Kulac I.,Johns Hopkins University |
Haffner M.C.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Yegnasubramanian S.,Johns Hopkins University |
Yegnasubramanian S.,Brady Urological Research Institute |
And 6 more authors.
Current Opinion in Urology | Year: 2015
Pupose of review The review covers arguments for and against removing the label of 'cancer' in Gleason score 6 prostate tumors. Recent findings While there are a number of factors that determine whether men elect active surveillance, the most powerful predictor remains the Gleason score. Gleason grading remains a robust and powerful predictor of outcome in patients with prostate cancer. A pure Gleason score 6 (GS6) tumor is exceedingly unlikely to cause harm in the near term, and there have been discussions regarding whether the term cancer should still be applied. In this review, we update the largely clinico-pathological arguments that have led to the suggestion to remove the cancer label from GS6 tumors, and we provide counter arguments on the basis of practical matters of needle biopsy sampling, classical histopathology, and molecular biology findings. Summary The implications are that by retaining the label of cancer and implementing the recently proposed concept of prognostic groups, with patients harboring GS6 tumors placed into the lowest category, there is still a strong rationale in support of the choice of active surveillance or watchful waiting for most patients with GS6 lesions. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Aloia A.L.,U.S. National Cancer Institute |
Sfanos K.S.,Brady Urological Research Institute |
Isaacs W.B.,Brady Urological Research Institute |
Isaacs W.B.,Sidney Kimmel Comprehensive Cancer Center |
And 6 more authors.
Cancer Research | Year: 2010
Several recent articles have reported the presence of a gammaretrovirus, termed "XMRV" (xenotropic murine leukemia virus-related virus) in prostate cancers (PCa). If confirmed, this could have enormous implications for the detection, prevention, and treatment of PCa. However, other articles report failure to detect XMRV in PCa. We tested nearly 800 PCa samples, using a combination of real-time PCR and immunohistochemistry (IHC). The PCR reactions were simultaneously monitored for amplification of a single-copy human gene, to confirm the quality of the sample DNA and its suitability for PCR. Controls showed that the PCR assay could detect the XMRV in a single infected cell, even in the presence of a 10,000-fold excess of uninfected human cells. The IHC used 2 rabbit polyclonal antisera, each prepared against a purified murine leukemia virus (MLV) protein. Both antisera always stained XMRV-infected or -transfected cells, but never stained control cells. No evidence for XMRV in PCa was obtained in these experiments. We discuss possible explanations for the discrepancies in the results from different laboratories. It is possible that XMRV is not actually circulating in the human population; even if it is, the data do not seem to support a causal role for this virus in PCa. ©2010 AACR.
Veltri R.W.,Brady Urological Research Institute |
Christudass C.S.,Johns Hopkins Hospital |
Isharwal S.,University of Minnesota
Asian Journal of Andrology | Year: 2012
Prostate cancer (PCa) results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults (such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks), followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, 'the tumor microenvironment' in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a 'seed and soil' site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin (DNA transcription) organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management. © 2012 AJA, SIMM & SJTU. All rights reserved.