Improve Cancer Diagnosis Research Articles

Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells

The nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis. By using multiple particle tracking (MPT) technique on chromatin granules, we designed a SURF (Speeded Up Robust Features)-based algorithm to study the mechanical properties of isolated nuclei and in living cells. We have determined the apparent shear stiffness, viscosity and optical density of the nucleus, and how the chromatin structure influences on these biophysical values. Moreover, we used our MPT-SURF analysis to study the apparent mechanical properties of isolated nuclei from patients of acute lymphoblastic leukemia. We found that leukemia cells exhibited mechanical differences compared to normal lymphocytes. Interestingly, isolated nuclei from high-risk leukemia cells showed increased viscosity than their counterparts from normal lymphocytes, whilst nuclei from relapsed-patient's cells presented higher density than those from normal lymphocytes or standard- and high-risk leukemia cells. Taken together, here we presented how MPT-SURF analysis of nuclear chromatin granules defines nuclear mechanical phenotypic features, which might be clinically relevant.

Super-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis

Genomic DNA is folded into a higher-order structure that regulates transcription and maintains genomic stability. Although progress has been made on understanding biochemical characteristics of epigenetic modifications in cancer, the in-situ higher-order folding of chromatin structure during malignant transformation remains largely unknown. Here, using optimized stochastic optical reconstruction microscopy (STORM) for pathological tissue (PathSTORM), we uncover a gradual decompaction and fragmentation of higher-order chromatin folding throughout all stages of carcinogenesis in multiple tumor types, and prior to tumor formation. Our integrated imaging, genomic, and transcriptomic analyses reveal functional consequences in enhanced transcription activities and impaired genomic stability. We also demonstrate the potential of imaging higher-order chromatin disruption to detect high-risk precursors that cannot be distinguished by conventional pathology. Taken together, our findings reveal gradual decompaction and fragmentation of higher-order chromatin structure as an enabling characteristic in early carcinogenesis to facilitate malignant transformation, which may improve cancer diagnosis, risk stratification, and prevention.

Characterization of the radiosensitization effect of pulsed laser ablated-gadolinium

Nanomedicine is a field of medical treatment research that has developed rapidly in recent years for the diagnosis and treatment of cancer. New strategies in nanomedicine are to improve cancer diagnosis and therapy at the cellular and molecular level. Materials that are often used for nanomedicine are metal-based gadolinium. This research presents a preliminary study of the radiosensitization properties of gadolinium nanoparticles colloid. Gadolinium nanoparticle colloid was synthesized using a pulsed laser ablation method in pure water. The gadolinium nanoparticle colloid was characterized using a Scanning Electron Microscope and UV-Vis Spectrophotometer. Radiosensitization properties of gadolinium nanoparticles colloid were examined based on the decomposition of x-ray irradiated methylene blue. The results show that gadolinium nanoparticle colloid consists of a spherical shape particle and has a bandgap energy of 5.76 eV. Gadolinium nanoparticle colloid possessed radiosensitization properties with a dose enhancement factor in the range of 1.51-1.54.

Abstract P3-06-15: Identifying genomic alterations in stage IV breast cancer patients using MammaSeq: An international collaborative study

Abstract Background: Identification of genomic alterations present in cancer patients can aid in improving cancer diagnosis and prognosis. In this study, we aimed to identify clinically actionable variations present in stage IV breast cancer (BC) samples. Methods: DNA was extracted from formalin fixed paraffin embedded samples of breast cancer (n=41). DNA was sequenced using MammaSeqTM, a breast cancer specific NGS panel targeting 79 genes and 1369 mutations. Ion Torrent Suite 4.0 was used to make variant calls on the raw data. Resulting single nucleotide variants (SNVs) were annotated using CRAVAT toolkit. CNVkit was employed to identify copy number variations (CNVs). The PMKB and OncoKB Precision Oncology Databases were used to associate clinical significance with the identified variants. Results: A total of 41 BC patient samples were sequenced (read depth of 94 - 13340, median of 1529). In total, 96 different alterations (84 SNVs and 12 CNVs) were identified. Frequent SNVs were seen in PIK3CA, TP53, IKBKE, ATM and MAP3K1 genes. Moreover, amplifications were found in ERBB2, FGFR and AR, and deletions in BRCA2, RUNX1 and RB1. 3 CNVs (ERRB2, FGFR and AR amplifications) and 7 SNVs (IDH1.R132H, TP53.E204*, AKT1.E17K, PI3KCA.E545K, PI3KCA.H1047R, PI3KCA.R88Q and ERBB2.V777L) were reported as clinically significant by PMKB and OncoKB. Conclusion: We identified 96 alterations in 50 genes in 41 stage IV BC tissue samples using MammaSeqTM. Ten of these alterations were reported as clinically significant. This study highlights the potential use of cancer specific NGS panels in clinic to get better insight into the cancer patient-specific genomic alterations. Citation Format: Atilla Soran, Mustafa Sahin, Serdar Ugras, Esin Celik, Osama Shiraz Shah, Peter C Lucas, Adrian V Lee. Identifying genomic alterations in stage IV breast cancer patients using MammaSeq: An international collaborative study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-06-15.

Selective Targeting of Lymphoma Cells by Monoclonal Antibody Grafted onto Zwitterionic‐Functionalized Nanoparticles

AbstractNanomedicine is considered a promising alternative to improve cancer diagnosis and treatment. Particularly, the use of nanoparticles (NPs) has enabled the encapsulation of highly toxic anticancer drugs, facilitated ultimate targeting, and allowed tailoring of drug delivery. However, when in biological fluids, these NPs are coated by proteins which hide the targeting moieties and suppress the engineered biological outcome. Herein, how the Ki‐1 monoclonal antibody (mAb) can preserve its targetability through grafting on the surface of zwitterionic‐functionalized nanoparticles, is unveiled. Zwitterions, known for their stealth ability, are used to minimize unspecific NPs protein adsorption and consequently maintain mAb functionality. In this work, Ki‐1 mAb is used as it recognizes TNFRSF8 (CD30+) transmembrane protein overexpressed on CD30+ lymphoma cells such as L540 cells. While nonfunctionalized NPs show negligible toxic effects toward L540 cells, the Ki‐1‐functionalized structure demonstrates cytotoxicity, since they undergo cellular uptake, suggesting a receptor‐mediated internalization. This dual‐functionalization strategy provides a promising multifunctional nanoplatform toward future personalized medicine applications, minimizing unspecific protein adsorption on NPs and ensuring selective cancer cell targeting.

Brain SegNet: 3D local refinement network for brain lesion segmentation

MR images (MRIs) accurate segmentation of brain lesions is important for improving cancer diagnosis, surgical planning, and prediction of outcome. However, manual and accurate segmentation of brain lesions from 3D MRIs is highly expensive, time-consuming, and prone to user biases. We present an efficient yet conceptually simple brain segmentation network (referred as Brain SegNet), which is a 3D residual framework for automatic voxel-wise segmentation of brain lesion. Our model is able to directly predict dense voxel segmentation of brain tumor or ischemic stroke regions in 3D brain MRIs. The proposed 3D segmentation network can run at about 0.5s per MRIs - about 50 times faster than previous approaches Med Image Anal 43: 98–111, 2018, Med Image Anal 36:61–78, 2017. Our model is evaluated on the BRATS 2015 benchmark for brain tumor segmentation, where it obtains state-of-the-art results, by surpassing recently published results reported in Med Image Anal 43: 98–111, 2018, Med Image Anal 36:61–78, 2017. We further applied the proposed Brain SegNet for ischemic stroke lesion outcome prediction, with impressive results achieved on the Ischemic Stroke Lesion Segmentation (ISLES) 2017 database.

The Role of Magnetic Nanoparticles in Cancer Nanotheranostics.

Technological development is in constant progress in the oncological field. The search for new concepts and strategies for improving cancer diagnosis, treatment and outcomes constitutes a necessary and continuous process, aiming at more specificity, efficiency, safety and better quality of life of the patients throughout the treatment. Nanotechnology embraces these purposes, offering a wide armamentarium of nanosized systems with the potential to incorporate both diagnosis and therapeutic features, towards real-time monitoring of cancer treatment. Within the nanotechnology field, magnetic nanosystems stand out as complex and promising nanoparticles with magnetic properties, that enable the use of these constructs for magnetic resonance imaging and thermal therapy purposes. Additionally, magnetic nanoparticles can be tailored for increased specificity and reduced toxicity, and functionalized with contrast, targeting and therapeutic agents, revealing great potential as multifunctional nanoplatforms for application in cancer theranostics. This review aims at providing a comprehensive description of the current designs, characterization techniques, synthesis methods, and the role of magnetic nanoparticles as promising nanotheranostic agents. A critical appraisal of the impact, potentialities and challenges associated with each technology is also presented.

A review of Kenya\u2019s cancer policies to improve access to cancer testing and treatment in the country

BackgroundCancer is the third-leading cause of mortality in Kenya, resulting in unique challenges to the country’s health system. An increase in the number of cancer cases in Kenya over the past decade resulted in legislative actions and policies to guide delivery of cancer services. Kenya’s new national cancer control strategy and past policy efforts provide an opportunity to synergise information and enhance understanding to improve cancer diagnosis and treatment in the country. The objectives of this study are to (1) document policy-modifiable factors based on a review of policy documents and results of a key informant survey and (2) develop recommendations to improve policies affecting cancer testing and treatment services in Kenya. This study builds upon our previous study Improving Access to Cancer Testing and Treatment in Kenya (Makau Barasa et al. J Global Oncol 2(216), 2017).MethodsThe study applied an in-depth systematic review of Kenya’s cancer policies and guidelines, a qualitative analysis of results from a section of a semi-structured key informant survey focused on the opinions of clinicians delivering cancer services as well as cancer support groups and advocacy leaders, and a stakeholder analysis identifying key policy-makers and implementers. Details of the complete key informant survey were published in our previous study.ResultsKenya’s cancer policies have guided progress made in providing the legal and implementation frameworks for the development and delivery of cancer services at the national and county levels. Some policy implementation gaps are noted. These include inadequate financing for cancer services, limited research and data to support policy formulation, and the concentration of cancer services in urban areas. The key informant survey identified policy-modifiable actions that can address some of the gaps and improve the delivery of and access to cancer testing and treatment services in the country. Some of these include addressing the financial barriers affecting cancer testing and treatment services; increasing stakeholder engagement in training health personnel to deliver cancer testing and treatment services; decentralising cancer services and improving cancer surveillance and research; and increasing education and awareness about cancer symptoms, screening procedures and treatment options. A set of priority policy actions were selected from the study findings and used to develop recommendations for Kenya’s policy-makers and stakeholders.ConclusionsRevisions to Kenya’s cancer policies are seeking to address gaps noted in past policies and to improve access to cancer testing and treatment in Kenya. However, based on study findings, additional actions can be taken to strengthen policy implementation. Considering the policy formulation and implementation process and costs, this study recommends focusing on three priority policy actions that can have significant impact on improving access to cancer testing and treatment services. These include addressing financing, insurance and human resources gaps; increasing stakeholder engagement; and decentralising health services for better surveillance and data to inform policies.

An Intricate Connection between Alternative Splicing and Phenotypic Plasticity in Development and Cancer.

During tumor progression, hypoxia, nutrient deprivation or changes in the extracellular environment (i.e., induced by anti-cancer drugs) elicit adaptive responses in cancer cells. Cellular plasticity increases the chance that tumor cells may survive in a challenging microenvironment, acquire new mechanisms of resistance to conventional drugs, and spread to distant sites. Re-activation of stem pathways appears as a significant cause of cellular plasticity because it promotes the acquisition of stem-like properties through a profound phenotypic reprogramming of cancer cells. In addition, it is a major contributor to tumor heterogeneity, depending on the coexistence of phenotypically distinct subpopulations in the same tumor bulk. Several cellular mechanisms may drive this fundamental change, in particular, high-throughput sequencing technologies revealed a key role for alternative splicing (AS). Effectively, AS is one of the most important pre-mRNA processes that increases the diversity of transcriptome and proteome in a tissue- and development-dependent manner. Moreover, defective AS has been associated with several human diseases. However, its role in cancer cell plasticity and tumor heterogeneity remains unclear. Therefore, unravelling the intricate relationship between AS and the maintenance of a stem-like phenotype may explain molecular mechanisms underlying cancer cell plasticity and improve cancer diagnosis and treatment.

Artificial intelligence in cancer diagnosis and prognosis: Opportunities and challenges.

Cancer is an aggressive disease with a low median survival rate. Ironically, the treatment process is long and very costly due to its high recurrence and mortality rates. Accurate early diagnosis and prognosis prediction of cancer are essential to enhance the patient's survival rate. Developments in statistics and computer engineering over the years have encouraged many scientists to apply computational methods such as multivariate statistical analysis to analyze the prognosis of the disease, and the accuracy of such analyses is significantly higher than that of empirical predictions. Furthermore, as artificial intelligence (AI), especially machine learning and deep learning, has found popular applications in clinical cancer research in recent years, cancer prediction performance has reached new heights. This article reviews the literature on the application of AI to cancer diagnosis and prognosis, and summarizes its advantages. We explore how AI assists cancer diagnosis and prognosis, specifically with regard to its unprecedented accuracy, which is even higher than that of general statistical applications in oncology. We also demonstrate ways in which these methods are advancing the field. Finally, opportunities and challenges in the clinical implementation of AI are discussed. Hence, this article provides a new perspective on how AI technology can help improve cancer diagnosis and prognosis, and continue improving human health in the future.

Reduction-Triggered Paclitaxel Release Nano-Hybrid System Based on Core-Crosslinked Polymer Dots with a pH-Responsive Shell-Cleavable Colorimetric Biosensor.

Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via π–π stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy.

Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loaded particles) that utilize passive targeting, active targeting, and/or stimulus responsiveness strategies. This review will summarize some main ideas about the effect of each strategy and how the combination of some or all of them has shown to be effective. After a brief introduction of current cancer therapies and their limitations, we describe the biological barriers that nanoparticles need to overcome, followed by presenting different types of drug delivery systems to improve drug accumulation in tumors. Then, we describe cancer cell membrane targets that increase cellular drug uptake through active targeting mechanisms. Stimulus-responsive targeting is also discussed by looking at the intra- and extracellular conditions for specific drug release. We include a significant amount of information summarized in tables and figures on nanoparticle-based therapeutics, PEGylated drugs, different ligands for the design of active-targeted systems, and targeting of different organs. We also discuss some still prevailing fundamental limitations of these approaches, eg, by occlusion of targeting ligands.

Improving Cancer Diagnosis and Care: Patient Access to High-Quality Oncologic Pathology.

Drawing on discussions at a workshop hosted by the National Cancer Policy Forum, current challenges in pathology are reviewed and practical steps to facilitate high‐quality cancer diagnosis and care through improved patient access to expertise in oncologic pathology are highlighted.

Oncology Program Planning

The field of oncology is rapidly advancing. Emerging research is fostering paradigm-altering changes to improve cancer diagnosis and treatment, and innovative technologies are expanding access to c...

Improving Cancer Diagnosis and Care: Patient Access to Oncologic Imaging Expertise.

Improving Cancer Diagnosis and Care: Patient Access to Oncologic Imaging Expertise.

Zwitterionic Gadolinium(III)-Complexed Dendrimer-Entrapped Gold Nanoparticles for Enhanced Computed Tomography/Magnetic Resonance Imaging of Lung Cancer Metastasis.

Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r1 relaxivity (13.17 mM s-1), acceptable cytocompatibility, and targeting specificity to αvβ3 integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.

THERAPEUTIC EFFECT OF PACLITAXEL LOADED ON GOLD NANOPARTICLES IN TREATMENT OF INDUCED ORAL SQUAMOUS CELL CARCINOMA

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with high mortality rate. Conventional treatment strategies have improved but remain far from optimal. Cancer research is focused on improving cancer diagnosis and treatment methods using nanotechnology, by the production and application of nanoscale drug delivery systems. In medicine, several types of nanoparticles have evolved, gold nanoparticle (AuNPs) are an excellent candidate as drug delivery vehicle due to their favorable chemical and optical properties. Paclitaxel (PTX) is an effective antineoplastic drug that has a wide spectrum of antitumor activity, against head and neck malignancies. The encapsulation of PTX in nanodelivery systems can protect the drug from degradation during circulation and protect the body from its toxic side effects. OBJECTIVES: To study the therapeutic efficacy of PTX-functionalized AuNPs versus the free form of the drug. Also the study will evaluate the treatment, by the use of proliferative immune-histochemical marker (PCNA). MATERIAL AND METHODS: Squamous cell carcinoma will be chemically induced in sixty Syrian hamsters. Then they will be divided into three groups, 20 in each. One group will be treated with free PTX, another group will be treated with PTX-AuNPs, and the last group will be given saline as negative control group. RESULTS: Group treated by PTX loaded on AuNPs showed significant results over group treated by free PTX. CONCLUSIONS: The unique AuNPs properties in combination to the chemotherapeutic drug target cancer cells while maintaining no adverse effects on the surrounding normal cells.

Label-Free Enrichment and Molecular Characterization of Viable Circulating Tumor Cells from Diagnostic Leukapheresis Products.

Circulating tumor cells (CTCs) may be used to improve cancer diagnosis, prognosis, and treatment. However, because knowledge regarding CTC biology is limited and the numbers of CTCs and CTC-positive cancer patients are low, progress in this field is slow. We addressed this limitation by combining diagnostic leukapheresis (DLA) and microfluidic enrichment to obtain large numbers of viable CTCs from metastasized breast cancer patients. DLA was applied to 9 patients, and 7.5 mL of peripheral blood was drawn. CTCs were enriched with the Parsortix™ system. The quality of CTCs from fresh and cryopreserved DLA products was tested, and CTCs were cultured in vitro. Single uncultured and cultured CTCs were isolated by micromanipulation to determine different parameters, such as genomic aberrations and mutation profiles of selected tumor-associated genes. Expression levels of estrogen receptor and HER2/neu were monitored during in vitro culture. Viable CTCs from peripheral blood and fresh or frozen DLA products could be enriched. DLA increased the likelihood of successful CTC culture. Cryopreserved DLA products could be stored with minimal CTC loss and no overt reduction in the tumor cell quality and viability during an observation period of up to 3 years. The analyzed parameters did not change during in vitro culture. DLA samples with high CTC numbers and lower ratios of apoptotic CTCs were more likely to grow in culture. The increased CTC numbers from fresh or cryopreserved DLA products facilitate multiple functional and molecular analyses and, thus, could improve our knowledge of their biology.

Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies.

Circulating tumor DNA can be detected in the blood and body fluids of patients using ultrasensitive technologies, which have the potential to improve cancer diagnosis, risk stratification, noninvasive tumor profiling, and tracking of treatment response and disease recurrence. As we begin to apply "liquid biopsy" strategies in children with cancer, it is important to tailor our efforts to the unique genomic features of these tumors and address the technical and logistical challenges of integrating biomarker testing. This article reviews the literature demonstrating the feasibility of applying liquid biopsy to pediatric solid malignancies and suggests new directions for future studies.

Cellular Interactions in the Tumor Microenvironment: The Role of Secretome.

Over the past years, it has become evident that cancer initiation and progression depends on several components of the tumor microenvironment, including inflammatory and immune cells, fibroblasts, endothelial cells, adipocytes, and extracellular matrix. These components of the tumor microenvironment and the neoplastic cells interact with each other providing pro and antitumor signals. The tumor-stroma communication occurs directly between cells or via a variety of molecules secreted, such as growth factors, cytokines, chemokines and microRNAs. This secretome, which derives not only from tumor cells but also from cancer-associated stromal cells, is an important source of key regulators of the tumorigenic process. Their screening and characterization could provide useful biomarkers to improve cancer diagnosis, prognosis, and monitoring of treatment responses.