Are serial CA 19-9 kinetics helpful in predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin?

Background: Serial kinetics of serum CA 19-9 levels have been reported to reflect response and survival in patients with pancreatic cancer undergoing surgery, radiotherapy, and chemotherapy. We prospectively studied serial kinetics of serum CA 19-9 levels of patients with locally advanced or metastatic disease treated with gemcitabine and cisplatin. Patients and Methods: Enrolled in the study were 87 patients (female/male = 26/61; stage III/IV disease = 24/63). Patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 50 mg/m(2) on days 1 and 15, every 4 weeks. Serum samples were collected at the onset of chemotherapy and before the start of a new treatment cycle (day 28). Results: 77 of 87 patients (88.5%) with initially elevated CA 19-9 levels were included for evaluation. According to imaging criteria, 4 (5.2%) achieved a complete remission and 11 (14.3%) achieved partial remission, yielding an overall response rate of 19.5%. 43 (55.8%) patients were CA 19-9 responders, defined by greater than or equal to50% decrease in CA 19-9 serum levels within 2 months after treatment initiation. Except for one, all patients who had responded by imaging criteria (n = 14) fulfilled the criterion of a CA 19-9 responder. Despite being characterized as non-responders by CT-imaging criteria (stable/progressive disease), 29 patients were classified as CA 19-9 responders (positive predictive value 32.5%). Independent of the response evaluation by CT, CA 19-9 responders survived significantly longer than CA 19-9 non-responders (295 d; 95% CI: 285-445 vs. 174 d; 95% CI: 134-198; p = 0.022). Conclusion: CA 19-9 kinetics in serum serve as an early and reliable indicator of response and help to predict survival in patients with advanced pancreatic cancer receiving effective treatment with gemcitabine and cisplatin

Комплексная эколого-геохимическая оценка состояния природной среды на территории г. Горняк (Алтайский край)

Объектом исследования является территория г. Горняк (Алтайский край). Предметом исследования являются компоненты природной среды (волосы, накипь, почва, материал хвостохранилищ и листья тополя). Цель работы – изучить элементный состав природной среды и организма человека на территории г. Горняк (Алтайский край).The object of the study is the territory of the town of Gornyak (Altai Territory). The subject of the study is the components of the natural environment (hair, scale, soil, tailings material and poplar leaves). The purpose of the work is to study the elemental composition of the natural environment and the human body in the city of Gornyak (Altai Territory)

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

Small molecule splicing modifiers have been previously described that target the general splicing machinery and thus have low specificity for individual genes. Several potent molecules correcting the splicing deficit of the SMN2 (survival of motor neuron 2) gene have been identified and these molecules are moving towards a potential therapy for spinal muscular atrophy (SMA). Here by using a combination of RNA splicing, transcription, and protein chemistry techniques, we show that these molecules directly bind to two distinct sites of the SMN2 pre-mRNA, thereby stabilizing a yet unidentified ribonucleoprotein (RNP) complex that is critical to the specificity of these small molecules for SMN2 over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work has wide-ranging implications in understanding how small molecules can interact with specific quaternary RNA structures

Predictors of overweight and obesity in five to seven-year-old children in Germany: Results from cross-sectional studies

BACKGROUND: Childhood obesity is a serious public health problem and epidemiological studies are important to identify predictive factors. It is the aim of this study to analyse factors associated with overweight/obesity in samples of German children. METHODS: 35,434 five to seven year-old children (50.9% boys) participated in cross-sectional studies between 1991 and 2000 in several rural and urban areas in East and West Germany. Weight and height were measured and body mass index was calculated. International cut-off points, recommended by the International Obesity Task Force, were used to classify childhood overweight and obesity. Predictive modelling was employed to analyse independently associated factors, using logistic regression to adjust for confounding. RESULTS: 15.5% were overweight, and 4.3% were obese. Female sex, other than German nationality, smoking in the living place and increasing birth weight were found to increase the odds of overweight and obesity, while increasing educational level, living space > 75 m2 and breastfeeding for more than three months were inversely associated. CONCLUSION: The findings add to the evidence informing public health action, both through health promotion strategies (promoting breastfeeding, tackling smoking) and wider societal change management (addressing children from migrant families and families with low educational level)

Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status

<p>Abstract</p> <p>Background</p> <p>Oncoprotein HCCR-1 functions as a negative regulator of the p53 and contributes breast tumorigenesis. The serum HCCR-1 assay is useful in diagnosing breast cancer and mice transgenic for HCCR developed breast cancers. But it is unknown how <it>HCCR-1 </it>contributes to human breast tumorigenesis.</p> <p>Methods</p> <p>Oncogene HCCR-1 expression levels were determined in normal breast tissues, breast cancer tissues and cancer cell lines. We examined whether HCCR-1 protein expression in breast cancer is related to different biological characteristics, including ER, PR, p53 genotype, and HER2 status in 104 primary breast cancer tissues using immunohistochemical analyses.</p> <p>Results</p> <p>HCCR-1 was upregulated in breast cancer cells and tissues compared with normal breast tissues. In this study, overexpression of HCCR-1 was well correlated with known breast cancer prognostic markers including the presence of steroid receptors (ER and PR), p53 mutation and high HER2 overexpression. HCCR-1 was not detected in the ER-negative, PR-negative, p53 negative and low HER2 breast cancer tissues. These data indicate that the level of HCCR-1 in breast cancer tissues is relatively well correlated with known breast cancer factors, including the HER2 overexpression, p53 mutation, and ER/PR status.</p> <p>Conclusion</p> <p>Determination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation.</p

Family-based factors associated with overweight and obesity among Pakistani primary school children

<p>Abstract</p> <p>Background</p> <p>Childhood obesity epidemic is now penetrating the developing countries including Pakistan, especially in the affluent urban population. There is no data on association of family-based factors with overweight and obesity among school-aged children in Pakistan. The study aimed to explore the family-based factors associated with overweight and obesity among Pakistani primary school children.</p> <p>Methods</p> <p>A population-based cross-sectional study was conducted with a representative multistage cluster sample of 1860 children aged five to twelve years in Lahore, Pakistan. Overweight (> +1SD BMI-for-age z-score) and obesity (> +2SD BMI-for-age z-score) were defined using the World Health Organization reference 2007. Chi-square test was used as the test of trend. Linear regression was used to examine the predictive power of independent variables in relation to BMI. Logistic regression was used to quantify the independent predictors of overweight and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. All regression analyses were controlled for age and gender and statistical significance was considered at P < 0.05.</p> <p>Results</p> <p>Significant family-based correlates of overweight and obesity included higher parental education (P < 0.001), both parents working (P = 0.002), fewer siblings (P < 0.001), fewer persons in child's living room (P < 0.001) and residence in high-income neighborhoods (P < 0.001). Smoking in living place was not associated with overweight and obesity. Higher parental education (P < 0.001) and living in high-income neighborhoods (P < 0.001) showed a significant independent positive association with BMI while greater number of siblings (P = 0.001) and persons in child's living room (P = 0.022) showed a significant independent inverse association. College-level or higher parental education as compared to high school-level or lower parental education (aOR 2.54, 95% CI 1.76-3.67), living in high-income neighborhoods as compared to low-income neighborhoods (aOR 2.13, 95% CI 1.31-3.46) and three or less siblings as compared to more than three siblings (aOR 1.75, 95% CI 1.26-2.42) were significant independent predictors of overweight.</p> <p>Conclusion</p> <p>Family-based factors were significantly associated with overweight and obesity among school-aged children in Pakistan. Higher parental education, living in high-income neighborhoods and fewer siblings were independent predictors of overweight. These findings support the need to design evidence-based child health policy and implement targeted interventions, considering the impact of family-based factors and involving communities.</p

Detection of Ki-ras mutations in tissue and plasma samples of patients with pancreatic cancer using PNA-mediated PCR clamping and hybridisation probes

In the present study, we combined the PCR-clamping approach with melting curve analysis using mutant specific hybridisation probes and wild-type specific peptide nucleic acids (PNAs) to determine the genotypes of the most frequent point mutation in codon 12 of the proto-oncogene Ki-ras in tissue and plasma samples of patients with pancreatic cancer. The sensitivity of our assay was 1–5 × 10−5. The melting curve analysis of tissue samples of four patients revealed two valine mutations, one none-valine mutation and one wild-type sequence. Ki-ras alterations were found in 28% of DNAs (18 out of 64) of nonrelated plasma samples of 10 patients with ductal adenocarcinoma of the pancreas. The valine mutation was the predominantly detected gene alteration (83%). Out of ten patients investigated, four patients (40%) became positive during clinical observation with respect to Ki-ras mutation. All four patients exhibited progressive disease and high levels of tumour marker CA 19-9. In conclusion, the one-step procedure discribed may be a useful clinical tool for analysing Ki-ras point mutations in tissue and plasmas samples. In addition, this method can be adapted for simultanous detection of multiple mutations and quantitation