BACKGROUND:Prostate cancer consists of multifactorial and multifocal events, generating differential gene expression in tumor cells.METHODS:The molecular profile of 14 gene expression was analyzed through cDNA array in blood samples of patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH).RESULTS:Messenger RNA from patient's blood showed significant differences between PCa and BPH groups only for the NOS3 gene, with an occurrence chance for PCa5.8-fold higher than BPH disease.CONCLUSION:The NOS3 gene expression in the patient's blood may be used as a putative biomarker for prostate cancer.
Background: Infrared imaging measures spatial variations in the skin temperature aiming to determine pathological processes; hence possible use of this non-invasive analytical method in cancer detection is emerging. Methods: Infrared thermal imaging was used to detect changes in rat skin surface temperature associated with experimental cancer development (Walker 256 carcinoma), inflammation (upon s.c. Sephadex injection) and haematoma (provoked by s.c. blood coagulate injection). Infrared camera with a geometric resolution of 76,800 pixels, spectral range of 8-14 mu m and the minimal detectable temperature resolution of 0.07 degrees C with spatial resolution of 0.48 mm at measuring distance of 30 cm was used to obtain computerised thermal scans. Genuine ThermoWEB software developed for remote internet control as open source software was used. Results: The raise of peripheral temperature was observed after induction of local inflammation or haematoma. Opposite to that, transient decrease of the skin surface temperature was observed after tumour transplantation. Progressive growth of tumour was associated with the raise of the skin surface temperature from the 10th day after tumour inoculation, when the tumours developed supportive neoangiogenic blood supply, as verified by histology. Conclusion: While the raise of peripheral temperature in advanced turnout, was caused by neoangiogenesis, the reduction in skin surface temperature in an early period after tumour cell inoculation indicated a decay of transplanted tumour cells due to the immune response and the lack of blood supply. Thus, infrared thermal imaging may have considerable value in evaluation of the tumour development and discrimination of cancer from inflammation and haematoma. (C) 2009 Elsevier Ltd. All rights reserved.
Background: Vitamin D (1,25-dihydroxyVitamin D3) has shown experimentally anticarcinogenic effects and is thought to protect against breast cancer. The actions of Vitamin D are mediated via the Vitamin D receptor (VDR), and the polymorphisms at 3′UTR region of this gene are associated with the risk and progression of breast carcinoma. The current study is an attempt to examine the association of these variations with breast cancer risk in north Indians. Methods: A total of 160 cases and 140 control subjects were studied for the polymorphisms at 3′ end of the VDR gene. A polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method and fragment analysis was performed to determine ApaI and TaqI polymorphisms and variable length poly-A microsatellite repeats. Linkage disequilibrium (LD) was calculated for each pair of polymorphisms. Unadjusted and adjusted odds ratios for breast cancer with genotypes comprising the polymorphic sites were calculated to understand their role towards breast cancer susceptibility. Results: Patient's with long poly-A repeat showed a significant association with disease (χ2 = 9.52, df = 2, P ≤ 0.01). Compared to subjects having two S alleles (SS), odds ratios (and 95% CI) were 0.75 (0.45–1.23) and 2.49 (1.18–5.27) for subjects having genotypes SL and LL, respectively. Among matched pairs (age), the poly-A LL genotype was found significantly associated with increased risk of breast cancer among early-onset cases (P = 0.02). The unconditional logistic regression analysis demonstrated a significant association between grade and LL genotype [(unadjusted odds ratio (95% CI): 4.45 (1.87, 10.63); adjusted odds ratio: 4.66 (1.88, 11.53)]. No significant association was observed for the VDR ApaI (χ2 = 1.00, df = 2, P = 0.60) and TaqI polymorphism (χ2 = 0.35, df = 2, P = 0.83). Although, strong LD was not observed among these polymorphic sites, it denies the total equilibrium at the same time. Based on haplotype distribution, the most common one observed among cases and controls was ATS while, genotype AATTLL had shown a significant association with the breast cancer risk (P = 0.02). Conclusions: The results indicate that the VDR poly-A polymorphism is significantly associated with breast cancer risk in north Indians especially with early onset disease. Although, ApaI and TaqI did not show any significant association with the disease when analyzed in isolation, but TaqI might modulate the risk associated with L alleles. Further, understanding the functional role of these variants residing on the VDR haplotype associated with disease susceptibility may suggest novel approaches for breast cancer prevention and therapy.
Background: This study was conducted to determine human papillomavirus (HPV) types in women with cervical cancer (CC) and normal cervical cytology in the Southern region of Mexico, and to know the contribution of HPV types and cofactors in cervical cancer etiology. Methods: A case–control study was performed in 133 women with CC and 256 controls. HPV detection was done by MY09/11 and GP5+/GP6+ PCR systems and typing by restriction fragment length polymorphism or DNA sequencing. Results: HPV was found in 100% of CC and 35.5% of controls. The genotype distribution in CC was: HPV 16 (66.8%), 18 (9%), 31 (7.5%), 45 (4.5%), 58 (3.7%), 69 (3%), 52 (1.6%), 6, 11, 33, 56, and 67 (0.8% each). Among controls, HPV 33 followed by HPV 16 were the most frequent. Cervical cancer was associated with HPV 16 (OR = 573.5), HPV 18 (OR = 804.4), and undetermined risk HPV (types 67 and 69) (OR = 434.3). Age at first intercourse <16 years (OR = 9.6) and ≥3 births (OR = 16) were significant risk factors for CC. Conclusions: HPV 16, by far, is the most frequent type in CC, HPV 16 and 18 are responsible for 75.8% of the CC cases and high-risk HPV for 94.7%, which is useful data to take into account in vaccination programs. HPV 33 is the most frequent type in controls and high-risk HPV are more common than low-risk HPV.
Background A convenient animal model of primary lung cancer is compelling for investigation into the disease mechanisms and for development of therapeutic strategies. This study aims to develop a reproducible rat model for lung carcinoma by intra-pulmonary injection of 3,4-benzopyrene, and to evaluate the preventive effect of green tea on the formation of lung carcinoma. Methods Sprague-Dawley rats of the same ages were randomly assigned into three groups treated differently. Rats in group one were given green tea in drinking water (tea concentration: 1.2%; tea polyphenols in the tea solution: 0.3%); rats in the groups two and three were given blank drinking water. Rats in the groups one and two were injected intra-pulmonarily with 3,4-benzopyrene dissolved in corn oil (2 mg/0.2 mL/injection, fortnightly, 4 times in all); rats in the group three were injected with the vehicle corn oil as the control for injection. All the rats were sacrificed one year after the first intra-pulmonary injection. Tumors developed in rats and lung tissues were collected for carcinoma diagnosis and for p53 and bcl-2 expression. Results Intra-pulmonary injection of 3,4-benzopyrene steady induced lung carcinoma at a success rate of 75%. Administration with green tea drinking significantly reduced the incidence of lung carcinoma to 30%. Green tea up-regulated p53 expression in lung carcinoma, but significantly down-regulated bcl-2 expression. Conclusions Intra-pulmonary injection of 3,4-benzopyrene can steady induce lung carcinoma in rats, and green tea has preventive effect against lung cancer possibly by regulating expression of some critical genes such as p53 and bcl-2. (C) 2009 Elsevier Ltd. All rights reserved.
BACKGROUND:This study focuses on age, race/ethnicity and regular cervical cancer screening of medically underserved Latina and non-Latina women enrolled in California's Cancer Detection Programs: Every Woman Counts (CDP: EWC). METHODS:Data from a cohort of women were evaluated for regularity of screening and ethnicity utilizing multi-category logistic regression models to investigate Pap test and biopsy results. RESULTS:There was no statistically significant difference among medically underserved Latina or non-Latina women in Pap test result and stage of cervical cancer after controlling for age and screening regularity. Rarely/never Pap-tested women were more likely to have 'SIL/ASC' (odds ratio=1.19; 95% confidence interval=1.08, 1.31) compared to women who were screened regularly. Medically underserved 25-39-year-old women were also more likely to be identified with 'SIL/ASC' (odds ratio=1.64; 95% confidence interval=1.50, 1.79) than women 50 and over. Younger were more likely to have low-grade 'HPV/Condylomata, Atypia/CINI/LSIL' (odds ratio=2.48; 95% confidence interval=1.66, 3.72) and high-grade 'CIN II/III/HSIL/CI/Other Cancers' (odds ratio=1.53; 95% confidence interval=1.08, 2.16) than women age 40 and above, similar to rarely/never Pap-tested women. CONCLUSIONS:Women were more likely to be identified with high-grade precancerous cervical lesions and cancer process when they did not have regular screening, Ethnic differences in screening outcomes seem to be minimized by participation in a program that provides consistent screening resources to the medically underserved women who enroll. These findings support prevention strategies that expand screening to all medically underserved younger women or that provide HPV vaccination at an early age.
Objective: To explore the association of polymorphisms in N-acetyltransferase 2 (NAT2), glutathione S-transferase (GST), cytochrome P450 (CYP) 2A6, and CYP 2A13 genes with susceptibility and clinicopathologic characteristics of bladder cancer in a Chinese population. Methods: In a hospital-based case-control study of 208 cases and 212 controls matched on age and gender, genotypes were determined by PCR-based methods. Risks were evaluated by unconditional logistic regression analysis. Results: It was found that significant associations of the NAT2 slow-acetylator genotype (odds ratio, OR: 2.42; 95% confidence interval, CI: 1.47–3.99), GSTM1 null genotype (OR: 1.64; 95% CI: 1.11–2.42) and GSTM1/GSTT1-double null genotype (OR: 1.72; 95% CI: 1.00–2.95) with increased risk of bladder cancer. Conversely, carriers with at least one CYP2A6*4 allele showed lower risk than the non-carriers (OR: 0.47; 95% CI: 0.28–0.79). The adjusted ORs (95% CI) for smokers with NAT2 slow-acetylator, GSTM1 null, GSTM1/GSTT1-double null genotype, and variant CYP2A6 genotypes were 2.99 (1.44–6.25), 1.98 (1.13–3.48), 2.66 (1.22–5.81) and 0.41 (0.20–0.86), respectively. Furthermore, NAT2 slow-acetylator, GSTM1 null, and GSTM1/GSTT1-double null genotypes were associated with higher tumor grade (P = 0.001, 0.022, and 0.036, respectively), and only NAT2 slow-acetylator genotype was associated with higher tumor stage (P = 0.007). CYP2A13 was not associated with risk or tumor characteristics. Conclusion: It is suggested that NAT2 slow-acetylator, GSTM1 null, GSTM1/GSTT1-double null, and variant CYP2A6 genotypes may play important roles in the development of bladder cancer in Henan area, China.
Background: Survivin, an inhibitor of apoptosis protein (IAP), has been regarded as a valuable tumor marker for diagnosis and prognosis of bladder cancer. Recently, three splice variants of the gene with different anti-apoptotic activities have been reported. However, there is no data on the expression and potential causative roles of these transcripts in bladder cancer. Here, we have investigated the expression pattern of survivin and two of its splice variants, survivin-ΔEx3 and survivin-2B, in malignant versus non-malignant bladder tissues. Methods: We used semi-quantitative RT-PCR analysis to examine the expression of survivin variants in 30 transitional cell carcinoma, 19 matched non-tumor, and 9 apparently healthy control tissue samples of the bladder. DNA sequencing was used to confirm the identity of amplified fragments. Results: For all examined samples, survivin was the predominant transcript, being present in 83% of tumor and 25% of non-tumor bladder tissue samples, and survivin-2B was the least detected isoform. The expression levels of survivin and survivin-ΔEx3 was significantly higher in neoplastic compared to non-neoplastic tissues (P < 0.001) and both the sensitivity and specificity of survivin were superior to survivin-ΔEx3 (83% and 75% for survivin and 76% and 64% for survivin-ΔEx3, respectively). Also, the expression levels of survivin and survivin-ΔEx3 showed a significant correlation (P = 0.02) with tumor invasiveness (pT1/pTa). Conclusion: Our data revealed for the first time a differential expression pattern of survivin splice variants in bladder tissues, which potentially could have a practical usefulness in diagnosis and/or therapy of the tumor.
Background: Breast metastasis is an extremely rare phenomenon. While nearly every malignancy has been described to metastasize to the breast; melanoma, lymphoma and leukemia tend to be the most common. Among these primary tumors, melanoma metastasis represents a diagnostic pitfall for both the clinicians and histopathologists. Methods: We report a case of widely metastatic malignant melanoma with diagnostic difficulties in both clinical and histopathological evaluation. Thorax CT, Abdominal MRI, tumor marker screening and two biopsies were performed to conclude the primary. Results: In clinical evaluation, there were rapidly proliferating multiple nodular lesions at the skin, breasts, lungs, ovaries and peritoneum accompanied by only increased CA 125 in tumor marker panel. The initial biopsy performed from a skin nodule was concordant with a metastatic carcinoma suggesting breast as the primary. The diagnosis was made by immunohistochemical staining of the second biopsy performed from a breast nodule. Conclusion: Although no strict clinical criteria exist to differentiate a melanoma metastasis to the breast from a primary breast carcinoma atypically rapid growth, normal Ca 15-3 level, and a history of prior melanoma may be helpful. However, it may be still misdiagnosed in some cases even histopathologically if the immunohistochemical staining is not performed.
Background: Intraoral lesions clinically suspicious for cancer/precancer should be biopsied and diagnosed histopathologically. We evaluated whether the frequency of oral cancer (OC) cases diagnosed in Puerto Rico (PR) is disproportionately high relative to the frequency of persons with histopathologic diagnoses that would have appeared clinically suspicious for OC/precancer at biopsy. Methods: All pathology reports for oral (ICD-O-3 C01-C06) soft tissue biopsies generated during 1/2004–5/2005 by seven PR and two New York City (NYC) pathology laboratories were reviewed. The analysis was restricted to persons diagnosed with invasive oral squamous cell carcinoma (OSCC), epithelial dysplasia, or hyperkeratosis/epithelial hyperplasia (HK/EH), i.e., diagnoses associated with lesions clinically suspicious for OC/precancer. The OC relative frequency measured the percentage of persons diagnosed with OSCC among persons with OSCC, dysplasia, or HK/EH. OC relative frequencies for PR and NYC laboratories were compared. Results: Overall, the OC relative frequency was 67% in PR and 40% and 4% in the NYC general and oral pathology laboratories, respectively (each p < 0.001). In PR, the OC relative frequency was highest for males (80%). When OC relative frequencies were stratified by pathology laboratory type (general/oral) and compared across PR and NYC, age/gender-specific OC relative frequencies were always higher in PR; however, differences were consistently statistically significant for males only. Conclusion: A disparity in the OC relative frequency exists in PR vs. NYC indicating a shortfall in biopsying potentially precancerous oral lesions in PR. PR residents with intraoral lesions suspicious for oral cancer/precancer are most likely to be biopsied only after developing an invasive OC.
Background: Cigarette smoking is the predominant risk factor for bladder cancer. This risk may be modified by polymorphisms in carcinogens metabolism genes; including those involving the N-acetyl transferase 2 (NAT2) which have been correlated with decreased enzyme activities. Moreover, folate insufficiency can induces carcinogenesis by decreasing DNA methylation. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are enzymes that play central roles in the folate metabolic pathway. The MTHFR 677*T and MTR 2756*G variants are associated with decreased enzyme activity. Methods: In this work, we have conducted a case-control study in order to assess the combined effect of tobacco, slow NAT2 variants, MTHFR 677*T and MTR 2756*G alleles on bladder cancer development in North Tunisia. Results: For MTR A2756G, alleles and genotypic distributions differed significantly between cases and controls (p=0.00009, OR=3.27, CI 95% 1.76–6.12). While, in non-smokers patients the slow NAT2 did not appear to influence bladder cancer susceptibility; our results suggested that it might act with an additive contribution with tobacco as well as with that determined by MTR 2756 AG or 2756 GG genotypes (p=0.0008). Identical cumulative effect was detected for slow NAT2 and MTHFR 677*T variant (p=0.0003; OR=36.6; CI 95% 3.4–935.3). Conclusion: The strongest result obtained by this study was for an additive effect between smoking status, slow NAT2 variants, MTR 2756*G and MTHFR 677*T alleles, in affecting bladder cancer risk.
Background: The Murine double minute 2 (MDM2) gene encodes a negative regulator of the p53 tumor suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumor formation. The aim of this study was to investigate whether this functional SNP is associated with an enhanced risk of liver tumorigenesis in Moroccan patients. Methods: The study consisted in the comparison of 96 hepatocellular carcinomas (HCC) cases and 222 controls without HCC matched for age, gender and ethnicity. PCR-RFLP and sequencing methods were used to determine the genotype at the MDM2 SNP309T>G locus. Results: Overall, our results indicate that the GG genotype of SNP309 is significantly associated with an increased risk of HCC (odds ratio, OR = 2.60, 95% CI, 1.08-6.28). Interestingly, despite a wide range of confidence interval, there is a trend associating the GG genotype with a high risk of HCC in males (OR = 3.31; 95% CI, 0.93-11.82) and in HCV-infected patients (OR = 3.7; 95% CI, 0.82-16.45). By contrast, no association between age at diagnosis and MDM2 SNP309 genotypes was observed in HCC patients (P = 0.610). Conclusion: Our findings suggest that the MDM2 309T>G polymorphism is an important modulator of hepatocellular carcinoma development in Moroccan patients. (C) 2009 Elsevier Ltd. All rights reserved.
BACKGROUND:The mechanism of emodin-mediated cell apoptosis has been investigated extensively in many types of human cancer cells. Our previous study demonstrated that emodin induced apoptosis through the decrease of Bcl-2/Bax ratio and the increase of cytoplasm cytochrome c concentration in human breast cancer BCap-37 cells. However, emodin's reaction to breast cancer cells remains elusive.MATERIALS AND METHODS:An apoptosis-associated cDNA microarray comprised of 458 known genes, namely, death receptors, calpains, death kinases, granzymes, DNA fragmentation proteins, caspases and Bcl-2 family, was used to determine the impact of emodin in breast cancer BCap-37 cells. Furthermore, the candidate emodin target genes were further evaluated via real-time quantitative PCR and Western blot analysis.RESULTS:We found that gene expression profiling in human breast cancer BCap-37 cells was altered when exposed to emodin. Thirty of the unique genes that were either induced or repressed in response to emodin-induced apoptosis were also identified. A follow-up study characterized p53, emodin-induced gene, IGF-2, and emodin-repressed gene, and the downstream proteins were also seen as possible molecular targets of emodin.CONCLUSION:Data from this study provide novel evidence that emodin induces gene expression profiling changes, but has no effects on caspases. In addition, the p53 pathway may cooperate with the IGF-2 pathway, resulting in an emodin-induced apoptosis through disruption of the mitochondrial signaling pathway in BCap-37 cells.
Objective: To explore possible relationships among blood factors, family history of breast cancer (BC) and the risk of the disease, a case–control study was carried out in Montevideo, Uruguay. Methods: Eight hundred and one patients were interviewed, including 252 certified cases of BC and 549 frequency-matched controls. Blood groups (ABO, Rh) were obtained from medical records. Multivariate analyses were performed, adjusting for age, selected menstrual and reproductive factors, and family history of BC as well as of other cancers. Results: We found that the absence of Rh factor (Rh−) was positively associated with the risk of BC (adjusted Odds Ratio [OR]=1.49, 95% Confidence Interval [95% CI] 1.05–2.11). Stratified analyses by family history of BC showed a strong association for Rh− with a positive history of first degree relatives (OR=3.17, 95% CI 1.06–9.47). Also stratified analyses by family history of other cancers showed a positive association for Rh− with a positive history of first degree relatives (OR=2.08, 95% CI 1.05–4.11). Conclusion: Regarding the implications of an inherited factor like Rh and its associations with the family history of BC, it might increase the probability to generate high-risk individuals if further studies confirm the present preliminary findings.
BACKGROUND:The aim of the study was to investigate the association between lifetime consumption of alcoholic beverages and cancer risk. METHODS:Data were collected in a population-based case-control study, conducted in Montreal in the mid-1980s, designed to assess the associations between hundreds of non-occupational and occupational exposures and multiple cancer sites in men. We present results for 13 cancer sites: oesophagus (n = 78), stomach (n = 215), colon (n = 427), rectum (n = 239), liver (n = 28), pancreas (n = 83), lung (n = 700), melanoma (n = 107), prostate (n = 374), bladder (n = 425), kidney (n = 156), Hodgkin's lymphoma (n = 42), and non-Hodgkin's lymphoma (n = 190), in comparison to population controls (n = 507). Odds ratios (OR) were estimated for the associations between lifetime consumption of total alcoholic beverages, beer, wine, and/or spirits, altogether and separately, and each cancer site, while carefully adjusting for smoking and other covariates using polytomous logistic regression. RESULTS:For several cancers (oesophagus, stomach, colon, liver, pancreas, lung, prostate) there was evidence of increased risk among alcohol consumers compared with abstainers and occasional drinkers. For most sites, it was beer and to a lesser extent spirits consumption that drove the excess risks. CONCLUSIONS:Our results support the hypothesis that moderate and high alcohol intake levels over the lifetime might increase cancer risk at several sites.
Background: Trans-rectal ultrasound (TRUS) guided systematic prostate biopsy is a standard tool in prostate cancer (CaP) diagnosis. Extended biopsy techniques using 10-12 cores are the norm. Controversy exists on extended TRUS biopsy in men with PSA > 10 ng/mL. We evaluated cancer detection rates on an individual core basis, to stratify prostate biopsy protocols based on PSA levels. Patients and methods: Over a five-year period, 1036 patients underwent TRUS guided prostate biopsy for raised serum PSA (>2.5 ng/mL). 436 patients had PSA > 10 ng/mL. Patients with PSA <50 ng/mL underwent a 12-core TRUS guided prostate biopsy including six peripheral biopsies. The six peripheral biopsies were directed laterally towards the base, mid-zone and apices. Remainder were standard para-sagittal sextant biopsies. Patients were stratified into three groups (PSA 10-20 ng/mL 20-50 ng/mL and >50 ng/mL). Results: Mean age of 436 patients with PSA > 10 ng/mL was 70.3years. 270 (62%) men had cancer. Cancer detection rates for different PSA levels were 46% (10-20 ng/mL), 76% (20-50 ng/mL) and 93% (>50 ng/mL). Higher PSA levels and advanced clinical stage were associated with increased cancer detection rates. All patients with clinical T3 and T4 disease had biopsy diagnosed CaP. Conclusion: TRUS guided prostate biopsy in patients with PSA >10 ng/mL did not require 12 cores to diagnose CaP. CaP diagnosis required 8 cores in men with PSA 10-20 ng/mL. These cores were right and left peripheral basal and apical, and right and left para-sagittal basal and apical biopsy. Only 6 cores were necessary to diagnose CaP in men with PSA >20 ng/mL which were right and left peripheral basal and apical, and para-sagittal apical biopsies. We suggest limited TRUS prostate biopsy protocols for men with PSA >10 ng/mL. (C) 2008 Elsevier Ltd. All rights reserved.
Introduction: Recent research indicates a close connection of inflammation and cancer as presumed by Virchow in 1893. The growing understanding of cellular signalling and regulatory pathways reveals multiple links between inflammation and cancer. This study was designed to evaluate the influence of the anti-inflammatory drug dexamethasone and the antioxidant alpha-tocopherol on oxidative induced DNA damage, a major factor in the development of malignancies. Material and methods: Miniorgan cultures (MOC) of fresh biopsied human nasal mucosa were used to keep cells in their microenvironment and thus to mimic in vivo conditions. MOC were pretreated with dexamethasone and alpha-tocopherol in different concentrations on 1 or on 5 days before oxidative DNA damage was introduced by hydrogen peroxide. The effect of these substances on DNA damage was evaluated using the alkaline single cell microgel electrophoresis (Comet Assay). Results: Dexamethasone induced slight, but considerable DNA fragmentation by itself. It effectively protected cells from hydrogen peroxide induced DNA damage, leading to a maximum decrease of about 45% when preincubated on 5 days at 20 mu M. alpha-Tocopherol most effectively reduced oxidative DNA fragmentation by about 38% when MOC were pretreated 5 days at 20 mu M. Discussion: Our experimental data clearly shows the DNA protective action of dexamethasone and alpha-tocopherol with regard to oxidatively induced DNA damage, a major pathogenetic factor that inflammation and cancer have in common. (C) 2008 Elsevier Ltd. All fights reserved.
Background: Previous experimental and laboratory studies have implicated antibodies against Hu proteins (anti-Hu) as a potential marker for small cell lung cancer (SCLC); there are no estimates of the association between anti-Hu and SCLC using a population-based design. Methods: We used stored plasma specimens to evaluate anti-Hu reactivity in relationship to small cell lung cancer in a population-based case–control study. Using Western Blot analysis, we measured anti-Hu reactivity against recombinant Hu family member, HuD, in plasma samples from 41 SCLC cases and 79 controls individually matched for age, race, sex, and smoking status (never, past, current). We analyzed the association between anti-Hu reactivity and SCLC using conditional logistic regression. Results: Anti-Hu reactivity was associated with SCLC, both before and after adjustment for amount of smoking. We observed a smoking-adjusted odds ratio of 3.2 (95% confidence interval from 0.98 to 13.4) comparing subjects above 1800 units (the lower limit of the second tertile of the distribution among antibody positive controls) to subjects with lower reactivity. We also found suggestive evidence in follow-up of our cases that anti-Hu above 1800 units was related to longer-term survival from SCLC. The present research is the first report of anti-Hu reactivity and SCLC in a population-based study. Conclusions: Given the suggestive evidence in this study, prospective analyses to examine whether anti-Hu reactivity might predict risk of developing SCLC, or whether anti-Hu reactivity could serve as an early marker for SCLC, may be warranted.
BACKGROUND:The fast growing Middle Eastern (ME) population has rarely been studied in the U.S.. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle Eastern White (NHNMW) in California.METHODS:ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant, 16 uncertain) in the ME and 15,589 cases (8352 benign, 6812 malignant, 425 uncertain) in the NHNMW were available for this study.RESULTS:ME patients were significantly (p < 0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p < 0.05). Rates for malignant tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors.CONCLUSIONS:This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to be evaluated in future studies.
Background: The purpose of our study was to show the apoptotic and anti-proliferative effects of phytosterols as distinct from cholesterol effects on prostate cancer cell lines, and also their differential expression of caveolin-1, and a prostate specific gene, PCGEM1. Methods: PC-3 and DU145 cells were treated with sterols (cholesterol and phytosterols) for 48h, followed by trypan blue dye exclusion measurement of cytotoxicity and MTT cell proliferation assays, respectively. Cell cycle analysis was carried out microscopically, and by propidium iodide uptake using flow cytometry. Sterol induction of oncogenic gene expression was evaluated by RT-PCR. Apoptotic cells were identified by immunocytochemistry using DNA fragmentation method, and by annexin V adhesion using flow cytometry. Results: Physiological doses (16μM) of these sterols were not cytotoxic in these cells. Cholesterol-enrichment promoted mitosis (54 and 61% by microscopy; 40.8 and 34.08% by FACS analysis in PC-3 and DU145, respectively) and cell growth (P<0.05), while phytosterols suppressed mitosis (29 and 35% by microscopy; 27.71 and 17.37% by FACS analysis in PC-3 and DU145, respectively), and significantly induced tumor-suppression (P<0.05) and apoptosis. We demonstrated for the first time that cholesterols upregulated the expression of PCGEM1 even in androgen-insensitive prostate cancer cell lines. Phytosterols reversed this effect, while upregulating the expression of caveolin-1, a known mediator of androgen-dependent proto-oncogene signals that presumably control growth and anti-apoptosis. Conclusions: Phytosterol inhibition of PCGEM1 and cell growth and the overexpression of caveolin-1, suggests that poor disease prognosis anchors on the ability of caveolin-1 to regulate downstream oncogene(s) and apoptosis genes. Sterol intake may contribute to the disparity in incidence of prostate cancer, and elucidation of the mechanism for modulation of growth and apoptosis signaling may reveal potential targets for cancer prevention and/or chemotherapeutic intervention. Sterol regulation of PCGEM1 expression suggests its potential as biomarker for prediction of neoplasms that would be responsive to chemoprevention by phytosterols.
