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

Sialic acids are key determinants in many carbohydrates involved in biological recognition. We studied the acceptor specificities of three cloned sialyltransferases (STs) [alpha2,3(N)ST, alpha2,3(O)ST, and alpha2,6(N)ST] and another alpha2,3(O)ST present in prostate cancer cell LNCaP toward mucin core 2 tetrasaccharide [Galbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-Bn] and Globo [Galbeta1,3GalNAcbeta1,3Galalpha-O-Me] structures containing sialyl, fucosyl, sulfo, methyl, or fluoro substituents by identifying the products by electrospray ionization tandem mass spectral analysis and other biochemical methods. The Globo precursor was an efficient acceptor for both alpha2,3(N)ST and alpha2,3(O)ST, whereas only alpha2,3(O)ST used its deoxy analogue (d-Fucbeta1,3GalNAcbeta1,3-Gal-alpha-O-Me); 2-O-MeGalbeta1,3GlcNAc and 4-OMeGalbeta1,4GlcNAc were specific acceptors for alpha2,3(N)ST. Other major findings of this study include: (i) alpha2,3 sialylation of beta1,3Gal in mucin core 2 can proceed even after alpha1,3 fucosylation of beta1,6-linked LacNAc. (ii) Sialylation of beta1,3Gal must precede the sialylation of beta1,4Gal for favorable biosynthesis of mucin core 2 compounds. (iii) alpha2,3 sialylation of the 6-O-sulfoLacNAc moiety in mucin core 2 (e.g., GlyCAM-1) is facilitated when beta1,3Gal has already been alpha2,3 sialylated. (iv) alpha2,6(N)ST was absolutely specific for the beta1,4Gal in mucin core 2. Either alpha1,3 fucosylation or 6-O-sulfation of the GlcNAc moiety reduced the activity. Sialylation of beta1,3Gal in addition to 6-O-sulfation of GlcNAc moiety abolished the activity. (v) Prior alpha2,3 sialylation or 3-O-sulfation of beta1,3Gal would not affect alpha2,6 sialylation of Galbeta1,4GlcNAc of mucin core 2. (vi) A 3- or 4-fluoro substituent in beta1,4Gal resulted in poor acceptors for the cloned alpha2,6(N)ST and alpha2,3(N)ST, whereas 4-fluoro- or 4-OMe-Galbeta1,3GalNAcalpha was a good acceptor for cloned alpha2,3(O)ST. (vii) 4-O-Methylation of beta1,4Gal abolished the acceptor ability toward alpha2,6(N)ST but increased the acceptor efficiency considerably toward alpha2,3(N)ST. (viii) Just like LNCaPalpha1,2-FT and Gal-3-O-sulfotransferase T2, the cloned alpha2,3(N)ST which modifies terminal Gal in Galbeta1,4GlcNAc also efficiently utilizes the terminal beta1,3Gal in the Globo backbone. Utilization of C-3 blocked compounds such as 3-O-sulfo-Galbeta1,3GalNAcbeta1,3Galalpha-OMe as acceptors by cloned alpha2,3(O)ST and analyses of the resulting products by lectin chromatography and mass spectrometry indicate that alpha2,3(O)ST is capable of attaching NeuAc to another position in C-3-substituted beta1,3Gal.
 ...
PMID:Analysis of the specificity of sialyltransferases toward mucin core 2, globo, and related structures. identification of the sialylation sequence and the effects of sulfate, fucose, methyl, and fluoro substituents of the carbohydrate chain in the biosynthesis of selectin and siglec ligands, and novel sialylation by cloned alpha2,3(O)sialyltransferase. 1630 Apr 12

Fine-needle aspiration cytology (FNAC) is an acknowledged method for diagnosing prostate cancer. False-positive results are uncommon, but concerns have been raised that prostatic intraepithelial neoplasia (PIN) could be misinterpreted as carcinoma. Therefore, we attempted to describe cytological features of PIN. Cells were scraped from macroscopically normal areas of 177 radical prostatectomy specimens, smeared and Giemsa-stained. Histological slides from these areas were reviewed, and 17 samples with high-grade PIN and with no invasive cancer were selected. Smears from 17 invasive cancers were used for comparison. Cancer showed high cellularity and dissociation, while PIN smears only contained a few clusters of atypical cells. Pronounced nuclear atypia, prominent or multiple nucleoli and mucin were more common in cancer, while cytoplasmic granules, crystalloids and cluster size did not distinguish between PIN and cancer. In conclusion, PIN should not be diagnosed by FNAC alone. However, a highly cellular smear with pronounced atypia seems to preclude PIN.
 ...
PMID:Cytological features of prostatic intraepithelial neoplasia. 1660 50

Prostate cancer has a distinctly recognized pattern of metastases: multifocal and osteoblastic lesions involving the axial skeleton and non-calcified lymph nodes in the pelvic and lumbar aortic groups. Most adenocarcinomas are capable of producing macrocalcification. We report a case of prostate cancer with de novo calcified metastases to the liver and retroperitoneal lymph nodes mimicking the pattern usually seen in mucin-producing adenocarcinomas arising from the gastrointestinal tract. To our knowledge, this is the first such case to be reported in the literature. We propose a multifactorial mechanism that supports dystrophic calcification in this case. The knowledge of atypical presentation of metastatic disease can prevent diagnostic delay and prompt initiation of therapy.
Prostate Cancer Prostatic Dis 2006
PMID:De novo calcification of liver and nodal metastases in prostate carcinoma. 1668 12

Rectal tissue is often seen in needle biopsies of the prostate gland. On rare occasion distorted rectal glands can mimic prostatic adenocarcinoma, an issue not previously addressed in the peer-reviewed literature. We evaluated 16 prostate needle biopsies received in consultation where the submitting pathologist questioned whether a focus of rectal tissue was prostate cancer. In addition to the distorted architecture, features mimicking prostate cancer included: (1) blue-tinged intraluminal mucinous secretions in 10 cases (63%), (2) prominent nucleoli in 6 cases (37%), (3) mitotic activity in 6 cases (37%), (4) extracellular mucin in 5 cases (31%), and (5) adenomatous changes of the rectal tissue in 1 case (6%). Immunohistochemical results further mimicked prostate cancer with negative stains for the basal cell markers high-molecular weight cytokeratin (n=6) and p63 (n=4), and positive stains for racemase in 4 of 5 biopsies. Diagnostic clues to recognizing that these foci were distorted rectal fragments were the presence of (1) lamina propria in 12 cases (75%), (2) rectal tissue located on a detached fragment of tissue in 10 biopsies (63%), (3) associated inflammation in 10 cases (63%), (4) goblet cells in 7 cases (44%), and (5) muscularis propria in 6 cases (37%). In 2 cases, there was negative staining for prostate specific antigen (PSA) and in 1 case negative staining for cytokeratin 7 and positivity for cytokeratin 20. Rectal glands are associated with many of the classical features of prostate cancer, and immunohistochemistry may be misleading. Recognition of these features mimicking prostate cancer and awareness of other findings that are diagnostic of rectal tissue on biopsy can prevent a misdiagnosis of atypical prostate glands or prostate cancer.
 ...
PMID:Distorted rectal tissue on prostate needle biopsy: a mimicker of prostate cancer. 1681 29

Prostate cancer is a major public health problem throughout the developed world. For patients with clinically localised prostate cancer, the diagnosis is typically established by histopathological examination of prostate needle biopsy samples. Major and minor criteria are used to establish the diagnosis, based on the microscopic appearance of slides stained using haematoxylin and eosin. Major criteria include an infiltrative glandular growth pattern, an absence of basal cells and nuclear atypia in the form of nucleomegaly and nucleolomegaly. In difficult cases, basal cell absence may be confirmed by immunohistochemical stains for high-molecular-weight cytokeratins (marked with antibody 34betaE12) or p63, which are basal cell markers. Minor criteria include intraluminal wispy blue mucin, pink amorphous secretions, mitotic figures, intraluminal crystalloids, adjacent high-grade prostatic intraepithelial neoplasia, amphophilic cytoplasm and nuclear hyperchromasia. Another useful diagnostic marker detectable by immunohistochemistry is alpha-methylacyl coenzyme A racemase (AMACR), an enzyme selectively expressed in neoplastic glandular epithelium. Cocktails of antibodies directed against basal cell markers and AMACR are particularly useful in evaluating small foci of atypical glands, and in substantiating a diagnosis of a minimal adenocarcinoma. Reporting of adenocarcinoma in needle biopsy specimens should always include the Gleason grade and measures of tumour extent in the needle core tissue. Measures of tumour extent are (1) number of cores positive for cancer in the number of cores examined, (2) percentage of needle core tissue affected by carcinoma and (3) linear millimetres of carcinoma present.
 ...
PMID:Diagnosis of adenocarcinoma in prostate needle biopsy tissue. 1721 47

The TMPRSS2-ETS fusion prostate cancers comprise 50-70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2-ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2-ERG fusion status using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2-ERG fusion status. Five morphological features were associated with TMPRSS2-ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p-values < 0.05. Only 24% (n=30/125) of tumours without any of these features displayed the TMPRSS2-ERG fusion. By comparison, 55% (n=38/69) of cases with one feature (RR=3.88), 86% (n=38/44) of cases with two features (RR=20.06), and 93% (n=14/15) of cases with three or more features (RR=44.33) were fusion positive (p<0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2-ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2-ERG fusion prostate cancer, which may have both prognostic and therapeutic implications.
 ...
PMID:Morphological features of TMPRSS2-ERG gene fusion prostate cancer. 1738 88

Pretargeted radioimmunotherapy (RIT) is a promising approach to increase the therapeutic index of RIT for malignant solid tumors. For pretargeted RIT of epithelial cancers, such as breast and prostate, mucin 1 (MUC1), the epithelial mucin, was chosen as a target antigen (Ag). Overexpression, hypoglycosylation and loss of apical distribution on the cellular membrane distinguish the tumor associated MUC1 from normal MUC1. These characteristics of MUC1, best known in breast cancer, were validated in prostate cancer. The multivalent bispecific MUC1 pretargeting molecule under development consists of a tumor binding module and a radioactive hapten capturing module. The building blocks of each module were chosen as single chain antibody fragments (scFv) to be covalently attached to a multifunctional polyethylene glycol (PEG) scaffold. PEGylation studies with scFvs selected from anti-MUC1 libraries and engineered with a free thiol for site-specific conjugation showed that highest reaction yields were obtained with short monofunctional PEG molecules. To accommodate the use of a bifunctional PEG for covalent assembly of binding and capturing modules, the MUC1 binding module was developed into a di-scFv-SH format and optimized for linker length and location of the free thiol in respect to Ag binding and site-specific conjugation. Approaches under study to improve PEGylation yields with bifunctional PEG molecules include alkyne-azide cycloaddition. Assembly efficiencies, through PEGylation, of the binding and capturing modules and pharmacokinetics will influence the final valency of the MUC1 pretargeting molecule: anti-MUC1 di-scFv-PEG- anti-radioactive hapten scFv or di-scFv-PEG-anti-radioactive hapten di-scFv.
 ...
PMID:Development of anti-MUC1 di-scFvs for molecular targeting of epithelial cancers, such as breast and prostate cancers. 1746 75

Prostate cancer (CaP) is one of the most common malignancies in men, and the incidence of CaP is increasing. Because of the limitations of current therapeutic approaches, many patients die of secondary disease (metastases). Mucins are used as diagnostic markers as well as therapeutic targets due to their aberrant and unique expression pattern during cancer progression. There is a growing interest in mucins as treatment targets in human malignancies, including CaP. So far, 21 mucin genes have been identified. Of these, MUC1 has been investigated most extensively. In neoplastic tissues, MUC1 is underglycosylated compared with that in normal tissues. The reduced glycosylation permits the immune system to access the peptide core of the tumor-associated underglycosylated MUC1 antigen (uMUC1) and reveal epitopes that are masked in the normal cell. This feature makes it possible to design an antibody that discriminates between normal and adenocarcinoma cells and target tumor-associated MUC1 with toxins or radionuclides, or use a vaccine targeting tumor-associated MUC1 antigen. The results from our recent study have shown that over-expression of MUC1 plays a very important role in CaP progression and MUC1 is an ideal target for targeted therapy to control micrometastases and hormone refractory disease. This review will cover our current understanding of the structure and functions of MUC1, summarize its expression on human CaP tissues and focus on the MUC1-based immunotherapy for control of metastatic CaP.
 ...
PMID:MUC1 is a promising therapeutic target for prostate cancer therapy. 1750 23

Recurrent gene fusions between TMPRSS2 and ETS family genes have recently been shown to occur at a high frequency in prostate cancer. In this study, we used formalin-fixed paraffin-embedded tissue and evaluated both TMPRSS2-ERG and TMPRSS2-ETV1 fusions by reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). The results were correlated to overexpression of the downstream ERG and ETV1 sequences. Of 82 cases examined, TMPRSS2-ETV1 fusion was seen in only one case, by FISH. In comparison, TMPRSS2-ERG fusion was documented in 35 cases (43%) by either RT-PCR or FISH. Deletion, rather than translocation, was found to be the main mechanism for TMPRSS2-ERG gene fusion (81 vs 19%). RT-PCR and FISH results correlated well, with most positive cases resulting in overexpression of downstream ERG sequences. Several TMPRSS2-ERG fusion transcript variants were identified, most of which are predicted to encode truncated ERG proteins. Prostate cancer of Gleason's scores 6 or 7 had more frequent TMPRSS2-ERG fusions than higher-grade tumors, but this difference was not statistically significant (P=0.42). On the other hand, mucin-positive carcinomas more often harbor such gene fusions when compared to mucin-negative tumors (P=0.004). These morphological correlates, and more importantly the potential correlation of such fusions to clinical outcome and treatment responses, should be further explored.
 ...
PMID:Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues. 1763 55

Nephrogenic adenomas demonstrate a variety of morphologic patterns that may occasionally be confused with malignant processes, including urothelial and prostatic carcinoma. In this series, we describe 8 cases of nephrogenic adenoma that contain an admixture of the classic tubular form of nephrogenic adenoma and an unusual spindled and fibromyxoid form of nephrogenic adenoma that closely mimics infiltrating carcinoma. In all cases, the classic tubular form of nephrogenic adenoma composed only a small proportion of the lesion, whereas the remainder consisted of compressed spindled cells within a fibromyxoid background, with only rare tubular and cordlike structures. On close examination, minimal nuclear atypia was identified in 2 cases, which included small, pinpoint nucleoli, and nuclear pseudoinclusions. All 8 patients were elderly men who had a prior or concurrent history of acinar prostate cancer (n=4), combined acinar prostate and urothelial carcinoma (n=1), urothelial-type adenocarcinoma of the prostate (n=1), bladder urothelial carcinoma (n=1), or no prior reported prostatic or urothelial abnormalities (n=1). Five patients received prior treatment with radiotherapy, 1 patient received intravesical mitomycin-C, and 1 also received bacillus Calmette-Guerin. The epithelial component of the lesions was positive in all cases for pancytokeratin (AE1/3) and racemase and demonstrated a variable cuff of type IV collagen surrounding the tubules. PAX-2 was positive with variable extent of labeling. Immunostains for prostate-specific antigen were negative. Histochemical stains identified some of the background matrix as mucin, with intense staining for periodic acid-Schiff and focal staining for mucicarmine. Stains for reticulin and amyloid (Congo red stain) and immunohistochemistry for Tamm-Horsfall protein were negative. This case series is the first report of a fibromyxoid subtype of nephrogenic adenoma. Awareness of this entity and the use of ancillary techniques can aid in the diagnosis of this unusual form of nephrogenic adenoma.
 ...
PMID:Fibromyxoid nephrogenic adenoma: a newly recognized variant mimicking mucinous adenocarcinoma. 1766 48


<< Previous 1 2 3 4 5 6 Next >>