Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies suggest that low prostate weight is a significant negative prognostic factor for prostate cancer. In the current study, the data for 431 men who underwent radical retropubic prostatectomy between 1990 and 1998 were analyzed for association between prostate weight and various clinical and pathologic parameters. These included age, preoperative prostate-specific antigen (PSA) level, PSA recurrence, pathologic stage, Gleason grade, extraprostatic extension, positive surgical margins, tumor volume, associated high-grade prostatic intraepithelial neoplasia, perineural invasion, and lymph node metastasis. Potential associations were probed by using Cox regression model analysis. A significant positive correlation was found between prostate weight and increasing patient age or increasing preoperative PSA level. There was no significant independent association between prostate weight and any of the other variables examined. No association was found between prostate weight and PSA recurrence. Although increasing prostate weight correlates with increased patient age and higher preoperative PSA level, it does not independently predict postoperative cancer recurrence.
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PMID:Does the size matter?: Prostate weight does not predict PSA recurrence after radical prostatectomy. 2023 20

In one-third of patients, prostate cancer (PCa) is monofocal. These patients can undergo focal high-intensity focused ultrasound (HIFU) therapy of the tumor without damage to surrounding structures and not compromising uro-oncologic safety. Robot-assisted HIFU coagulates the entire targeted volume within the prostate transrectally, in one session, without direct tumor contact and without adjuvant endourologic therapy. It is performed with the patient receiving spinal anesthesia and without blood loss; negative immunologic influence can be excluded. Heat-destroyed cancer cells that act as tumor vaccination are discussed. Right now, the limitation of focal therapy is caused by the lack of diagnostic accuracy to determine multifocal stages of PCa reliably. Discussions of tumor development, triggering primary lesion monotherapy, do not overcome skepticism about leaving invisible tumor foci untreated. This explains why PCa therapy today treats always the entire gland. Furthermore, the thought that the problem could be solved "radically, once forever," ignores the fact that in all PCa therapies, local recurrence rates are between 10% and 50%. Considering the longer survival of men in industrialized countries, a structured multimodal therapy concept should be created and evaluated in studies and should replace the competition between classic therapies. Focal therapy in most cases should be the first approach in cancer therapy because it is noninvasive, has low side effects, and is a single-session therapy. It does not exclude but may delay other, more invasive therapies in cases of cancer recurrence. Focal therapy should not be misunderstood as substitution for existing classic therapies but as a therapeutic first choice in monofocal, low-aggressive PCa cases.
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PMID:Robot-assisted high-intensity focused ultrasound in focal therapy of prostate cancer. 2036 10

T-cell costimulatory molecules deliver positive or negative signals to govern the ultimate fate of immune responses. These ligands and receptors that negatively costimulate T cells (including cytotoxic T-lymphocyte antigen [CTLA]-4, B7-H1, programmed death [PD]-1, B7-H3 and B7x) have received significant interest recently owing to their proposed ability to form a molecular shield for tumor cells. CTLA-4 represents the most extensively studied receptor in the costimulatory pathway and functions as a potent inhibitor of T-cell-mediated immunity. Clinical trials with anti-CTLA-4 are ongoing, although numerous objective responses have been observed in heavily pretreated patients, albeit with autoimmune side effects. In renal cell carcinoma, B7-H1, PD-1 and B7x have been observed to be expressed on tumor cells or infiltrating lymphocytes and are individually associated with adverse pathologic features and poor clinical outcome. In prostate cancer, B7-H3 and B7x immunostaining intensity correlate with disease spread, clinical cancer recurrence and cancer-specific death. External validation and prospective studies are now needed to confirm these findings, while further development of humanized monoclonal antibodies, similar to the experience with anti-CTLA-4, are underway. Herein, we review the B7-CD28 family as it applies to urologic malignancies.
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PMID:Inhibitors of B7-CD28 costimulation in urologic malignancies. 2044 72

Statistical models predicting cancer recurrence after surgery are based on biologic variables. We have shown previously that prostate cancer recurrence is related to both tumor biology and to surgical technique. Here, we evaluate the association between several biological predictors and biochemical recurrence across varying surgical experience. The study included two separate cohorts: 6,091 patients treated by open radical prostatectomy and an independent replication set of 2,298 patients treated laparoscopically. We calculated the odds ratios for biological predictors of biochemical recurrence-stage, Gleason grade and prostate-specific antigen (PSA)-and also the predictive accuracy (area under the curve, AUC) of a multivariable model, for subgroups of patients defined by the experience of their surgeon. In the open cohort, the odds ratio for Gleason score 8+ and advanced pathologic stage, though not PSA or Gleason score 7, increased dramatically when patients treated by surgeons with lower levels of experience were excluded (Gleason 8+: odds ratios 5.6 overall vs. 13.0 for patients treated by surgeons with 1,000+ prior cases; locally advanced disease: odds ratios of 6.6 vs. 12.2, respectively). The AUC of the multivariable model was 0.750 for patients treated by surgeons with 50 or fewer cases compared to 0.849 for patients treated by surgeons with 500 or more. Although predictiveness was lower overall for the independent replication set cohort, the main findings were replicated. Surgery confounds biology. Although our findings have no direct clinical implications, studies investigating biological variables as predictors of outcome after curative resection of cancer should consider the impact of surgeon-specific factors.
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PMID:Surgery confounds biology: the predictive value of stage-, grade- and prostate-specific antigen for recurrence after radical prostatectomy as a function of surgeon experience. 2053 47

Although surgery provides excellent control for localized prostate cancer, pathologic examination of more than one-third of specimens will reveal positive surgical margins, seminal vesicle invasion, and/or extracapsular extension, thus putting these patients at increased risk of cancer recurrence. "Adjuvant" radiotherapy (ART) refers to treatment of patients with an undetectable PSA that is delivered after surgery (usually less than 12-16 weeks from the time of surgery). Currently, there are no standardized guidelines for the use of ART and the bulk of patients are solely monitored for signs of recurrence after prostatectomy. In this article, we review the evidence for ART from three randomized clinical trials. Although radiation therapy in the adjuvant setting has generally been well tolerated, we also examine the complication data associated with treatment. In addition, we discuss the technical aspects of treatment, including dose escalation and treatment target volume. The ability to increase dose and limit target volume would likely result in higher cure rates and decreased side effects, thus ensuring a better clinical outcome and increasing quality of life. Finally, we discuss the cost-effectiveness of ART, in the context of other medical interventions.
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PMID:Adjuvant radiotherapy after radical prostatectomy: evidence and analysis. 2066 60

The possibility that anesthetic drugs can influence cancer recurrence rate is a subject of recent interest. Based on early in vitro data demonstrating opiates on breast cancer xenografts and two recent epidemiologic studies suggesting differences in recurrence rates in both breast and prostate cancer contingents dependent on whether patients received a combined regional-general anesthetic or a general anesthetic with opioid analgesia, there has been recent interest in the role of the micro-opioid receptor (MOR) in angiogenesis and oncogenic signaling. We recently demonstrated that morphine causes reciprocal transactivation of the MOR and VEGF receptors and that MOR-knockout mice do not develop significant tumors when injected with lung cancer cells as do their wild-type controls. Furthermore, infusion of the peripheral MOR antagonist methylnaltrexone markedly attenuates tumor growth in experimental mouse models. These experimental data support the hypothesis that opioids affect tumor progression and suggest the MOR as a potential target for chemotherapeutic drugs.
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PMID:Effect of perioperative opioids on cancer recurrence: a hypothesis. 2079 70

In patients with prostate cancer, a positive surgical margin is associated with an increased risk of cancer recurrence and poorer outcome, yet margin status cannot be determined during the surgery. An in vivo optical imaging probe that could identify the tumor margins during surgery could result in improved outcomes. The design of such a probe focuses on a highly specific targeting moiety and a near-infrared (NIR) fluorophore that is activated only when bound to the tumor. In this study, we successfully synthesized an activatable monoclonal antibody-fluorophore conjugate consisting of a humanized anti-Prostate-Specific Membrane Antigen (PSMA) antibody (J591) linked to an indocyanine green (ICG) derivative. Prior to binding to PSMA and cellular internalization, the conjugate yielded little light; however, after binding an 18-fold activation was observed permitting the specific detection of PSMA+ tumors up to 10 days after injection of a low dose (0.25 mg/kg) of the reagent. This agent demonstrates promise as a method to image the extent of prostate cancer in vivo and could assist with real-time resection of extracapsular extension of tumor and positive lymph nodes.
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PMID:Targeted, activatable, in vivo fluorescence imaging of prostate-specific membrane antigen (PSMA) positive tumors using the quenched humanized J591 antibody-indocyanine green (ICG) conjugate. 2174 58

The bone marrow microenvironment provides a site for cancer cells to evade systemic anticancer therapy. Dormant tumor micrometastases are believed to be the source of disease persistence and relapse; however, the exact characteristics of cancer stem cells vs. cancer cells with limited metastatic potential have yet to be elucidated. Bisphosphonates inhibit osteoclast-mediated bone resorption, are approved for treating malignant bone disease from advanced cancers, and have shown efficacy for preventing cancer treatment-induced bone loss. Altering the bone marrow microenvironment to make it less conducive to cancer cell survival is now emerging as an important means to prevent cancer recurrence. This review aims to distill the diverse literature and provide a brief overview of the numerous preclinical and early clinical studies of bisphosphonates demonstrating a variety of direct and indirect anticancer activities that affect both the tumor cell (the "seed") and surrounding microenvironment (the "soil"). Recently, zoledronic acid was found to improve disease-free survival and overall survival in some adjuvant breast cancer settings and prolonged survival in patients with multiple myeloma and other advanced cancers. In the prostate cancer setting, antiresorptive therapy was reported to delay the development of overt bone metastases. Ongoing studies will provide further insight regarding the anticancer potential of bisphosphonates and other antiresorptive agents.
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PMID:Direct and indirect anticancer activity of bisphosphonates: a brief review of published literature. 2198 64

Paraneoplastic neurological syndromes are defined as the remote effects of cancer on the nervous system. Here we report a 68-year-old man who initially presented with worsening paresthesia in the lower extremities. Although the culprit lesion remained to be identified, he coincidentally had diagnosis of prostate cancer by an annual prostate-specific antigen examination. Leukocytosis and elevated granulocyte colony-stimulating factor in serum were also detected. Neurological symptoms and leukocytosis improved after initiation of androgen-deprivation therapy followed by external beam radiotherapy. A total of 9 months after treatment, the patient showed no evidence of cancer recurrence or neurological signs. Paraneoplastic neurological syndromes are rare in prostate cancer and therefore have received little attention. We should be aware that when paraneoplastic neurological syndromes occur, they usually occur as the first sign of or during progression of prostate cancer. Furthermore, we should take into account the existence of malignancy when the cause of neurological symptoms cannot be specified.
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PMID:Paraneoplastic neurological and hematological syndromes associated with prostate cancer. 2222 Sep 77

The majority of cancer patients experience some form of body composition change during the disease trajectory. For example, breast cancer patients undergoing chemotherapy and prostate cancer patients undergoing androgen deprivation therapy gain fat and lose skeletal muscle, which are associated with increased risk of cancer recurrence and clinical comorbidities. In contrast, advanced cancer patients, such as lung and colorectal cancer patients, experience symptoms of cancer cachexia (accelerated loss of skeletal muscle with or without adipose tissue loss), which are associated with decreased treatment response and poorer survival rates in advanced cancers. The heterogeneity of body composition features and their diverse implications across different cancer populations supports the need for accurate quantification of muscle and adipose tissue. Use of appropriate body composition modalities will facilitate an understanding of the complex relationship between body composition characteristics and clinical outcomes. This will ultimately support the development and evaluation of future therapeutic interventions that aim to counter muscle loss and fat gain in cancer populations. Despite the various metabolic complications that may confound the accurate body composition measurement in cancer patients (i.e., dehydration may confound lean tissue measurement), there are no guidelines for selecting the most appropriate modalities to make these measurements. In this review we outline specific considerations for choosing the most optimal approaches of lean and adipose tissue measurements among different cancer populations. Anthropometric measures, bioelectrical impedance analysis, air displacement plethysmography, dual-energy X-ray absorptiometry, computed tomography, and magnetic resonance imaging will be discussed.
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PMID:A critical evaluation of body composition modalities used to assess adipose and skeletal muscle tissue in cancer. 2273 36


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