Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC) undergoing surgical treatment.</p> <p>Methods</p> <p>Between January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely.</p> <p>Results</p> <p>Of 1367 CRC patients, there were seven hundred and fifty-seven males (55.4%) and 610 (44.6%) females. The median follow-up period was 60 months (range, 3–132 months). A multivariate analysis identified that low serum albumin level (<it>P </it>= 0.011), advanced UICC stage (<it>P </it>< 0.001), and high carcinoembryonic antigen (CEA) level (<it>P </it>< 0.001) were independent prognostic factors of cancer-specific survival. Meanwhile, a multivariate analysis showed age over 65 years (<it>P </it>< 0.001), advanced UICC stage (<it>P </it>< 0.001), and high CEA level (<it>P </it>< 0.001) were independent prognostic factors of overall survival. Furthermore, combination of UICC stage, serum CEA and albumin levels as predictors of cancer-specific survival showed that the poorer the prognostic factors involved, the poorer the cancer-specific survival rate. Likewise, combination of UICC stage, age and serum CEA level as predictors of overall survival showed that the poorer the prognostic factors involved, the poorer the overall survival rate. Of these prognostic factors, preoperative serum CEA level was the only significant prognostic factor for patients with stage II and III CRCs in both cancer-specific and overall survival categories.</p> <p>Conclusion</p> <p>Preoperative serum albumin level, CEA level and age could prominently affect postoperative outcome of CRC patients undergoing surgical treatment. In addition to conventional UICC staging system, it might be imperative to take these additional characteristics of factors into account in CRC patients prior to surgical treatment.</p

Human Wharton’s Jelly Mesenchymal Stem Cell-Mediated Sciatic Nerve Recovery Is Associated with the Upregulation of Regulatory T Cells

The acceleration of peripheral nerve regeneration is crucial for functional nerve recovery. Our previous study demonstrated that human Wharton&rsquo;s jelly-derived mesenchymal stem cells (hWJ-MSC) promote sciatic nerve recovery and regeneration via the direct upregulation and release of neurotrophic factors. However, the immunomodulatory role of hWJ-MSC in sciatic nerve recovery remains unclear. The effects of hWJ-MSC on innate immunity, represented by macrophages, natural killer cells, and dendritic cells, as well as on adaptive immunity, represented by CD4+ T, CD8+ T, B, and regulatory T cells (Tregs), were examined using flow cytometry. Interestingly, a significantly increased level of Tregs was detected in blood, lymph nodes (LNs), and nerve-infiltrating cells on POD7, 15, 21, and 35. Anti-inflammatory cytokines, such as IL-4 and IL-10, were significantly upregulated in the LNs and nerves of hWJ-MSC-treated mice. Treg depletion neutralized the improved effects of hWJ-MSC on sciatic nerve recovery. In contrast, Treg administration promoted the functional recovery of five-toe spread and gait stance. hWJ-MSC also expressed high levels of the anti-inflammatory cytokines TGF-&beta; and IL-35. This study indicated that hWJ-MSC induce Treg development to modulate the balance between pro- and anti-inflammation at the injured sciatic nerve by secreting higher levels of anti-inflammatory cytokines

The immunomodulatory activity of meningococcal lipoprotein Ag473 depends on the conformation made up of the lipid and protein moieties.

We have previously demonstrated that the meningococcal antigen Ag473 in the presence of Freund's adjuvant can elicit protective immune responses in mouse challenge model. In this study, we evaluated the structural requirement for the immunological activity and the possible signaling pathway of recombinant Ag473 antigen produced in E. coli. We found that lipidated Ag473 (L-Ag473) possesses an intrinsic adjuvant activity that could be attributed to its ability to activate dendritic cells and promote their maturation. In addition, we found that L-Ag473 can activate human monocytes and promote maturation of human monocyte-derived dendritic cells. These results provide an indirect support that L-Ag473 may also be immunogenic in human. Interestingly, the observed activity is dependent on the overall conformation of L-Ag473 because heating and proteinase K treatment can diminish and abolish the activity. Furthermore, our data suggest a species-differential TLR recognition of L-Ag473. Overall, these data suggest a new paradigm for the ligand-TLR interaction in addition to demonstrating the self-adjuvanting activity of the vaccine candidate L-Ag473

The Immunomodulatory Activity of Meningococcal Lipoprotein Ag473 Depends on the Conformation Made up of the Lipid and Protein Moieties

We have previously demonstrated that the meningococcal antigen Ag473 in the presence of Freund’s adjuvant can elicit protective immune responses in mouse challenge model. In this study, we evaluated the structural requirement for the immunological activity and the possible signaling pathway of recombinant Ag473 antigen produced in E. coli. We found that lipidated Ag473 (L-Ag473) possesses an intrinsic adjuvant activity that could be attributed to its ability to activate dendritic cells and promote their maturation. In addition, we found that L-Ag473 can activate human monocytes and promote maturation of human monocyte-derived dendritic cells. These results provide an indirect support that L-Ag473 may also be immunogenic in human. Interestingly, the observed activity is dependent on the overall conformation of LAg473 because heating and proteinase K treatment can diminish and abolish the activity. Furthermore, our data suggest a species-differential TLR recognition of L-Ag473. Overall, these data suggest a new paradigm for the ligand-TLR interaction in addition to demonstrating the self-adjuvanting activity of the vaccine candidate L-Ag473

Induction of specific T cell activation by Ag473 immunization in recall assay.

<p>C57BL/6 mice were immunized with IFA alone, IFA + L-Ag473 or NL-Ag473 (10 µg) via footpad injection. Draining lymph node cells were collected after 10 days and cultured in 96-well plates with indicated concentration of Ag473 for 3 days. (A) T cell proliferation was determined by [³H]thymidine incorporation. (B) IFN-γ production was measured by ELISA. Data are shown as mean <u>+</u> SD from triplicate cultures; ^NS<i>p</i>>0.05; *<i>p</i><0.05; **<i>p</i><0.01 (Student’s <i>t</i>-test), comparing L-Ag473/NL-Ag473-immunized to control mice. All data are representative of two to three independent experiments.</p

Promotion of specific antibodies by Ag473 immunization.

<p>Antibody titers (A) and the IgG isotype profiles (B) of the Ag473-immune sera determined by ELISA. (A) AP- anti-mouse Ig (μγα) was used as the secondary antibody; (B) anti-NL-Ag473 was 100X diluted while others were 1000X. The shown readings were obtained by subtracting the readings of preimmune sera from that of immune sera.</p

The biological activity of L-Ag473 is retained after pretreatment with PMB but abolished by heat or proteinase K treatment.

<p>BMDCs were treated with L-Ag473 (100 ng/ml) or LPS (20 ng/ml) for 6 hours and the intracellular TNF-α of CD11c⁺ cells were determined by flow cytometry. Dotted and grey lines represent the isotype-matched control Ab and untreated cell, respectively. PNaseK, proteinase K.</p

L-Ag473 induces cytokine and chemokine production by BMDCs.

<p>BMDCs were incubated with L-Ag473 for 24 hours (or 6 hours for TNF-α and RANTES). Supernatants were collected and (A) TNF-α, IL-6, and IL-12; (B) MCP-1, MIP-1, and RANTES were determined by ELISA. Data are shown as mean ± SD from triplicate DC cultures; ^NS<i>p</i>>0.05; *<i>p</i><0.05; **<i>p</i><0.01 (Student’s <i>t</i>-test), comparing Ag473-treated to non-treated cells. All data are representative of three independent experiments.</p