Abstract Background Failure after radical prostatectomy can occur even out to 25 years after surgery. Therefore, it is important that studies have sufficient follow-up to determine more accurately ...the risk of failure. We evaluated a large cohort of patients for pathologic findings and risk of failure with a median follow-up of 9.5 years. Material and Methods Between 1985 and 1995, 719 patients underwent radical prostatectomy for lymph node negative prostate cancer. The prostate was inked and evaluated for: (1) positive bladder neck or urethral margin, (2) positive seminal vesicle, (3) into capsule, (4) through capsule, and (5) positive margin. These were considered positive pathologic findings. Results Overall, 264 (37%) of the patients had biochemical recurrence. For those patients with failure, median time to biochemical recurrence was 2.4 years. Five and 10-year biochemical failure rates were 28% and 38%, respectively. Pathologic stage of disease significantly (<0.0001) predicted for subsequent failure. If there were no positive pathology findings, the recurrence rate was 25%, compared to 63% for any of the 3 findings. Overall, 212 (29%) of the patients have died. Five and 10-year survival were 91% and 75%, respectively. A total of 45 patients (6%) died of prostate cancer. For patients with negative pathology findings, 3% died as a direct consequence of prostate cancer, compared to 13% if the pathology was positive. Of the patients with positive seminal vesicle, 28% died of cancer. Conclusion Patients with any of the following factors have a risk of failure exceeding 40% and are candidates for studies of adjuvant therapy: seminal vesicle involvement, extension through the capsule, or margin involvement.
Fumed silica nanoparticles (FSN) are one of the most common synthetic forms of silica, but prolonged exposure leads to cell toxicity and apoptosis due to reactive oxygen species (ROS) generation and ...cell membrane perturbation resulting from hydrogen bonding and electrostatic interactions. Increasing attention is being put on synthesizing FSN material that is safer both for workers involved in large-scale industrial production, and consumers coming in contact with FSN additives. In the present work, we explore the molecular structural differences and efficacy of Al- and Ti-metal-doped FSN which has previously been shown to reduce toxicity effects of FSN. We use a combination of
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Si and
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Al solid-state magic angle spinning (MAS) NMR, Raman spectroscopy, and thermogravimetric analysis (TGA) to probe the surface and bulk structure and quantify the adsorption capacity and reactivity of the metal-doped FSN with respect to amino acid thermal condensation. Alanine was selected as the amino acid of choice for its simplicity and ubiquity in biochemical reactions. The results indicate that metal doping has a modest impact on the fumed silica molecular structure with a small decrease in amino acid adsorption capacity and thermal condensation reactivity as a function of increased metal doping.
Graphical Abstract
Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for ...7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab.
Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completion rate, and survival.
A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2.
In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.
Surveillance and focal therapy are increasingly considered for low risk prostate cancer (PC). We describe pathological characteristics of low risk PC at radical prostatectomy in contemporary ...patients.
Five-hundred-fifty-two men from 2008 to 2012 with low risk (stage T1c/T2a, PSA ≤ 10 ng/ml, Gleason score ≤6) PC underwent radical prostatectomy. Slides were re-reviewed to grade and stage the tumor, map separate tumor nodules, and calculate their volumes.
Ninety-three (16.9%) men had prostatectomy Gleason score 3 + 4 = 7 or higher and were excluded. Five (0.9%) men had no residual carcinoma. Remaining 454 patients composed the study cohort. The median age was 57 years (36-73) and median PSA 4.4 ng/ml (0.4-9.9). Racial distribution was 77.5% Caucasian, 15.5% African American, and 7% other. The median total tumor volume was 0.38 cm(3) (0.003-7.22). Seventy percent of the patients had bilateral tumor and 34% had a tumor nodule >0.5 cm(3) . The index lesion represented 89% (median) of the total tumor volume. Extraprostatic extension and positive margin were present in 5.7% and 9% of cases, respectively. The tumor nodules measuring >0.5 cm(3) were located almost equally between the anterior (53%) and peripheral (47%) gland. The relationship between PSA and total tumor volume was weak (r = 0.13, P = 0.005). The relationship between PSA density and total tumor volume was slightly better (r = 0.26, P < 0.001).
Low risk prostate cancer is generally a low volume disease. Gleason score upgrade is seen in 16.9% of cases at radical prostatectomy. While the index lesion accounts for the bulk of the disease, the cancer is usually multifocal and bilateral. Neither PSA nor PSA density correlates well with the total tumor volume. Prostate size has a significant contribution to PSA level. These factors need to be considered in treatment planning for low risk prostate cancer.
•Radiation therapy alone has dramatic effects on lymphocyte subgroups.•CD4+, CD8+ and CD56+ counts drop by >70%, CD 19+ by >90%.•Three months post exposure, no subgroup has returned to baseline ...levels.•All subgroups except CD 56+ (including CD19+) recovered modestly to about 40% of pre-treatment levels.•CD56+ were more resistant and recovered to 64% of pretreatment levels.•CD56+ cells recover more fully (to >60% of pretreatment levels).
There is a lack of information on the radiosensitivity of lymphocyte subgroups to radiation alone. CD4+ and CD8+ lymphocytes respond similarly. CD 19+ dropped most precipitously, but recovered to levels similar to the other subgroups by 3 months. NK cells decline more modestly and recover more fully by 3 months.
Purpose Patients with high-risk prostate cancer after radical prostatectomy are at risk for death. Adjuvant androgen-deprivation therapy (ADT) may reduce this risk. We hypothesized that the addition ...of mitoxantrone and prednisone (MP) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone. Methods Eligible patients had cT1-3N0 prostate cancer with one or more high-risk factors after radical prostatectomy (Gleason score GS ≥ 8; pT3b, pT4, or pN+ disease; GS 7 and positive margins; or preoperative prostate-specific antigen PSA > 15 ng/mL, biopsy GS score > 7, or PSA > 10 ng/mL plus biopsy GS > 6. Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage, GS, and adjuvant radiation plan and randomly assigned to ADT (bicalutamide and goserelin for 2 years) or ADT plus six cycles of MP. The primary end point was overall survival (OS). Median OS was projected to be 10 years in the ADT arm, requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92% power and one-sided α = .05. Results Nine hundred sixty-one eligible intent-to-treat patients were randomly assigned to ADT or ADT + MP from October 1999 to January 2007, when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP. Median follow-up was 11.2 years. The 10-year OS estimates were 87% with ADT (expected 50%) and 86% with ADT + MP (hazard ratio, 1.06; 95% CI, 0.79 to 1.43). The 10-year estimate for disease-free survival was 72% for both arms. Prostate cancer was the cause of death in 18% of patients in the ADT arm and 22% in the ADT + MP arm. More patients in the MP arm died of other cancers (36% v 18% in ADT alone arm). Conclusion MP did not improve OS and increased deaths from other malignancies. The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates, although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm.
Soil viruses are potentially of great importance as they may influence the ecology and evolution of soil biological communities through both an ability to transfer genes from host to host and as a ...potential cause of microbial mortality. Despite this importance, the area of soil virology is understudied. Here, we report the isolation and preliminary characterisation of viruses from soils in the Dundee area of Scotland. Different virus morphotypes including tailed, polyhedral (spherical), rod shaped, filamentous and bacilliform particles were detected in the soil samples. An apparent predominance of small spherical and filamentous bacteriophages was observed, whereas tailed bacteriophages were significantly less abundant. In this report, we also present observations and characterisation of viruses from different soil functional domains surrounding wheat roots: rhizosheath, rhizosphere and bulk soil. In spite of the differences in abundance of bacterial communities in these domains, no significant variations in viral population structure in terms of morphology and abundance were found. Typically, there were approximately 1.1-1.2 x 10⁹ virions g⁻¹ dry weight, implicating remarkable differences in virus-to-bacteria ratios in domains close to roots, rhizosphere and rhizosheath (approximately 0.27) and in bulk soil (approximately 4.68).
Background. Only truly long-term follow-up can determine the ultimate outcome in prostate cancer. Most studies have a median follow-up of less than 10 years and then project outcomes out to 15 and 20 ...years. We sought to follow patients for at least 20 years. Materials and Methods. We followed 754 prostate cancer patients treated with radical prostatectomy from 1988 to 1995 for a median follow-up (in survivors) of 23.9 years. We excluded lymph node and seminal vesicle positive patients and an additional 47 patients that did not have baseline prostate-specific antigen (PSA). This left 581 patients for analysis. Results. With the factors of PSA, Gleason score, and extraprostatic extension/margin positivity, we could partition patients into three risk groups for biochemical failure (low, intermediate, and high). In further analysis, we found that the risk of metastatic disease in the first two groups was almost identical (4% and 5%, respectively), while it was 19% in the high-risk group. High-risk patients were those with PSA >20 ng/ml and/or Gleason >7, or Gleason 7 + PSA 10–20 + epe (and or margin) positive. They had a 22% prostate cancer mortality. Conclusion. In patients with truly long-term follow-up after prostatectomy for prostate cancer, the risk of metastatic disease and cancer death is very low. Patients with the lower risk findings do not appear to benefit from routine follow-up after 10 years free of biochemical recurrence. With a higher risk of later failure, we recommend that the higher risk patients be followed at least intermittently for another 5 years (out to 15 years).
Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible ...by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations.
•Nexrutine pre-treatment sensitized prostate cancer cells to radiation.•Radiation-mediated suppression of tumor progression was enhanced upon combination with Nexrutine.•Ribosomal protein RPS6KB1 silencing increased sensitivity to radiation.•p-RPS6KB1 is elevated in human prostate tumors.
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