Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist - from mice to men

UNLABELLED Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy. METHODS Biodistribution, dosimetry and tumor uptake of the GRPr antagonist ⁶⁴Cu-CB-TE2A-AR06 [(⁶⁴Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG₄-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH₂] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). RESULTS No adverse events were observed after injection of ⁶⁴Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time. CONCLUSION ⁶⁴Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating ⁶⁴Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary.

Salivary cortisol, psychological stress and depressive symptoms among patients undergoing colon cancer screenings

As the second leading cause of cancer-related deaths in the United States, colon cancer has a high cure rate if detected early by a colonoscopy (U.S. Cancer Statistics Working Group, 2007). However, more than 41 million at-risk Americans are not properly receiving colonoscopy screenings according to the recommendations of the Center for Disease Control. This study provides insight into the physiological and psychological benefits of the colonoscopy procedure over and above cancer detection and prevention. Thirty-six patients receiving colonoscopic screening at the University of Connecticut Health Center participated in this study. A questionnaire battery that assessed perceived stress, depressive symptoms, colon cancer related worry, and social support, and optional saliva sampling was completed 2 weeks prior to and post colonoscopy. It was hypothesized that salivary cortisol concentrations, perceived stress, and self-reported depressive symptoms would show significant decreases from pre to post colonoscopy, and that these variables would all be positively correlated with one another. Results showed significant, positive correlations between depressive symptoms and both salivary cortisol (r (34)= .348, p< .05) and perceived stress (r (34)= .635, p< .01). Morning salivary cortisol levels decreased significantly from pre to post colonoscopy to levels below the population mean (t (16)=-3.711, p<. 01). No such differences were observed in either perceived stress or depressive symptoms. These results indicate that by decreasing cortisol concentrations to levels below that of the population mean, the colonoscopy provided physiological health benefits to patients beyond cancer screening. From a health psychology standpoint, this may encourage some of the 41 million Americans not receiving proper colon cancer screenings to adopt this potentially life-saving health behavior.

Improvement for detection of microcalcifications through clustering algorithms and artificial neural networks

A new method for detecting microcalcifications in regions of interest (ROIs) extracted from digitized mammograms is proposed. The top-hat transform is a technique based on mathematical morphology operations and, in this paper, is used to perform contrast enhancement of the mi-crocalcifications. To improve microcalcification detection, a novel image sub-segmentation approach based on the possibilistic fuzzy c-means algorithm is used. From the original ROIs, window-based features, such as the mean and standard deviation, were extracted; these features were used as an input vector in a classifier. The classifier is based on an artificial neural network to identify patterns belonging to microcalcifications and healthy tissue. Our results show that the proposed method is a good alternative for automatically detecting microcalcifications, because this stage is an important part of early breast cancer detection

Microcalcifications Detection using PFCM and ANN

This work presents a method to detect Microcalcifications in Regions of Interest from digitized mammograms. The method is based mainly on the combination of Image Processing, Pattern Recognition and Artificial Intelligence. The Top-Hat transform is a technique based on mathematical morphology operations that, in this work is used to perform contrast enhancement of microcalcifications in the region of interest. In order to find more or less homogeneous regions in the image, we apply a novel image sub-segmentation technique based on Possibilistic Fuzzy c-Means clustering algorithm. From the original region of interest we extract two window-based features, Mean and Deviation Standard, which will be used in a classifier based on a Artificial Neural Network in order to identify microcalcifications. Our results show that the proposed method is a good alternative in the stage of microcalcifications detection, because this stage is an important part of the early Breast Cancer detection

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Expression of prostate-specific antigen variant MRNA transcripts in prostate cancer and benign prostatic hyperplasia

Prostate-specific antigen (PSA) is important in tumour detection, monitoring disease progression and tumour recurrence. however, PSA is not a cancerspecific marker as levels can also be elevated in benign prostatic disease. A number of different mRNA transcripts of PSA have also been identified in prostatic tissue, but have not been fully characterized (PSA 424, PSA 525, Schulz transcript). Tissue specimens from transurethral resection of the prostate (TURP) or radical prostatectomy were obtained from 17 men with BPH and 15 men with prostate cancer. Total RNA was extracted, and reverse-transcriptionpolymerase chain reaction (RT-PCR) and Southern analysis carried out using transcript-specific primers and probes to determine which mRNA PSA transcripts were expressed. Real-time PCR was performed to determine transcript levels between the two groups using transcript-specific primers and SYBR green fluorescence. Values obtained were normalized to a standard housekeeping gene, B2-microglobulin. Transcripts amplified by RT-PCR and real-time PCR were confirmed by DNA sequencing. Our results show that the transcripts were present in some, but not all, BPH and cancer samples indicating that they are not specific to either BPH or cancer. Analysis of real-time PCR normalized values using a Student’s t -test, shows that there is a significant difference between the two groups for PSA 424, but not wild-type PSA, PSA 525 or the Schulz transcript. Although a larger cohort of samples is needed to further confirm these results, these findings suggest that mRNA levels of PSA 424 may have some utility as a diagnostic or prognostic marker in prostate cancer detection.

Fractal Analysis for Cancer Research: Case Study and Simulation of Fractals

2010 Mathematics Subject Classification: 65D18.

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93-1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93-1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82-1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76-1.10]). Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).

Virtual Clinical Trials in PET Imaging for Improved Diagnosis of and Evaluation of Therapies for Cancer

Thesis (Ph.D.)--University of Washington, 2016-08

Rs266882 polymorphism analysis in KLK3 gene by RFLPPCR in cases of prostate cancer

Poster presented at the From Basic Sciences to Clinical Research - First International Congress of CiiEM. Egas Moniz, Caparica, Portugal, 27-28 November 2015

Community perceptions of bowel cancer: A survey of Queenslanders

Bowel cancer is the third most common cancer in Australia. The Australian Cancer Society has set a national goal 'to exploit prevention opportunities and to increase early detection'. To address this goal, information about community perceptions is required. Through the use of a Delphi process, a questionnaire was developed to investigate community knowledge, attitudes and beliefs regarding primary prevention and early detection activities. This paper describes the results of a postal survey of a random sample of 855 Queensland adults selected from electoral rolls. Results indicate that there is a high level of uncertainty about bowel cancer and a belief that many behaviours are related to bowel cancer. While 74 per cent believed that tests could detect bowel cancer, only 52 per cent were confident that a doctor could accurately diagnose it. Only 35 per cent agreed that the public should be screened for bowel cancer and only 10 per cent would get a check-up. Perhaps reflecting the degree of uncertainty among health professionals about bowel cancer, there appears to be a high level of misinformation and confusion in the community. The need for an educational programme to address these issues is discussed. Article in Health Education Journal 54(3):331-339 September 1995

Changes in skin protection behaviors, attitudes, and sunburn: In a population with the highest incidence of skin cancer in the world

This study describes changes in skin protection attitudes and outdoor behaviors of adults in Queensland, Australia, using two cross-sectional telephone surveys conducted in 1988/89 (N = 1699) and 1991/92 (N = 2317). After adjustment for potential confounders, there were significant improvements in some skin protection attitudes, time spent outside, hat wearing, sunscreen use, overall skin protection (p < 0.01) and shade use (p < 0.05) between 11:00 AM and 3:00 PM on the previous Sunday. The degree of attitudinal and behavioral change varied with age, gender, region, and reported skin type. However, recent sunburn experience remained unchanged. A similar study in Victoria, Australia, observed changes in skin protection attitudes, behaviors, and recent sunburn. We speculate on possible explanations for the lack of improvement in recent sunburn experience despite the improvement in skin protection attitudes, and behaviors, and suggest that part of the explanation may be environmental differences. This has implications for generalizability of such studies outside the geographical region in which they were conducted. Article in Cancer Detection and Prevention 20(6):566-75 · January 1996

Comparison of multispectral wide-field optical imaging modalities to maximize image contrast for objective discrimination of oral neoplasia

Multispectral widefield optical imaging has the potential to improve early detection of oral cancer. The appropriate selection of illumination and collection conditions is required to maximize diagnostic ability. The goals of this study were to (i) evaluate image contrast between oral cancer/precancer and non-neoplastic mucosa for a variety of imaging modalities and illumination/collection conditions, and (ii) use classification algorithms to evaluate and compare the diagnostic utility of these modalities to discriminate cancers and precancers from normal tissue. Narrowband reflectance, autofluorescence, and polarized reflectance images were obtained from 61 patients and 11 normal volunteers. Image contrast was compared to identify modalities and conditions yielding greatest contrast. Image features were extracted and used to train and evaluate classification algorithms to discriminate tissue as non-neoplastic, dysplastic, or cancer; results were compared to histologic diagnosis. Autofluorescence imaging at 405-nm excitation provided the greatest image contrast, and the ratio of red-to-green fluorescence intensity computed from these images provided the best classification of dysplasia/cancer versus non-neoplastic tissue. A sensitivity of 100% and a specificity of 85% were achieved in the validation set. Multispectral widefield images can accurately distinguish neoplastic and non-neoplastic tissue; however, the ability to separate precancerous lesions from cancers with this technique was limited. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3516593]

Building a Open Source Framework for Virtual Medical Training

This paper presents a framework to build medical training applications by using virtual reality and a tool that helps the class instantiation of this framework. The main purpose is to make easier the building of virtual reality applications in the medical training area, considering systems to simulate biopsy exams and make available deformation, collision detection, and stereoscopy functionalities. The instantiation of the classes allows quick implementation of the tools for such a purpose, thus reducing errors and offering low cost due to the use of open source tools. Using the instantiation tool, the process of building applications is fast and easy. Therefore, computer programmers can obtain an initial application and adapt it to their needs. This tool allows the user to include, delete, and edit parameters in the functionalities chosen as well as storing these parameters for future use. In order to verify the efficiency of the framework, some case studies are presented.

Optimization of breast tomosynthesis image reconstruction using parallel computing

Breast cancer is the most common cancer among women, being a major public health problem. Worldwide, X-ray mammography is the current gold-standard for medical imaging of breast cancer. However, it has associated some well-known limitations. The false-negative rates, up to 66% in symptomatic women, and the false-positive rates, up to 60%, are a continued source of concern and debate. These drawbacks prompt the development of other imaging techniques for breast cancer detection, in which Digital Breast Tomosynthesis (DBT) is included. DBT is a 3D radiographic technique that reduces the obscuring effect of tissue overlap and appears to address both issues of false-negative and false-positive rates. The 3D images in DBT are only achieved through image reconstruction methods. These methods play an important role in a clinical setting since there is a need to implement a reconstruction process that is both accurate and fast. This dissertation deals with the optimization of iterative algorithms, with parallel computing through an implementation on Graphics Processing Units (GPUs) to make the 3D reconstruction faster using Compute Unified Device Architecture (CUDA). Iterative algorithms have shown to produce the highest quality DBT images, but since they are computationally intensive, their clinical use is currently rejected. These algorithms have the potential to reduce patient dose in DBT scans. A method of integrating CUDA in Interactive Data Language (IDL) is proposed in order to accelerate the DBT image reconstructions. This method has never been attempted before for DBT. In this work the system matrix calculation, the most computationally expensive part of iterative algorithms, is accelerated. A speedup of 1.6 is achieved proving the fact that GPUs can accelerate the IDL implementation.