Proximity-Induced Bipedal DNA Walker for Accurately Visualizing microRNA in Living Cancer Cell.

DNA walker, a type of dynamic DNA device that is capable of moving progressively along prescribed walking tracks, has emerged as an ideal and powerful tool for biosensing and bioimaging. However, most of the reported three-dimensional (3D) DNA walker were merely designed for the detection of a single target, and they were not capable of achieving universal applicability. Herein, we reported for the first time the development of a proximity-induced 3D bipedal DNA walker for imaging of low abundance biomolecules. As a proof of concept, miRNA-34a, a biomarker of breast cancer, is chosen as the model system to demonstrate this approach. In our design, the 3D bipedal DNA walker can be generated only by the specific recognition of two proximity probes for miRNA-34a. Meanwhile, it stochastically and autonomously traveled on 3D tracks (gold nanoparticles) via catalytic hairpin assembly (CHA), resulting in the amplified fluorescence signal. In comparison with some conventional DNA walkers that were utilized for living cell imaging, the 3D DNA walkers induced by proximity ligation assay can greatly improve and ensure the high selectivity of bioanalysis. By taking advantage of these unique features, the proximity-induced 3D bipedal DNA walker successfully realizes accurate and effective monitoring of target miRNA-34a expression levels in living cells, affording a universal, valuable, and promising platform for low-abundance cancer biomarker detection and accurate identification of cancer.

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. METHODS: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. RESULTS: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). CONCLUSIONS: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.

Characteristics of Chinese Families in Which Children and Both Parents Are Diagnosed with Malignant Tumors: A Retrospective Study.

Objective To characterize Chinese families in which both parents and at least one child are diagnosed with malignant diseases and provide reference for cancer screening or early detection in people whose both parents are diagnosed with cancer. Methods Medical records of all clients to the center of cancer screening and prevention of the National Cancer Center/Cancer Hospital between January 2008 and February 2018 were screened to select families in which both parents and at least one child were diagnosed with malignant diseases. The cancer profiles of fathers, mothers, sons and daughters, their age distribution at diagnosis, and similarity of cancers between two generations were analyzed. The proportions of each cancer in males and females of the cohort were compared with corresponding data from the National Cancer Center Registry of China (NCCRC) in 2013. Results Totally 135 families were identified from records of 33 200 clients. Proportion of lung cancer in fathers (40/135, 29.6%) and in mothers (38/135, 28.1%) were higher than the national data (23.9% in males and 14.9% in females, respectively). The proportion of breast cancer in daughters (35/109, 32.1%) was higher than that of mothers (14/135, 10.4%) and the national data (17.1%). In 71 father-son pairs of cancer, 46.5% (33/71) were of the same systematic disease, and 16.9% (12/71) were of the same cancer. These two indexes were 31.2% (n=34) and 10.1% (n=11), respectively in the 109 father-daughter pairs of cancer, 36.6% (n=26) and 8.5% (n=6) respectively in the 71 mother-son pairs of cancer, and 31.2% (n=34) and 20.2% (n=20) respectively in the 109 mother-daughter pairs of cancer. Sons were more likely to suffer from cancers originated from the same system as father's cancer than daughters (χ 2=4.299, P<0.05), and daughters were more likely to suffer from the same cancer as their mother's cancer than sons (χ 2=4.506, P<0.05). The age (mean ± standard deviation) of the daughters (52.4±12.7) and the sons (59.4±10.9) at diagnosis were significantly younger than the fathers (65.5±12.2) and the mothers (65.7 ±12.5) (all P<0.001). Conclusions For people whose both parents are diagnosed as cancer, screening or early detection examinations should cover a full range of cancers rather than the cancers their father and mother have suffered, or cancers stemmed from the same system as their parent's cancers. We suggest screening or early detection program for these special population start earlier than that for the general population, with emphasis on cancers derived from digestive system for males and women-specific cancers, i.e., breast cancer, ovarian cancer, cervical cancer and uterine cancer for females.

Observation of the retarded transportation of a photogenerated hole on epitaxial graphene.

Graphene is usually adopted as an assistant additive for catalysts in photocatalytic processes, because of its ability to accelerate the separation of photogenerated charge carriers. To elucidate the mechanism, hydrogen peroxide is adopted to convert the O2(-)˙ active species into OH˙ for degradation of an organic dye. If the pH value is less than 7, the concentration of the OH˙ species can be reduced more quickly with the addition of graphene than without, because negatively charged electrons can be transported quickly on graphene. If the pH value is larger than 7, the concentration of OH˙ can be promoted by the catalyst SiC with photogenerated h(+) release and reaction with OH(-), however the concentration is reduced if the SiC catalyst is covered by a graphene sheet, as it retards h(+) release from the SiC substrate. Our findings have provided a certification for the role of graphene in photo-catalytic processes.

Liquid chromatography-tandem mass spectrometry-based plasma metabonomics delineate the effect of metabolites' stability on reliability of potential biomarkers.

Metabonomics is an important platform for investigating the metabolites of integrated living systems and their dynamic responses to changes caused by both endogenous and exogenous factors. A metabonomics strategy based on liquid chromatography-mass spectrometry/mass spectrometry in both positive and negative ion modes was applied to investigate the short-term and long-term stability of metabolites in plasma. Principal components analysis and ten types of identified metabolites were used to summarize the time-dependent change rules in metabolites systematically at different temperatures. The long-term stability of metabolites in plasma specimens stored at -80 °C for five years was also studied. Analysis of these subjects identified 36 metabolites with statistically significant changes in expression (p < 0.05) and found a kind of metabolite with a hundred-fold change. The stability of metabolites in blood at 4 °C for 24 h was also investigated. These studies show that a thorough understanding of the effects of metabolite stability are necessary for improving the reliability of potential biomarkers.

Plasma metabolome analysis by integrated ionization rapid-resolution liquid chromatography/tandem mass spectrometry.

RATIONALE: Acquiring global information on plasma-endogenous metabolites challenges metabolomics. This study has been designed to investigate the suitability of integrated ionization rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC/MS/MS) for different kinds of metabolites in complex plasma, and provides an approach for plasma metabolomics in acquiring more comprehensive data of metabolites. METHODS: Integrated ionization of electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI) combined with RRLC/MS/MS has been carried out to perform analysis on the global plasma metabolome of healthy volunteers. The contributions to the total numbers of ion features by RRLC/MS with ESI, APCI, and APPI in positive and negative ion modes were calculated. Representative unique and identical ions were identified. The intensities of identical ions were compared. RESULTS: Each of ESI, APCI, and APPI coupled with RRLC/MS has its own advantage over the other two techniques for certain types of metabolites in plasma. LC/ESI-MS is very sensitive for detecting glycerophosphocholines, glycerophosphoethanolamines, acyl carnitines, bile acids, sulfate, etc. LC/APCI-MS is suitable for analyzing cyclic alcohols, fatty acids, and linoleic acids. LC/APPI-MS proves to be appropriate in detecting steroids, sphingolipids, some amino acids, nucleosides, and purines in plasma. CONCLUSIONS: It is suggested that the integrated ionization LC/MS approach should be applied for global plasma metabolomics. Moreover, the results obtained demonstrate that it is preferable to choose certain techniques from LC/ESI-MS, LC/APCI-MS, and LC/APPI-MS for metabolite target analysis.

Genetic polymorphisms in IL10RA and TNF modify the association between blood transfusion and risk of non-Hodgkin lymphoma.

We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes may modify the association between blood transfusion and risk of non-Hodgkin lymphoma (NHL). Compared with women without blood transfusion, women with a history of transfusion had an increased risk of NHL if they carried IL10RA (rs9610) GG genotype [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.1-3.2] or TNF (rs1800629) AG/AA genotypes (OR = 1.6, 95% CI: 0.9-2.7). We also found women with a history of transfusion had a decreased risk of NHL if they carried IL10RA (rs9610) AG/AA genotypes (OR = 0.6, 95% CI: 0.4-0.9) or TNF (rs1800629) GG genotype (OR = 0.7, 95% CI: 0.5-1.0). A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. Statistically significant interactions with blood transfusion were observed for IL10RA (rs9610) (P(forinteraction) = 0.003) and TNF (rs1800629) (P(forinteraction) = 0.012) for NHL overall and IL10RA (rs9610) (P(forinteraction) = 0.001) and TNF (rs1800629) (P(forinteraction) = 0.019) for B-cell lymphoma. The results suggest that genetic polymorphisms in TNF and IL10RA genes may modify the association between blood transfusion and NHL risk.

Human papillomavirus infection and sporadic breast carcinoma risk: a meta-analysis.

Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between HPV infection and risk of breast carcinoma, the studies remain inconclusive. Here, a meta-analysis was conducted to estimate the prevalence of HPV in breast carcinoma and test the association. Studies on HPV DNA detection in sporadic breast carcinoma in female using polymerase chain reaction were included. Information on overall and type-specific (HPV 6, 11, 16, 18, 31, 33, 35, 45 and 51) HPV prevalence were required, plus detailed descriptions of study populations, HPV DNA source, publication calendar period and PCR primers used for HPV DNA detection and typing. We revealed that 24.49% of the breast carcinoma cases were associated with HPV, 32.42% occurred in Asia and 12.91% in Europe. The four most commonly identified HPV types, in the order of decreased prevalence, were HPV33, 18, 16, and 35. The detection of HPV was mostly influenced by publication calendar period and PCR primers used. In addition, the analysis of ten case-control studies containing 447 breast carcinoma cases and 275 controls showed a significant increase in breast carcinoma risk with HPV positivity (OR = 3.63, 95% CI = 1.42-9.27). These results suggest that it's difficult to rule out the possibility of the association of HPV and breast carcinoma at present according to available publication proofs.

[Expression pattern of E-cadherin and p120-catenin in infiltrating lobular carcinoma and ductal carcinoma of the breast and its significance].

OBJECTIVE: To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC), and observe the different expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs. METHODS: The patients with ILC admitted to our hospital from Jan 1999 to Dec 2006 and patients with IDC from Jan 2000 to Dec 2000 were included in this study. All their pathological slides were reviewed, and their clinical data and treatment variables were analyzed retrospectively. Then the expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs were detected by immunohistochemistry on tissue microarray. RESULTS: The 5-year overall survival was 81.7% for ILCs and 79.1% for IDCs (P = 0.055). The 5-year disease-free survival was 61.8% for ILCs and 83.7% for IDCs (P < 0.001). Cytoplasmic localization of p120-catenin and loss of E-cadherin expression were more common in ILCs than in IDCs. The complete losses of E-cadherin in ILCs and IDCs were 55.6% (20/36) and 20.4% (45/221, P < 0.001), respectively. The p120-catenin showed a diffuse cytoplasmic localization in 66.7% (24/36) of ILCs and 16.3% (36/221) of IDCs (P < 0.001). Interestingly, the cytoplasmic localization of p120-catenin was clearly associated with the absence of E-cadherin expression in ILCs (P = 0.002), cytoplasmic localization of p120-catenin and absence of E-cadherin expression were observed 55.6% (20/36) in ILCs compared with 4.1% (9/221) in IDCs (P < 0.001). CONCLUSION: ILC has several specific biological and prognostic characteristics which are different in IDC. Different expression patterns of E-cadherin and p120-catenin proteins can be helpful to recognize ILC from IDC.

[Clinicopathological characteristics and prognosis of patients with breast cancer over 65 years of age].

OBJECTIVE: To study clinicopathological characteristics and prognosis of elderly women with breast cancer. METHODS: The data of 399 patients with breast cancer over 65 years of age was analyzed retrospectively in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1989 to December 2003. RESULTS: Curative resection was performed for all patients, including modified radical mastectomy 277 (69.4%), radical mastectomy 12 (3.0%), breast-conserving therapy 59 (15.8%), mammectomy 24 (6.0%), breast segmentectomy 25 (6.3%) and breast segmentectomy with sentinel node biopsy 2 (0.5%). Major pathological type was invasive ductal carcinoma (337/399, 85.5%). The positive rates of estrogen receptor (ER) and progesterone receptor (PR) were 71.4% and 69.6%, respectively. The overall 5-and 10- year survival rates were 78.9% and 56.3%, respectively. Univariate analysis showed that ER status, PR status, T stage, lymph node status and histological grade were significant statistically (P < 0.05). The multivariate analysis showed ER status, lymph node status and histological grade were the independent prognostic factors. CONCLUSION: Elderly women with breast cancer should be given multimodality therapy. Surgery and endocrine therapy are crucial, but the surgical style should be individuation. ER status, lymph node status and histological grade were the independent prognostic factors.

Towards well-defined MoS2 nanoribbons on a large scale.

High quality molybdenum dioxide plates are engineered as templates for epitaxial growth of well-defined MoS2 nanoribbons (MNRs). The obtained MNRs possess prominent ferromagnetism, suggesting edge zigzag topologies. Our findings have opened an alternative route to large-scale synthesis of well-defined 1D materials.

Characteristics of malignant tumors in 230 husband-wife pairs.

The aim of this study is to obtain a reference point for early detection of tumors in individuals whose spouses were diagnosed with malignant tumors. Data from 230 husband and wife pairs with malignant tumors were collected and analyzed from the family history records of 15,000 people who came to the Department of Cancer Prevention, Cancer Institute/Hospital, Chinese Academy of Medical Sciences for cancer screening between January 2009 and May 2012. The median diagnosis age was 67 years for husbands and 65 years for wives. A total of 214 cases (46.5 %) had digestive system malignancies. Respiratory system cancers were diagnosed in 64 husbands, of whom 20 (31.3 %) had spouses also with respiratory system cancer. Lung cancer ranked first for the females. The total number of lung cancer and commonly seen female-specific cancers (breast, ovarian, uterine, and cervical) was 127 (55.2 %). The difference in age at diagnosis between spouses was less than 10 years in 134 couples (58.3 %), while 77 (33.5 %) couples had an age difference less than 5 years. A family history of malignant tumors in first-degree relatives was documented in 48.3 % of the husbands and 48.7 % of the wives. The occurrence of cancer in both spouses of the couples studied resulted from an interaction between genetic and environmental factors. Nonhereditary factors such as diet, smoking, passive smoking, and air pollution also contributed to the development of cancers. It is recommended that when husband is diagnosed with cancer, the wife should be screened focusing on lung, breast, and gynecological cancers. If the wife was diagnosed with malignant disease, then screening for lung and digestive system cancers should be emphasized in the husband.

The risk of second cancers after diagnosis of primary thyroid cancer is elevated in thyroid microcarcinomas.

BACKGROUND: Thyroid cancers have increased dramatically over the past few decades. Comorbidities may be important, and previous studies have indicated elevated second cancer risk after initial primary thyroid cancers. This study examined the risk of second cancers after development of a thyroid cancer, primary utilizing the Surveillance, Epidemiology, and End Results (SEER) program database. METHODS: The cohort consisted of men and women diagnosed with first primary thyroid cancer who were reported to a SEER database in 1973-2008 (n=52,103). Standardized incidence ratios (SIR) were calculated for all secondary cancers. Confidence intervals and p-values are at 0.05 significance alpha level and are two-sided based on Poisson exact methods. RESULTS: In this cohort, 4457 individuals developed second cancers. The risk of developing second cancers after a primary thyroid cancer varied from 10% to 150% depending on different cancer types. Cancers in all sites, breast, skin, prostate, kidney, brain, salivary gland, second thyroid, lymphoma, myeloma, and leukemia were elevated. The magnitude of the risk varied by histology, tumor size, calendar year of first primary thyroid cancer diagnosis, and the treatment of the primary thyroid cancer. The risk of a second cancer was elevated in patients whose first primary thyroid carcinomas were small, or were diagnosed after 1994, or in whom some form of radiation treatment was administered. CONCLUSIONS: This large population-based analysis of second cancers among thyroid cancer patients suggests that there was an increase of second cancers in all sites, and the most commonly elevated second cancers were the salivary gland and kidney. Additionally, the increase in second cancers in patients with recently diagnosed thyroid microcarcinomas (<10 mm) suggests that aggressive radiation treatment of the first primary thyroid cancer, the environment, and genetic susceptibility, may increase the risk of a second cancer.

Occupational solvent exposure, genetic variation of DNA repair genes, and the risk of non-Hodgkin's lymphoma.

The main objective of this study was to test the hypothesis that genetic variations in DNA repair genes may modify the association between occupational exposure to solvents and the risk of non-Hodgkin's lymphoma (NHL). A population-based case-control study was conducted on Connecticut women including 518 histologically confirmed incident NHL cases and 597 controls. Unconditional logistic regression models were used to estimate the odds ratios and effect modification from the 30 single nucleotide polymorphisms in 16 DNA repair genes of the association between solvent exposure and the risk of NHL overall and subtypes. Single nucleotide polymorphisms in MGMT (rs12917) and NBS1 (rs1805794) significantly modified the association between exposure to chlorinated solvents and the risk of NHL (Pfor interaction=0.0003 and 0.0048, respectively). After stratification by major NHL histological subtypes, MGMT (rs12917) modified the association between chlorinated solvents and the risk of diffuse large B-cell lymphoma (Pfor interaction=0.0027) and follicular lymphoma (Pfor interaction=0.0024). A significant interaction was also observed between occupational exposure to benzene and BRCA2 (rs144848) for NHL overall (Pfor interaction=0.0042). Our study results suggest that genetic variations in DNA repair genes modify the association between occupational exposure to solvents and the risk of NHL.

Polymorphisms in Th1/Th2 cytokine genes, hormone replacement therapy, and risk of non-Hodgkin lymphoma.

We conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between hormone replacement therapy (HRT) and risk of non-Hodgkin lymphoma (NHL). Compared to women without a history of HRT use, women with a history of HRT use had a significantly decreased risk of NHL if they carried IFNGR2 (rs1059293) CT/TT genotypes (OR = 0.5, 95%CI: 0.3-0.9), IL13 (rs20541) GG genotype (OR = 0.6, 95%CI: 0.4-0.9), and IL13 (rs1295686) CC genotype (OR = 0.6, 95%CI: 0.4-0.8), but not among women who carried IFNGR2 CC, IL13 AG/AA, and IL13CT/TT genotypes. A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. A statistically significant interaction was observed for IFNGR2 (rs1059293 P(for interaction) = 0.024), IL13(rs20541 P(for interaction) = 0.005), IL13 (rs1295686 P(for interaction) = 0.008), and IL15RA (rs2296135 P(for interaction) = 0.049) for NHL overall; IL13 (rs20541 P(for interaction) = 0.0009), IL13(rs1295686 P(for interaction) = 0.0002), and IL15RA (rs2296135 P(for interaction) = 0.041) for B-cell lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between HRT and NHL risk.

[Correlation of peripheral blood micrometastasis to distant metastasis of breast cancer].

BACKGROUND & OBJECTIVE: Breast cancer, a whole body disease, can metastasize at early stage. This study was to explore the correlation of peripheral blood cancer cell (PBCC) content to distant metastasis of breast cancer. METHODS: The PBCC content of 65 breast cancer patients and 8 healthy donors was detected by multi-parameter flow cytometry (FCM) with CD45 and cytokeratin staining. RESULTS: Cancer cells were detected in peripheral blood samples from 57 of the 65 patients; the positive rate was 87.7%. No cancer cell was found in peripheral blood samples from healthy donors. The positive rate of PBCCs was correlated to T stage (r=0.271,P=0.017) and N stage (r=0.393, P=0.002). The patients were followed for 5 years; 2 were lost. Distant metastasis was found in 25 patients with PBCCs. In contrast, no metastasis was found in 8 patients without PBCCs (P<0.05). CONCLUSION: Preoperative PBCC content is closely related to distant metastasis of breast cancer. The detection of PBCCs might be useful for individual treatment decision for breast cancer.