Molecular Pathogenesis of Colorectal Cancer with an Emphasis on Recent Advances in Biomarkers, as Well as Nanotechnology-Based Diagnostic and Therapeutic Approaches

Colorectal cancer (CRC) is a serious disease that affects millions of people throughout the world, despite considerable advances in therapy. The formation of colorectal adenomas and invasive adenocarcinomas is the consequence of a succession of genetic and epigenetic changes in the normal colonic epithelium. Genetic and epigenetic processes associated with the onset, development, and metastasis of sporadic CRC have been studied in depth, resulting in identifying biomarkers that might be used to predict behaviour and prognosis beyond staging and influence therapeutic options. A novel biomarker, or a group of biomarkers, must be discovered in order to build an accurate and clinically useful test that may be used as an alternative to conventional methods for the early detection of CRC and to identify prospective new therapeutic intervention targets. To minimise the mortality burden of colorectal cancer, new screening methods with higher accuracy and nano-based diagnostic precision are needed. Cytotoxic medication has negative side effects and is restricted by medication resistance. One of the most promising cancer treatment techniques is the use of nano-based carrier system as a medication delivery mechanism. To deliver cytotoxic medicines, targeted nanoparticles might take advantage of differently expressed molecules on the surface of cancer cells. The use of different compounds as ligands on the surface of nanoparticles to interact with cancer cells, enabling the efficient delivery of antitumor medicines. Formulations based on nanoparticles might aid in early cancer diagnosis and help to overcome the limitations of traditional treatments, including low water solubility, nonspecific biodistribution, and restricted bioavailability. This article addresses about the molecular pathogenesis of CRC and highlights about biomarkers. It also provides conceptual knowledge of nanotechnology-based diagnostic techniques and therapeutic approaches for malignant colorectal cancer.

High Sensitivity Detection of Tumor Cells in Biological Samples using Multivalent Aptamer Strand Displacement Strategy

Monitoring the cell surface-expressed nucleolin facilitates early cancer diagnosis. Herein, we developed multivalent aptamer displacement strand duplex strategy on the cell membranes utilizing a multi-receptor co-recognition design for improving sensitivity...

Deep Learning Application in Leukemia Diagnosis

Cancer is an aggressive disease with a low median survival rate. Technically, the cost of the treatment is high due to its high recurrence and mortality rates. Accurate and early diagnosis is needed to cure cancer. Even though, there is a lot of applications in the field of medical by using Artificial Intelligence. Artificial Intelligence (AI), especially machine learning and deep learning, has found as popular application in clinical cancer researches in recent years. The prediction of cancer cells has been reached new heights, as the technology is improved day-by-day and lots of devices are invented to detect and to cure cancer cells. Artificial Intelligence (AI)assist cancer diagnosis and prognosis, specifically with regards with unprecedented accuracy, which is even higher than that of general statistical applications in Oncology. There are different types of cancer cells and to destroy these cells, humans required certain technologies to locate and identify the type of cancer. It is very complicated to cure the cancer if it is not found in the early days. This article is about the LEUKEMIA (Blood cancer) and the technologies used for curing Leukemia. The opportunities and the challenges faced in the clinical implementation of Artificial Intelligence (AI).Machine Learningis used to save a life in advance by the early cancer diagnosis and prognosis in the present and in future too.

Zinc-Based Metal-Organic Frameworks in Drug Delivery, Cell Imaging, and Sensing

The design and structural frameworks for targeted drug delivery of medicinal compounds and improved cell imaging have been developed with several advantages. However, metal-organic frameworks (MOFs) are supplemented tremendously for medical uses with efficient efficacy. These MOFs are considered as an absolutely new class of porous materials, extensively used in drug delivery systems, cell imaging, and detecting the analytes, especially for cancer biomarkers, due to their excellent biocompatibility, easy functionalization, high storage capacity, and excellent biodegradability. While Zn-metal centers in MOFs have been found by enhanced efficient detection and improved drug delivery, these Zn-based MOFs have appeared to be safe as elucidated by different cytotoxicity assays for targeted drug delivery. On the other hand, the MOF-based heterogeneous catalyst is durable and can regenerate multiple times without losing activity. Therefore, as functional carriers for drug delivery, cell imaging, and chemosensory, MOFs’ chemical composition and flexible porous structure allowed engineering to improve their medical formulation and functionality. This review summarizes the methodology for fabricating ultrasensitive and selective Zn-MOF-based sensors, as well as their application in early cancer diagnosis and therapy. This review also offers a systematic approach to understanding the development of MOFs as efficient drug carriers and provides new insights on their applications and limitations in utility with possible solutions.

Overhaul of Radiological Mammography Check-ups for Early Malignancy Diagnosis during COVID-19 Pandemic

Background. The article reports the number of examinations with stationary mammography systems, in outpatient screenings, as well as in a mobile mammography survey across the Sverdlovsk Region.Aim. A study of expedience and design of radiological breast check-ups (exemplified by mammography) for early cancer diagnosis under the COVID-19 pandemic situation.Materials and methods. A survey based at the Sverdlovsk Regional Oncology Dispensary’s Department of Diagnostic Radiology analysed the expedience and design of non-invasive diagnostic procedures in a case study of breast X-ray checkups (mammography) in the Sverdlovsk Region during 2019—2020. Th e survey used the Sverdlovsk Region population statistics on breast malignancy incidence for 2019—2020.Results. According to reports, the number of outpatient screening surveys significantly decreased in 2020 vs. 2019 due to the coronavirus pandemic and effective ban on screenings and medical check-ups. Th e mobile mammography screening numbers increased more than twice in 2020 vs. 2019.Discussion. Screening measures continued during the COVID-19 pandemic. Clinicians adhered to local guidelines, while fully complying with the recommendations to contain SARS-CoV-2 infection. Th e growth of mobile mammography screenings enabled completion of the annual check-up plan, however, the breast malignancy detection rate slightly dropped in 2020 compared to 2019.Conclusion. Mammography screenings at the Sverdlovsk Regional Oncology Dispensary in 2019--2020 demonstrate the expedience and good organisation of breast radiological check-ups (mammography) in Sverdlovsk Region. Accounting for the epidemiological state of coronavirus infection, a positive trend is evident towards growing examinations and improved breast malignancy detection, which lowers mortality accordingly among the female population of Sverdlovsk Region.

Can Circulating Tumor DNA Support a Successful Screening Test for Early Cancer Detection? The Grail Paradigm

Circulating tumor DNA (ctDNA) is a new pan-cancer tumor marker with important applications for patient prognosis, monitoring progression, and assessing the success of the therapeutic response. Another important goal is an early cancer diagnosis. There is currently a debate if ctDNA can be used for early cancer detection due to the small tumor burden and low mutant allele fraction (MAF). We compare our previous calculations on the size of detectable cancers by ctDNA analysis with the latest experimental data from Grail’s clinical trial. Current ctDNA-based diagnostic methods could predictably detect tumors of sizes greater than 10–15 mm in diameter. When tumors are of this size or smaller, their MAF is about 0.01% (one tumor DNA molecule admixed with 10,000 normal DNA molecules). The use of 10 mL of blood (4 mL of plasma) will likely contain less than a complete cancer genome, thus rendering the diagnosis of cancer impossible. Grail’s new data confirm the low sensitivity for early cancer detection (<30% for Stage I–II tumors, <20% for Stage I tumors), but specificity was high at 99.5%. According to these latest data, the sensitivity of the Grail test is less than 20% in Stage I disease, casting doubt if this test could become a viable pan-cancer clinical screening tool.

Nucleases as molecular targets for cancer diagnosis

Early cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.

Engineering Breast Cancer Cells and hUMSCs Microenvironment in 2D and 3D Scaffolds: A Mechanical Study Approach of Stem Cells in Anticancer Therapy

Cell biomechanics plays a major role as a promising biomarker for early cancer diagnosis and prognosis. In the present study, alterations in modulus of elasticity, cell membrane roughness, and migratory potential of MCF-7 (ER+) and SKBR-3 (HER2+) cancer cells were elucidated prior to and post treatment with conditioned medium from human umbilical mesenchymal stem cells (hUMSCs-CM) during static and dynamic cell culture. Moreover, the therapeutic potency of hUMSCs-CM on cancer cell’s viability, migratory potential, and F-actin quantified intensity was addressed in 2D surfaces and 3D scaffolds. Interestingly, alterations in ER+ cancer cells showed a positive effect of treatment upon limiting cell viability, motility, and potential for migration. Moreover, increased post treatment cell stiffness indicated rigid cancer cells with confined cell movement and cytoskeletal alterations with restricted lamellipodia formation, which enhanced these results. On the contrary, the cell viability and the migratory potential were not confined post treatment with hUMSCs-CM on HER2+ cells, possibly due to their intrinsic aggressiveness. The increased post treatment cell viability and the decreased cell stiffness indicated an increased potency for cell movement. Hence, the therapy had no efficacy on HER2+ cells.

Hairpin structure facilitates high-fidelity DNA amplification reactions in both qPCR and high-throughput sequencing

Effective polymerase chain reactions (PCR) are important in bio-laboratories. It is essential to detect rare DNA-sequence variants for early cancer diagnosis or for drug-resistance mutations identification. Some of the common detection quantitative PCR (qPCR) methods are restricted in the limit of detection (LoD) because of the high polymerase misincorporation rate in Taq DNA polymerases. High-fidelity (HiFi) DNA polymerases have a 50- to 250-fold higher fidelity. Yet, there are currently no proper designs for multiplexed HiFi qPCR reactions. Moreover, the popularity of targeting highly multiplex DNA sequences requires minimizing PCR side products, as the potential of dimerization grows quadratically as the plexes of primers increases. Efforts tried before were either an add-on step, or technology-specific, or requiring high-level computing skills. There lacks an easy-to-apply and cost-effective method for dimerization reduction. Here, we presented the Occlusion System, composed of a 5'-overhanged primer and a probe with a short-stem hairpin. We demonstrated that it allowed multiplexing high-fidelity qPCR reaction, it was also compatible with the current variant-enrichment method to improve the LoD by 10-fold. Further, we found that the Occlusion System reduced the dimerization up to 10-fold in highly multiplexed PCR. Thus, the Occlusion System satisfactorily improved both qPCR sensitivity and PCR efficiency.

Interventions to improve early cancer diagnosis of symptomatic individuals: a scoping review

ObjectivesTo summarise the current evidence regarding interventions for accurate and timely cancer diagnosis among symptomatic individuals.DesignA scoping review following the Joanna Briggs Institute’s methodological framework for the conduct of scoping reviews and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist.Data sourcesMEDLINE (Ovid), CINAHL (EBSCOhost) and PsycINFO (Ovid) bibliographic databases, and websites of relevant organisations. Published and unpublished literature (grey literature) of any study type in the English language were searched for from January 2017 to January 2021.Eligibility and criteriaStudy participants were individuals of any age presenting at clinics with symptoms indicative of cancer. Interventions included practice guidelines, care pathways or other initiatives focused on achieving predefined benchmarks or targets for wait times, streamlined or rapid cancer diagnostic services, multidisciplinary teams and patient navigation strategies. Outcomes included accuracy and timeliness of cancer diagnosis.Data extraction and synthesisWe summarised findings graphically and descriptively.ResultsFrom 21 298 retrieved citations, 88 unique published articles and 16 unique unpublished documents (on 18 study reports), met the eligibility for inclusion. About half of the published literature and 83% of the unpublished literature were from the UK. Most of the studies were on interventions in patients with lung cancer. Rapid referral pathways and technology for supporting and streamlining the cancer diagnosis process were the most studied interventions. Interventions were mostly complex and organisation-specific. Common themes among the studies that concluded intervention was effective were multidisciplinary collaboration and the use of a nurse navigator.ConclusionsMultidisciplinary cooperation and involvement of a nurse navigator may be unique features to consider when designing, delivering and evaluating interventions focused on improving accurate and timely cancer diagnosis among symptomatic individuals. Future research should examine the effectiveness of the interventions identified through this review.