Cancer/Testis antigens as potential predictors of biochemical recurrence of prostate cancer following radical prostatectomy

<p>Abstract</p> <p>Background</p> <p>The Cancer/Testis Antigens (CTAs) are an important group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. As a result of their restricted expression patterns, the CTAs could serve as unique biomarkers for cancer diagnosis/prognosis. The aim of this study was to identify promising CTAs that are associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP).</p> <p>Methods</p> <p>The expression of 5 CTAs was measured by quantitative multiplex real-time PCR using prostate tissue samples obtained from 72 patients with apparently clinically localized PCa with a median of two years follow-up (range, 1 to 14 years).</p> <p>Results</p> <p>The expression of CTAs namely, CEP55, NUF2, PBK and TTK were significantly higher while PAGE4 was significantly lower in patients with recurrent disease. All CTAs with the exception of TTK were significantly correlated with the prostatectomy Gleason score, but none were correlated with age, stage, or preoperative PSA levels. In univariate proportional hazards models, CEP55 (HR = 3.59, 95% CI: 1.50-8.60), p = 0.004; NUF2 (HR = 2.28, 95% CI: 1.11-4.67), p = 0.024; and PAGE4 (HR = 0.44, 95% CI: 0.21-0.93), p = 0.031 were significantly associated with the risk of PCa recurrence. However, the results were no longer significant after adjustment for prostatectomy Gleason score.</p> <p>Conclusions</p> <p>To our knowledge, this is the first study to identify CTAs as biomarkers that can differentiate patients with recurrent and non-recurrent disease following RP and underscores its potential impact on PCa prognosis and treatment.</p

Development and External Validation of a Nomogram Predicting the Probability of Significant Gleason Sum Upgrading among Japanese Patients with Localized Prostate Cancer

Objective. The aim of this study is to develop a prognostic model capable of predicting the probability of significant upgrading among Japanese patients. Methods. The study cohort comprised 508 men treated with RP, with available prostate-specific antigen levels, biopsy, and RP Gleason sum values. Clinical and pathological data from 258 patients were obtained from another Japanese institution for validation. Results. Significant Gleason sum upgrading was recorded in 92 patients (18.1%) at RP. The accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 88.9%. Overall AUC was 0.872 when applied to the validation data set. Nomogram predictions of significant upgrading were within 7.5% of an ideal nomogram. Conclusions. Nearly one-fifth of Japanese patients with prostate cancer will be significantly upgraded. Our nomogram seems to provide considerably accurate predictions regardless of minor variations in pathological assessment when applied to Japanese patient populations

Outcomes of dutasteride discontinuation in patients with benign prostatic hypertrophy

To the Editor, Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in elderly males. The current guidelines recommend the use of a 5-alpha reductase inhibitor (5ARI) to treat males with moderate-to-severe LUTS and an enlarged prostate. Combination therapy with an alpha blocker and a 5ARI has proven effective at ameliorating LUTS and reducing the total prostate volume (TPV) and the risk of the disease progression

High Serum Alkaline Phosphatase Flare after First-Line Androgen Deprivation Therapy Predicts Poor Prognosis in Metastatic Prostate Cancer Patients Treated with Second-Generation Androgen Receptor Targeted Therapy

Objectives. To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. Methods. One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. Results. The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio (p=0.0367). However, no difference was seen between a high and low ALP flare ratio (p=0.8054) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS (p<0.0001). Conclusions. A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision

Biphenyl/PCB Degrading <i>bph</i> Genes of Ten Bacterial Strains Isolated from Biphenyl-Contaminated Soil in Kitakyushu, Japan: Comparative and Dynamic Features as Integrative Conjugative Elements (ICEs)

We sequenced the entire genomes of ten biphenyl/PCB degrading bacterial strains (KF strains) isolated from biphenyl-contaminated soil in Kitakyushu, Japan. All the strains were Gram-negative bacteria belonging to &#946;- and &#947;-proteobacteria. Out of the ten strains, nine strains carried a biphenyl catabolic bph gene cluster as integrative conjugative elements (ICEs), and they were classified into four groups based on the structural features of the bph genes. Group I (five strains) possessed bph genes that were very similar to the ones in Pseudomonas furukawaii KF707 (formerly Pseudomonas pseudoalcaligenes KF707), which is one of the best characterized biphenyl-utilizing strains. This group of strains carried salicylate catabolic sal genes that were approximately 6-kb downstream of the bph genes. Group II (two strains) possessed bph and sal genes similar to the ones in KF707, but these strains lacked the bphX region between bphC and bphD, which is involved in the downstream catabolism of biphenyl. These bph-sal clusters in groups I and II were located on an integrative conjugative element that was larger than 110 kb, and they were named ICEbph-sal. Our previous study demonstrated that the ICEbph-sal of Pseudomonas putida KF715 in group II existed both in an integrated form in the chromosome (referred to as ICEbph-salKF715 (integrated)) and in a extrachromosomal circular form (referred to as ICEbph-sal (circular)) (previously called pKF715A, 483 kb) in the stationary culture. The ICEbph-sal was transferred from KF715 into P. putida AC30 and P. putida KT2440 with high frequency, and it was maintained stably as an extrachromosomal circular form. The ICEbph-salKF715 (circular) in these transconjugants was further transferred to P. putida F39/D and then integrated into the chromosome in one or two copies. Meanwhile, group III (one strain) possessed bph genes, but not sal genes. The nucleotide sequences of the bph genes in this group were less conserved compared to the genes of the strains belonging to groups I and II. Currently, there is no evidence to indicate that the bph genes in group III are carried by a mobile element. Group IV (two strains) carried bph genes as ICEs (59&#8722;61 kb) that were similar to the genes found in Tn4371 from Cupriavidus oxalacticus A5 and ICEKKS1024677 from the Acidovorax sp. strain KKS102. Our study found that bph gene islands have integrative functions, are transferred among soil bacteria, and are diversified through modification

A New ICEclc Subfamily Integrative and Conjugative Element Responsible for Horizontal Transfer of Biphenyl and Salicylic Acid Catabolic Pathway in the PCB-Degrading Strain Pseudomonas stutzeri KF716

Integrative and conjugative elements (ICEs) are chromosomally integrated self-transmissible mobile genetic elements. Although some ICEs are known to carry genes for the degradation of aromatic compounds, information on their genetic features is limited. We identified a new member of the ICEclc family carrying biphenyl catabolic bph genes and salicylic acid catabolic sal genes from the PCB-degrading strain Pseudomonas stutzeri KF716. The 117-kb ICEbph-salKF716 contains common core regions exhibiting homology with those of degradative ICEclc from P. knackmussii B13 and ICEXTD from Azoarcus sp. CIB. A comparison of the gene loci collected from the public database revealed that several putative ICEs from P. putida B6-2, P, alcaliphila JAB1, P. stutzeri AN10, and P. stutzeri 2A20 had highly conserved core regions with those of ICEbph-salKF716, along with the variable region that encodes the catabolic genes for biphenyl, naphthalene, toluene, or phenol. These data indicate that this type of ICE subfamily is ubiquitously distributed within aromatic compound-degrading bacteria. ICEbph-salKF716 was transferred from P. stutzeri KF716 to P. aeruginosa PAO1 via a circular extrachromosomal intermediate form. In this study, we describe the structure and genetic features of ICEbph-salKF716 compared to other catabolic ICEs

再燃前立腺癌患者に対するビスホスホネート・低容量デキサメサゾン治療

We evaluated the effects of bisphosphonate (BP) treatment in five patients with hormone-refractory prostate cancer (HRPC), experiencing bone pain from metastases to the bone, and assessed changes in serum prostate specific antigen (PSA) levels, bone pain, and quality of life (QOL). Treatment with incadronate disodium (10 mg) in saline was administered at 2-week intervals for a total of 6 times. Evaluation of the treatment included the incidence of adverse events, QOL, bone pain, pain scale, and blood analyses including tumor markers. BP treatment was generally well tolerated by all five patients. The effects of BP treatment on serum PSA values were evaluated as prominent response (PR), no change (NC) and progressive disease (PD) in one, two and two cases of PD, respectively. During BP treatment, serum type I procollagen values decreased in patients, but there was no large change in serum type I collagen values. Only one patient experienced increased pain; pain was well controlled in the others. The QOL evaluation by Short-Form 36 (SF-36), showed no change in scores during BP treatment except for general health. These results suggested that BP treatment is safe and feasible. It may be effective for the treatment of those HRPC patients with bone pain and may become one of the choices for treatment of HRPC.われわれは, 骨転移による骨痛有するホルモン不応性前立腺癌(HRPC)5例においてビスホスホネート(BP)治療を行い, 血清PSA値, 骨痛と生活の質(QOL)を評価した.インカドロン2ナトリウム(10mg)を2週ごと, 合計6回施行した.治療効果判定を腫瘍マーカー, 副作用, QOL, 骨痛・疼痛スケールと血液検査で行った.BP治療は, 5例すべて問題なく終了した.治療効果における血清PSA値は, 1例PR, 2例NCと2例PDであった.BP治療期間中血清I型プロコラーゲン値は患者で減少した.しかしながら, 血清I型コラーゲン値の大きな変化はみられなかった.1人の患者において疼痛の増加が見られたが, 他の症例では疼痛の悪化を認めなかった.Short-Form 36(SF-36)によるQOL評価では, 全体的健康感以外BP治療の間のスコアは不変であった.これらの結果からBP治療が安全に施行でき, 骨痛を伴ったHRPC患者に効果的である可能性が認められ, HRPCに対する治療の1つの選択肢になることが示唆された(著者抄録