Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies
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Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies
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Scooped by Miguel Martín-Landrove!

Tumor-Specific Binding of Radiolabeled PEGylated GIRLRG Peptide: A Novel Agent for Targeting Cancers

Vaishali Kapoor, David Y.A. Dadey, Kim Nguyen, Scott A. Wildman, Kelly Hoye, Arpine Khudanyan, Nilantha Bandara, Buck E. Rogers, Dinesh Thotala, Dennis E. Hallahan

J Nucl Med December 1, 2016 vol. 57 no. 12 1991-1997

Cancer-specific targeting sparing normal tissues would significantly enhance cancer therapy outcomes and reduce cancer-related mortality. One approach is to target receptors or molecules that are specifically expressed on cancer cells. Peptides as cancer-specific targeting agents offer advantages such as ease of synthesis, low antigenicity, and enhanced diffusion into tissues. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum stress chaperone that regulates the unfolded protein response and is overexpressed in various cancers. In this study, we evaluated GIRLRG peptide that specifically targets GRP78 for cancer-specific binding (in vitro) and noninvasive tumor imaging (in vivo). Methods: GIRLRG peptide was modeled into the GRP78 ATPase domain using computational modeling. Surface plasmon resonance studies were performed to determine the affinity of GIRLRG peptide to GRP78 protein. GIRLRG was conjugated with PEG to prolong its circulation in mice. Tumor binding efficacy of PEG-GIRLRG peptide was evaluated in nude mice bearing heterotopic cervical (HT3), esophageal (OE33), pancreatic (BXPC3), lung (A549), and glioma (D54) tumors. Nano-SPECT/CT imaging of the mice was performed 48 and 72 h after injection with 111In-labeled PEG-GIRLRG or PEG-control peptide. Post-SPECT biodistribution studies were performed 96 h after injection of the radiolabeled peptides. Results: Using molecular modeling and surface plasmon resonance, we identified that GIRLRG was binding with an affinity constant of 2.16 × 10−3 M in the ATPase domain of GRP78. GIRLRG peptide specifically bound to cervical, lung, esophageal, and glioma cells. SPECT imaging revealed that 111In-PEG-GIRLRG specifically bound to cervical, esophageal, pancreatic, lung, and brain tumors. Post-SPECT biodistribution data also validated the SPECT imaging results. Conclusion: GIRLRG peptide specifically binds to the ATPase domain of GRP78. Radiolabeled PEG-GIRLRG could be used to target various cancers. Further studies would be required to translate PEG-GIRLRG peptide into the clinic.

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Scientists reveal genetic root of prostate cancer

Scientists reveal genetic root of prostate cancer | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |

By James McIntosh

The research, published in Nature, is part of the International Cancer Genome Consortium - a global project committed to revealing genetic changes driving prostate cancer, using the most up-to-date gene-sequencing technology available.

Tumor samples from 10 men with prostate cancer were analyzed, allowing the researchers to map a "family tree" of changes occurring at a genetic level as the cancer develops.

The researchers also learned more about how the disease spreads through the body and forms new tumors. They discovered that the first group of cells that spread from the prostate continues to travel throughout the body, developing new tumors as it goes.

"We gained a much broader view of prostate cancer by studying both the original cancer and the cells that had spread to other parts of the body in these men," says study author Prof. Ros Eeles from the Institute of Cancer Reseach in London, UK. "And we found that all of the cells that had broken free shared a common ancestor cell in the prostate."

Prostate cancer is the second most common cancer in American men behind skin cancer and the second most common cause of cancer death behind lung cancer. Around 1 in 7 men will be diagnosed with prostate cancer during their lifetime.

According to American Cancer Society (ACS) estimates, in 2015, around 220,800 new cases of prostate cancer will be diagnosed, and 27,540 deaths will occur attributable to the disease.

The researchers have already discovered that cancer cells taken from different sites within a man's prostate can be very diverse genetically. Despite this, the new study found that cancer cells moving away from the prostate share genetic faults that are unique to the man whose cancer it is.

"The common faults we found in each man could potentially offer new targets for treatment," states Prof. Eeles. "But we found that, once cancer cells have spread, they continue to evolve genetically, so choosing the most effective treatments will remain a key challenge."

Shared mutations represent 'a potential Achilles heel' for prostate cancer Prof. Steven Bova from the University of Tampere in Finland believes that in order to find these shared genetic faults, multiple biopsies may be needed. "We must also study more patients to learn how to apply these findings to develop more personalized treatments for people with the disease," he adds.

Learning how cancer cells change and evolve as they metastasize (spread to other parts of the body) and thus become resistant to certain forms of treatment is crucial to developing future treatments for all forms of cancer.

Senior author Dr. Ultan McDermott says that while the shared tumor-causing genetic faults mapped by their "family tree" represent a potential Achilles heel for prostate cancer, "many of these shared mutations are in tumor suppressor genes and our approach to therapeutically targeting these needs to be prioritized."

"We have to zoom in on this crucial junction and gather more data on the impact different therapies have on prostate cancer's evolution and spread," he adds.

The study authors conclude that these findings "elucidate in detail the complex patterns of metastatic spread and further our understanding of the development of resistance to androgen-deprivation therapy in prostate cancer."

Recently, Medical News Today reported on new research suggesting that taking vitamin D supplements could slow or reverse the progression of low-grade prostate tumors, reducing the need for surgery or radiation therapy.

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Neoadjuvant Systemic Therapy in Breast Cancer: Association of Contrast-enhanced MR Imaging Findings, Diffusion-weighted Imaging Findings, and Tumor Subtype with Tumor Response

Gorane Santamaría, Xavier Bargalló, Pedro Luis Fernández, Blanca Farrús, Xavier Caparrós, Martin Velasco,

Radiology, 2016


To investigate the performance of tumor subtype and various magnetic resonance (MR) imaging parameters in the assessment of tumor response to neoadjuvant systemic therapy (NST) in patients with breast cancer and to outline a model of pathologic response, considering pathologic complete response (pCR) as the complete absence of any residual invasive cancer or ductal carcinoma in situ (DCIS).

Materials and Methods

This was an institutional review board–approved retrospective study, with waiver of the need to obtain informed consent. From November 2009 to December 2014, 111 patients with histopathologically confirmed invasive breast cancer who were undergoing NST were included (mean age, 54 years; range, 27–84 years). Breast MR imaging was performed before and after treatment. Presence of late enhancement was assessed. Apparent diffusion coefficients (ADCs) were obtained by using two different methods. ADC ratio (mean posttreatment ADC/mean pretreatment ADC) was calculated. pCR was defined as absence of any residual invasive cancer or DCIS. Multivariate regression analysis and receiver operating characteristic analysis were performed.


According to their immunohistochemical (IHC) profile, tumors were classified as human epidermal growth factor receptor 2 (HER2) positive (n = 51), estrogen receptor (ER) positive/HER2 negative (n = 40), and triple negative (n = 20). pCR was achieved in 19% (21 of 111) of cases; 86% of them were triple-negative or HER2-positive subtypes. Absence of late enhancement at posttreatment MR imaging was significantly associated with pCR (area under the curve [AUC], 0.85). Mean ADC ratio significantly increased when pCR was achieved (P < .001). A κ value of 0.479 was found for late enhancement (P < .001), and the intraclass correlation coefficient for ADCs was 0.788 (P < .001). Good correlation of ADCs obtained with the single-value method and those obtained with the mean-value methods was observed. The model combining the IHC subtype, ADC ratio, and late enhancement had the highest association with pathologic response, achieving an AUC of 0.92 (95% confidence interval: 0.86, 0.97).


Triple-negative or HER2-positive tumors showing absence of late enhancement and high ADC ratio after NST are associated with pCR.

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MIPT researchers put safety of magic anti-cancer bullet to test

MIPT researchers put safety of magic anti-cancer bullet to test | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |

A group of MIPT researchers together with their colleagues from Moscow, Nizhny Novgorod, Australia and the Netherlands have carried out the first systematic study analyzing the safety of so-called upconversion nanoparticles that may be used to treat skin cancer and other skin diseases. This study is one of the most important steps on the path to new, safe and effective methods to diagnose and treat cancer.

This image shows fluorescent nanoparticles in cells. Credit: Elena Petersen It was back in 1908 that the German naturalist and doctor Paul Ehrlich came up with the idea of a "magic bullet"- a drug that would fight only pathogenic microbes or cancer cells, without affecting the healthy cells. One century later chemists and physicians are closer than ever before to turning this idea into reality, thanks to nanotechnology.

Entering the body, the nanoparticles of certain substances may accumulate in the tumor cells, "ignoring" the healthy ones. It's possible to attach the molecules of drugs or diagnostic agents to such nanoparticles to find cancer cells and destroy them without damaging the other cells in the body.

For this purpose, researchers use nanoparticles of gold and ferromagnetic materials, heating them with high frequency electric currentsso that they kill cancer cells from the inside. One of the most promising types of nanoparticles for diagnosing and treating cancer is so-called upconversion nanoparticles (UCNPs). They convert near-infrared radiation, which can penetrate deep into human tissue, in visible light, making it possible to detect cancerous cells in body tissues, change them and monitor the progress of treatment. UCNP scan be configured so that they will release drugs with the help of light.

However, before developing therapeutic methods based on the use of nanoparticles, it must be determined whether they can cause any harm to healthy cells or not - that is the subject of the research done by Elena Petersen and Inna Trusova of MIPT and their colleagues from Moscow, Nizhny Novgorod, Australia and the Netherlands.

"Despite the fact that there're a large number of studies on the cytotoxicity of UCNPs, all of them are circumstantial in a way, because the study of this problem was peripheral for their authors," says Petersen, the head of the Laboratory of Cellular and Molecular Technologies at MIPT. "We've done the first systematic study of the effects of nanoparticles on cells."

The researchers studied the properties of one of the most common types of UCNPs, which is derived from sodium yttrium fluoride (Na[YF4]) doped with the rare-earth elements erbium and ytterbium. The group tested how these nanoparticles are absorbed by fibroblasts (the cells of human connective tissue)and keratinocytes (epidermal cells), and studied how nanoparticles affect these cells' viability.

The results show that the cytotoxicity of UCNPs depends on the cell type. They are not toxic for dermal fibroblasts and slightly toxic for keratinocytes. However, the toxicity for keratinocytes depends on the concentration of the nanoparticles, meaning that these cells can be used as a biological indicator for evaluating the safety of different types of UCNPs.

In addition to the "naked" nanoparticles, there searchers tested several modifications of polymer-coated nanoparticles. In these cases, the difference between the response of fibroblasts and keratinocytes was even higher, for example, the particles coated with polyethylenimine interfered with the intracellular metabolism of the keratinocytes, but had no effect on the fibroblasts. The group identified the types of polymer coating that made the nanoparticles as safe as possible.

"This study is an important step towards beginning to use UCNPs to diagnose and treat skin cancer and other skin diseases," says Petersen. According to her, there are already studies of the use of nanoparticles for the treatment of skin diseases, but to utilize them on a large scale it is necessary to prove that they are safe and efficient.

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Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking

Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |

Mahla Poudineh, Peter M. Aldridge, Sharif Ahmed, Brenda J. Green, Leyla Kermanshah, Vivian Nguyen, Carmen Tu, Reza M. Mohamadi, Robert K. Nam, Aaron Hansen, Srikala S. Sridhar, Antonio Finelli, Neil E. Fleshner, Anthony M. Joshua, Edward H. Sargent, Shana O. Kelley

Nature Nanotechnology,n(2016)

Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in whole blood is critical to unravelling the complex and dynamic properties of these potential clinical markers. This task is challenging because these cells are present at parts per billion levels among normal blood cells. Here we report a new nanoparticle-enabled method for CTC characterization, called magnetic ranking cytometry, which profiles CTCs on the basis of their surface expression phenotype. We achieve this using a microfluidic chip that successfully processes whole blood samples. The approach classifies CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers, which is read out using magnetic nanoparticles. We deploy this new technique to reveal the dynamic phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth and aggressiveness. We also test magnetic ranking cytometry using blood samples collected from cancer patients.

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CRISPR gene editing will transform cancer treatment

Gene-editing technique CRISPR-cas works like a pair of scissors to cut DNA, inserting or reordering bits of genetic code with remarkable, science-fiction-like results. Subscribe:

In humans, the technology is being tested to battle cancer — by removing patients’ immune cells, editing them, and reinserting the weaponized cells into the body to hunt cancer.

One of the leading scientists who developed the technique is Jennifer Doudna, a biochemist at the University of California, Berkeley.
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Enhanced Thermographic Detection of Skin Cancer Through Combining Laser Scanning and Biodegradable Nanoparticles

Enhanced Thermographic Detection of Skin Cancer Through Combining Laser Scanning and Biodegradable Nanoparticles | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |
Chao Jin, Zhi-Zhu He, Jie Zhang, Xue-Yao Yang and Jing Liu

J. Nanotechnol. Eng. Med 4(1), 011004 (Jul 11, 2013)

Through introducing biodegradable magnesium nanoparticles (Mg-NPs) with excellent property in absorbing laser photon, this paper is dedicated to present a laser scanning based thermogaphic strategy for detecting the skin cancer. It aims at selectively enhancing the thermal responses of the target regions so as to distinguish the tumor from the normal tissues on the infrared images. The carried out three-dimensional simulations and conceptual experiments quantitatively demonstrated the feasibility of the present method in improving the sensitivity and targeting-ability (i.e., specificity) of the thermography. Further parametric studies on the thermal enhanced effects such as by varying the parameters of laser beam (i.e., laser power, action time, and moving frequency) and Mg-NPs (i.e., nanoparticle concentration) disclose more quantitative mechanisms for achieving a better output of the diagnosis. The results indicate the following facts: (1) The parameters could be selected to significantly improve the sensitivity of the thermal detection, such that the maximum temperature difference could even reach 2.31 °C; (2) for safety concern to human body, the default parameter setting (P = 1 W, Δt = 40 ms, f = 1 Hz, n = 0.02 mg/ml) can be a good choice and enhanced results can thus be easily detected; and (3) with the unique biodegradable merits, the Mg-NPs can be considered as an extremely useful agent for enhancing thermogaphy in identifying the early stage tumor.
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Novel Machine-Learning Tool Opens Door to Improved Cancer Therapies

Novel Machine-Learning Tool Opens Door to Improved Cancer Therapies | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |
Scientists have described about 1100 antimicrobial peptides (AMP) with diverse sequences that can permeate microbial membranes. Now researchers from the University of Illinois at Urbana-Champaign and UCLA report the development of a new machine learning approach to discover and design alpha-helical membrane-active peptides based on their physicochemical properties.

"In this work, we have trained a machine learning classifier—known as a support vector machine (SVM)—to recognize membrane activity and experimentally calibrated the recognition metric by peptide synthesis and characterization," explained Andrew Ferguson, Ph.D., an assistant professor of materials science and engineering at Illinois. "We use machine learning to not only discover new membrane-active peptides, but to also identify membrane activity in known peptides with previously defined functions, leading us to discover membrane activity in diverse and unexpected peptide families."

"Since getting cargo into a cell is important for many applications, we anticipate that this tool can have broad biomedical implications, including in immunotherapy and in broad-spectrum membrane-active antimicrobial peptides, to combat the rising incidence of drug resistance, design of cationic cell-penetrating peptides for nucleic acid transfection into cells, and in targeting and permeating anticancer therapeutics into tumors.”

In this collaborative work, the Illinois researchers developed the computational innovations, with the experimental testing of the predictions accomplished, at UCLA. The results, which highlight the difference between the efficacy of an antimicrobial and its recognizability as such, are surprising.

"AMPs do not share a common core structure, but tend to be short, cationic, and amphiphilic," Dr. Ferguson said. "By training our machine learning classifier over a training set comprising peptides with known antimicrobial activity (hits) and decoy peptides with no activity (misses), the classifier learned the physical and chemical properties of a peptide that make for good membrane activity. We anticipated that the classifier would learn to discriminate the "antimicrobial-ness" of a particular peptide sequence, but through experimental testing of its predictions we found that it actually learned a much more general and physical rule to discriminate peptides based on membrane activity. In effect, the classifier learned membrane activity as the underlying physical determinant of antimicrobial activity within the training set, and allows us to use our classifier to discover membrane-active peptides in other diverse peptide classes."

"Using the SVM as an efficient discovery tool for membrane activity, we performed a guided search of peptide sequence space to discover new membrane-active peptides that would be difficult for nature to evolve by simple mutation from existing alpha-helical membrane-active peptides," added UCLA’s Ernest Y. Lee, first author of the paper (“Mapping Membrane Activity in Undiscovered Peptide Sequence Space Using Machine Learning"), which appears in PNAS.

"What emerges is a diverse taxonomy of sequences that are expected to be not only just as membrane active as known antimicrobial peptides, but also have a broad range of putative primary functions beyond antimicrobial activity including neuropeptides, viral fusion proteins, topogenic peptides, and amyloids," according to Gerard Wong, Ph.D., a professor of bioengineering at UCLA and senior experimental investigator on the study. "Had their primary functions been undiscovered, these peptides could have been classified as AMPs. Not only is membrane activity not coextensive with antimicrobial activity, it is surprisingly common for many classes of natural peptides as one component of multiplexed functionality."
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In Silico Oncology: Quantification of the In Vivo Antitumor Efficacy of Cisplatin-Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model

Eleni Kolokotroni, Dimitra Dionysiou, Christian Veith, Yoo-Jin Kim, Jörg Sabczynski, Astrid Franz, Aleksandar Grgic, Jan Palm, Rainer M. Bohle, Georgios Stamatakos

PLoS Comput Biol. 2016 Sep; 12(9): e1005093.

The 5-year survival of non-small cell lung cancer patients can be as low as 1% in advanced stages. For patients with resectable disease, the successful choice of preoperative chemotherapy is critical to eliminate micrometastasis and improve operability. In silico experimentations can suggest the optimal treatment protocol for each patient based on their own multiscale data. A determinant for reliable predictions is the a priori estimation of the drugs’ cytotoxic efficacy on cancer cells for a given treatment. In the present work a mechanistic model of cancer response to treatment is applied for the estimation of a plausible value range of the cell killing efficacy of various cisplatin-based doublet regimens. Among others, the model incorporates the cancer related mechanism of uncontrolled proliferation, population heterogeneity, hypoxia and treatment resistance. The methodology is based on the provision of tumor volumetric data at two time points, before and after or during treatment. It takes into account the effect of tumor microenvironment and cell repopulation on treatment outcome. A thorough sensitivity analysis based on one-factor-at-a-time and latin hypercube sampling/partial rank correlation coefficient approaches has established the volume growth rate and the growth fraction at diagnosis as key features for more accurate estimates. The methodology is applied on the retrospective data of thirteen patients with non-small cell lung cancer who received cisplatin in combination with gemcitabine, vinorelbine or docetaxel in the neoadjuvant context. The selection of model input values has been guided by a comprehensive literature survey on cancer-specific proliferation kinetics. The latin hypercube sampling has been recruited to compensate for patient-specific uncertainties. Concluding, the present work provides a quantitative framework for the estimation of the in-vivo cell-killing ability of various chemotherapies. Correlation studies of such estimates with the molecular profile of patients could serve as a basis for reliable personalized predictions.

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Nanocarrier drugs in the treatment of brain tumors

Tereza Cerna, Marie Stiborova, Vojtech Adam, Rene Kizek, Tomas Eckschlager

J Cancer Metastasis Treat 2016;2:407-16.

Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties, increase specificity and bioavailability, improve shelf life, and reduce toxicity. Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors. Vessels in tumors have abnormal architecture and are highly permeable; moreover, tumors also have poor lymphatic drainage, allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment. Nanoparticles exploit this feature, known as the enhanced permeability and retention effect, to target solid tumors. Active targeting, i.e. surface modification of nanoparticles, is a way to decrease uptake in normal tissue and increase accumulation in a tumor, and it usually involves targeting surface membrane proteins that are upregulated in cancer cells. The targeting molecules are typically antibodies or their fragments; aptamers; oligopeptides or small molecules. There are currently several FDA-approved nanomedicines, but none approved for brain tumor therapy. This review, based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors.

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Analysis of computer-aided detection techniques and signal characteristics for clustered microcalcifications on digital mammography and digital breast tomosynthesis

Analysis of computer-aided detection techniques and signal characteristics for clustered microcalcifications on digital mammography and digital breast tomosynthesis | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |

Ravi K Samala, Heang-Ping Chan, Lubomir M Hadjiiski, Mark A Helvie

Physics in Medicine and Biology, Volume 61, Number 19, 19 September 2016

With IRB approval, digital breast tomosynthesis (DBT) images of human subjects were collected using a GE GEN2 DBT prototype system. Corresponding digital mammograms (DMs) of the same subjects were collected retrospectively from patient files. The data set contained a total of 237 views of DBT and equal number of DM views from 120 human subjects, each included 163 views with microcalcification clusters (MCs) and 74 views without MCs. The data set was separated into training and independent test sets. The pre-processing, object prescreening and segmentation, false positive reduction and clustering strategies for MC detection by three computer-aided detection (CADe) systems designed for DM, DBT, and a planar projection image generated from DBT were analyzed. Receiver operating characteristic (ROC) curves based on features extracted from microcalcifications and free-response ROC (FROC) curves based on scores from MCs were used to quantify the performance of the systems. Jackknife FROC (JAFROC) and non-parametric analysis methods were used to determine the statistical difference between the FROC curves. The difference between the CADDM and CADDBT systems when the false positive rate was estimated from cases without MCs did not reach statistical significance. The study indicates that the large search space in DBT may not be a limiting factor for CADe to achieve similar performance as that observed in DM.

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18F-FDG PET/CT Diagnosis of Bronchopulmonary Carcinoids Versus Pulmonary Hamartomas

Uhlén N, Grundberg O, Jacobsson H, Sundin A, Dobra K, Sánchez-Crespo A, Axelsson R, Kölbeck KG.

Clin Nucl Med. 2016 Apr;41(4):263-7.


Radiological characterization of pulmonary tumors may be difficult and invasive. Needle biopsy may produce false-negative results. 18F-FDG PET/CT is an established noninvasive procedure for lung tumor characterization and staging. This study was aimed at differentiating bronchopulmonary carcinoids from hamartomas and typical from atypical bronchopulmonary carcinoids by means of 18F-FDG PET/CT.


In a retrospective analysis of 118 patients, with surgically resected pulmonary carcinoid tumors and hamartomas, 87 of those selected had also undergone 18F-FDG PET/CT preoperatively and constituted the study population. To better assess the tracer accumulation, especially in small lesions, the 18F-FDG uptake (SUV) in the tumors was corrected for partial volume effect by applying recovery coefficients corresponding to the respective various specific tumor volumes, as extrapolated from those obtained from experiments in a NEMA phantom.


The SUVmax was higher in the pulmonary carcinoids (mean, 3.9) than in the hamartomas (mean, 1.4; P ≤ 0.00001) and higher in the subgroup of peripheral carcinoids than in hamartomas (P ≤ 0.00001). The SUVmax was similar for the atypical and typical carcinoids, 5.0 and 3.8, respectively, because of the large variation in the data (P = 0.11).


Using PET measurements of the 18F-FDG uptake (SUVmax) in the tumors, corrected for partial volume effects, it was possible to differentiate the carcinoids from the hamartomas, but the clinically more aggressive atypical carcinoids could not be differentiated from the typical carcinoids.

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Normal vs Cancer Cells

NCI B-roll: Black and white footage of normal and cancer cells. This segment depicts cell growth, with the first segment displaying normal cells, the second segment (#) displaying cancer cells and the third segment (#) showing both normal and cancer cells. Differences in ruffling (changes in the cell membrane) and movement are emphasized.This video has no audio.
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Effects of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) on glioblastoma cells (U87)

Zeinab Akbarnejad, Hossein Eskandary, Cristian Vergallo, Seyed Noureddin Nematollahi-Mahani, Luciana Dini, Fatemeh Darvishzadeh-Mahani, Meysam Ahmadi

Electromagnetic Biology and Medicine, Pages 1-10, 22 Nov 2016

The impact of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) at various frequencies and amplitudes was investigated on cell cycle, apoptosis and viability of the Glioblastoma Multiforme (GBM) cell line (U87), in vitro. The GBM is a malignant brain tumor with high mortality in humans and poorly responsive to the most common type of cancer treatments, such as surgery, chemotherapy and radiation therapy. U87 cells with five experimental groups (I–V) were exposed to various ELF-PEMFs for 2, 4 and 24 h, as follows: (I) no exposure, control; (II) 50 Hz 100 ± 15 G; (III) 100 Hz 100 ± 15 G; (IV) 10 Hz 50 ± 10 G; (V) 50 Hz 50 ± 10 G. The morphology properties, cell viability and gene expression of proteins involved in cell cycle regulation (Cyclin-D1 and P53) and apoptosis (Caspase-3) were investigated. After 24 h, the cell viability and Cyclin-D1 expression increased in Group II (30%, 45%), whereas they decreased in Groups III (29%, 31%) and IV (21%, 34%); P53 and Caspase-3 elevated only in Group III; and no significant difference was observed in Group V, respectively, compared with the control (p < 0.05). The data suggest that the proliferation and apoptosis of human GBM are influenced by exposure to ELF-PEMFs in different time-dependent frequencies and amplitudes. The fact that some of the ELF-PEMFs frequencies and amplitudes favor U87 cells proliferation indicates precaution for the use of medical devices related to the MFs on cancer patients. On the other hand, some other ELF-PEMFs frequencies and intensities arresting U87 cells growth could open the way to develop novel therapeutic approaches.

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Immunotherapy: Conquering Cancer from the Inside

Brodsky offers an outline of how Immunotherapy (working to strengthen the immune system) is working against cancer, and how Immunotherapy is advancing in different ways to match the complex machinations of cancer.

Arthur Brodsky, Ph.D. is the principal science writer at the Cancer Research Institute (CRI), where he specializes in cancer immunotherapy. His work involves translating the science behind this exciting revolution in cancer treatment into clear and concise content that all can appreciate. Through his work at CRI he also collaborates with the leading cancer doctors, researchers, and nonprofit organizations, to develop blueprints for moving the field of cancer immunotherapy forward. Before turning to science communication full-time, Arthur completed his doctorate in Bioengineering at Clemson University, where researched diverse topics including biopharmaceuticals, stem cells, and breast cancer.

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at
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Using Polio as a Cancer Therapy

Using Polio as a Cancer Therapy

Michael C. Brown, Ph.D.; The Preston Robert Tisch Brain Tumor Center at Duke University- Duke Cancer Institute

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at
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A new magnetic nanoparticle tool to track circulating tumour cells

A new magnetic nanoparticle tool to track circulating tumour cells | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |
Cancerous tumours are known to release cells into the bloodstream, and it is these circulating tumour cells (CTC) that are the sources of metastatic tumours – tumours that spread and form in distant locations in the body and can eventually kill patients.
A breakthrough by Professor Shana Kelley’s research group at the University of Toronto published in Nature Nanotechnology ("Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking") provides a new tool to characterize CTCs that may help cancer biologists and clinicians understand how to use these cells to provide better treatment.
Circulating tumour cells are targeted with magnetic nanoparticles
Circulating tumour cells are targeted with magnetic nanoparticles and then trapped using x-shaped microscale obstacles (Image: Ella Marushchenko)
Monitoring circulating tumour cells has been a tremendous challenge as they are outnumbered in blood by healthy cells at a level of over 1 billion-1. Moreover, they can display varied and dynamic properties, and the collection of CTCs found in the bloodstream of a cancer patient may have differing metastatic potential. Consequently, efforts to integrate the analysis of these cells into mainstream clinical medicine have been limited because it has been difficult to pinpoint what types of cells and what phenotypic properties should be targeted.
But the potential of CTCs to allow the collection of a non-invasive “liquid biopsy” to monitor cancer progression is a tantalizing possibility that has continued to attract significant attention to this problem.
The Kelley research group found that by using magnetic nanoparticles, CTCs in blood samples could be targeted based on proteins displayed on the cell surface, and separated based on the levels of the protein present. Using a high–resolution microfluidic device, cells were then separated into 100 different capture zones to generate a profile that provides phenotypic information related to metastatic potential.
Using this approach and monitoring cells generated in animal models of cancer and in samples collected from prostate cancer patients, the properties of CTCs were shown to evolve and become more aggressive as tumours became more advanced.
“Through this approach, we aimed to provide a new way to profile CTCs beyond simply counting their numbers in clinical samples,” explained Mahla Poudineh, lead author of the paper who is a graduate student at the Faculty of Applied Science & Engineering. “Instead, we wanted to provide phentotypic information that might allow these cells to be classified as benign or more dangerous, which would then inform treatment options.”
Kelley is a professor at the Faculty of Pharmacy and the Institute for Biomaterials and Biomedical Engineering. The Kelley group along with collaborators at the Sargent Group, Faculty of Applied Science & Engineering Professor Ted Sargent's research lab, hope to turn the approach they reported into a device that can be used by cancer researchers and eventually clinicians to allow CTC analysis to be monitored routinely and used to limit the progression of cancer.
“We were very fortunate to collaborate with a number of oncologists at the Sunnybrook Research Centre and Princess Margaret Hospital as we developed this technology so that we could test our approach with real patient specimens and better understand how to adapt it for use in the clinic,” Kelley said.
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Visualizing Solid Tumour Physiology

Visualizing Solid Tumour Physiology | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |

By Brennan Wadsworth

Physicians started using radiation to treat cancers almost immediately after x-rays were just discovered – a tip to the desperation for a cure – back in the 1890s. In 2016 radiation therapy is still a large part of cancer treatment with most cancer societies referencing more than 50% of patients receiving some type of radiation.

In my previous blog posts on radiation biology I have described ‘tumour hypoxia’ as a challenge to radiation treatment. The short story is that tumours with regions of hypoxia – low oxygen – are resistant to radiation. With the goal of improving cancer care, the two major steps to take after any problem is identified are: (1) developing an effective intervention and (2) identifying who will benefit from the intervention. I discussed the current status of hypoxia targeting interventions previously, here I will discuss how we can identify tumours that are hypoxic

The presence of molecular oxygen in a mammalian cell strongly dictates the metabolism and inner chemistry of that cell. Chemistry experts are able to take this type of knowledge and produce compounds that will undergo a chemical reaction specifically within hypoxic cells. The key is that the chemical reaction result in the compound becoming trapped inside of the cell. With this strategy the chemical will accumulate inside hypoxic cells, and you have yourself a chemical that can be used as a reporter of hypoxic cells. The next step is deciding on how to detect reporter. An easy way to do this is to make the reporter radioactive!

Positron emission tomography (PET scan) is really just a method to detect a particular type of radiation. A radioactive isotope of fluorine (18F) will do the trick, and 18F can be chemically incorporated to a wide variety of organic compounds relatively easily. Adding 18F to one of the hypoxia reporter chemicals has produced is 18FMISO – the most commonly used hypoxia radiotracer.

When you inject a small amount of 18FMISO into the body it accumulates in hypoxic cells*. A PET scan detects the radioactivity and determines the source of radioactivity in 3D space. In this way 18FMISO can identify regions of hypoxia in a tumour with reasonable resolution and without the need for surgical biopsy, which traditionally was the only way to characterize a tumour. This is particularly appealing for brain cancer, where 18FMISO in particular has been successfully used to identify those who need aggressive treatment and those who do not1.

Above figure from Toyonaga et al (2016) displays how 18FMISO is excluded from tumours without hypoxia (a) and taken up strongly in hypoxic tumours (b). Authors validate 18FMISO specificity using other indicators of hypoxia later in the study.

18FMISO is just one example of a PET radiotracer. The beauty of PET is the ability to radiolabel such a wide variety of organic chemicals that tumour cells perceive as normal. Combined with the collective knowledge of cellular metabolism this means that we can create PET radiotracers to learn a lot more about tumours than their size and shape, we can investigate their cellular activity and internal chemistry – such as oxygen content.

Non-invasive imaging is just one of an infinite number of success stories in science. Developing 18FMISO required the work of biologists to characterize the tumour hypoxia phenomenon, chemists to develop chemicals that label hypoxic cells, physicists to study the nature of radioactivity, engineers to develop PET scanners, and a great deal of creativity at every step.

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Programming probiotics for early detection of liver cancer metastases

Scientists at the University of California, San Diego and the Massachusetts Institute of Technology (MIT) have described a new method for detecting liver cancer metastases in mice. The approach uses over-the-counter probiotics genetically programmed to produce signals easily detectable in urine when liver cancer metastases are present. The results of the new study, published in Science Translational Medicine, indicate that genetically-programmed probiotics may be useful for detecting liver cancer metastases early-on in the progression of the disease.

Liver cancer metastases are difficult to detect with conventional imaging, and new methods are needed that can detect the metastases in a timely matter. The metastatic spread of cancer is ultimately responsible for 90 percent of all cancer-related deaths, and liver metastases are particularly challenging for clinicians due in part to their small size and multiplicity. If metastases are detected early, patients have a much higher chance of survival.

By using probiotics as a platform for early detection of liver metastases in mice, the researchers took advantage of the fact that certain bacteria are able to pass from the gastrointestinal tract directly into the liver - and the fact that certain bacteria are drawn to tumors.

Over the last 100 years or so, scientists have become increasingly aware of bacteria in environments previously thought to be sterile, such as tumors, indicating that bacteria are part of normal human physiology.

"It was discovered in the early 1900s that certain bacteria selectively colonize tumors," said Arthur Prindle, one of two first-authors on the study, who performed this research as a bioengineering Ph.D. student at UC San Diego. "No one knows for sure, but this could be due to the lack of immune surveillance and availability of nutrients inside the tumor - the bacteria can grow freely without the interference of the immune system."

Armed with this knowledge, the researchers set out to develop a simple method for detecting liver metastases using a mouse model for liver cancer and the probiotic bacterium E. coli Nissle 1917 (EcN). First, they needed to test the idea that a probiotic taken orally would colonize metastases, something that was only previously demonstrated when bacteria were injected directly into the bloodstream.

"EcN is a safe and widely used probiotic," said Prindle. "In fact, we were able to order it from Amazon and engineer it to express the genes we wanted. Next, we needed to see how it would behave in our mouse model."

This meant shipping off their probiotic to the study's other first author, Tal Danino and senior author and MIT professor Sangeeta Bhatia from the Koch Institute for Integrative Cancer Research at MIT. When Danino received the bacteria, the cells had been engineered by the team at UC San Diego to contain a circular piece of DNA called a plasmid, which expressed a gene that caused the bacteria to generate a luminescent signal from the bacterium's natural production of enzymes.

"Because the bacteria were giving off light, we were able to see that they were localizing to the metastases as we had hoped," said Danino, who earned his Ph.D. in bioengineering at UC San Diego before moving on to MIT. "However, the signal is difficult to detect inside a mouse, and even more so within a human. We needed to come up with another way the bacteria could report the presence of a tumor."

To do that, the group engineered the bacteria to overexpress a LacZ reporter.

LacZ is a gene that encodes the protein beta-galactosidase, an enzyme that causes bacteria to appear blue when grown on a medium that contains its substrate. When inside an animal, the product of the enzymatic activity is excreted in urine and causes it to change color; if liver metastases were present, the urine of the mice turned red.

The researchers also added gene cassettes that would ensure the bacteria that colonized the tumor contained their plasmid - one such set of genes contained a toxin that would kill the bacteria if they mutated so as to lose the plasmid. Another caused the plasmid to move to opposite ends of the bacterial cell during DNA replication, which ensured that each daughter cell would receive a copy.

Possible impact

UC San Diego bioengineering and biological sciences professor and the other senior author on the work, Jeff Hasty, expects the new method will enable the detection of liver cancer at an earlier stage, increasing the chances that it will be treated successfully.

"There are multiple reasons to use probiotics in the early detection of cancer," said Hasty. "First, probiotic bacteria are susceptible to antibiotics, which enables their rapid removal from a patient's system once they've done their job. Second, probiotics will do what they do best - grow. That means that patients only need to be given enough probiotic bacteria to ensure that one bacterium arrives at its target location."

The study followed these mice for over a year after oral delivery and found no deleterious health effects.

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Diagnostic Value of 68Ga PSMA-11 PET/CT Imaging of Brain Tumors-Preliminary Analysis

Sasikumar A, Joy A, Pillai MR, Nanabala R, Anees K M, Jayaprakash PG, Madhavan J, Nair S.

Clin Nucl Med. 2016 Nov 11.


To evaluate the feasibility of using Ga PSMA-11 PET/CT for imaging brain lesions and its comparison with F-FDG.


Ten patients with brain lesions were included in the study. Five patients were treated cases of glioblastoma with suspected recurrence. F-FDG and Ga PSMA-11 brain scans were done for these patients. Five patients were sent for assessing the nature (primary lesion/metastasis) of space occupying lesion in brain. They underwent whole body F-FDG PET/CT scan and a primary site elsewhere in the body was ruled out. Subsequently they underwent Ga PSMA-11 brain PET/CT imaging. Target to background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background.


In five treated cases of glioblastoma with suspected recurrence the findings of Ga PSMA-11 PET/CT showed good correlation with that of F-FDG PET/CT scan. Compared to the F-FDG, Ga PSMA-11 PET/CT showed better visualization of the recurrent lesion (presence/absence) owing to its significantly high TBR. Among the five cases evaluated for lesion characterization glioma and atypical meningioma patients showed higher SUVmax in the lesion with Ga PSMA-11 than with F-FDG and converse in cases of lymphoma. TBR was better with Ga PSMA PET/CT in all cases.


Ga PSMA-11 PET/CT brain imaging is a potentially useful imaging tool in the evaluation of brain lesions. Absence of physiological uptake of Ga PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of metabolically active disease in brain.

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A review of Raman spectroscopy advances with an emphasis on clinical translation challenges in oncology

A review of Raman spectroscopy advances with an emphasis on clinical translation challenges in oncology | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |

Michael Jermyn, Joannie Desroches, Kelly Aubertin, Karl St-Arnaud, Wendy-Julie Madore, Etienne De Montigny, Marie-Christine Guiot, Dominique Trudel7, Brian C Wilson, Kevin Petrecca

Physics in Medicine and Biology, Volume 61, Number 23, 2 November 2016

There is an urgent need for improved techniques for disease detection. Optical spectroscopy and imaging technologies have potential for non- or minimally-invasive use in a wide range of clinical applications. The focus here, in vivo Raman spectroscopy (RS), measures inelastic light scattering based on interaction with the vibrational and rotational modes of common molecular bonds in cells and tissue. The Raman 'signature' can be used to assess physiological status and can also be altered by disease. This information can supplement existing diagnostic (e.g. radiological imaging) techniques for disease screening and diagnosis, in interventional guidance for identifying disease margins, and in monitoring treatment responses. Using fiberoptic-based light delivery and collection, RS is most easily performed on accessible tissue surfaces, either on the skin, in hollow organs or intra-operatively. The strength of RS lies in the high biochemical information content of the spectra, that characteristically show an array of very narrow peaks associated with specific chemical bonds. This results in high sensitivity and specificity, for example to distinguish malignant or premalignant from normal tissues. A critical issue is that the Raman signal is often very weak, limiting clinical use to point-by-point measurements. However, non-linear techniques using pulsed-laser sources have been developed to enable in vivo Raman imaging. Changes in Raman spectra with disease are often subtle and spectrally distributed, requiring full spectral scanning, together with the use of tissue classification algorithms that must be trained on large numbers of independent measurements. Recent advances in instrumentation and spectral analysis have substantially improved the clinical feasibility of RS, so that it is now being investigated with increased success in a wide range of cancer types and locations, as well as for non-oncological conditions. This review covers recent advances and continuing challenges, with emphasis on clinical translation.

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Gold nanoparticles help deliver lethal one-two punch to cancer

TAGGING gold nanoparticles with a small dose of radiation has helped researchers trace the precious metal as it delivers a drug right into the heart of cancer cells, according to new laboratory research* being presented at the 2016 National Cancer Research Institute (NCRI) Cancer conference.

Researchers from the CRUK/MRC Oxford Institute for Radiation Oncology have been working on better ways to transport a drug directly into the control room of cancer cells, where the chromosomes are kept. This specific drug targets a molecule – telomerase – that builds up the protective caps at the end of chromosomes called telomeres.

In most cells of the body, telomeres act like an in-built timer to ensure that the cell does not live past its expiry date. Telomeres shorten each time the cell divides. Once a critical length is reached, the cell can no longer divide and it dies. Cancer cells manage to get around this safety check by reactivating telomerase allowing them to continue to grow out of control.

One of the biggest hurdles in treating cancer is getting effective drugs into cancer cells, particularly to where the chromosomes are stored. Gold nanoparticles have proven to be well suited to being absorbed into cells, safely delivering drugs that could otherwise be blocked.

By engineering the gold nanoparticles and adding the radioactive tracer, the researchers were able to prove that their drug was reaching the desired target in skin cancer cells grown in the lab and was shutting telomerase down, halting cancer's growth.

While the radioactive tracer was used to precisely follow the drug in this study, the same method can also be used to deliver a dose of radioactivity to cancer cells, helping to kill them. This second dose is especially powerful because inactivation of telomerase makes cancer cells more sensitive to radiation.

Professor Kate Vallis, lead researcher based at the CRUK/MRC Oxford Institute for Radiation Oncology, said: "Gold is precious in more than one way. We have used tiny gold nanoparticles loaded with targeted drugs to kill cancer cells in the laboratory. Our long term goal is to design new treatments for cancer patients based on this promising approach."

Sir Harpal Kumar, Cancer Research UK's chief executive, said: "Gold has been used in medicine for many years and this research adds further insight into its potential. Ensuring that treatment is accurately targeted at cancer and avoids healthy cells is the goal for much of cancer research, and this is an exciting step towards that."

Dr Karen Kennedy, Director of the NCRI, said: "Research continues to shed light on how cancer cells behave and how to effectively deliver a lethal payload to the tumour. This exciting research offers that potential and needs further investigation to see how it would be used in patients. The future looks exciting with research such as this improving the way the disease is treated."
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CAD supports digital breast tomosynthesis

CAD supports digital breast tomosynthesis | Project Virtual Tumor Cancer in silico and Alternative Cancer Therapies |

Increasingly popular in cancer screening, digital breast tomography (DBT) generates pseudo 3D images of the breast. Interpreting the large number of slices per scan, however, poses a bigger challenge than analysis of 2D digital mammography (DM), the current standard of care. Applied to DBT, computer-aided detection (CADe) has the potential to play an important role, helping radiologists search for often subtle signs of disease more accurately and quickly than a single, visual inspection.

In new research, a CADe system that detects clustered microcalcifications in DBT images performed comparably to a system used in DM. Such comparisons are essential, given that DBT has the potential to replace DM, said first author Ravi Samala, a radiology researcher at the University of Michigan in Ann Arbor (Phys. Med. Biol. 61 7092).

"At the push of a button, CAD systems are used as a 'second' reader by the radiologists with the DM systems," Samala told medicalphysicsweb. "Our results indicate that CAD systems developed for DBT have the potential to be similarly used to assist radiologists and potentially improve the accuracy of interpretation."

Study data

The researchers performed DBT scans on 160 individuals who had already had clinical DM, resulting in 237 matching views with the two modalities. They used a prototype system, built by GE Global Research, to acquire 21 projections over a 60° tomographic angle in craniocaudal and mediolateral oblique views. Observations from DM informed subsequent biopsies, the findings of which were, in turn, used by an experienced radiologist to mark the clusters on the DBT images.

DBT data were reconstructed into 1-mm thick contiguous slices with a simultaneous algebraic reconstruction technique (SART) and multiscale bilateral filtering regularization (MSBF). A third image, a planar projection view (PPJ), was reconstructed from DBT data by extracting the high spatial frequencies and projecting them onto a 2D plane. This approach retains the microcalcifications, but removes the tissue background.

CAD systems

Three separate CADe systems – CADDBT, CADPPJ and CADDM – were applied to the respective images. Each is a pattern recognition strategy based on machine learning, but with varying implementations appropriate to the different characteristics of each image type. CADDBT and CADPPJ systems were trained with 63 views and tested with the remaining 174 views. The CADDM system had been previously trained and validated on an independent set of 192 views.

Each system includes pre-processing to enhance the appearance of microcalcifications over the image background, using techniques including contrast-to-noise ratio enhancement. Iterative thresholding and region growing were used to segment and detect individual microcalcification candidates, providing seeds for more precise segmentation. Segmented candidates were then analysed to identify clusters. Classifiers were used in all three systems to identify false positives clusters and, in a prior step, in CADDM and CADPPJ, to identify false positive individual candidates.

The researchers quantified the performance of the CADe systems against the cluster locations – verified using the biopsies – using free-response receiver operating curves (FROC). They compared their performance using a Jackknife FROC analysis. False positive results, a key limitation of current clinical techniques, were compared between systems using only those test images where no microcalcifications had been independently detected (n = 74). The subset provided the most realistic representation of the largely normal screening population.
Comparable performance

When the CADe systems were set to detect clusters with 85% sensitivity, the average false positive rates for DM, DBT and PPJ were 6.10, 2.19 and 0.93 per view, respectively. However, the difference between DM and both DBT and PPJ was not statistically significant (p values: DM versus DBT = 0.924, DM versus PPJ = 0.059).

"Our near-term goal is to increase the sensitivity and reduce the false positive rate of the DBT CADe system," said Samala of the group's ongoing research. In the longer term, projects include the development of CADe systems based on deep learning techniques and new image reconstruction methods, both with the goal of improving the detection of breast masses and microcalcifications.

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Scientists say blood pressure medication could help prevent lung cancer

Korean researchers may have discovered a new way to help prevent lung cancer.
They've found that certain kinds of blood pressure medication can inhibit the generation of cancer cells.
Kim Jung-soo has more.
Lung cancer is the leading cause of cancer-related deaths in Korea.
The biggest cause of lung cancer is smoking, and 90 percent of lung cancer patients are reported to have smoked.
Now, researchers in Korea have found how lung cancer forms as a result of smoking, and they may also have found a way to prevent it.

When cancer-causing agents in cigarettes enter the body, they stimulate calcium channels and calcium enters the cells.
Substances that help promote cell growth are pushed out, inducing cancer cell development.

The researchers discovered that blocking the calcium channels stops cancer cells from forming.
When mice that were fed tobacco constituent were treated with calcium channel blockers for 12 weeks, the rate of cancer cell formation was reduced to one-tenth that of the control group.
The blockers also proved effective in preventing lung cancer caused by stress.
Many existing blood pressure medications are being used to block calcium channels, but they could also be used to prevent lung cancer.
In a study of seven-point-five million patients with hypertension, the incidence of lung cancer was reduced by about 30 percent among those that took drugs with calcium channel blocking effects... compared to those who did not.

"Based on the data for patients who took medications to suppress high blood pressure, we believe the medicines could be used to prevent or treat cancer. The dosage used to treat high blood pressure could inhibit the development of lung cancer."

The researchers believe their findings will help those at risk for lung cancer and patients who have overcome the illness.
Kim Jung-soo, Arirang News.
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