Both baseline CTC number and change in CTC number after one cycle of chemotherapy are independent prognostic factors for SCLC. Molecular comparison of CTCs to cells in CTM may provide novel insights into SCLC biology.
Recent advances in technology now permit robust and reproducible detection of circulating tumour cells (CTCs) from a simple blood test. Standardization in methodology has been instrumental in facilitating multicentre trials with the purpose of evaluating the clinical utility of CTCs. We review the current body of evidence supporting the prognostic value of CTC enumeration in breast, prostate and colorectal cancer, using standardized approaches, and studies evaluating the correlation of CTC number with radiological outcome. The exploitation of CTCs in cancer management, however, is now extending beyond prognostication. As technologies emerge to characterize CTCs at the molecular level, biological information can be obtained in real time, with the promise of serving as a 'surrogate tumour biopsy'. Current studies illuminate the potential of CTCs as pharmacodynamic and predictive biomarkers and potentially their use in revealing drug resistance in real time. Approaches for CTC characterization are summarized and the potential of CTCs in cancer patient management exemplified via the detection of epidermal growth factor receptor mutations from CTCs in patients with non-small cell lung cancer. The opportunity to learn more about the biology of metastasis through CTC analysis is now being realized with the horizon of CTC-guided development of novel anticancer therapies.
The breaking of immune tolerance of "selfantigens" associated with angiogenesis is an attractive approach to cancer therapy by active immunity. We used vascular endothelial growth factor receptor-2 (VEGFR-2) as a model antigen to explore the feasibility of the immunotherapy with a vaccine based on a xenogeneic homologous protein.
We introduce a novel computational approach, CoReCo, for comparative metabolic reconstruction and provide genome-scale metabolic network models for 49 important fungal species. Leveraging on the exponential growth in sequenced genome availability, our method reconstructs genome-scale gapless metabolic networks simultaneously for a large number of species by integrating sequence data in a probabilistic framework. High reconstruction accuracy is demonstrated by comparisons to the well-curated Saccharomyces cerevisiae consensus model and large-scale knock-out experiments. Our comparative approach is particularly useful in scenarios where the quality of available sequence data is lacking, and when reconstructing evolutionary distant species. Moreover, the reconstructed networks are fully carbon mapped, allowing their use in 13C flux analysis. We demonstrate the functionality and usability of the reconstructed fungal models with computational steady-state biomass production experiment, as these fungi include some of the most important production organisms in industrial biotechnology. In contrast to many existing reconstruction techniques, only minimal manual effort is required before the reconstructed models are usable in flux balance experiments. CoReCo is available at http://esaskar.github.io/CoReCo/.
The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.
The effects of maternal hypothyroidism on neonatal outcomes were not definitely confirmed. We conduct a systematic review of the literatures on the impact of maternal hypothyroidism on neonatal outcomes. We searched Pubmed, Embase and the Cochrane Controlled Trials Register databases complemented by manual searches in article references without language restrictions published from 1946 to April 2015. Nine trials are included. For preterm birth in pregnancies of hypothyroidism women, there is an increased tendency (RR 1.18; 95% CI 0.99 to 1.40; p = 0.06). The same result is seen relating to the low birth weight (RR 1.31; 95% CI 1.00 to 1.72; p = 0.05). Regarding small for gestational age there is no significant increase. Children who were born from mothers with hypothyroidism during pregnancy have increased birth weight (MD 32.35, 95% CI 7.46 to 57.24; p = 0.01). The impact of maternal hypothyroidism shows a trend of reduced risk of large for gestational age (RR 1.17; 95% CI 0.99 to 1.38; p = 0.06). Our review suggests that mothers with hypothyroidism during pregnancy are more likely to give birth to children with higher birth weight or LGA, and L-T4 supplementation should be recommended. The risk of preterm birth and low birth weight also tends to be higher in children with hypothyroidism mothers.
Bromocriptine-QR (quick release) is a novel treatment for type 2 diabetes. The objective of this study is to assess the efficacy and safety of bromocriptine-QR in adults with type 2 diabetes mellitus based on randomized controlled trials published in peer-reviewed journals or as abstracts. We performed a comprehensive literature search of MEDLINE, Pubmed, Web of Science, EMBASE, and the Cochrane Library up to May 2015. Randomized controlled trials of bromocriptine-QR therapy in type 2 diabetes mellitus were eligible. Two reviewers independently assessed the eligibility of trials based on predefined inclusion criteria. Information was collected concerning basic study data, patient characteristics, efficacy and safety outcomes, and methodological quality. Bromocriptine-QR add-on therapy lowered hemoglobin A1c compared with placebo (weighted mean difference, - 6.52 mmol/mol; 95% CI, - 8.07 to - 4.97 mmol/mol). Bromocriptine-QR exhibited an increase in achieving an HbA1c level ≤ 53 mmol/mol (≤ 7.0%) (32.0 vs. 9.5%; odds ratio, 4.57; 95% CI, 2.42-8.62). Fasting plasma glucose was reduced with bromocriptine-QR compared with placebo (weighted mean difference,-1.04 mmol/l; 95% CI,-1.49 to-0.59 mmol/l). Moreover, bromocriptine-QR had neutral effects on postprandial glycemia, Body Mass Index (BMI), and lipid profile. Bromocriptine-QR had more gastrointestinal side effects of nausea and vomiting. Bromocriptine-QR had no increased risk of hypoglycemia, hypotension, or cardiovascular effects. Bromocriptine-QR therapy offers an alternative option to currently available antidiabetic agents for type 2 diabetes mellitus adults. Neither hypoglycemia nor other metabolic changes occur with this drug. More data for long-term efficacy and safety are needed for further observation.
Objective to evaluate the modified NUTRIC score in identifying nutritional risk patients and predicting mortality in septic shock patients. Methods A retrospective study was performed with septic shock patients admitted to the intensive care unit (ICU) from January 2018 to December 2019. A receiver operating characteristic (ROC) curve was used to identify the performance of the instruments to predict mortality. Results Among the patients, 46 patients were non-survivors and 78 were survivors. The median mNUTRIC score was 5.41±1.69 vs 4.29±1.58(P<0.0001). 28-day mortality increased with higher modified NUTRIC score. In the ROC curve of mNUTRIC score, the best cut-off point was at 4. It was identified for our sample, showing the best parameters of both sensitivity and specificity for the prediction of mortality 28 days after ICU admission. The area under the curves (AUCs) of the mNUTRIC score for predicting 28-day mortality was 0.664(95%CI:0.574, 0.746). Conclusions The modified NUTRIC score was a good nutritional risk assessment tool for septic shock patients. mNUTRIC score showed a good performance for the prediction of 28-day mortality. A new cutoff value was identified for septic shock patients.
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