Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.

International scientific communications in the field of colorectal tumour markers

AIM To analyze scientometrically the dynamic science internationalization on colorectal tumour markers as reflected in five information portals and to outline the significant journals, scientists and institutions.METHODS A retrospective problem-oriented search was performed in Web of Science Core Collection(Wo S), MEDLINE, BIOSIS Citation Index(BIOSIS) and Scopus for 1986-2015 as well as in Dervent Innovations Index(Derwent) for 1995-2015. Several specific scientometric parameters of the publication output and citation activity were comparatively analyzed. The following scientometric parameters were analyzed:(1) annual dynamics of publications;(2) scientific institutions;(3) journals;(4) authors;(5) scientific forums;(6) patents-number of patents, names and countries of inventors, and(7) citations(number of citations to publications by single authors received in WoS, BIOSIS Citation Index and Scopus).RESULTS There is a trend towards increasing publication output on colorectal tumour markers worldwide along with high citation rates. Authors from 70 countries have published their research results in journals and conference proceedings in 21 languages. There is considerable country stratification similar to that in most systematic investigations. The information provided to end users and scientometricians varies between these data-bases in terms of most parameters due to different journal coverage, indexing systems and editorial policy. The lists of the so-called "core" journals and most productive authors in Wo S, BIOSIS, MEDLINE and Scopus along with the list of the most productive authors-inventors in Derwent present a particular interest to the beginners in the field, the institutional and national science managers and the journal editorial board members. The role of the purposeful assessment of scientific forums and patents is emphasized. CONCLUSION Our results along with this problem-oriented collection containing the researchers' names, addresses and publications could contribute to a more effective international collaboration of the coloproctologists from smaller countries and thus improve their visibility on the world information market.

Primary rectal signet ring cell carcinoma with peritoneal dissemination and gastric secondaries

Disseminated signet ring cell carcinomas frequently arise from the stomach. However, primaries in the colon and rectum have also been reported. We present a 68 year old lady who presented with a change in her bowel habit. Colonoscopy showed a stenosing rectal tumour at 7 cm to 8 cm from the anal verge. Multiple scattered ulcers were also noted along the entire length of the colon. Biopsy of the lesions revealed signet ring cell adenocarcinoma. Gastroscopy showed multiple nodules with ulceration over several areas of the stomach which were similar in appearance to the colonic lesions. However, no primary tumour of the stomach was seen. Biopsy of the gastric lesions also showed signet ring cell adenocarcinoma. Computed tomography scan of the abdomen and pelvis revealed circumferential tumour at the rectosigmoid junction with possible invasion into the left ischiorectal fossa. The overall picture was that of a primary rectal signet ring cell carcinoma with peritoneal dissemination. The patient was referred for palliative chemotherapy in view of the disseminated disease. In the present report, we discuss this interesting pathological entity and review the role of various histolological techniques in helping to identify the primary tumor.

Change of apoptotic status in the human colorectal adenoma-carcinoma sequences and its correlation with carcinogenesis and prognosis

Obejctive To assess apoptotic status during the development of colorectal cancer and its prognostic value Methods The apoptotic frequency of 168 fresh adenocarcinoma specimens and primary cultured cells at 2, 12, 24 and 48 hours (9 normal mucosa, 4 adenomas and 9 adenocarcinomas) were measured by flow cytometry (FCM) Apoptotic indices (AI) in situ for 25 adenomas and 77 adenocarcinomas were visualized by TdT mediated dUTP nick end labeling (TUNEL), Ki s5 labeling indices (KI), bcl 2, bax, waf1 and p53 were immunostained with ABC method Results The culture related apoptosis at 24-48 hours in vitro was obviously decreased in cultured tumor cells when compared with mucosa cells Spontaneous apoptosis in situ occurred more frequently in tumor with aneuploid type at late stage There was positive relationship between apoptosis and proliferative activity, determined by both TUNEL and FCM methods The well differentiated or early stage lesions with intensive bcl 2/bax expression were significantly more likely to have low AI p53 accumulation and waf1 depression were mainly related to KI, whereas bax and waf1 overexpression led to a comparatively higher AI/KI ratio bcl 2 and KI were found to be independent risk factors Conclusions The data suggest that the depressed susceptibility to inductive apoptosis may contribute to the initial phase of tumorigenesis, and spontaneous apoptosis in vivo may serve as a marker of tumor progression The bcl 2 and KI may be valuable in predicting prognosis in colorectal cancer