RESUMEN

BACKGROUND: Colon cancer (CC) is the third most commonly diagnosed cancer in the USA. While the overall incidence is declining, it is rising alarmingly in young patients (EOCC). CC in young patients tends to be more aggressive and often diagnosed at more advanced stages and portend poorer prognosis. Our recently published data showed that EOCC is a distinct disease with unique molecular features compared to late-onset CC (LOCC). The Cartilage Oligomeric Matrix Protein (COMP) was shown to be significantly upregulated in EOCC and correlated with poor survival. However, the role of COMP in CC tumorigenesis, especially in young patients, is not well understood. Thus, the aim of this study was to elucidate the role of COMP in CC tumorigenesis by modulating COMP levels in vitro and test how it affects proliferation. Then, patient samples were evaluated by testing the levels of proliferation marker Ki67. In addition, this study investigates whether higher transcriptional mRNA levels of COMP seen in more aggressive early-onset CC correlate with protein levels compared to late-onset CC. METHODS: COMP mRNA levels in fresh frozen colon tumors (young: n = 5; old: n = 5) were assessed by quantitative PCR (qPCR). Additionally, CC cell lines were profiled for COMP expression to choose an in vitro model to study the role of COMP in CC tumorigenesis. HT-29 (low COMP expression) and CaCo-2 (high COMP expression) cells were used for in vitro proliferation studies. Immunohistochemical (IHC) analysis was conducted to assess COMP and Ki67 protein levels in formalin-fixed paraffin-embedded (FFPE) colon tumors. RESULTS: Significantly higher COMP expression levels were observed in fresh frozen EOCC compared to LOCC tumors. This observation confirmed our previously reported results from NanoString gene expression assay using FFPE samples. Cell proliferation was significantly increased in HT-29 and CaCo-2 cells upon treatment with human recombinant COMP protein after 48 and 72 h (P < 0.05). This increase was more profound in HT-29 cells. Staining for COMP and Ki67 revealed high COMP protein levels in EOCC compared to LOCC patients. CONCLUSION: COMP mRNA and protein levels are significantly higher in EOCC patients. Higher COMP levels correlate with increased proliferation suggesting a role in CC tumorigenesis.

Asunto(s)

RESUMEN

INTRODUCTION: Native Americans (NA) form a unique cohort of colon cancer (CC) patients among whom the variability in demographics and cancer characteristics remains unclear. METHODS: We abstracted the national estimates for NA with CC using the Surveillance, Epidemiology, and End Result (SEER) database. Trend analysis of incidence, variation in location and patient demographic analysis were performed. RESULTS: A total number of 26,674 NA with CC were reported during the 12-year study period. While the overall incidence of CC decreased by 12% during the study period, incidence increased by 38% in NA. Incidence of CC was more prevalent and higher increase (42%) seen in NA females than males (p = 0.02; 34%). Stage III tumors represented 29% of all CC, sigmoid colon the most common site location (38%) with 72% of all tumors being moderately differentiated. 55% tumors were localized in left, 36% in right and 9% in transverse colon. 92% of the NA were insured. CONCLUSION: Incidence of CC continues to rise in NA with majority of CC presented at higher stage and moderate differentiation.

Asunto(s)

RESUMEN

BACKGROUND: Overall declines in incidence of rectal cancer (RC) in patients older than 50 years have been mostly attributed to improvement in treatment modalities and introduction of age-based screening. Recent studies, however, have shown a rise in the incidence of RC in patients younger than 50 years. The etiology of early-onset (EO) RC is not well understood. The aim of this study is to elucidate the molecular features of (EO) RC and show its uniqueness compared to late-onset (LO) disease. METHODS: Two cohorts of patients with sporadic RC were identified. Tumors and matching non-involved tissues from six (EO) RC patients (< 50 years) and six (LO) RC patients (>65 years) were obtained from Pathology archives. Deparaffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for expression profiling of 770 cancer related genes representing 13 canonical pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05. RESULTS: When we compared rectal tumors to non-involved rectal tissues, changes in expression levels of 171 genes were statistically significant in early-onset group and 151 genes in late-onset group. Further comparative gene expression analysis between early- and late-onset rectal tumors normalized to their matching non-involved tissues revealed that changes in expression of 65 genes were unique to early-onset rectal tumors with 16 genes being up- and 49 genes down-regulated using the cutoff criteria of expression levels difference >2 fold and p-value <0.01. At the pathway level, MAPK signaling was the most deregulated pathway in early-onset rectal tumors compared to PI3K-AKT signaling pathway being the most deregulated in late-onset rectal tumors. CONCLUSIONS: Results of this study suggest that sporadic early-onset rectal cancer is characterized by distinct molecular events compared to late-onset disease.

RESUMEN

UNLABELLED: Lung cancer is one of the leading cause of cancer-related death around the world with the majority of diagnoses being non-small cell lung cancer (NSCLC). Given the poor survival rate and efficacy of current therapy for NSCLC, there is a need to identify and develop new therapeutic targets for treatment. We have observed significantly up-regulated levels of Fn14 in clinical samples of lung cancer relative to normal adjacent tissue. However, the functional role of Fn14 in these tumors is not understood yet. We used RT-PCR to establish the Fn14 expression profile in various NSCLC cell lines. Using isogenic variants of H460 NSCLC cell line with low, intermediate and high Fn14 expression as a cellular model, we determined that increased levels of integrin α6 in cells over-expressing Fn14 is suggestive of an important role of α6ß1-fn14 interactions in motility of lung carcinoma and formation of metastases. Enhanced levels of Fn14 correlated with higher tumor cell migration and invasion in an MMP-1 dependent manner. Cells over-expressing Fn14 showed increased in vivo tumor formation with metastatic capacity to lymph nodes, lungs and liver. Thus, this research may be a step toward developing improved treatment strategies for NSCLC by improved detection and inhibition of metastases. KEYWORDS: Fn14, TNFRSF12A, non-small cell lung cancer, H460 cells, motility, tumor formation and metastasis, integrin α6.

Asunto(s)

RESUMEN

The objectives of this open-perspective clinical study were to test the effect of a new type of anaesthesia using sevofluran during surgical treatment of patients with burns, and to compare it with that of ketamin, at present the most frequently used anaesthetic. The study, conceived as a pilot study, was performed on 10 paediatric and 8 adult patients with 2nd degree burns covering between 7% and 35% of body surface. Owing to highly significant differences in parameters in favour of sevofluran, it was recommended by our ethical committee not to increase the number of patients. The parameters considered were ease of induction, undesirable effects, span of time before oral administration of liquids. Daily uptake of energy was measured for both types of anaesthetics in another group of 10 patients. In adult patients the two anaesthetics, ketamin versus sevofluran, differed in terms of incidence of unrest during surgery (ketamin 50% vs. sevofluran 0%, p < 0.05), time between end of surgery and return to full consciousness (11.3 min. vs. 2.7 min. p < 0.001), post-surgical inhibition (75% vs. 0%, p < 0.01) psychomimetic reactions after surgery (50% vs. 0%, p < 0.05), time until first intake of liquids (86.7 min. vs. 8.5 min, p < 0.001), and mobilisation (110.8 min. vs. 17 min., p < 0.001). In paedriatic patients, differences in speed of onset of anaesthesia (216 sec. vs. 66 sec., p < 0.001) and time until first uptake of liquids (75 min. vs. 22 min., p < 0.001) were statistically significant. Apart from problems associated with anesthesia, another considerable advantage of the new anaesthetic sevofluran was a significantly increased uptake of calories after use than was the case after ketamin (1645 kJ higher on the average, p < 0.05). Based on these results, sevofluran was introduced to burns surgery as a routine anaesthetic.

Asunto(s)

Asunto(s)

RESUMEN

Once the notion of the "quality of life" has been used in deliberations about straight-forward cases, it may be given wider application. It may be invoked in intensive care, in care of the handicapped and in any of medicine's specialist areas. In severe burns to keep the patient alive occurs at the cost of a degree of discomfort and disability caused by scar formation and following deformities. Severe anterior neck burn scar contracture issues in serious functional embarrassment, requiring early neck reconstruction based on three principles: releasing shrinked area, restoring contour of the mento-collical angle and preventing recurrence. Performing the surgical procedure demands endotracheal intubation which is impossible to accomplish because of chin adherent to jugulum. Combined technique of anesthesia using intravenous introduction (Ketalar) with or without local infiltration of the anterior neck scarring and immediate cutting through to the healthy muscle layer is necessary. Then follows insertion of endotracheal tube. The interval between incision and insertion may be rather crucial, as will be demonstrated in one of the cases treated in the Prague Burn Center during the last two decades.

Asunto(s)