Establishment of serum protein pattern for screening colorectal cancer using SELDI-TOF-MS

Aim: The purpose of this study is to develop a proteomic pattern for distinguishing individuals with colorectal cancer from healthy controls and monitoring micrometastasis using SELDI-TOF-MS. Methods: A training set consisting of 63 patients with colorectal cancer, 20 patients with benign colorectal diseases and 26 healthy volunteers was used to develop a proteomic model that discriminated colorectal cancer effectively. The sensitivity and specificity of this model was validated by an independent test set. To explore serum proteins changed after operation, the protein profiles of 31 postoperative patients were compared with those of preoperative patients. We also analyzed protein profiles of patients with and without metastasis to monitor micrometastasis. Results: Our study yielded a four-peak model (m/z: 3191.5, 3262.9, 3396.3 and 5334.4) that discriminated cancer from non-cancer samples with sensitivity of 90.3% and specificity of 95.7%. This model was validated in the test set with sensitivity of 87.5% and specificity of 93.8% which was significantly better than the combination use of CEA, CA199 and CA242 (sensitivity 62.4%) for early detection of colorectal cancer. Two peaks (m/z: 2753.8 and 4172.4) were found down-regulated in postoperative samples comparing with preoperative samples. We also detected two proteins (m/z: 9184.4 and 9340.9) that can discriminate patients with primary colorectal cancer from metastatic colorectal cancer. Conclusions: The four-peak model and two peaks (m/z: 2753.8 and 4172.4) detected in this study have the potential for assistance in diagnostics and therapeutic strategies in colorectal cancer and the two proteins (m/z: 9184.4 and 9340.9) were effective biomarkers for monitoring micrometastasis.Цель: исследование белкового профиля сыворотки крови больных колоректальным раком и здоровых доноров методом SELDI-TOF-MS для диагностики заболевания и мониторинга микрометастазов. Методы: методом SELDI-TOF-MS исследованы сыворотки крови 63 больных колоректальным раком, 20 больных с доброкачественными новообразованиями прямой кишки и 26 — здоровых доноров. Проведено сравнение профилей белков сыворотки крови 31 больного до и после хирургического вмешательства, а также больных с метастазами или без таковых. Результаты: получена 4-пиковая модель (m/z: 3191,5; 3262,9; 3396,3 и 5334,4), позволяющая отличить опухолевые образцы от неопухолевых с чувствительностью 90,3% и специфичностью 95,7%. Такая модель проверена в тест-системе с чувствительностью 87,5% и специфичностью 93,8%, что является лучшим результатом, чем комбинированное применение CEA, CA199 и CA242 (чувствительность 62,4%) для раннего выявления колоректального рака. Выявлено снижение интенсивности двух пиков (m/z: 2753,8 и 4172,4) при сравнении образцов до и после проведения операции, и идентифицированы два белка (m/z: 9184,4 и 9340,9), позволяющие выявлять больных колоректальным раком с метастазами. Выводы: полученная мо

Transgenic and Knockout Mice Models to Reveal the Functions of Tumor Suppressor Genes

Cancer is caused by multiple genetic alterations leading to uncontrolled cell proliferation through multiple pathways. Malignant cells arise from a variety of genetic factors, such as mutations in tumor suppressor genes (TSGs) that are involved in regulating the cell cycle, apoptosis, or cell differentiation, or maintenance of genomic integrity. Tumor suppressor mouse models are the most frequently used animal models in cancer research. The anti-tumorigenic functions of TSGs, and their role in development and differentiation, and inhibition of oncogenes are discussed. In this review, we summarize some of the important transgenic and knockout mouse models for TSGs, including Rb, p53, Ink4a/Arf, Brca1/2, and their related genes

Detection of polymorphisms and protein domain architectures in rabbit toll-like receptor 2

[EN] Toll-like receptors (TLRs) recognise pathogen-associated molecular patterns (PAMPs) derived from pathogens and participate in activation of the immune responses. The TLR2 gene can recognise PAMPs specific to bacterial diseases such as pneumonia. In the present study, we sequenced the coding regions of the TLR2 gene in 18 rabbits from 5 breeds, including New Zealand White, Californian, Flemish Giant, Chinchilla and Fu Jian Yellow. In total, we discovered 11 single nucleotide polymorphisms (SNPs), including 4 non-synonymous SNPs located within the predicted TLR domains. Two non-synonymous SNPs (G205A and G265C) were located in the LRR (leucine-rich repeat) domains of the predicted protein, while another non-synonymous SNP (C943T) was situated in the regions involved in binding to ligands. In addition, one synonymous SNP (C1174T) was distributed in the nucleus regions of heterodimers formed. Then, we revealed five conservative regions in the LRR patterning by prediction and comparison of TLR2 protein domain architectures for multiple species. The SNPs in the TLR2 gene may increase the probability of adaptation to variability of PAMPs due to the rapid evolution of pathogens and the possibility of survival in rabbit populations. The SNPs reported here will be useful to investigate the association between the TLR2 gene and disease resistance in future studies.This work was supported by funding from Sichuan Animal Science Academy and Applied Basic Research Programmes of the Science and Technology Foundation of Sichuan Province.Zhang, X.; Lei, M.; Xie, L.; Zhang, C.; Zheng, J.; Yang, C.; Deng, XD.... (2014). Detection of polymorphisms and protein domain architectures in rabbit toll-like receptor 2. World Rabbit Science. 22(1):83-90. doi:10.4995/wrs.2014.1457SWORD839022

Partial wave analysis of J/\psi \to \gamma \phi \phi

Using $5.8 \times 10^7 J/\psi$ events collected in the BESII detector, the radiative decay $J/\psi \to \gamma \phi \phi \to \gamma K^+ K^- K^0_S K^0_L$ is studied. The $\phi\phi$ invariant mass distribution exhibits a near-threshold enhancement that peaks around 2.24 GeV/$c^{2}$. A partial wave analysis shows that the structure is dominated by a $0^{-+}$ state ($\eta(2225)$) with a mass of $2.24^{+0.03}_{-0.02}{}^{+0.03}_{-0.02}$ GeV/$c^{2}$ and a width of $0.19 \pm 0.03^{+0.06}_{-0.04}$ GeV/$c^{2}$. The product branching fraction is: $Br(J/\psi \to \gamma \eta(2225))\cdot Br(\eta(2225)\to \phi\phi) = (4.4 \pm 0.4 \pm 0.8)\times 10^{-4}$.Comment: 11 pages, 4 figures. corrected proof for journa

Measurements of the observed cross sections for e+e−→e^+e^-\to exclusive light hadrons containing π0π0\pi^0\pi^0 at s=3.773\sqrt s= 3.773, 3.650 and 3.6648 GeV

By analyzing the data sets of 17.3, 6.5 and 1.0 pb$^{-1}$ taken, respectively, at $\sqrt s= 3.773$, 3.650 and 3.6648 GeV with the BES-II detector at the BEPC collider, we measure the observed cross sections for $e^+e^-\to \pi^+\pi^-\pi^0\pi^0$, $K^+K^-\pi^0\pi^0$, $2(\pi^+\pi^-\pi^0)$, $K^+K^-\pi^+\pi^-\pi^0\pi^0$ and $3(\pi^+\pi^-)\pi^0\pi^0$ at the three energy points. Based on these cross sections we set the upper limits on the observed cross sections and the branching fractions for $\psi(3770)$ decay into these final states at 90% C.L..Comment: 7 pages, 2 figure

Direct Measurements of Absolute Branching Fractions for D0 and D+ Inclusive Semimuonic Decays

By analyzing about 33 $\rm pb^{-1}$ data sample collected at and around 3.773 GeV with the BES-II detector at the BEPC collider, we directly measure the branching fractions for the neutral and charged $D$ inclusive semimuonic decays to be $BF(D^0 \to \mu^+ X) =(6.8\pm 1.5\pm 0.7)$ and $BF(D^+ \to \mu^+ X) =(17.6 \pm 2.7 \pm 1.8)$, and determine the ratio of the two branching fractions to be $\frac{BF(D^+ \to \mu^+ X)}{BF(D^0 \to \mu^+ X)}=2.59\pm 0.70 \pm 0.25$

A study of charged kappa in J/ψ→K±Ksπ∓π0J/\psi \to K^{\pm} K_s \pi^{\mp} \pi^0

Based on $58 \times 10^6$ $J/\psi$ events collected by BESII, the decay $J/\psi \to K^{\pm} K_s \pi^{\mp} \pi^0$ is studied. In the invariant mass spectrum recoiling against the charged $K^*(892)^{\pm}$, the charged $\kappa$ particle is found as a low mass enhancement. If a Breit-Wigner function of constant width is used to parameterize the kappa, its pole locates at $(849 \pm 77 ^{+18}_{-14}) -i (256 \pm 40 ^{+46}_{-22})$ MeV/$c^2$. Also in this channel, the decay $J/\psi \to K^*(892)^+ K^*(892)^-$ is observed for the first time. Its branching ratio is $(1.00 \pm 0.19 ^{+0.11}_{-0.32}) \times 10^{-3}$.Comment: 14 pages, 4 figure

Measurements of the observed cross sections for exclusive light hadron production in e^+e^- annihilation at \sqrt{s}= 3.773 and 3.650 GeV

By analyzing the data sets of 17.3 pb$^{-1}$ taken at $\sqrt{s}=3.773$ GeV and 6.5 pb$^{-1}$ taken at $\sqrt{s}=3.650$ GeV with the BESII detector at the BEPC collider, we have measured the observed cross sections for 12 exclusive light hadron final states produced in $e^+e^-$ annihilation at the two energy points. We have also set the upper limits on the observed cross sections and the branching fractions for $\psi(3770)$ decay to these final states at 90% C.L.Comment: 8 pages, 5 figur