Effect of Retinoic Acid on the Growth and the Expression of the Human Papillomavirus 16 E6 and E7 Genes of the Cervical Carcinoma Cell Lines

Human papillomavirus type 16 (HPV16) is involved in the development of cervical carcinoma and its viral gene products E6 and E7 are believed to be essential for the carcinogenic process. We analyzed the effect of retinoic acid (RA) on the growth and/or HPV16 E6 and E7 gene expression in the HPV16-containing cervical carcinoma cell lines SiHa, CaSki and QG-U and the HPV-free cell lines C33A and EBC-1. RA (10-6 M) suppressed the growth of SiHa cells by more than 90% and of QG-U cells by about 40% ; however, the growth of CaSki, C33A and EBC-1 cells was not affected by RA. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was applied for investigation of the relationship between RA and the level of HPV16 E6/E7 mRNA. As a result, the E6/E7 mRNA level in SiHa and QG-U was reduced by RA by about 60% and 75%, respectively, while RA had no obvious effect on the E6 and E7 gene expression in CaSki cells. The chloramphenicol acetyltransfer-ase (CAT) assay showed that transcription driven by HPV16 non-coding region (NCR) was suppressed by RA by about 75%. These results suggest that at least a part of the growth suppression of SiHa and QG-U by RA is mediated by sup-pression of E6 and E7 expression

Clinical Indication of Laparoscopic Surgery for Colorectal Cancer: The Optimal Extent of Lymph Node Dissection based on Depth of Colorectal Cancer and Technical Feasibility of Laparoscopic Colorectal Surgery.

Recently, laparoscopic colorectal surgery has been considered to be appropriate for colorectal cancer, and the feasibility of many laparoscopic techniques has been established; however, the indication for curative colorec-tal cancers is controversial. In this study, before laparoscopic procedure was performed on patients with colorectal cancers, 641 patients who had under-gone open laparotomy for colorectal cancer during the past 16 years were ev-aluated for the distribution of metastatic lymph nodes classified by depth of invasion. The results obtained were as follows: The rate of all lymph node metastasis of patients with pTis was 0%. The rate of intermediate lymph node (n2) metastasis of patients with pT1 and pT2 tumor was low (3.4% and 4.1% respectively) , however, in patients with pT3 and pT4 tumors, this rate was much higher (15.9% and 15.8% respectively) . Therefore, with re-gard to lymph nodes dissection for colorectal cancer it might be concluded that the intermediate lymph nodes metastases in patients with pT1 and pT2 tumors (less than 5%) were negligible. However, in patients with pT3 and pT4 tumors, for the purpose of performing a complete harvest of intermedi-ate lymph nodes, D3-dissection (including principal lymph node dissection) is required. it is questionable whether or not performance of the laparoscopic procedure for cancer achieves the same extent of lymph node dissection as compared with open laparotomy. Dissection was restricted to intermediate grade lymph node including the paracolic lymph nodes (D2) . Accordingly, patients with pT3 and pT4 tumor should be excluded from indication for laparoscopic procedure. Between October 1997 and November 1998, laparoscopic colorectal resec-actions were performed on a limited number of the above mentioned patients with Tis, Ti and T2 tumor. The grade of lymph node dissection was deter-mined by the results of a preoperative assessment of the depth of cancer in-vasion. With the exception of one patient, whose preoperative assessment for depth of cancer invasion was a limitation at the muscularis propria, but whose histological outcome had been pT3 tumor, all the other patients were able to undergo laparoscopic colorectal resection. The final histological results were as follows: 3 patients with pTis tumor, 6 pTl tumor, and 3 pT2 tumor. One of the pT3 patients alone was converted from a laparoscopic pro-cedure to open laparotomy because of the intraoperative proof of intermediate lymph node metastases, and subsequently this patient underwent principal lymph node dissection (D3-dissection) . With regard to the histological metas-tasis of harvested lymph nodes, no patients was found to have regional lymph node metastasis except for one patient only who had a pT3 tumor. Thus the histological findings were similar to those for conventional open laparotomy. In this study, it was concluded that by laparoscopic procedure a safe and complete dissection of intermediate lymph nodes including the paracolic lymph nodes (nl and n2) could be achieved. On the other hand, the true incidence of port site recurrence, and also its mechanism remain unknown to date. However, it is considered that the incidence of port site recurrence in patients with serosal invasion (T4 tumor) is higher than in those without (i.e., patients with pTis, pTl, pT2 and pT3 tumor) . We are also convinced that a number of patients with pTis, pTl and pT2 undergoing laparoscopic procedure were able to gain curative colorectal resection in terms of port site non-recurrence, and strongly believe that the application of laparoscopic col-orectal surgery for cancer might be acceptable

Short-and Midterm Outcomes of Laparoscopy Assisted Colectomy for Colon and Rectosigmoid Cancer

Background: Laparoscopy-assisted colectomy (LAC) has gained acceptance for the treatment of colon cancer. Objective: To evaluate the use and outcomes of LAC. Patients: Patients who underwent LAC (n = 176) for colon and rectosigmoid cancer (2001-2008). Results: There were 97 men (55.1%) and 79 women(44.9%), whose median age was 67.5 years (range, 33-99 years). The median operating time for patients who underwent LAC was 216 minutes (range, 70-440). The median blood loss was 60 ml (range 10-610 ml). Intra- and postoperative complicacomplications occurred in 3 (1.7%) and 16 patients (9.1%), respectively. The morbidity rate of patients was 0%. The overall survival rates for 3 years were 100.0%, 97.5%, 95.9%, 90.1% and 77.9% for stages 0,Ⅰ,Ⅱ,Ⅲa and Ⅲb, respectively. The relapse-free survival rates for 3 years were 100.0%, 100.0%, 90.1%, 65.7% and 62.3% for stages 0, Ⅰ,Ⅱ,Ⅲa and Ⅲb, respectively. Conclusion: This study confirmed the favorable short-and midterm operative results in patients who underwent LAC

Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

Survivin is a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL) recognized by CD8+ cytotoxic T lymphocytes (CTLs). We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2), general malaise (grade 1), and fever (grade 1). No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9) decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer

Surgical benefits of liver hanging maneuver for hepatectomy of huge liver tumor

In hepatic surgery, it is very important to control bleeding during liver resection. However, in hepatectomy for a huge liver tumor it is often difficult to reduce bleeding volume and maintain an excellent surgical view. The anterior pproach, which is hepatectomy done using the liver hanging maneuver, has beneficial effects reducing bleeding volume and preventing scattering of cancer cells from huge liver tumors. W e investigated the surgical benefits of the liver anging maneuver during hepatectomy for huge liver tumors in our department.

Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

<p>Abstract</p> <p>Background</p> <p>We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to <b>c</b>linically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.</p> <p>Methods</p> <p>We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks.</p> <p>Results</p> <p>In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols.</p> <p>Conclusion</p> <p>This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.</p

Clinical Survey of the Results on Colorectal Surgery in the Elderly

From 1978 to 1996, 69 patients who were 80 years of age or older (Group Ⅰ), 75 patients who were between 75 and 79 years of age (Group Ⅱ) and 618 patients who were between 50 and 69 years of age (Group Ⅲ) received surgical treatment for colorectal cancer in our department, A retrospective comparative study of the three groups was made to assess the relevant pathological and surgical factors, preoperative co-existent disease and postoperative complications, postoperative mortality and survival rates, Statistically significant differences were observed in lymph node dissection, the frequency of preoperative co-existent disease, and the frequency of total postoperative complications between Group Ⅰ and Group Ⅲ. The total perioperative mortality rates and 3 years survival rates of the three groups were not significantly different, These results led us to the conclusion that a better prognosis for elderly patients can be achieved if surgery is performed.Therefore, better management and a better rationale governing operative procedures are needed for the treatment of colorectal cance