Gastrointestinal malignancies are among the leading causes of cancer-related deaths worldwide. Like all human malignancies they are characterized by accumulation of mutations which lead to inactivation of tumor suppressor genes or activation of oncogenes. Advances in Molecular Biology techniques have allowed for more accurate analysis of tumors’ genetic profiling using new breakthrough technologies such as next generation sequencing (NGS), leading to the development of targeted therapeutical approaches based upon biomarker-selection. During the last 10 years tremendous advances in the development of targeted therapies for patients with advanced cancer have been made, thus various targeted agents, associated with predictive biomarkers, have been developed or are in development for the treatment of patients with gastrointestinal cancer patients. This review summarizes the advances in the field of molecular biomarkers in tumors of the gastrointestinal tract, with focus on the available NGS platforms that enable comprehensive tumor molecular profile analysis. 相似文献
Socioeconomic factors cannot entirely explain why black women have an earlier age of breast cancer onset and higher mortality rates, stage for stage, than whites. We and others have shown that prostate-specific antigen [PSA, also known as human kallikrein (hK) 3] is a marker of breast as well as prostate cancer, that hK2 and hK3 are highly homologous at the DNA and protein level and that the level of progesterone, which appears to upregulate hK3, is influenced by ethnicity. We hypothesized that nipple aspiration fluid (NAF) hK2 and hK3 levels are (i) lower in black than white women; (ii) independently associated with breast cancer; (iii) influenced by menopausal status; and (iv) in combination are more informative about whether a woman has breast cancer than either marker alone. NAF was assayed for hK2 and hK3, and the results were stratified by ethnicity, presence or absence of cancer and menopausal status. Statistical analysis was then performed. When stratified by ethnicity, hK2 (p = 0.003) and hK3 (p = 0.027) levels in blacks were lower than in whites. hK2 was lower in premenopausal black than in white subjects, regardless of cancer status. Overall, hK2, hK3 and the ratio hK2/hK3 were lower in subjects with breast cancer than in normal subjects. hK3 was lower in postmenopausal women with breast cancer, regardless of ethnicity. hK2 and hK3 levels were higher in pre- than in postmenopausal whites. Using logistic regression and considering hK2, hK3, hK2/hK3 and ethnicity, hK3 was significantly associated with breast cancer in both pre- (p < 0.001) and postmenopausal women (p = 0.023). In conclusion, whereas hK2, hK3, hK2/hK3 and ethnicity are each significantly associated with breast cancer bivariately, after entering the strongest predictor, hK3, into a logistic regression model, no other variable accounted for additional variation, although this observation is preliminary due to the limited number of black subjects in the study. 相似文献
BACKGROUND: Limited data are available on the genetic events underlying gastric cancer. Studying a few cases by conventional cytogenetic techniques, we previously reported that chromosome 8 might be frequently involved. The aim of our study was to evaluate the numerical aberrations of chromosome 8 in gastric cancer using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: FISH, with an a-satellite DNA probe specific for chromosome 8, was applied to 37 primary gastric tumors directly processed for cytogenetic study. RESULTS: Numerical aberrations of chromosome 8 were observed in 23 out of 37 tumors (62.16%). Trisomy was detected in 16 cases (43.24%), tetrasomy in 4 cases (10.81%) and monosomy in 3 cases (8.10%). No correlation was found between polysomy 8 and the histopathologic characteristics of the tumors. CONCLUSION: An increase in the number of chromosome 8 may frequently occur in gastric cancer. Advanced and more aggressive gastric tumors did not harbor polysomy 8. Further studies at molecular and clinical level must be carried out to identify the gene alterations reflected by polysomy 8 and possibly to facilitate the detection of specific tumors subtypes. 相似文献
The presence of ciprofloxacin resistance commensal Escherichia coli (C-R-Ec) was determined for goats in the absence of selective pressure in Northern and Central Greece. The C-R-Ec was categorized in 3 groups with respect to their phenotypic resistance to other antibiotics as well as the carriage of antibiotic resistance genes. The first group consisted of 7 C-R-Ec that were found also resistant to tetracycline. Among them tet(B) (n = 7), qnr(S) (n = 7), and qnr(B) (n = 3) producers were identified by polymerase chain reaction. The second group consisted of 10 C-R-Ec that were found sensitive to all other antibiotics, and their phenotypic resistance to ciprofloxacin was not attributed to the presence of resistance genes. Finally, the third group consisted of 2 C-R-Ec also resistant to sulfamethoxazole. These strains were not carrying any transferable elements that contribute to resistance either to ciprofloxacin or to sulfamethoxazole. This is the first report of ciprofloxacin-resistant E. coli isolated from goats in Greece. 相似文献
Genetic variation can directly cause or increase susceptibility to neurologic diseases. An explosion of new genetic technologies has enabled the characterization of specific genes responsible for many neurologic diseases and has provided fundamentally new insight into their pathophysiology. These advancements, along with recent breakthroughs in gene therapy, are beginning to result in the translation of an individual's genetic sequence into targeted treatment strategies. This review aims to introduce key genetic concepts and to illustrate how these principles apply in cases of rare, single-gene neurologic diseases as well as more common, polygenic diseases that are encountered frequently in clinical practice. 相似文献
Background/aims: To study the correlation between stinging and skin barrier and to make the lactic acid stinging test much safer. Methods: The modified lactic acid stinging test with 3% and/or 5% aqueous solution of lactic acid combined with transepidermal water loss (TEWL) and capacitance (CAP) was used. The amount of 50 µL-test material was applied on test areas, the skin of both sides nasolabial fold of 50 healthy subjects. Subjects assessed stinging basing on a 4-point scale at 0, 2.5, 5.0 and 8 min TEWL and CAP were measured at baseline and 8 min. Results: The results show that the tendency of decrease in baseline CAP and increase in baseline TEWL are proportional with the increase of the sum of clinical scores (CSS) . In 5% lactic acid test, negative correlation between changing ratio of TEWL (PTEWL) and clinical score at 5 min (CS5 min), and negative correlation between changing ratio of capacitance (PCAP) and CS5 min are registered. Conclusion : Our data indicate that there is certain relationship between the degree of stinging and the skin barrier. The stinging test method modified by lower concentration aqueous lactic acid and the assessment combined with PTEWL and PCAP is suitable for Chinese to evaluate the skin susceptibility. 相似文献
Arsenic trioxide (As(2)O(3)) shows a significant therapeutic effect upon acute promyelocytic leukemia (APL) and can induce the apoptosis of NB(4) cells, which attracts scholars' great attention. Especially, the therapeutic effect on solid carcinoma has been paid more close attention to. The present study is to evaluate the effect of As(2)O(3) on human colorectal carcinoma cells (LS-174T cell) and the activity of telomerase in vitro and in vivo. This research made use of the electron microscope, polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), fluorescence-activated cell sorter (FACS), MTT in vitro and in vivo (LS-174T xenograft model of nude mice). With the increasing concentration of As(2)O(3), the ratio of living cells to dead cells decreased significantly, and the IC(50) value was 5.23mumol/L; cells of the experimental groups endured a series of morphological changes similar to the features of apoptosis. Apoptosis curve of FACS pictures appeared after 24h, and the cells showed apoptosis in a time-dependent manner; As(2)O(3) can inhibit the activity of telomerase of the cell extraction, obviously, in a concentration-dependent and time-dependent manner after 24h. As to the inhibition impact of As(2)O(3) on the xenograft model of nude mice in the two indexes, tumor volume and weight, there was a significant difference between As(2)O(3) and the control group; there was no difference between As(2)O(3) and the fluorouracil (5-FU) group; in the group of peritoneal injections of As(2)O(3), the cancer cells connected loosely with each other, nucleus changed markedly, and heterochromatin concentrated under the nucleus membrane. From the in vitro and in vivo experiment, we can see that As(2)O(3) inhibited LS-174T cell growth mainly by inducing cell apoptosis, partly by the inhibition of telomerase activity. 相似文献
Background: In conscious humans, reduction in hemoglobin concentration to 5 g/dl did not produce inadequate systemic oxygenation. However, systemic measures of inadequate oxygenation may not be sufficiently sensitive to detect inadequate oxygenation in individual organs such as splanchnic organs. The authors tested the hypothesis that acute normovolemic anemia to hemoglobin less than 6.0 g/dl in anesthetized humans reduces splanchnic oxygen consumption because of diminished whole body oxygen delivery.
Methods: Elective spine (n = 12) and abdominal (n = 7) surgery patients underwent acute normovolemic anemia to decrease the hemoglobin concentration close to 6.0 g/dl. The authors assessed the development of supply-dependent conditions in systemic and regional vascular beds by two primary measures before and after acute normovolemic anemia: oxygen consumption and surrogate biochemical markers of anaerobic metabolism, including plasma lactate, regional lactate kinetics, and ketone body ratio.
Results: When hemoglobin was reduced from 13.6 +/- 1.2 to 5.9 +/- 0.3 g/dl, oxygen supply dependency occurred in the splanchnic and preportal tissues but not at the systemic level. Regional supply dependency was accompanied by biochemical markers of anaerobic metabolism. 相似文献