The Algorithms Cruz Rodriguez (CR) are Proposing A Novel Vaccine RNA-Peptide against Breast, Ovarian, and Lung Cancers Disease: Exosomes as Carrier in Cancer Progression and Metastasis

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Cruz-Rodriguez L ◽  
Dilsiz N ◽  
Barea R ◽  
Ziarati P ◽  
Hochwimmer B ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Drug Transport ◽  
Peptide Vaccine ◽  
Experimental Studies ◽  
Cell Types ◽  
Biological Action ◽  
Cancer Disease ◽  
Lung Cancers ◽  
Cancer Management ◽  
Peptide Molecule

Exosomes are a novel horizon in modern therapy and open exciting new opportunities for advanced drug transport and targeted release. Exosomes are biological nanoparticles with dimensions ranging from 30 to 100 nm and are generated by all cell types in the human body. Exosomes-which are extracellular vesicles that function in intercellular communication-may play a key role in the dissemination of vaccine as well as host-derived molecules during cancer disease. We highlight the composition and function of exosomes produced during cancer disease in our work, how these vesicles could function as carriers of the RNA-peptide molecule. Finally, according to the algorithms CRUZ RODRIGUEZ (CR) we are proposing various methods to develop a novel vaccine against breast, ovarian, and lung cancers. Therefore, six RNA-peptides from our previous study were chosen based on the potential of inducing strong fusion stability (FS=58.50 cruz) and exosome affinity (EA=59.80 ro), Biological Action (BA= 1.0223 ro/cruz). This result may lead to the development of promising new therapeutic approaches in cancer management by using exosome-mediated miRNA-peptide vaccine therapy. Due to, according to the algorithm CR the Optimal Biological Action (OBA) value for antitumoral RNA-peptide with Exosome as carrier are: 0.8 < OBA < 1.3. These results suggest that the designed vaccine can elicit specific immune responses against three types of cancer; however, these results need experimental studies to confirm the efficacy and safety profile of the proposed vaccine structure.

scholarly journals The “Janus Face” of Platelets in Cancer

2020 ◽  
Vol 21 (3) ◽  
pp. 788 ◽  
Author(s):  
Maria Valeria Catani ◽  
Isabella Savini ◽  
Valentina Tullio ◽  
Valeria Gasperi
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Cell Types ◽  
Vital Role ◽  
Bioactive Molecules ◽  
Cancer Type ◽  
Cancer Management ◽  
The Impact

Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression. To this end, we will describe the impact of (i) platelet count, (ii) bioactive molecules secreted upon platelet activation, and (iii) microvesicle-derived miRNAs on cancer behavior. Potential explanations of conflicting results are also reported: Both intrinsic (heterogeneity in platelet-derived bioactive molecules with either inhibitory or stimulatory properties; features of cancer cell types, such as aggressiveness and/or tumour stage) and extrinsic (heterogeneous characteristics of cancer patients, study design and sample preparation) factors, together with other confounding elements, contribute to “the Janus face” of platelets in cancer. Given the difficulty to establish the univocal role of platelets in a tumor, a better understanding of their exact contribution is warranted, in order to identify an efficient therapeutic strategy for cancer management, as well as for better prevention, screening and risk assessment protocols.

scholarly journals Sympathetic activity in breast cancer and metastasis: partners in crime

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Francisco Conceição ◽  
Daniela M. Sousa ◽  
Joana Paredes ◽  
Meriem Lamghari
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Bone Remodeling ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Sympathetic Innervation ◽  
Breast Cancer Progression ◽  
Vicious Cycle ◽  
Native Bone ◽  
Cancer Management

AbstractThe vast majority of patients with advanced breast cancer present skeletal complications that severely compromise their quality of life. Breast cancer cells are characterized by a strong tropism to the bone niche. After engraftment and colonization of bone, breast cancer cells interact with native bone cells to hinder the normal bone remodeling process and establish an osteolytic “metastatic vicious cycle”. The sympathetic nervous system has emerged in recent years as an important modulator of breast cancer progression and metastasis, potentiating and accelerating the onset of the vicious cycle and leading to extensive bone degradation. Furthermore, sympathetic neurotransmitters and their cognate receptors have been shown to promote several hallmarks of breast cancer, such as proliferation, angiogenesis, immune escape, and invasion of the extracellular matrix. In this review, we assembled the current knowledge concerning the complex interactions that take place in the tumor microenvironment, with a special emphasis on sympathetic modulation of breast cancer cells and stromal cells. Notably, the differential action of epinephrine and norepinephrine, through either α- or β-adrenergic receptors, on breast cancer progression prompts careful consideration when designing new therapeutic options. In addition, the contribution of sympathetic innervation to the formation of bone metastatic foci is highlighted. In particular, we address the remarkable ability of adrenergic signaling to condition the native bone remodeling process and modulate the bone vasculature, driving breast cancer cell engraftment in the bone niche. Finally, clinical perspectives and developments on the use of β-adrenergic receptor inhibitors for breast cancer management and treatment are discussed.

scholarly journals The Fluorescent Probe Bodipy-FL-Verapamil Is a Substrate for Both P-glycoprotein and Multidrug Resistance-related Protein (MRP)-1

2002 ◽  
Vol 50 (5) ◽  
pp. 731-734 ◽  
Author(s):  
Enrico Crivellato ◽  
Luigi Candussio ◽  
Anna M. Rosati ◽  
Fiora Bartoli-Klugmann ◽  
Franco Mallardi ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Drug Transport ◽  
Mrna Level ◽  
Fluorescent Microscopy ◽  
Flow Cytometric Analysis ◽  
Cell Types ◽  
Multidrug Resistant ◽  
Related Protein ◽  
P Glycoprotein ◽  
Multidrug Resistance Related Protein

Several fluorescent probes have been used in functional studies to analyze drug transport in multidrug-resistant cells by fluorescent microscopy. Because many of these molecules have some drawbacks, such as toxicity, nonspecific background, or accumulation in mitochondria, new fluorescent compounds have been proposed as more useful tools. Among these substances, Bodipy-FL-Verapamil, a fluorescent conjugate of the drug efflux blocker verapamil, has been used to study P-glycoprotein activity in different cell types. In this study we tested by fluorescent microscopy the accumulation of Bodipy-FL- Verapamil in cell lines that overexpress either P-glycoprotein (P-gp) or multidrug resistance-related protein 1 (MRP1). Expression of P-gp and MRP1 was evaluated at the mRNA level by RT-PCR technique and at the protein level by flow cytometric analysis using C219 and MRP-m6 monoclonal antibodies. Results indicate that Bodipy-FL-Verapamil is actually a substrate for both proteins. As a consequence, any conclusion about P-gp activity obtained by the use of Bodipy-FL-Verapamil as fluorescent tracer should be interpreted with caution.

scholarly journals Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

2015 ◽  
Vol 17 ◽  
Author(s):  
Esak Lee ◽  
Niranjan B. Pandey ◽  
Aleksander S. Popel
Keyword(s):  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Lymphatic Vessels ◽  
Cell Types ◽  
Malignant Cell ◽  
Lymphatic Endothelial Cells ◽  
Tumour Blood

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.

scholarly journals Exploring Hyperoxia Effects in Cancer—From Perioperative Clinical Data to Potential Molecular Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1213
Author(s):  
Anca Irina Ristescu ◽  
Crina Elena Tiron ◽  
Adrian Tiron ◽  
Ioana Grigoras
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Studies ◽  
Perioperative Period ◽  
Postoperative Recovery ◽  
Mesenchymal Transition ◽  
Oncological Treatment

Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects of perioperative hyperoxia exposure on distal micro-metastases and on circulating cancer cells can potentially play a role in cancer progression or recurrence. In clinical trials, hyperoxia seems to increase the rate of postoperative complications and, by delaying postoperative recovery, it can alter the return to intended oncological treatment. The effects of supplemental oxygen on the long-term mortality of surgical cancer patients offer, at this point, conflicting results. In experimental studies, hyperoxia effects on cancer biology were explored following multiple pathways. In cancer cell cultures and animal models, hyperoxia increases the production of reactive oxygen species (ROS) and increases the oxidative stress. These can be followed by the induction of the expression of Brain-derived neurotrophic factor (BDNF) and other molecules involved in angiogenesis and by the promotion of various degrees of epithelial mesenchymal transition (EMT).

scholarly journals Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongyu Zhao ◽  
Yu Teng ◽  
Wende Hao ◽  
Jie Li ◽  
Zhefeng Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Cell ◽  
Cancer Progression ◽  
Cox Regression ◽  
Single Cell Analysis ◽  
Cell Types ◽  
In Vitro Assays ◽  
Migration And Invasion ◽  
Dominant Type

Abstract Background Ovarian cancer was one of the leading causes of female deaths. Patients with OC were essentially incurable and portends a poor prognosis, presumably because of profound genetic heterogeneity limiting reproducible prognostic classifications. Methods We comprehensively analyzed an ovarian cancer single-cell RNA sequencing dataset, GSE118828, and identified nine major cell types. Relationship between the clusters was explored with CellPhoneDB. A malignant epithelial cluster was confirmed using pseudotime analysis, CNV and GSVA. Furthermore, we constructed the prediction model (i.e., RiskScore) consisted of 10 prognosis-specific genes from 2397 malignant epithelial genes using the LASSO Cox regression algorithm based on public datasets. Then, the prognostic value of Riskscore was assessed with Kaplan–Meier survival analysis and time-dependent ROC curves. At last, a series of in-vitro assays were conducted to explore the roles of IL4I1, an important gene in Riskscore, in OC progression. Results We found that macrophages possessed the most interaction pairs with other clusters, and M2-like TAMs were the dominant type of macrophages. C0 was identified as the malignant epithelial cluster. Patients with a lower RiskScore had a greater OS (log-rank P < 0.01). In training set, the AUC of RiskScore was 0.666, 0.743 and 0.809 in 1-year, 3-year and 5-year survival, respectively. This was also validated in another two cohorts. Moreover, downregulation of IL4I1 inhibited OC cells proliferation, migration and invasion. Conclusions Our work provide novel insights into our understanding of the heterogeneity among OCs, and would help elucidate the biology of OC and provide clinical guidance in prognosis for OC patients.

scholarly journals Analysis of the anticancer effect of endostatin on oral squamous cell carcinoma based on results of experimental studies

2020 ◽  
pp. 134-139
Author(s):  
Г.М. Тугузбаева ◽  
В.Н. Павлов ◽  
Д.А. Еникеев
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Experimental Studies ◽  
Antitumor Agent ◽  
Regional Lymph Nodes ◽  
Tumour Shrinkage ◽  
Oral Malignancy

При плоскоклеточном раке полости рта основной причиной летальных исходов является метастазирование в регионарные лимфатические узлы. Злокачественный рост и формирование метастазов напрямую зависят от степени кровоснабжения первичного очага новообразования. Известно, что по мере прогрессирования опухолевый процесс сопровождается нарушением сбалансированной в норме системы регуляции ангиогенеза с превалированием уровня ангиогенных стимуляторов над ингибиторами. В связи с этим, использование антиангиогенных средств является патофизиологически обоснованным методом борьбы со злокачественным ростом. В обзоре обсуждаются данные доклинических исследований участия эндостатина, природного ингибитора ангиогенеза, в процессах подавления прогрессии и метастазирования плоскоклеточного рака челюстно-лицевой области. Проанализированы патогенетические механизмы ингибирования эндостатином опухолевого роста в экспериментальных моделях рака полости рта. Эндостатин можно рассматривать в качестве потенциального противоопухолевого средства для лечения данной нозологии. The main reason for cancer-associated mortality in patients with oral squamous cell carcinoma is metastatic spread to regional lymph nodes. It is known that the processes of malignant growth and metastasis are highly dependent on blood supply to the primary cancerous focus. The development of malignancy is accompanied by failure of the normally well-balanced system of angiogenesis regulation with prevalence of proangiogenic factors over inhibitors. Therefore, the use of angiogenic inhibitors is a pathophysiologically justified method aimed at suppression of cancer progression. This review presents reports of experimental studies on the role of endostatin, a natural inhibitor of angiogenesis, in processes of tumour shrinkage in squamous cell carcinoma of the maxillofacial region. The authors analysed pathogenic mechanisms of the anticancer effects exhibited by endostatin in preclinical models of oral malignancy. Endostatin can be regarded as a potential antitumor agent for the treatment of oral squamous cell carcinoma.

scholarly journals Beyond the GFAP-Astrocyte Protein Markers in the Brain

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1361
Author(s):  
Agnieszka M. Jurga ◽  
Martyna Paleczna ◽  
Justyna Kadluczka ◽  
Katarzyna Z. Kuter
Keyword(s):  
Nervous System ◽  
Experimental Studies ◽  
Structural Diversity ◽  
Cell Types ◽  
Cellular Interactions ◽  
Quick Response ◽  
Protein Markers ◽  
Marker Proteins ◽  
Functional Efficiency ◽  
The Brain

The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that neurons and neuroglia are team players and constant communication between those various cell types is essential to maintain functional efficiency and a quick response to danger. Here, we summarize and discuss known and new markers of astroglial multiple functions, their natural heterogeneity, cellular interactions, aging and disease-induced dysfunctions. This review is focused on newly reported facts regarding astrocytes, which are beyond the old stereotypes. We present an up-to-date list of marker proteins used to identify a broad spectrum of astroglial phenotypes related to the various physiological and pathological nervous system conditions. The aim of this review is to help choose markers that are well-tailored for specific needs of further experimental studies, precisely recognizing differential glial phenotypes, or for diagnostic purposes. We hope it will help to categorize the functional and structural diversity of the astroglial population and ease a clear readout of future experimental results.

scholarly journals Extracellular Vesicles and Thrombosis: Update on the Clinical and Experimental Evidence

2021 ◽  
Vol 22 (17) ◽  
pp. 9317
Author(s):  
Konstantinos Zifkos ◽  
Christophe Dubois ◽  
Katrin Schäfer
Keyword(s):  
Experimental Evidence ◽  
Extracellular Vesicles ◽  
Thrombus Formation ◽  
Experimental Studies ◽  
Cell Types ◽  
Heterogenous Group ◽  
Clearance Mechanism ◽  
And Function ◽  
Role And Function

Extracellular vesicles (EVs) compose a heterogenous group of membrane-derived particles, including exosomes, microvesicles and apoptotic bodies, which are released into the extracellular environment in response to proinflammatory or proapoptotic stimuli. From earlier studies suggesting that EV shedding constitutes a cellular clearance mechanism, it has become evident that EV formation, secretion and uptake represent important mechanisms of intercellular communication and exchange of a wide variety of molecules, with relevance in both physiological and pathological situations. The putative role of EVs in hemostasis and thrombosis is supported by clinical and experimental studies unraveling how these cell-derived structures affect clot formation (and resolution). From those studies, it has become clear that the prothrombotic effects of EVs are not restricted to the exposure of tissue factor (TF) and phosphatidylserines (PS), but also involve multiplication of procoagulant surfaces, cross-linking of different cellular players at the site of injury and transfer of activation signals to other cell types. Here, we summarize the existing and novel clinical and experimental evidence on the role and function of EVs during arterial and venous thrombus formation and how they may be used as biomarkers as well as therapeutic vectors.

scholarly journals Human vulnerability to cancer malignancy is enhanced by evolution of higher mesenchymal CD44 expression compared to other mammals

2020 ◽  
Author(s):  
Xinghong Ma ◽  
Anasuya Dighe ◽  
Jamie Maziarz ◽  
Edwin Neumann ◽  
Eric Erkenbrack ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Bos Taurus ◽  
Cell Types ◽  
Skin Fibroblasts ◽  
Proximal Promoter ◽  
Promoting Effect ◽  
Stromal Fibroblasts ◽  
Human Vulnerability ◽  
Cd44 Expression ◽  
Regulatory Effects

AbstractCD44 is a membrane-bound extracellular matrix (ECM) receptor interacting, among others, with hyaluronic acid (HA) and osteopontin (OPN). Cancer progression and metastasis are greatly influenced by the cancer micro-environment, consisting of ECM, immune cells and cancer-associated fibroblasts (CAF). Recruitment of fibroblasts (FB) into the role as CAFs is caused by paracrine signals from the tumor, including TGFb1, PDGF and OPN. The effect of OPN on the transformation of FB into CAF is mediated by CD44. CD44 expression in human skin and endometrial stromal fibroblasts (SF and ESF, respectively) also enhances invasibility of stroma by trophoblast as well as cancer cells. Here we study the evolution of CD44 expression in therian mammals in both SF as well as ESF and demonstrate that the human lineage has experienced a concerted evolutionary enhancement of CD44 expression in SF and ESF, correlating with an increase in human vulnerability to cancer malignancy. In both human and cattle (Bos taurus), the dominant isoforms are CD44s and CD44v10 with 9 and 10 exons, respectively. CD44s is an isoform strongly associated with malignancy. In humans, an additional isoform is expressed: HsaCD44-205 with 8 exons not found in cattle. We show that the concerted increase of CD44 expression in SF and ESF is largely due to cis-regulatory effects in the proximal promoter of CD44. We identify a primate specific acquisition of CEBPB binding sites in the CD44 promoter. Recruitment of CEBPB into CD44 regulation explains almost 50% of the lineage-specific increased CD44 expression in primate skin fibroblasts but is not necessary for high CD44 expression in ESF. All these results suggest that selective modulation of CD44 expression in skin fibroblasts could attenuate the cancer-promoting effect of CAF recruitment in the skin with minimal side effects on other cell types. Additional experimental data is needed to explore this possibility.

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