Cancer Fighting SiRNA-RRM2 Loaded Nanorobots

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.

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Genetic polymorphisms of EGF 5'-UTR in patients with glioma: A possible predictive marker of outcome.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e13009 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e13009-e13009

Author(s):

Emanuela Vattemi ◽

Giovanna Cipollini ◽

Cristina Dealis ◽

Lorena Rossi ◽

Susanne Baier ◽

...

Keyword(s):

Cancer Progression ◽

Direct Sequencing ◽

Predictive Marker ◽

Reference Sequence ◽

Published Data ◽

Sequencing Method ◽

Number Of Patients ◽

Predictive Role ◽

Epidermal Growth

e13009 Background: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer otucome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. Methods: EGF 61A/G polymorphism (rs4444903) was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method (GenBank reference sequence-accession no. AC005509) from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. Results: We investigated EGF +61G/A polymorphism in 24 glioma patients . EGF +61G allele has been found in 67% of glioma patients (25% G/G genotype and 42% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 71% and 50%. In WHO IV gliomas, the EGF +61G allele represents a 63% frequency, (27% G/G and 36% A/G ), in WHO III gliomas a 77% frequency (33% G/G and 44% A/G ) and in WHO II gliomas a 50% frequency (100% A/G ). Median PFS of glioblastoma patients was 9 months. 83% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. Conclusions: Our data conferm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

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Adiponectin, Obesity, and Cancer: Clash of the Bigwigs in Health and Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20102519 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2519 ◽

Cited By ~ 25

Author(s):

Sheetal Parida ◽

Sumit Siddharth ◽

Dipali Sharma

Keyword(s):

Cancer Progression ◽

Protective Role ◽

The Body ◽

Biological Functions ◽

Anti Cancer ◽

Guardian Angel ◽

Health And Disease ◽

Obesity And Cancer ◽

Multiple Signaling

Adiponectin is one of the most important adipocytokines secreted by adipocytes and is called a “guardian angel adipocytokine” owing to its unique biological functions. Adiponectin inversely correlates with body fat mass and visceral adiposity. Identified independently by four different research groups, adiponectin has multiple names; Acrp30, apM1, GBP28, and AdipoQ. Adiponectin mediates its biological functions via three known receptors, AdipoR1, AdipoR2, and T-cadherin, which are distributed throughout the body. Biological functions of adiponectin are multifold ranging from anti-diabetic, anti-atherogenic, anti-inflammatory to anti-cancer. Lower adiponectin levels have been associated with metabolic syndrome, type 2 diabetes, insulin resistance, cardiovascular diseases, and hypertension. A plethora of experimental evidence supports the role of obesity and increased adiposity in multiple cancers including breast, liver, pancreatic, prostrate, ovarian, and colorectal cancers. Obesity mediates its effect on cancer progression via dysregulation of adipocytokines including increased production of oncogenic adipokine leptin along with decreased production of adiponectin. Multiple studies have shown the protective role of adiponectin in obesity-associated diseases and cancer. Adiponectin modulates multiple signaling pathways to exert its physiological and protective functions. Many studies over the years have shown the beneficial effect of adiponectin in cancer regression and put forth various innovative ways to increase adiponectin levels.

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The Hidden Role of Hydrogen Sulfide Metabolism in Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22126562 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6562

Author(s):

Rong-Hsuan Wang ◽

Yu-Hsin Chu ◽

Kai-Ti Lin

Keyword(s):

Hydrogen Sulfide ◽

Cancer Therapy ◽

Cancer Progression ◽

Cancer Development ◽

Cancer Types ◽

Cellular Bioenergetics ◽

H2s Production ◽

Anti Inflammation ◽

Stimulation Of

Hydrogen Sulfide (H2S), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of H2S-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived H2S plays various roles during cancer development reveals opportunities to target H2S-mediated signaling pathways in cancer therapy. In this review, we will focus on the mechanism of H2S-mediated protein persulfidation and the detailed information about the dysregulation of H2S-producing enzymes and metabolism in different cancer types. We will also provide an update on mechanisms of H2S-mediated cancer progression and summarize current options to modulate H2S production for cancer therapy.

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The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization

Cancers ◽

10.3390/cancers12082179 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2179 ◽

Cited By ~ 2

Author(s):

Cinzia Giordano ◽

Giusi La Camera ◽

Luca Gelsomino ◽

Ines Barone ◽

Daniela Bonofiglio ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Metastatic Breast ◽

The Body ◽

Secondary Site ◽

Long Distance ◽

Metastatic Colonization ◽

Pleiotropic Functions ◽

Intracellular Pathway

In recent decades, the study of exosome biology has gained growing interest, representing an active area of cancer research with many potential clinical applications. Exosomes are small lipid bilayer particles released by cells with pleiotropic functions that have been reported to regulate the complex intracellular pathway involved in all steps of breast cancer development—from initiation to progression toward a metastatic dissemination. Particularly, the role of these microvesicles has been explored in metastasis, which represents the leading cause of breast cancer morbidity and mortality worldwide. Reports highlight that the plasticity of breast cancer cells, fundamental for the establishment of distant metastasis, may be in part attributed to exosome-carried signals shared between adjacent cells and long-distance cells in the body. In the present review, we will discuss the functions of exosomes in the metastatic breast cancer process and secondary site outgrowth. The possibility to decode the exosome functions in advanced diseases may offer new opportunities for early detection, molecular targeted therapies and exosome-based therapeutics in breast cancer.

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Dormancy of growth-stunted malignant melanoma: sustainable and smoldering patterns

Oncology Reviews ◽

10.4081/oncol.2014.252 ◽

2014 ◽

Cited By ~ 5

Author(s):

Claudine Piérard-Franchimont ◽

Trinh Hermanns-Lê ◽

Philippe Delvenne ◽

Gérald E. Piérard

Keyword(s):

Malignant Melanoma ◽

Cancer Progression ◽

Immune Surveillance ◽

Lymph Node Involvement ◽

The Body ◽

Node Involvement ◽

Visceral Metastases ◽

Disease Free ◽

Stimulation Of

The presentations of primary and metastatic cutaneous malignant melanoma (CMM) are very diverse. Evidence increasingly indicates that single CMM cells spread to distant sites quite early during cancer progression and are soon eliminated before they become clinically detectable. However bulky metastases which appear at a later stage might derive from some of these early neoplastic cells. It seems that local CMM single cell micro-metastases commonly predict sentinel lymph node involvement without overtly reflecting CMM progression to bulky visceral metastases. This study is intended to review the current understanding of the mechanisms underlying two CMM presentations. The first is the long interval, apparently disease-free, with persistent CMM dormancy, which may precede overt metastatic growth. Immunosurveillance may induce dormancy in single CMM cells disseminated in the body by blocking their proliferation cycle. The second is the socalled CMM smoldering phenomenon, which is marked by an alternate progression and regression of CMM locally with metastases that wax and wane for long periods of time over restricted skin areas. These very diverse patterns of CMM progression are likely to be ascribable to a number of biological factors, including the activation of CMM stem cells, and the combined phenotypic heterogeneity and variability in proliferative amplification in CMM cell clusters. Furthermore an adequate stimulation of CMM immune-surveillance and the induction of a specific stromal structure and vascular response are required. In this context, most early CMM tumors are in part controlled by lymphocytemediated responses before they become clinically detectable. However both the role of immune-surveillance and the mechanisms underlying both persistent and smoldering CMM dormancy remain unclear.

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Interleukin 1β—A Potential Salivary Biomarker for Cancer Progression?

Biomarkers in Cancer ◽

10.4137/bic.s25375 ◽

2015 ◽

Vol 7 ◽

pp. BIC.S25375 ◽

Cited By ~ 8

Author(s):

Adi Idris ◽

Nur B. Ghazali ◽

David Koh

Keyword(s):

Cancer Progression ◽

Biological Fluid ◽

Short Review ◽

The Body ◽

Immunological Factors ◽

Cancer And Inflammation ◽

The Relationship ◽

Pathological Consequence ◽

Potential Cancer

The relationship between cancer and inflammation is a complex but intimate one. Decades of work has shown to us that cancer progression is influenced by a multitude of factors, including genetic, environmental, and immunological factors. We often overlook that cancer progression is also a pathological consequence of a dysregulated inflammatory control in the body. A current emerging topic in cancer research is the role of inflammasomes in carcinogenesis. The inflammasome is a multicomplex protein platform that when activated results in the release of proinflammatory cytokines, such as interleukin (IL)-1β. There is increasing evidence suggesting that IL-1β plays a pivotal role in cancer progression. This short review proposes the possibility of using IL-1β as a potential cancer progression biomarker and discusses the use of saliva as a model biological fluid for measuring physiological IL-1β levels in the body.

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Autophagy and Its Role in Protein Secretion: Implications for Cancer Therapy

Mediators of Inflammation ◽

10.1155/2018/4231591 ◽

2018 ◽

Vol 2018 ◽

pp. 1-17 ◽

Cited By ~ 15

Author(s):

Israel Cotzomi-Ortega ◽

Patricia Aguilar-Alonso ◽

Julio Reyes-Leyva ◽

Paola Maycotte

Keyword(s):

Cancer Therapy ◽

Cancer Progression ◽

Protein Secretion ◽

Survival Function ◽

Degradation Pathway ◽

Intercellular Signaling ◽

Tumor Survival ◽

Response To Stress ◽

Secretion Pathways

Autophagy is a protein and organelle degradation pathway important for the maintenance of cytoplasmic homeostasis and for providing nutrients for survival in response to stress conditions. Recently, autophagy has been shown to be important for the secretion of diverse proteins involved in inflammation, intercellular signaling, and cancer progression. The role of autophagy in cancer depends on the stage of tumorigenesis, serving a tumor-suppressor role before transformation and a tumor-survival function once a tumor is established. We review recent evidence demonstrating the complexity of autophagy regulation during cancer, considering the interaction of autophagy with protein secretion pathways. Autophagy manipulation during cancer treatment is likely to affect protein secretion andinter-cellular signaling either to the neighboring cancer cells or to the antitumoral immune response. This will be an important consideration during cancer therapy since several clinical trials are trying to manipulate autophagy in combination with chemotherapy for the treatment of diverse types of cancers.

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Role of chromosomal instability in cancer progression

Endocrine Related Cancer ◽

10.1530/erc-17-0187 ◽

2017 ◽

Vol 24 (9) ◽

pp. T23-T31 ◽

Cited By ~ 30

Author(s):

Sarah E McClelland

Keyword(s):

Cancer Cells ◽

Cancer Progression ◽

Chromosomal Instability ◽

Genetic Material ◽

The Body ◽

Haploid Number ◽

Normal Cells ◽

Structural Alterations ◽

Novel Approaches

Cancer cells often displaychromosomal instability(CIN), a defect that involves loss or rearrangement of the cell’s genetic material – chromosomes – during cell division. This process results in the generation of aneuploidy, a deviation from the haploid number of chromosomes, and structural alterations of chromosomes in over 90% of solid tumours and many haematological cancers. This trait is unique to cancer cells as normal cells in the body generally strictly maintain the correct number and structure of chromosomes. This key difference between cancer and normal cells has led to two important hypotheses: (i) cancer cells have had to overcome inherent barriers to changes in chromosomes that are not tolerated in non-cancer cells and (ii) CIN represents a cancer-specific target to allow the specific elimination of cancer cells from the body. To exploit these hypotheses and design novel approaches to treat cancer, a full understanding of the mechanisms driving CIN and how CIN contributes to cancer progression is required. Here, we will discuss the possible mechanisms driving chromosomal instability, how CIN may contribute to the progression at multiple stages of tumour evolution and possible future therapeutic directions based on targeting cancer chromosomal instability.

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The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma

Current Oncology ◽

10.3390/curroncol28060385 ◽

2021 ◽

Vol 28 (6) ◽

pp. 4542-4552

Author(s):

Shantanu Banerji ◽

Daniel E. Meyers ◽

Craig Harlos ◽

David E. Dawe

Keyword(s):

Cancer Progression ◽

Malignant Pleural Mesothelioma ◽

Late Phase ◽

Eligible Patient ◽

The Body ◽

Pleural Mesothelioma ◽

Modest Improvement ◽

Immune Therapies ◽

The Relationship

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward.

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Specialized Pro-Resolving Mediators Mitigate Cancer-Related Inflammation: Role of Tumor-Associated Macrophages and Therapeutic Opportunities

Frontiers in Immunology ◽

10.3389/fimmu.2021.702785 ◽

2021 ◽

Vol 12 ◽

Author(s):

Margot Lavy ◽

Vanessa Gauttier ◽

Nicolas Poirier ◽

Sophie Barillé-Nion ◽

Christophe Blanquart

Keyword(s):

Cancer Therapy ◽

Tumor Progression ◽

Cancer Progression ◽

Immune Escape ◽

Therapy Resistance ◽

High Plasticity ◽

Tumor Cell Death ◽

Tumor Associated Macrophages ◽

Inflammation Resolution

Inflammation is a fundamental physiological response orchestrated by innate immune cells to restore tissue homeostasis. Specialized pro-resolving mediators (SPMs) are involved in active resolution of inflammation but when inflammation is incomplete, chronic inflammation creates a favorable environment that fuels carcinogenesis and cancer progression. Conventional cancer therapy also strengthens cancer-related inflammation by inducing massive tumor cell death that activate surrounding immune-infiltrating cells such as tumor-associated macrophages (TAMs). Macrophages are key actors of both inflammation and its active resolution due to their plastic phenotype. In line with this high plasticity, macrophages can be hijacked by cancer cells to support tumor progression and immune escape, or therapy resistance. Impaired resolution of cancer-associated inflammation supported by TAMs may thus reinforces tumor progression. From this perspective, recent evidence suggests that stimulating macrophage’s pro-resolving functions using SPMs can promote inflammation resolution in cancer and improve anticancer treatments. Thus, TAMs’ re-education toward an antitumor phenotype by using SPMs opens a new line of attack in cancer treatment. Here, we review SPMs’ anticancer capacities with special attention regarding their effects on TAMs. We further discuss how this new therapeutic approach could be envisioned in cancer therapy.

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