Robotic Mechanical Localization of Prostate Cancer Correlates with Magnetic Resonance Imaging Scans

Purpose

To evaluate the concordance of cancer location of the tissue mapping from a mechanical pressure transducer with magnetic resonance imaging (MRI) scans.

Materials and Methods

A total of 60 indentations were performed on 5 prostate specimens obtained after radical prostatectomy utilizing a robotic indentation system. The mechanical elastic moduli of suspected malignant lesions were calculated and mapped, and their locations were compared with suspicious areas of malignancy on MRI scans.

Results

The concordance rate between the location mapping from the robotic indentation system and MRI scans results was 90.0% (54/60). The sensitivity and specificity of the robotic indentation system were 87.9% (29/33) and 92.6% (25/27), respectively. The positive predictive value and negative predictive value were 93.5% (29/31) and 93.1% (27/29), respectively.

Conclusion

The locations of malignant lesions derived from our robotic indentation system correlated strongly with the locations of suspected areas of malignancy on MRI scans. Our robotic system may provide a more targeted biopsy of the prostate than conventional non-targeted systemic biopsy, possibly improving the diagnostic accuracy of prostatic biopsies for cancer.     

脂肪酸合成酶在肿瘤中表达的调节机制

脂肪酸合成酶(fatty acid synthase,FASN)是肿瘤脂质生成的一种关键酶,在催化脂肪酸合成的最后一步中发挥重要作用.FASN在许多肿瘤细胞中过表达而在相应的正常细胞中却不表达.有证据表明FASN是一个代谢性癌基因,在癌细胞中高表达,在肿瘤生长和存活中有重要的作用.FASN在肿瘤中的表达调节是一个很复杂的过程,包括转录水平、翻译后控制和微环境状态的影响.正确认识FASN在肿瘤中的表达调节机制和研究新的FASN抑制剂,为成功治疗肿瘤提供一种新的思路.     

Prognostic Value of Prostaglandin-endoperoxide Synthase 2 Polymorphisms in Prostate Cancer Recurrence after Radical Prostatectomy

Backgroud: Increasing evidence suggests the involvement of chronic inflammation in the progression of prostate cancer, and prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase-2, catalyzes the rate-limiting steps of the pathway. We hypothesized that genetic variants of PTGS2 can influence the outcome of prostate cancer patients.Methods: We genotyped five haplotype-tagging single-nucleotide polymorphisms (SNPs) to detect common genetic variations across the PTGS2 region in 458 prostate cancer patients treated with radical prostatectomy.Results: One SNP, rs4648302, was associated with disease recurrence. Five-year recurrence-free survival rate increased according to the number of variant alleles inherited (55.6%, 70.7%, and 100.0% for patients with different genotypes; P = 0.037), and the effect was maintained in multivariable analysis. Public dataset analyses also suggested that PTGS2 expression was correlated with prostate cancer prognosis.Conclusion: Our results indicated that PTGS2 could be a potential prognostic marker to improve the prediction of disease recurrence in prostate cancer patients.     

Nuclear Localization of Annexin A1 Correlates With Advanced Disease and Peritoneal Dissemination in Patients with Gastric Carcinoma

Annexin A1 (ANXA1) is a multifunctional molecule, which mediates various important physiologic processes depending on its subcelluar localization. The purpose of this study was to investigate the expression of ANXA1 level and its subcellular localization in paired clinical samples of gastric adenocarcinoma and adjacent normal counterpart. The study also assesses the clinical significance of ANXA1 subcelluar localization in gastric adenocarcinoma. A total of 104 paired resected gastric adenocarcinoma and corresponding normal specimens were collected in this study. Expression of ANXA1 was examined by immunohistochemical staining. Both cytoplasmic and nuclear ANXA1 expression levels and their correlation with clinicopathological parameters were assessed. ANXA1 protein expression was positive in 72 of 104 (69.2%) normal tissues and 47 of 104 (45.2%) gastric adenocarcinoma tissues. ANXA1 staining was predominantly localized in the cytoplasm in all 72 ANXA1‐positive normal specimens, whereas 12 ANXA1‐positive gastric adenocarcinoma specimens showed positive nuclear staining. The positive nuclear staining correlated well with serosal invasion, peritoneal dissemination and TNM stage. Cases with positive nuclear staining presented more peritoneal dissemination (41.7%, 5/12) than those with negative nuclear staining (8.7%, 8/92; P = 0.007). A logistic regression model revealed that positive ANXA1 nuclear staining had an independent association with peritoneal dissemination (P = 0.039; hazards ratio, 9.499; 95% confidence interval, 1.159–77.815). These results indicated that ANXA1 is expressed in both gastric adenocarcinoma and normal tissues. In gastric adenocarcinoma tissues ANXA1 is expressed both in cytoplasm and nucleus and its nuclear localization correlates with advanced disease stage and peritoneal dissemination. Anat Rec 293:1310–1314, 2010. © 2010 Wiley‐Liss, Inc.     

Inhibition of Prostate Cancer Cell Colony Formation by the Flavonoid Quercetin Correlates with Modulation of Specific Regulatory Genes

The natural product quercetin is a flavonoid found in many fruits and vegetables. Previous research has shown that quercetin has antitumor, anti-inflammatory, antiallergic, and antiviral activities. In the present investigation we studied the effect of quercetin on the ability of prostate cancer cell lines with various degrees of aggressive potential to form colonies in vitro. Specifically, we examined the molecular mechanisms underlying this effect, including the expression of cell cycle and tumor suppressor genes as well as oncogenes. We observed that quercetin at concentrations of 25 and 50 μM significantly inhibited the growth of the highly aggressive PC-3 prostate cancer cell line and the moderately aggressive DU-145 prostate cancer cell line, whereas it did not affect colony formation by the poorly aggressive LNCaP prostate cancer cell line or the normal fibroblast cell line BG-9. Using the gene array methodology, we found that quercetin significantly inhibited the expression of specific oncogenes and genes controlling G₁, S, G₂, and M phases of the cell cycle. Moreover, quercetin reciprocally up-regulated the expression of several tumor suppressor genes. In conclusion, our results demonstrate that the antitumor effects of quercetin directly correlate with the aggressive potential of prostate cancer cells and that the mechanism(s) of quercetin-mediated antitumor effects may involve up-regulation of tumor suppressor genes and reciprocal down-regulation of oncogenes and cell cycle genes. The results of these studies provide a scientific basis for the potential use of flavonoids as nutraceuticals in the chemoprevention of cancer.     

Identification of Novel Residues Involved in Nuclear Localization of a Baculovirus Polyhedrin Protein

A baculovirus polyhedrin protein has proven to possess a nuclear localization signal (NLS) sequence and a domain required for supramolecular assembly. Here we investigated five Bombyx mori nucleopolyhedrovirus (BmNPV) mutants that did not produce polyhedra. Two of five mutants were generated during routine baculoviral expression vector screening, and three were isolated by treatment with the mutagen 5-bromo-2-deoxyuridine (BrdU). Marker rescue mapping and nucleotide sequence analysis showed that mutations in the polyhedrin gene caused the altered phenotype of these mutants. Biochemical fractionation indicated that cells infected with these mutants exhibited polyhedrin protein in both the nucleus and the cytoplasm. Electron microscopic observation revealed that polyhedrin produced by these mutants ocurred in both the nucleus and the cytoplasm, but did not form a crystalline lattice. Despite the incompleteness of polyhedrin nuclear localization, the NLSs of the five mutants were unchanged, although some of the mutations occurred within residues just outside of the domain reported to be required for polyhedron assembly (4). This result suggests that (a) the polyhedrin NLS directs polyhedrin to the nucleus, but the efficiency of this localization is regulated by regions other than the NLS (probably, polyhedrin conformation and its association with the nucleus are also involved), and (b) formation of a crystalline lattice may also be determined by several domains within polyhedrin.     

Trophoblastic Neoplasms Express Fatty Acid Synthase,Which May Be a Therapeutic Target via Its Inhibitor C93

Fatty acid synthase (FASN) is an emerging tumor-associated marker and a promising antitumor therapeutic target. In this study, we analyzed the expression of FASN in normal and molar placentas, as well as gestational trophoblastic neoplasia, and assessed the effects of a new FASN inhibitor, C93, on cellular proliferation and apoptosis in choriocarcinoma cells. Using a FASN-specific monoclonal antibody, we found that FASN immunoreactivity was detected in the cytotrophoblast and intermediate (extravillous) trophoblast of normal and molar placentas, as well as in placental site nodules. All choriocarcinomas (n = 33), 90% of epithelioid trophoblastic tumors (n = 20), and 60% of placental site trophoblastic tumors (n = 10) exhibited FASN positivity. FASN expression was further confirmed in vitro by Western blot and real-time PCR. Treatment of JEG3 and JAR cells with C93 induced significant apoptosis through the caspase-3/caspase-9/poly(ADP)ribose polymerase pathway. Cell cycle progression was not affected by the inhibitor. In summary, the data indicate that FASN is expressed in the majority of gestational trophoblastic neoplasias, and is essential for choriocarcinoma cells to survive and escape from apoptosis. FASN inhibitors such as C93 warrant further investigation as targeted therapeutic agents for metastatic and chemoresistant gestational trophoblastic neoplasia.Gestational trophoblastic neoplasms (GTNs) represent a relatively uncommon type of gynecological tumor that behaves differently from other cancers. GTNs include choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT).¹ Clinically, GTNs are one of the few human tumors that are often cured by chemotherapy and/or local tumor resection. More specifically, nonmetastatic, low-risk GTNs treated with methotrexate or actinomycin D are almost always successfully treated, but cure rates in high-risk metastatic disease decrease to 80% to 90%, despite combination chemotherapy, surgery, and radiation.^2,3 Also, approximately 5% of low-risk and 25% of high-risk patients respond poorly to initial treatment and require salvage chemotherapeutic regimens that include platinum or paclitaxel. Unfortunately, high-risk patients who fail or relapse after first-line EMA-CO (etoposide, methotrexate, dactinomycin, vincristine, and cyclophosphamide) therapy demonstrate an overall survival of 60% to 80%.^2,4,5 Therefore, newer therapeutic regimens are needed to reduce the toxicity associated with current multi-agent chemotherapies and to salvage the occasional nonoperable patient with recurrent or chemoresistant disease.⁶ Until the fundamental biology of GTNs becomes more clearly understood, development of more novel therapies remains empirical.Clinical promise has been shown by target-based therapies designed to inactivate molecular pathways that are essential for tumor cell growth and survival. Unlike standard chemotherapy, which indiscriminately affects proliferating cells, whether normal or neoplastic, inhibitors that target specific pathways in cancer have the potential to selectively eliminate tumor cells, thereby achieving maximal therapeutic effect with minimal adverse side effects. Recent examples of successful anticancer agents include gefitinib, a small kinase inhibitor that targets epidermal growth factor receptors, and trastuzumab (Herceptin), a humanized antibody that targets HER2/neu receptors. Given the success of molecular targeting in previous clinical trials, targeted therapy in the treatment of metastatic GTNs might be applied by tailoring management based on the expression profile of tumor’s specific markers.Fatty acid synthase (FASN) is an intracellular enzyme that promotes the NADPH-dependent condensation of malonyl-CoA and acetyl-CoA to palmitate in endogenous lipogenesis.^7,8 In normal cells, FASN levels are generally low due to the presence of abundant dietary lipids, but in neoplastic cells, FASN expression is up-regulated despite the presence of dietary lipids. Upregulation of FASN is observed in several types of human cancer including carcinomas of the breast, colon, ovary, and prostate.^{9,10,11,12,13,14} In this study, we assessed the biological role of FASN in GTN and in normal and molar placentas. We found that FASN expression in cytotrophoblast and intermediate (extravillous) trophoblastic cells is unique in that both normal and neoplastic trophoblastic cells express FASN. This is in contrast to most other tissue types, which preferentially express FASN in tumor cells, but not in their normal or benign counterparts. Moreover, inactivation of FASN led to massive apoptosis in choriocarcinoma cell lines, suggesting that FASN expression is required for the survival of choriocarcinoma cells. These results suggest that FASN inhibitor may be potentially useful as a new therapeutic reagent for advanced stage choriocarcinoma.     

Coping with Prostate Cancer: A Meta-Analytic Review

The present meta-analytic review assessed the relations between coping categories and indices of adjustment in men with prostate cancer. Relevant methodological and statistical information was extracted from 33 target studies (n = 3,133 men with prostate cancer). Men with prostate cancer who used approach, problem-focused, and emotion-focused coping were healthier both psychologically and physically, although the effect sizes for problem-focused coping and emotion-focused coping were more modest. For approach coping these effect sizes were particularly strong for measures of self-esteem, positive affect, depression, and anxiety. Conversely, men with prostate cancer who used avoidance coping experienced heightened negative psychological adjustment and physical health, and particularly for measures of positive mood and physical functioning. The findings of this study suggest that active approaches to coping with prostate cancer are beneficial psychologically, physically, and are positively associated with a return to pre-cancer activities.