumorigenesis

Genetic alterations in the Wnt/β-catenin/TCF-signaling pathway are commonly found in human tumors, but not in glioblastomas. In this issue of Cancer Cell, Zhang et?al. report that FoxM1 mediates β-catenin nuclear translocation in glioblastoma, suggesting a novel mechanism for glioblastoma progression in the absence of conventional Wnt/β-catenin pathway activation.     

Immunolocalization of Vimentin,Keratin 17, Ki-67, Involucrin, β-Catenin and E-Cadherin in Cutaneous Squamous Cell Carcinoma

Skin squamous cell carcinoma (SCC) is a subtype of very aggressive skin cancers. To investigate if epithelial-mesenchymal transition (EMT), a process for epitheloid cells losing their polarity and cohesiveness and transform into spindle-shaped cells, occurs in skin SCC. By using immunofluorescence, we defined the immunolocalization of vimentin, Keratin 17, β-catenin, E-cadherin, Ki-67 and involucrin, in SCC samples. Our results show reduced activity of involucrin and E-cadherin, and increased expression of Ki-67, β-catenin, Keratin 17 and vimentin in SCC. These data propose that EMT really occurs in poorly differentiated SCC and keratin 17 and involucrin may be another two biomarkers for EMT.     

Epidermal growth factor receptor regulates β-catenin location,stability, and transcriptional activity in oral cancer

Background  

Many cancerous cells accumulate β-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of β-catenin in the nuclei of oral cancer cells.     

α-Catenin inhibits glioma cell migration,invasion, and proliferation by suppression of β-catenin transactivation

Patients with glioblastomas, the most common primary tumors of the central nervous system, have poor prognoses because of uncontrolled tumor cell invasion and proliferation. β-Catenin plays an important role in tumor development. However, whether α-catenin expression contributes to β-catenin transactivation in glioma cells is largely unknown. We report here that α-catenin expression abrogates epidermal growth factor receptor (EGFR)-activation-induced β-catenin nuclear translocation in human glioblastoma cells, thereby attenuating β-catenin transactivation and the expression of its downstream genes CCND1 and c-myc. In addition, ectopic expression of α-catenin or depletion of β-catenin suppresses EGF-promoted glioblastoma cell migration, invasion, and proliferation. In contrast, α-catenin depletion promotes β-catenin nuclear translocation and transactivation, and tumor cell motility and growth. These findings reveal the importance of β-catenin regulation by α-catenin in cellular activities of glioblastoma cells.     

Role of β-catenin in cisplatin resistance,relapse and prognosis of head and neck squamous cell carcinoma

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of β-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis.

Methods

In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess β-catenin expression in the cut margin and tumor areas of each sample. Kaplan-Meier analyses were performed to correlate β-catenin expression with the survival and prognosis of HNSCC patients. In addition, chemo-resistance, DNA damage response and DNA repair capacities were evaluated in HNSCC-derived cell lines through LiCl-mediated up-regulation and siRNA-mediated silencing of β-catenin expression.

Results

We observed β-catenin up-regulation in cut margin areas of recurrent patients compared to their corresponding tumor regions, which subsequently could be associated with poor prognosis. In addition, we found that LiCl-mediated up-regulation of β-catenin in HNSCC-derived cells led to cisplatin resistance, evasion of apoptosis, enhanced DNA repair and enhanced migration. The effects of β-catenin silencing correlated with its putative role in chemo-resistance and DNA damage response.

Conclusion

From our results we conclude that β-catenin may contribute to HNSCC therapy resistance and disease relapse. As such, β-catenin may be explored as a therapeutic target along with conventional therapeutics.

     

Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis

Background:

The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear.

Methods:

We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes.

Results:

No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes.

Conclusions:

Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.     

Osteopontin,E-cadherin,and β-catenin expression as prognostic biomarkers in patients with radically resected gastric cancer

A correlation between osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, β-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal β-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.     

Relationship between antibiotic resistance,efflux pumps,and biofilm formation in extended-spectrum β-lactamase producing Klebsiella pneumoniae

Klebsiella pneumoniae is an important pathogen both in community and hospital environment. In this study, we aimed to determine the antibiotic susceptibilities, expression levels of AcrA, ketM, kdeA, kpnEF, and kexD genes related to efflux pump and biofilm formation in 100 extended-spectrum β-lactamase producing Klebsiella pneumoniae. The relative expression levels of AcrA, ketM, kdeA, kpnEF, and kexD were determined by quantitative real-time PCR and biofilm formation was screened by microtiter plate assay. Based on CLSI breakpoints, zone diameters showed that 72% of isolates were resistant to ceftazidime, 79% to aztreonam, 54% to ciprofloxacin, 32% to ertapenem, 74% to tobramycin, 65% to tetracycline and all isolates were resistant to ampicillin, ceftriaxone, and cefotaxime. The relative expression of AcrA was upregulated in ciprofloxacin susceptible isolates and also upregulation of newly described efflux pump, kexD, was correlated with tobramycin and aztreonam resistance. A significant correlation was observed between resistance-nodulation-division and single-type efflux pumps. On the other hand, ciprofloxacin susceptible isolates formed stronger biofilms than resistant isolates. The up or down regulation of efflux pumps didn’t enhance biofilm formation capacity.     

AXIN2 Polymorphisms,the β-Catenin Destruction Complex Expression Profile and Breast Cancer Susceptibility

Background: The Wnt/β-catenin signaling pathway is an important regulator of cellular functions suchas proliferation, survival and cell adhesion. Wnt/β-catenin signaling is associated with tumor initiation andprogression; β-catenin mutations explain only 30% of aberrant signaling found in breast cancer, indicating thatother components and/or regulation of the Wnt/β-catenin pathway may be involved. Objective: We evaluatedAXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of β-catenin destruction complexgenes in breast cancer patients. Materials and Methods: We collected peripheral blood samples from 102 breastcancer and 102 healthy subjects. The identification of the genetic variation was performed using PCR-RFLPsand DNA sequencing. RT-qPCR was used to determine expression profiles. Results: We found significantassociation of AXIN2 rs151279728 and rs2240308 polymorphisms with breast cancer risk. Significant increasewas observed in AXIN2 level expression in breast cancer patients. Further analyses showed APC, β-catenin,CK1α, GSK3β and PP2A gene expression to be associated to clinic-pathological characteristics. Conclusions:The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of β-catenindestruction complex expression may be found in breast cancer patients, providing additional support for rolesof Wnt/β-catenin pathway dysfunction in breast cancer tumorigenesis. However, the functional consequencesof the genetic alterations remain to be determined.