scholarly journals Therapeutic Potential of Naturally Occurring Small Molecules to Target the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 403
Author(s):  
Luiz F. S. Oliveira ◽  
Danilo Predes ◽  
Helena L. Borges ◽  
Jose G. Abreu
Keyword(s):  
Colorectal Cancer ◽  
Small Molecules ◽  
Tumor Tissue ◽  
Patient Survival ◽  
Therapeutic Potential ◽  
Antitumor Activities ◽  
The Past ◽  
Naturally Occurring ◽  
Promising Strategy ◽  
Antitumor Properties

Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to radiotherapy and systemic chemotherapy sessions. However, almost half of patients are resistant to these treatments, especially in metastatic cases, where the 5-year survival rate is only 12%. This factor may be related to the intratumoral heterogeneity, tumor microenvironment (TME), and the presence of cancer stem cells (CSCs), which is impossible to resolve with the standard approaches currently available in clinical practice. CSCs are APC-deficient, and the search for alternative therapeutic agents such as small molecules from natural sources is a promising strategy, as these substances have several antitumor properties. Many of those interfere with the regulation of signaling pathways at the central core of CRC development, such as the Wnt/β-catenin, which plays a crucial role in the cell proliferation and stemness in the tumor. This review will discuss the use of naturally occurring small molecules inhibiting the Wnt/β-catenin pathway in experimental CRC models over the past decade, highlighting the molecular targets in the Wnt/β-catenin pathway and the mechanisms through which these molecules perform their antitumor activities.

scholarly journals Novel weapon to conquer human glioblastoma: G-quadruplexes and neuro-inducers

2021 ◽  
Author(s):  
Galina Pavlova ◽  
Varvara Kolesnikova ◽  
Nadezhda Samoylenkova ◽  
Sergey Drozd ◽  
Alexander Revishchin ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cell Cultures ◽  
Tumor Tissue ◽  
Therapy Resistance ◽  
Cell Reprogramming ◽  
Tumor Resistance ◽  
New Approach ◽  
Promising Strategy ◽  
Glioblastoma Recurrence ◽  
Different Response

Abstract Cancer cell reprogramming based on aptamers with antiproliferative properties in combination with small molecules that are used for conversion iPSCs into neurons represents a new approach to reduce the probability of glioblastoma recurrence and tumor resistance to therapy. In this research we tested several combinations of factors on whole cell cultures, derived from tumor tissue after surgical resection, and on cell cultures divided in CD133 enriched and depleted populations, as CD133 marker is believed to be characteristic for glioblastoma stem cells. We showed that CD133+ and CD133- cells have a different response to tested combinations of factors and CD133-positive cells are more stable and possess stemness properties. Thus, affecting these cells will lead to decrease of therapy resistance. Moreover, we found a combination of factors that is able to inhibit proliferation of both CD133+ and CD133- cells. Our results reveal a promising strategy to improve treatment of patients with glioblastoma.

scholarly journals Novel weapon to conquer human glioblastoma: G-quadruplexes and neuro-inducers

2021 ◽  
Author(s):  
Galina Pavlova ◽  
Varvara Kolesnikova ◽  
Nadezhda Samoylenkova ◽  
Sergey Drozd ◽  
Alexander Revishchin ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cell Cultures ◽  
Tumor Tissue ◽  
Therapy Resistance ◽  
Cell Reprogramming ◽  
Tumor Resistance ◽  
New Approach ◽  
Promising Strategy ◽  
Glioblastoma Recurrence ◽  
Different Response

Abstract Cancer cell reprogramming based on aptamers with antiproliferative properties in combination with small molecules that are used for conversion iPSCs into neurons represents a new approach to reduce the probability of glioblastoma recurrence and tumor resistance to therapy. In this research we tested several combinations of factors on whole cell cultures, derived from tumor tissue after surgical resection, and on cell cultures divided in CD133 enriched and depleted populations, as CD133 marker is believed to be characteristic for glioblastoma stem cells. We showed that CD133+ and CD133- cells have a different response to tested combinations of factors and CD133-positive cells are more stable and possess stemness properties. Thus, affecting these cells will lead to decrease of therapy resistance. Moreover, we found a combination of factors that is able to inhibit proliferation of both CD133+ and CD133- cells. Our results reveal a promising strategy to improve treatment of patients with glioblastoma.

RNAs hold a lot of potential when it comes to druggable molecular targets

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Small Molecules ◽  
Drug Targets ◽  
Gene Sequencing ◽  
Molecular Targets ◽  
Effective Strategies ◽  
The Past ◽  
Promising Strategy ◽  
Non Coding Rna ◽  
Human Genes ◽  
Non Coding Rnas

Small molecules drugged just about 700 molecular targets. Most of these molecular targets are proteins, representing 0.5% of the proteome and 0.05% of the genome. It has also been proven that whereas 90% of human genes are transcribed into RNAs, only 2% are translated into proteins. Non-coding RNAs are transcribed from around 70% of human genes. As a result, RNAs hold a lot of potential when it comes to druggable molecular targets, yet they've long been regarded as intractable.MiRNAs are a sort of non-coding RNA that finely regulates gene expression in human cells and has been connected to the development of diseases such as cancer. Using small compounds to drug miRNAs is a distinct and promising strategy, while miRNAs have long been recognized as drug targets and ASOs that block miRNAs have been used in clinical studies. In the past, small drugs targeting alternative biomolecules to indirectly influence miRNAs have been found, but small compounds directly targeting miRNAs offer more potential as therapeutic possibilities. This review summarized recently found chemicals that might directly target miRNAs. When these small molecules connect to miRNAs, they either block or degrade miRNA. These small molecules have also been shown to be beneficial in cancer therapy.In the future, several challenges must be solved to boost the potency of small molecules in drug miRNAs. For starters, discovering a strongly specific miRNA SMI is crucial for medicinal development. While the strategies previously released have shown promise in discovering SMIs, new effective strategies must be created or existing approaches must be enhanced. Second, biotechnologies like gene sequencing and pull-down methods should be combined to test and boost the specificity of identified SMIs. Third, new small-molecule functionalities that can more efficiently degrade RNAs are needed to generate SMDs that work as miRNA degraders. Fourth, most SMIs and SMDs' on-target and off-target toxicity was not adequately examined. This requires detailed bio-safety analyses of manufactured SMIs and SMDs.Finally, a brief summary of small drugs that can directly target miRNAs. MiRNA inhibition and cancer therapy revealed both the efficacy and selectivity of these small molecules. Hopefully, these and other future small molecules will open the door for therapy development that targets druggable miRNAs.

scholarly journals Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuang Wang ◽  
Yang Liu ◽  
Jun Li ◽  
Lei Zhao ◽  
Wei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Tumor Tissue ◽  
Symbiotic Bacterium ◽  
Fusobacterium Nucleatum ◽  
Future Studies ◽  
The Past ◽  
Common Cancer ◽  
Research Gap

Colorectal cancer (CRC) is a common cancer worldwide with complex etiology. Fusobacterium nucleatum (F. nucleatum), an oral symbiotic bacterium, has been linked with CRC in the past decade. A series of gut microbiota studies show that CRC patients carry a high abundance of F. nucleatum in the tumor tissue and fecal, and etiological studies have clarified the role of F. nucleatum as a pro-carcinogenic bacterium in various stages of CRC. In this review, we summarize the biological characteristics of F. nucleatum and the epidemiological associations between F. nucleatum and CRC, and then highlight the mechanisms by which F. nucleatum participates in CRC progression, metastasis, and chemoresistance by affecting cancer cells or regulating the tumor microenvironment (TME). We also discuss the research gap in this field and give our perspective for future studies. These findings will pave the way for manipulating gut F. nucleatum to deal with CRC in the future.

scholarly journals Antibody-Based Immunotoxins for Colorectal Cancer Therapy

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1729
Author(s):  
Laura Sanz ◽  
Raquel Ibáñez-Pérez ◽  
Patricia Guerrero-Ochoa ◽  
Javier Lacadena ◽  
Alberto Anel
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Clinical Activity ◽  
Comprehensive Overview ◽  
Ongoing Research ◽  
Promising Strategy ◽  
Selection Of ◽  
Target Cancer

Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates.

Stress management: Corpus-based insights into vernacular interpretations of stress

2014 ◽  
Vol 10 (1) ◽  
pp. 81-93
Author(s):  
Laurel Smith Stvan
Keyword(s):  
Traumatic Stress ◽  
American English ◽  
Physical Symptom ◽  
The Body ◽  
Post Traumatic Stress ◽  
The Past ◽  
Academic Texts ◽  
Naturally Occurring ◽  
Post Traumatic ◽  
Semantic Shift

Examination of the term stress in naturally occurring vernacular prose provides evidence of three separate senses being conflated. A corpus analysis of 818 instances of stress from non-academic texts in the Corpus of Contemporary American English (COCA) and the Corpus of American Discourses on Health (CADOH) shows a negative prosody for stress, which is portrayed variously as a source outside the body, a physical symptom within the body and an emotional state. The data show that contemporary speakers intermingle the three senses, making more difficult a discussion between doctors and patients of ways to ‘reduce stress’, when stress might be interpreted as a stressor, a symptom, or state of anxiety. This conflation of senses reinforces the impression that stress is pervasive and increasing. In addition, a semantic shift is also refining a new sense for stress, as post-traumatic stress develops as a specific subtype of emotional stress whose use has increased in circulation in the past 20 years.

The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations

2019 ◽  
Vol 26 (13) ◽  
pp. 2330-2355 ◽  
Author(s):  
Anutthaman Parthasarathy ◽  
Sasikala K. Anandamma ◽  
Karunakaran A. Kalesh
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
The Past ◽  
Recombinant Production ◽  
Tremendous Progress ◽  
Recent Developments ◽  
Therapeutic Peptides ◽  
Development Processes ◽  
Delivery Strategies

Peptide therapeutics has made tremendous progress in the past decade. Many of the inherent weaknesses of peptides which hampered their development as therapeutics are now more or less effectively tackled with recent scientific and technological advancements in integrated drug discovery settings. These include recent developments in synthetic organic chemistry, high-throughput recombinant production strategies, highresolution analytical methods, high-throughput screening options, ingenious drug delivery strategies and novel formulation preparations. Here, we will briefly describe the key methodologies and strategies used in the therapeutic peptide development processes with selected examples of the most recent developments in the field. The aim of this review is to highlight the viable options a medicinal chemist may consider in order to improve a specific pharmacological property of interest in a peptide lead entity and thereby rationally assess the therapeutic potential this class of molecules possesses while they are traditionally (and incorrectly) considered ‘undruggable’.

Enzyme-Instructed Self-assembly in Biological Milieu for Theranostics Purpose

2019 ◽  
Vol 26 (8) ◽  
pp. 1351-1365 ◽  
Author(s):  
Zhentao Huang ◽  
Qingxin Yao ◽  
Simin Wei ◽  
Jiali Chen ◽  
Yuan Gao
Keyword(s):  
Small Molecules ◽  
Precision Medicine ◽  
Self Assembly ◽  
Public Healthcare ◽  
Enzymatic Conversion ◽  
Vaccine Adjuvants ◽  
New Paradigm ◽  
Cancer Treatments ◽  
The Past ◽  
Biological Milieu

Precision medicine is in an urgent need for public healthcare. Among the past several decades, the flourishing development in nanotechnology significantly advances the realization of precision nanomedicine. Comparing to well-documented nanoparticlebased strategy, in this review, we focus on the strategy using enzyme instructed selfassembly (EISA) in biological milieu for theranostics purpose. In principle, the design of small molecules for EISA requires two aspects: (1) the substrate of enzyme of interest; and (2) self-assembly potency after enzymatic conversion. This strategy has shown its irreplaceable advantages in nanomedicne, specifically for cancer treatments and Vaccine Adjuvants. Interestingly, all the reported examples rely on only one kind of enzymehydrolase. Therefore, we envision that the application of EISA strategy just begins and will lead to a new paradigm in nanomedicine.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

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