We have evaluated by numerical simulation the average size R(K) of random polygons of fixed knot topology K=,3(1),3(1) musical sharp 4(1), and we have confirmed the scaling law R(2)(K) approximately N(2nu(K)) for the number N of polygonal nodes in a wide range; N=100-2200. The best fit gives 2nu(K) approximately 1.11-1.16 with good fitting curves in the whole range of N. The estimate of 2nu(K) is consistent with the exponent of self-avoiding polygons. In a limited range of N (N greater, similar 600), however, we have another fit with 2nu(K) approximately 1.01-1.07, which is close to the exponent of random polygons.

These results might encourage the further evaluation of the combination of peptide vaccination and a low dose of estramustine phosphate for HLA-A24+ HRPC patients.

To evaluate the safety and toxicity of peptide vaccination for patients with metastatic hormone-refractory prostate cancer (HRPC) based on pre-existing peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the circulation, 10 patients positive for human leukocyte antigen (HLA)-A2 with metastatic HRPC were enrolled in a phase I study. Peptide-specific CTL-precursors reactive to 16 kinds of vaccine candidates in the pre-vaccination peripheral blood mononuclear cells (PBMCs) were measured, and patients were followed by vaccination with only positive peptides (up to 4 kinds of peptides). Serum prostate-specific antigen (PSA) levels were monitored regularly. The peptide vaccination was safe and well tolerated with no major adverse effects. The most common toxicities were dermatologic reactions at the injection site. Increased CTL response to peptides was observed in 4 of 10 patients. Anti-peptide IgG was also detected in post-vaccination sera of 7 of 10 patients. One patient showed the disappearance of a pelvic bone metastasis after five vaccinations. Three patients showed a decrease of serum PSA level from the baseline after the vaccination, but no patients showed a serum PSA level decrease of ≥ ≥ ≥ ≥50%. The median survival duration of study patients was 22 months with follow-up from 3 to 27 months. We consider that the increase in cellular and humoral immune responses, and decrease in PSA level in some patients justify further development of peptide vaccination for metastatic HRPC patients.

Increased immune responses, at both the circulation and tumor sites in the vaccinated group, support the further development of personalized peptide vaccines for patients with localized prostate cancer.

Abbreviations & Acronyms ASA = American Society of Anesthesiologists BCa = bladder cancer BMI = body mass index CCI = Charlson Comorbidity Index CI = confidential interval CRP = C-reactive protein DSS = disease-specific survival ECOG = Eastern Cooperative Oncology Group eGFR = estimated glomerular filtration rate HB = hemoglobin HR = hazard ratio LDH = lactate dehydrogenase LNM = lymph node metastasis LVI = lympho-vascular invasion NA = not available PS = performance status PSM = positive surgical margin RC = radical cystectomy SD = standard deviation Objectives: The present study investigated prognostic indicators, including clinicopathological and preoperative hematological factors, and developed a prognostic factorbased risk stratification model in bladder cancer patients treated with radical cystectomy. Methods: Data were collected from 249 consecutive bladder cancer patients treated with radical cystectomy without neoadjuvant therapy. Prognostic values of the preoperative hematological parameters, along with the patients' clinicopathological parameters were evaluated. A risk stratification model was developed to predict disease-specific survival after radical cystectomy using the regression coefficients of multivariate analysis. Results: In the multivariate analysis, preoperative hemoglobin and C-reactive protein levels, as well as the pathological factors of T stage, positive surgical margin and lymph node metastasis, were independently predictive of disease-specific survival. Low hemoglobin (<10.5 g/dL), a high C-reactive protein (>0.5 mg/dL), extravesical T stage (≥pT3a) and positive surgical margin were independent predictors of poor disease-specific survival. The risk stratification model showed significant differences in disease-specific survival between the three subgroups. Conclusions: This is the first report to show the significance of combining preoperative hemoglobin with the pathology of radical cystectomy specimens as an independent predictor for disease-specific survival, and it also represents the largest contemporary series to date demonstrating that two types of preoperative hematological disorders, assessed by hemoglobin and C-reactive protein, are independent predictors in bladder cancer patients treated with radical cystectomy. Our risk stratification model could provide physicians with useful prognostic information for identifying patients who might be candidates for multimodal treatments.

Purpose: The purpose is to identify a gene coding for tumor-associated antigen and peptide capable of inducing CTLs reactive to tumor cells with a HLA-A33-restricted fashion to provide scientific basis for specific immunotherapy to HLA-A33 ؉ cancer patients. Experimental Design: An expression gene-cloning method was used to identify the tumor-associated antigen gene. Northern blot analysis and immunohistochemistry were used to examine the mRNA and protein expression levels in various cells and tissues, respectively. Synthetic peptides were examined for their ability to induce HLA-A33؉ tumor-reactive CTLs in peripheral blood mononuclear cells from cancer patients.Result: A gene of small GTPase, Ran, which controls the cell cycle through the regulation of nucleocytoplasmic transport, mitotic spindle organization, and nuclear envelope formation, was found to encode epitopes recognized by the HLA-A33-restricted CTLs established from T cells infiltrating into gastric adenocarcinoma. The expression of the Ran gene was increased in most cancer cell lines and cancer tissues at both the mRNA and protein levels. However, it was not enhanced in the surrounding normal cells or tissues. It was also undetectable in normal tissues as far as tested. Ran-derived peptides at positions 48 -56 and 87-95 could induce CD8؉ peptide-specific CTLs reactive to tumor cells from HLA-A33؉ epithelial cancer patients in a HLA class I-restricted manner.Conclusions: Because of its increased expression in cancer cells and involvement in malignant transformation and/or the enhanced proliferation of cancer cells, the two Ran-directed peptides could be potent candidates in use for specific immunotherapy against HLA-A33 ؉ epithelial cancers.

Purpose: The peptide vaccine candidates identified to date have been focused on the HLA-A2and HLA-A24 alleles.The HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs and belong to an HLA-A3 supertype family. In this study, we attempted to identify CTL-directed peptide candidates, derived from prostate-related antigens and shared by HLA-A11 + , HLA-A31 + , and HLA-A33 + prostate cancer patients. Experimental Design: Based on the binding motif to the HLA-A3 supertype alleles, 42 peptides were prepared from prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and prostatic acid phosphatase (PAP).These peptides were first screened for their ability to be recognized by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific and prostate cancer^reactive CTLs from peripheral blood mononuclear cells (PBMC) of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Results: Five peptide candidates, including the PSA 16-24 , PAP [155][156][157][158][159][160][161][162][163] , and PSMA 431-440 peptides, were frequently recognized by IgGs of prostate cancer patients. These peptides efficiently induced peptide-specific and prostate cancer^reactive CTLs from PBMCs of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Antibody blocking and cold inhibition experiments revealed that the HLA-A3 supertype^restricted cytotoxicity against prostate cancer cells could be ascribed to peptide-specific and CD8 + Tcells. Conclusions: We identified prostate-related antigen-derived new peptide candidates for HLA-A11-, HLA-A31-, and HLA-A33-positive prostate cancer patients.This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLA-A2 and HLA-A24.Prostate cancer is one of the most common cancers among elderly men (1). Despite the fact that androgen withdrawal therapy is transiently effective for prostate cancer, there is no effective therapy against recurrent hormone-refractory and metastatic prostate cancer. For such patients, specific immunotherapy may be a promising option because prostate cancerreactive T cells could detect multiple metastases with fine specificity. Thus far, many cancer-related antigens and their peptides that are recognized by CTLs have been identified (2). In addition, several antigenic peptides derived from prostatespecific antigen (PSA; refs. 3 -5), prostate-specific membrane antigen (PSMA; refs. 6, 7), prostatic acid phosphatase (PAP; refs. 8, 9), or prostate stem cell antigen (10 -12) have been identified. As is the case with melanocyte differentiation antigens for melanoma, these prostate-related antigens have been considered promising targets in specific immunotherapy for prostate cancer patients (13). However, the peptide vaccine candidates identified to date have been focused on the HLA-A2 and HLA-A24 alleles because of the higher worldwide frequency of these alleles.Based on the structural similarities of the group of HLA all...

The objective of this study was to characterize time-dependent recovery of erectile function in Japanese patients following robot-assisted radical prostatectomy (RARP) using the erection hardness score (EHS). This study prospectively included 170 Japanese patients with localized prostate cancer (PC) undergoing RARP without neoadjuvant hormonal therapy. The erectile function of each patient was assessed based on the International Index of Erectile Function-5 (IIEF-5) and EHS at the baseline and on every visit to an outpatient clinic after RARP. In this series, potency was defined as the ability to have an erection sufficient for intercourse, corresponding to EHS ≥3, while patients with EHS ≥2 were regarded as those with erectile function. Of these 170 patients, 20 and 75 underwent bilateral and unilateral nerve-sparing procedures, respectively; however, non-nerve-sparing procedures were performed in the remaining 75. A proportional increase in the IIEF-5 score according to EHS was noted at 24 months after RARP. At 6, 12 and 24 months after RARP, the recovery rates of erectile function were 11.9, 21.7 and 35.8 %, respectively, while those of potency were 3.8, 9.8 and 13.7 %, respectively. Of several factors examined, the age, preoperative IIEF-5 score and nerve-sparing procedure were identified as independent predictors of erectile function recovery. These findings suggest that favorable erectile function recovery could not be achieved in Japanese PC patients even after the introduction of RARP; therefore, it might be preferable for such a cohort to use EHS rather than IIEF-5 as an assessment tool for the postoperative recovery of erectile function.