Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is the most common cancer in men, both in the USA and Europe. Although incurable, metastatic disease can often be controlled for years with anti-androgen therapy. Once the disease becomes castrate resistant, the median survival is 18 months. There is growing evidence that the immune system, and in particular cytokines, play an important role in prostate cancer immunosurveillance and progression. Here, we have undertaken a clinical investigation of the role of two closely related cytokines, IL-4 and IL-13 in prostate cancer. In the largest series studied to date, we show that serum IL-4, but not IL-13 is significantly elevated in castrate resistant, compared to androgen sensitive disease. Notably however, serum IL-4 levels are also raised in patients with benign prostatic disease. Analysis of benign and malignant prostate tissue demonstrates that the source of IL-4 is epithelial cells rather than infiltrating leukocytes. Together, our data are consistent with a dual role for IL-4 in prostate cancer development. In benign disease, our data add to the evidence that IL-4 serves a protective role. By contrast, the data support a direct role for IL-4 in the progression of prostate cancer from androgen responsive, to advanced castrate-resistant disease.
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PMID:Clinical investigation of the role of interleukin-4 and interleukin-13 in the evolution of prostate cancer. 2421 39

The 68Ga-prostate-specific membrane antigen ( 68Ga-PSMA) has been recently developed to be used, as a ligand, in positron emission tomography/computed tomography (PET/CT) prostate cancer imaging, to detect prostate disease. The main objective of this review was to collect data and findings from other studies and articles to assess, theoretically, if 68GA-PSMA PET/CT is a more appropriate prostate cancer diagnostic technique in comparison with others available such as CT, 18F-fluoro-2-deoxyglucose PET/CT, or 18F-fluoromethylcholine ( 18F-choline) PET/CT. For that purpose, PubMed, the online scientific articles' database, was consulted where the keywords "PSMA" and "PET" were used to find relevant articles. The clinicaltrials.gov, clinical trials' database, was also consulted where the keywords "68Ga-PSMA" and "prostate" were used to search clinical trials. Based on the reviewed scientific literature, several studies were conducted to assess and compare the 68Ga-PSMA PET/CT detection rate in prostate cancer with other available techniques. One of those studies, conducted by Giesel et al., concluded, within study sample, that 75% of patients with lymph nodes detected by 68Ga-PSMA PET/CT would have not been identified using other conventional morphological criteria based techniques. In Eiber et al.'s study, 68Ga-PSMA PET detected prostatic disease findings in 67% of patients with prostate-specific antigen levels <1 ng/mL, when compared with choline-based PET that presented detection rates between 19% and 36%. In Bluemel et al.'s study, 68Ga-PSMA identified positive prostatic disease in 43.8% of the patients with negative findings in F-choline PET/CT. Findings from this review demonstrate that 68Ga-PSMA PET/C is more effective in detecting metastases, lymph nodes, and recurrent prostate cancer when compared to 18F-choline-based PET/CT and CT. 68Ga-PSMA PET/CT presents also more imaging contrast and can be more cost-effective. 68Ga-PSMA has already been subjected to first-in-human trials, and it is now being tested in Phase II and III trials.
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PMID:68Ga-prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Prostate Cancer Imaging: A Narrative Literature Review. 2821 12

Telomere shortening has been demonstrated in benign prostatic hypertrophy (BPH), which is associated with prostate epithelial cell senescence. Telomere shortening is the most frequently observed genetic alteration in prostatic intraepithelial neoplasia, and is associated with poor clinical outcomes in prostate cancer. Gene expression database analysis revealed decreased TRF2 expression during malignant progression of the prostate gland. We reasoned that reduced TRF2 expression in prostate epithelium, by activating the telomere DNA damage response, would allow us to model both benign and malignant prostate disease. Prostate glands with reduced epithelial TRF2 expression developed age- and p53-dependent hypertrophy, senescence, ductal dilation, and smooth muscle hyperplasia similar to human BPH. Prostate tumors with reduced TRF2 expression were classified as high-grade androgen receptor-negative adenocarcinomas, which exhibited decreased latency, increased proliferation, and distant metastases. Prostate cancer stem cells with reduced TRF2 expression were highly tumorigenic and maintained telomeres both by telomerase and alternative lengthening (ALT). Telomerase inhibition in prostate glands with reduced TRF2 expression produced significant reduction in prostate tumor incidence by halting progression at intraepithelial neoplasia (PIN). These lesions were highly differentiated, exhibited low proliferation index, and high apoptotic cell fraction. Prostate tumors with reduced TRF2 expression and telomerase inhibition failed to metastasize and did not exhibit ALT. IMPLICATIONS: Our results demonstrate that the telomere DNA damage response regulates BPH, PIN, and prostate cancer and may be therapeutically manipulated to prevent prostate cancer progression.
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PMID:Telomere DNA Damage Signaling Regulates Prostate Cancer Tumorigenesis. 3246 72

Canine prostatic adenocarcinoma is an aggressive malignancy characterized by rapid growth, local invasiveness, and early metastatic spread. Metastases of prostatic cancer are generally diffuse at the time of diagnosis due to hematogenous or lymphatic spread and by direct exfoliation of neoplastic cells into the peritoneal cavity. Here we describe two dogs with prostatic adenocarcinoma and skin metastases. The first was a 12-year-old intact male German Shepherd dog that was presented with a history of chronic prostatic disease and multiple skin nodules that recently appeared on the ventral abdomen. The second was an 8-year-old intact male mixed breed dog that was referred for a neurologic examination because of a 1-month history of back pain and kyphosis of undefined origin. Cutaneous cytology of the first case was suggestive of carcinoma, and at necropsy, prostatic adenocarcinoma with metastases to the skin, spleen, liver, pancreas, kidneys, and lungs were found. In the second case, a computed tomographic examination revealed a prostatic neoplasm with inguinal, subcutaneous, and cutaneous nodular metastases. Cytology and histopathology were suggestive of primary prostatic adenocarcinoma with cutaneous and subcutaneous metastases. To the authors' knowledge, these are the first reported cases of prostatic adenocarcinoma skin metastases in dogs with cytologic descriptions.
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PMID:Cutaneous metastases of prostatic adenocarcinoma in two dogs. 3286 40


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