Research frontiers The authors focused on differences in expression of MUC2, MUC5AC, MUC6 and CD10, p53 alteration, nuclear http://www.selleckchem.com/products/crenolanib-cp-868596.html translocation of ��-catenin, cell proliferation, and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)/v-raf murine sarcoma viral oncogene homologue B1 mutations in morphologically different LST subtypes. Innovations and breakthroughs The authors showed that the two types of LSTs have different phenotypes, particularly with respect to MUC5AC (expression greater in Gr- vs NGr- types) and MUC6 (only expressed in NGr-type). They showed a higher nuclear ��-catenin expression in NGr-type, and Ki-67 was much more prevalent in the Gr-type. Finally, the incidence of KRAS mutations was much more frequent in Gr-LST.

Applications The subtypes of LSTs may be different candidates for alternative pathways of colorectal tumorigenesis. The results of the study represent a further impact on research in colorectal carcinogenesis. Peer review This is a good descriptive study in which the authors clarify differences in mucin phenotype, proliferative activity and oncogenetic alteration among subtypes of LST. The results are interesting and suggest that they are different candidates for alternative pathways of colorectal carcinogenesis. Footnotes Supported by A grant-in-aid for General Scientific Research from the Ministry of Education, Science, Sports and Culture to Hiroyuki Mitomi, No. 21590394; and to Tsuyoshi Saito, No. 23590434, Tokyo, Japan Peer reviewer: Dr.

Inti Zlobec, PhD, Institute for Pathology, University Hospital Basel, Schoenbeinstrasse 40, CH-4031 Basel, Switzerland S- Editor Lv S L- Editor Rutherford A E- Editor Lu YJ
Patients from 4 participating tertiary referral centers were considered eligible for inclusion when they had histologically proven, advanced and irresectable adenocarcinoma of the pancreas (UICC Stage IV), had a Karnofsky performance status of >60 and declared their written informed consent to participate. The CARPAN protocol was approved by the ethics committee of Greifswald University (Reg.Nr.IIIUV73/05) and registered at clinical-trials.gov (NCT01330823) and under ISRCTN83465351. Patients were recruited regardless of concomitant or scheduled chemotherapy. Exclusion criteria were liver failure, a second malignancy, treatment with omega-3-fatty acids and the presence of a mental disorder precluding informed consent.

From May 2006 until October 2009 a total of 152 patients were screened and 72 enrolled in the study (Figure (Figure1).1). Reasons for non-enrollment were mostly due to poor performance status or withheld consent. Patients were randomized (sequential series of 4 per block, sealed envelopes, computer generated randomization code) to receive either an oral liquid formulation of L-Carnitine (4g/d, obtained from AV-951 Lonza, Basel, CH) or identically formulated placebo with follow up visits at 6 and 12weeks after entry.