A 55-year-old-man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Preoperative barium enema showed a slightly medial displacement of the descending colon, and the sigmoid colon was quite long. The operative findings showed that the descending colon was not fused with the retroperitoneum and shifted to the midline and the left colon adhered to the small mesentery and right pelvic wall. Thus, a diagnosis of persistent descending mesocolon (PDM) was made. The left colon, sigmoid colon, and superior rectal arteries often branch radially from the inferior mesenteric artery. The sigmoid mesentery shortens, and the inferior mesenteric vein is often close to the marginal vessels. By understanding the anatomical feature of PDM and devising surgical techniques, laparoscopic sigmoidectomy for sigmoid colon cancer with PDM could be performed without compromising its curative effect and safety.
Abstract Background: The conventional chemosensitivity test employs a growth suppression assay. However, surgically removed specimens often have low viability which makes the assay unreliable, since the poor cell growth may be associated with the low viability instead of the chemosensitivity of the cell. On the other hand, we do know that the level of proteins involved in signal transduction is changed prior to cellular responses to the anti-cancer agents. In the present study, we investigated if protein signaling within a 24-hour exposure of the anti-cancer agents can predict the cellular fate at 72-hour time points. Materials and Methods: The human colon cancer cell line, HCT116, was exposed to three different DNA-damaging anti-cancer agents including gamma irradiation, ultraviolet, and doxorubicin. The anti-cancer agent-exposed cell pellets from different conditions (e.g., doses, and time-points) were collected to produce a lysate array, which finally accommodated more than 500 samples on a single glass slide. Array image and quantitative protein analyses were performed with the P-SCAN and ProteinScan programs. Results: A total of 19 protein species were tested on a lysate array, providing kinetic information of the protein. In response to all three agents, p53 protein was stabilized and the level increased over time in a dose-dependent manner. Upon detailed time-course analysis, however, an oscillation was seen in response to gamma irradiation, indicating the presence of a feedback loop. Comparing the rate of increasing levels of p21 and CyclinD3 within 24 hours in response to doxorubicin administration, the rates are well associated with the status of cell fate. In other words, when the rate of p21 is higher than CyclinD3, it is associated with a G2 arrest at 72 hours, whereas a higher CyclinD3 rate is associated with apoptosis at 72 hours after drug administration. Conclusion: Some events occurring at 72 hours can be predicted by seeing the quantitative level of protein kinetics within 24 hours. Most of the primary culture cells can survive for only a short period of time. The protein kinetics may be a useful clinical chemosensitivity predictor even when using low viability specimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5502.
The binding of EGFR and its ligands leads to autophosphorylation of receptor tyrosine kinase as well as subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. An EGFR inhibitor, cetuximab binds to EGFR and consequently blocks a variety of cellular processes. KRAS/BRAF mutations are known to be associated with a low response rate to cetuximab. In the present study, to clarify the anti-tumor mechanisms of cetuximab, we evaluated the KRAS/BRAF status, phosphorylation level of the EGFR pathway, and the tumor suppression effect in vivo, using a human colon cancer cell line HT29, which exhibited the highest EGFR expression in response to the cetuximab therapy among the 6 colorectal cancer cell lines tested.The conventional growth suppression assay did not work efficiently with cetuximab. EGF, TGF-α, and IGF activated the EGFR/MAPK cell signaling pathway by initiating the phosphorylation of EGFR. Cetuximab partially inhibited the EGFR/MAPK pathway induced by EGF, TGF-α, and IGF. However, cetuximab exposure induced the EGFR, MEK, and ERK1/2 phosphorylation by itself. Mouse xenograft tumor growth was significantly inhibited by cetuximab and both cetuximab-treated and -untreated xenograft specimens exhibited phosphorylations of the EGFR pathway proteins.We have confirmed that cetuximab inhibited the EGFR/MAPK pathway and reduced tumor growth in the xenografts while the remaining tumor showed EGFR pathway activation. These results suggest that: ( i ) The effect of cetuximab in growth signaling is not sufficient to induce complete growth suppression in vitro; ( ii ) time-course monitoring may be necessary to evaluate the effect of cetuximab because EGFR signaling is transmitted in a minute order; and ( iii ) cetuximab treatment may have cells acquired resistant selectively survived in the heterogeneous cancer population.
