Exploration of Multigene, Mulfistep and Multipathway Models of Nasopharyngeal and Colorectal Carcinogenesis

OBJECTIVE To construct tree models for nasopharyngeal carcinoma (NPC) and colorectal carcinoma (CC) and explore the oncogeneic process of NPC and CC .METHODS Based on the software that Desper et al. developed, tree models were constructed for CC from the comparative genomic hybridization (CGH) data of 118 CC patients and for NPC from the CGH data of 140 southern Chinese patients, respectively. RESULTS Tree models for CC suggested that loss of 18q and gain of 20q were important early events in colorectal carcinogenesis. As changes in -18q occurred prior to those in -17p, a cause-effect relationship might exist between them. Tree models for NPC suggested that loss of 3p was an important early event in nasopharyngeal carcinogenesis, and deletion of 11q, 14q, 16q and 9p were also nonrandom genetic events in carcinogenesis, suggesting that there might be tumor-associated genes existing on these chromosome arms. The tree model also indicated the existence of oncogenes on the short arm of chromosome 12.CONCLUSION Constructing tree models based on the CGH data to demonstrate the initiation and progression of NPC might help elucidate its multigene, multistep and multipathway development. It may provide valuable clues to explore the mechanism of tumorigenesis.     

Dietary intake of vegetables, folate, and antioxidants and the risk of Barrett’s esophagus

Purpose

Diet is a potentially modifiable risk factor for Barrett’s esophagus (BE). We investigated the associations between intakes of fruits and vegetables and risk of BE.

Methods

We identified study subjects from 1,859 participants who underwent the endoscopy in a single VA Medical Center in the US between 2008 and 2011. Dietary intake in the previous year was elicited using a self-administered Block food frequency questionnaire (FFQ). Logistic regression model was used to estimate odds ratio (OR) and its 95 % confidence interval (CI) for BE.

Results

A total of 151 cases with definite BE and 777 controls completed the FFQ. When highest tertile of intake was compared with the lowest, the OR (95 % CI) was 0.46 (0.26–0.81) for dark green vegetables, 0.52 (0.30–0.90) for legumes, 0.50 (0.28–0.90) for total fiber, 0.45 (0.25–0.81) for isoflavones, 0.52 (0.30–0.67) for total folate, and 0.45 (0.26–0.79) for lutein, adjusting for multiple confounding factors including use of aspirin or proton pump inhibitor, gastro-esophageal reflux symptoms, and physical activity. The association for dark green vegetables was attenuated after adjustment for lutein, total fiber, and total folate (OR = 0.82; 95 % CI 0.30–2.22).

Conclusion

Higher intake of dark green vegetables was associated with a decreased risk of BE in a veteran population. Such an inverse association may be partially mediated by lutein, fiber, and folate. The novel findings on the association between intake of lutein, total folate, or isoflavones and risk of BE need further confirmation.     

A pooled analysis of case–control studies of thyroid cancer: cigarette smoking and consumption of alcohol, coffee, and tea

Objective: To analyze the role of smoking, alcohol, coffee and tea in relation to thyroid cancer, we conducted a pooled analysis of 14 case–control studies conducted in the United States, Europe, and Asia. Methods: The sample consisted of 2725 thyroid cancer cases (2247 females, 478 males) and 4776 controls (3699 females, 1077 males). Conditional logistic regression with stratification on study, age at diagnosis, and gender was used to compute odds ratios and 95% confidence intervals. Results: Thyroid cancer risk was reduced in persons who had ever smoked. The relationship was more pronounced in current smokers (OR = 0.6, 95% CI = 0.6–0.7) than former smokers (OR = 0.9, 95% CI = 0.8–1.1). There were significant trends of reduced risk with greater duration and frequency of smoking. For consumption of wine and beer, there was a significant trend of decreasing thyroid cancer risk (p = 0.02) that was not maintained after adjustment for current smoking (p = 0.12). Thyroid cancer risk was not associated with consumption of coffee or tea. These findings were consistent in both gender-specific and histology-specific (papillary and follicular) analyses. Conclusions: Pooled analyses of these geographically diverse case–control data indicate a reduced thyroid cancer risk associated with current smoking. A reduced risk associated with alcohol was eliminated after adjustment for smoking, and caffeinated beverages did not alter thyroid cancer risk.     

Glycemic index, carbohydrate and fiber intakes and risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma

Objective  To examine the association between dietary glycemic index (GI), glycemic load (GL), total carbohydrate, sugars, starch, and fiber intakes and the risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Methods  In an all-Ireland study, dietary information was collected from patients with esophageal adenocarcinoma (n = 224), long-segment Barrett’s esophagus (n = 220), reflux esophagitis (n = 219), and population-based controls (n = 256). Multiple logistic regression analysis examined the association between dietary variables and disease risk by tertiles of intake and as continuous variables, while adjusting for potential confounders. Results  Reflux esophagitis risk was positively associated with starch intake and negatively associated with sugar intake. Barrett’s esophagus risk was significantly reduced in people in the highest versus the lowest tertile of fiber intake (OR 0.44 95%CI 0.25–0.80). Fiber intake was also associated with a reduced risk of esophageal adenocarcinoma, as was total carbohydrate intake (OR 0.45 95%CI 0.33–0.61 per 50 g/d increase). However, an increased esophageal adenocarcinoma risk was detected per 10 unit increase in GI intake (OR 1.42 95%CI 1.07–1.89). Conclusions  Our findings suggest that fiber intake is inversely associated with Barrett’s esophagus and esophageal adenocarcinoma risk. Esophageal adenocarcinoma risk is inversely associated with total carbohydrate consumption but positively associated with high GI intakes.     

Impact of hysterectomy and bilateral oophorectomy prevalence on rates of cervical,uterine, and ovarian cancer among American Indian and Alaska Native women, 1999–2004

Objective  

To present more accurate incidence rates of cervical, uterine, and ovarian cancer by geographic region in American Indian/Alaska Native (AI/AN) women.     

Citizenship,length of stay,and screening for breast,cervical, and colorectal cancer in women, 2000–2010

Background

Two factors jointly account for significant gaps in access to health care among immigrants who are present in the U.S.—legal status, and length of residence. The objective of this study is to examine the association between citizenship and length of residence in the U.S. and cancer screening (breast, cervical, and colorectal) among women.

Methods

We analyzed 11 years (2000–2010) of consolidated data from the Medical Expenditure Panel Survey linked with the National Health Interview Survey. Multivariate analyses compared cancer screening among U.S.-born citizens (n?=?58,484), immigrant citizens (n?=?8,404), and immigrant non-citizens (n?=?6,564).

Results

Immigrant non-citizens living in the U.S. for less than 5 years were less likely to receive guideline-concordant breast (OR?=?0.68 [0.53–0.88]), cervical (OR?=?0.65 [0.54–0.78]), and colorectal (OR?=?0.31 [0.19–0.50]) cancer screening compared to U.S.-born citizens. Immigrant citizens and non-citizens living in the U.S. for 5 years or more had higher odds of being screened for breast and cervical cancer compared to U.S.-born citizens; (OR?=?1.26 [1.13–1.41] and OR?=?1.17 [1.06–1.29]) for immigrant citizens, (OR?=?1.28 [1.13–1.45] and OR?=?1.23 [1.09–1.38]) for non-citizens. Immigrant non-citizens living in the U.S. for 5 years or more had lower odds of being screened for colorectal cancer compared to U.S.-born citizens (OR?=?0.76 [0.65–0.90]).

Conclusions

Based on these findings, duration mandates in immigration policy may indirectly influence future pathways to preventive health care and cancer disparities disproportionately affecting immigrant women. We suggest that limits of duration mandates be reevaluated, as they may offer pathways to preventive health care for this vulnerable population, and prevent future cancer disparities.

     

Histochemical and Immunohistochemical Study of α-SMA,Collagen, and PCNA in Epithelial Ovarian Neoplasm

Background: Alpha-smooth muscle actin (α-SMA) is an isoform of actin, positive in myofibroblasts and is an epithelial to mesenchymal transition (EMT) marker. EMT is a process by which tumor cells develop to be more hostile and able to metastasize. Progression of tumor cells is always followed by cell composition and extracellular matrix component alteration. Increased α-SMA expression and collagen alteration may predict the progressivity of ovarian neoplasms. Objective: The aim of this research was to analyse the characteristic of α-SMA and collagen in tumor cells and stroma of ovarian neoplasms. In this study, PCNA (proliferating cell nuclear antigen) expression was also investigated. Methods: Thirty samples were collected including serous, mucinous, endometrioid, and clear cell subtypes. The expression of α-SMA and PCNA were calculated in cells and stroma of ovarian tumors. Collagen was detected using Sirius Red staining and presented as area fraction. Results: The overexpressions of α-SMA in tumor cells were only detected in serous and clear cell ovarian carcinoma. The histoscore of α-SMA was higher in malignant than in benign or borderline ovarian epithelial neoplasms (105.3±129.9 vs. 17.3±17.1, P=0.011; mean±SD). Oppositely, stromal α-SMA and collagen area fractions were higher in benign than in malignant tumors (27.2±6.6 vs 20.5±8.4, P=0.028; 31.0±5.6 vs. 23.7±6.4, P=0.04). The percentages of epithelial and stromal PCNA expressions were not significantly different between benign and malignant tumors. Conclusion: Tumor cells of serous and clear cell ovarian carcinoma exhibit mesenchymal characteristic as shown by α-SMA positive expression. This expression might indicate that these subtypes were more aggressive. This research showed that collagen and α-SMA area fractions in stroma were higher in benign than in malignant neoplasms.     

Viagra, cialis, impase--which of them, to whom, when and how?

The study has been performed of the efficacy in the treatment of erectile dysfunction (ED) of oral drugs affecting nitric oxide: impase and phosphodiesterase-5 (PDE-5) inhibitors--sildenafil citrate (viagra), tadalafil (sialis)--alone and in combination with impase. A total of 218 ED patients aged 21-73 years (mean age 58.1 +/- 13.2 years) were divided into 3 groups comparable by the number of the patients, age, suspected etiology, pathogenesis and ED severity. Group 1 (n = 81) took viagra in the individually adjusted dose for 6 months; group 2 (n = 64) received sialis in a dose 20 mg for 6 months; group 3 (n = 73) took impase 1 tablet each other day sublingually for 6 months. Overall efficacy made up 77.8, 81.3 and 56.2% for viagra, sialis and impase, respectively. In view of different mechanism of action of PDE-5 inhibitors (viagra, sialis) and impase we combined the drugs in those who failed monotherapy or had drastic side effects. The combination raised efficacy of pharmacotherapy from 56.2 to 92.2%. We came to the conclusion that in psychogenic, isolated neurogenic, compensated and subcompensated arteriogenic ED of a mild or moderate degree, the treatment can be started with impase. If it was uneffective, in severe ED or moderate venoocclusive ED it is better to use PDE-5 inhibitors (viagra, sialis). If one of the latter fails, the other should be administered. If the inhibitors have low efficacy or in side effects, it is indicated to use their combination with impase.     

Binding capacity of ER-α ligands and SERMs: comparison of the human, dog and cat

The estrogen molecule is the major risk factor related to mammary gland tumors, with estrogen receptor alpha (ER- α) as the important target stimulating growth. Therefore one alternative approach to treatment of breast cancer is to use selective estrogen receptor modulator (SERM), hormonal therapy. In this study, the structures of ER- α in humans, dogs and cats were predicted using the amino acid sequencing data bank and corrected for general protein structures, receptor sites and docking by adding 2,344 ligands with 15 SERMs into the database and calculating estimated inhibition constants (Ki). Thereby, ranking of best ligands of SERMs in humans, dogs and cats could be achieved. The results show that the shapes of ER- α differ between species but the major pocket sites are the same. Bazedoxifene, a new SERM proved to be the best estrogen antagonist and ER- α inhibitor in all species (human, dog, cat) with the lowest Ki. The other good ligands for dogs and cats are Neohesperidin, Dihydrochalcone, and Schreiber2. The differences in these protein structures may explain why there are only a few SERMs or other ligands which can be used as anti-cancer drugs.     

Prospective study of serum retinol, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China

Objective: This study examined the relationship between pretrial serum concentrations of retinol, -carotene, -cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer. Methods: We used a stratified case–cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models. Results: Median values in our cohort were low for serum retinol (33.6 g/dl), -carotene (4.3 g/dl), and -cryptoxanthin (3.5 g/dl) , but were high for lutein/zeaxanthin (40.0 g/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83–0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63–0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31–0.96). For -cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76–1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0–1.3) with increasing concentration of serum lutein/zeaxanthin. Conclusions: In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.     

Social class, race/ethnicity, and incidence of breast, cervix, colon, lung, and prostate cancer among Asian, black, Hispanic, and white residents of the San Francisco Bay Area, 1988–92 (United States)

Background: To date only eight US studies have simultaneously examined cancer incidence in relation to social class and race/ethnicity; all but one included only black and white Americans. To address gaps in knowledge we thus investigated socioeconomic gradients in cancer incidence among four mutually exclusive US racial/ethnic groups – Asian and Pacific Islander, black, Hispanic, and white – for five major cancer sites: breast, cervix, colon, lung, and prostate cancer.Methods: We generated age-adjusted cancer incidence rates stratified by socioeconomic position using: (a) geocoded cancer registry records, (b) census population counts, and (c) 1990 census block-group socioeconomic measures. Cases (n=70,899) were diagnosed between 1988 and 1992 and lived in seven counties located in California's San Francisco Bay Area.Results: Incidence rates varied as much if not more by socioeconomic position than by race/ethnicity, and for each site the magnitude – and in some cases direction – of the socioeconomic gradient differed by race/ethnicity and, where applicable, by gender. Breast cancer incidence increased with affluence only among Hispanic women. Incidence of cervical cancer increased with socioeconomic deprivation among all four racial/ethnic groups, with trends strongest among white women. Lung cancer incidence increased with socioeconomic deprivation among all but Hispanics, for whom incidence increased with affluence. Colon and prostate cancer incidence were inconsistently associated with socioeconomic position.Conclusions: These complex patterns defy easy generalization and illustrate why US cancer data should be stratified by socioeconomic position, along with race/ethnicity and gender, so as to improve cancer surveillance, research, and control.     

Expression and prognostic value of VEGFR-2, PDGFR-β, and c-Met in advanced hepatocellular carcinoma

Background

We explore the clinical and prognostic significance of expression of vascular endothelial growth factor receptor (VEGFR)-2, platelet-derived growth factor receptor (PDGFR)-β, and c-Met in patients with hepatocellular carcinoma (HCC).

Methods

The expression of VEGFR-2, PDGFR-β, and c-Met were determined by immunohistochemical examination of the tissues of 93 HCC patients. The relationships of these markers with clinicopathological factors and prognosis were then analyzed.

Results

High expression of VEGFR-2, PDGFR-β, and c-Met was found in 86%, 19.4%, and 80.6% of patients, respectively. Expression of VEGFR-2 correlated with gender (P = 0.044), hepatitis B surface antigen positivity (P = 0.024), degree of tumor differentiation (P = 0.023), and hepatic cirrhosis (P = 0.026). Expression of PDGFR-β correlated with alpha-fetoprotein level (P = 0.029), tumor size (P = 0.033), and hepatic cirrhosis (P = 0.023). No significant correlations were identified between expression of c-Met and clinicopathological factors. Expression of PDGFR-β correlated with overall survival (P = 0.046) and expression of c-Met correlated with progression-free survival (P = 0.01).

Conclusions

We found that in patients with HCC, high expression of VEGFR-2 correlates with chronic hepatitis B virus infection and hepatic cirrhosis. High expression of PDGFR-β is a predictor of poor prognosis. High expression of C-Met may predict therapeutic effectiveness of sorafenib in HCC patients.     

Caregiver–Oncologist Prognostic Concordance,Caregiver Mastery,and Caregiver Psychological Health and Quality of Life

BackgroundCaregivers of adults with cancer often report a different understanding of the patient''s prognosis than the oncologist. We examine the associations of caregiver–oncologist prognostic concordance with caregiver depressive symptoms, distress, and quality of life (QoL). We also explore whether these relationships differed by caregiver environment mastery, an individual''s sense of control, and effectiveness in managing life situations.Materials and MethodsWe used data from a national geriatric assessment cluster‐randomized trial (URCC 13070) that recruited patients aged 70 years and older with incurable cancer considering any line of cancer treatment at community oncology practices, their caregivers, and their oncologists. At enrollment, caregivers and oncologists estimated the patient''s prognosis (0–6 months, 7–12 months, 1–2 years, 2–5 years, and >5 years; identical responses were concordant). Caregivers completed the Ryff''s environmental mastery at enrollment. At 4–6 weeks, caregivers completed the Patient Health Questionnaire‐2 (depressive symptoms), distress thermometer, and 12‐Item Short‐Form Health Survey (quality of life [QoL]). We used generalized estimating equations in models adjusted for covariates. We then assessed the moderation effect of caregiver mastery.ResultsOf 411 caregiver–oncologist dyads (mean age = 66.5 years), 369 provided responses and 28% were concordant. Prognostic concordance was associated with greater caregiver depressive symptoms (β = 0.30; p = .04) but not distress or QoL. A significant moderation effect for caregiver depressive symptoms was found between concordance and mastery (p = .01). Specifically, among caregivers with low mastery (below median), concordance was associated with greater depressive symptoms (β = 0.68; p = .003).ConclusionsCaregiver–oncologist prognostic concordance was associated with caregiver depressive symptoms. We found a novel moderating effect of caregiver mastery on the relationship between concordance and caregiver depressive symptoms.Implications for PracticeCaregiver–oncologist prognostic concordance is associated with greater caregiver depressive symptoms, particularly in those with low caregiver mastery. When discussing prognosis with caregivers, physicians should be aware that prognostic understanding may affect caregiver psychological health and should assess their depressive symptoms. In addition, while promoting accurate prognostic understanding, physicians should also identify strengths and build resilience among caregivers.     

Nannochloropsis Extract–Mediated Synthesis of Biogenic Silver Nanoparticles,Characterization and In Vitro Assessment of Antimicrobial,Antioxidant and Cytotoxic Activities

Objective: To investigate the biogenic synthesis of silver nanoparticles (AgNPs) using partially purified ethylacetate extract of Nannochloropsis sp. hexane (EAENH) fraction of microalga. Methods: The green synthesis ofAgNPs was confirmed with UV-Vis spectrum which shows the surface plasmon resonance (SPR) at 421 nm. FourierTransform Infrared Spectra (FTIR) presented the involvement of functional groups like carboxyl groups of fatty acids,tetraterpenoids of xanthophylls, hydroxyl groups of polyphenols, carbonyl and amide linkage of proteins in the AgNPsynthesis. Gas Chromatography-Mass Spectrometry analysis (GCMS) revealed that phytochemicals like octadecanoicacid and hexadecanoic acid imply in capping, bioreduction, and stabilization of AgNps. Result: High-resolutionTransmission electron microscope (HRTEM), Dynamic light scattering (DLS), X-ray diffraction (XRD) and EDXanalysis showed the crystalline form of the AgNPs with Z-average size 57.25 nm. The zeta potential value of -25.7mV demonstrated the negative surface charge and colloidal stability of AgNPs. The antimicrobial activity of AgNPsdisplayed effective inhibition zone against selected bacterial and fungal pathogens. In vitro, antioxidant effects wereassessed by 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydrogen peroxide and reducing power assays which revealedexcellent scavenging potential for AgNPs than the extracts. The anti-proliferative potential of biofabricated AgNPsand extracts on Human Non-small lung cancer cell line (A549) was assessed using 3–(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay with IC50 values of 15 μgmL-1 and 175 μgmL-1 respectively. Conclusion:The study reveals that the microalgae-mediated AgNPs possesses potent antimicrobial and antioxidant activity alongwith the ability to stimulate apoptosis in A-549 cell line.     

Expression of TGF-β1, Snail, E-cadherin and N-cadherin in Gastric Cancer and Its Significance

OBJECTIVE To investigate the expression of TGF-β1,Snail,E-cad-herin and N-cadherin in gastric cancer(GC),and to examine its relationship to malignant features of the tumors. METHODS The expression of TGF-β1,Snail,E-cadherin and N-cadherin proteins was detected in GC and adjacent tissues by immunohistochemical staining,and compared with the clinico-pathological data. RESULTS Positive rates of expression for TGF-β1,Snail,E-cadherin and N-cadherin were 63.5%,83.3%,37.5%and 44.8%in GC,and 28.8%, 41.3%,100%,11.3%in adjacent tissues,respectively.The expression of all four proteins showed a significant difference between the GCs and adjacent tissues(P<0.05).The positive rate of TGF-β1,Snail and N-cadherin,or the negative rate of E-cadherin expression was significantly related to the differentiated degree,histological type,invasion and metastasis of GC.In addition,the expression of N-cadherin was positively related to that of TGF-β1, but negatively related to that of E-cadherin.There was negative correlation between expression of E-cadherin and TGF-β1 and Snail in GC(P<0.05). CONCLUSION The over-expression of TGF-β1 and Snail and decreased expression of E-cadherin and the abnormal expression of N-cad-herin were involved in the process of invasion and metastasis of GC.The data showed that E-cadherin might switch to N-cadherin.TGF-β1 and Snail might play a fundamental role in the process.     

Effect of gastrectomy on the pharmacokinetics of tegafur,uracil, and 5-fluorouracil after oral administration of a 1∶4 tegafur and uracil combination

The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 14, were examined in 26 patients with macroscopic State I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28±26.88, 4.41±1.78, and 0.51±0.20 g h ml^–1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.     

Expression of cGMP-dependent protein kinase, PKGIα, PKGIβ, and PKGII in malignant and benign breast tumors

Cyclic GMP-dependent protein kinases (PKG) constitute a small family of enzymes that are encoded by two genes. Two major forms of PKG have been identified in mammalian cells, PKG I and PKG II. In addition, there are two splice variants of PKG I, which are designated as I?? and I??. There are increasing evidences that PKG can play an important role in the inhibition of cell proliferation and induction of apoptosis. In our previous studies, the inhibitory effects of cGMP/PKG on the cell growth were indicated using breast cancer cell lines. Accordingly, the present study was designed to compare the expression levels of three PKG isoforms in normal, benign, and malignant breast tissues. The expression level of PKG isoforms was assayed using quantitative real-time RT-PCR. The correlation between relative expression of PKG isoforms and clinicopathological characteristics were also analyzed. Downregulation of PKG isoforms was observed in the malignant and benign tumors when compared to those of respective normal tissues. No significant correlation was found between PKGI??, PKGI??, and PKGII expression and clinicopathological features. The present study is the first to evaluate the expression level of PKG isoforms PKGI??, PKGI??, and PKGII in the malignant and benign breast tumors. Reduction in the PKG expression is an important evidence to support the antitumor activity of this enzyme in vivo.