scholarly journals Cancer Stem and Progenitor-Like Cells as Pharmacological Targets in Breast Cancer Treatment

2015 ◽  
Vol 9s2 ◽  
pp. BCBCR.S29427 ◽  
Author(s):  
Valéria B. De Souza ◽  
André A. Schenka
Keyword(s):  
Breast Cancer ◽  
Clonal Evolution ◽  
Treatment Strategies ◽  
Tumor Initiating Cells ◽  
Pharmacological Targets ◽  
New Treatment ◽  
Carcinogenesis Models ◽  
Comprehensive Compilation ◽  
New Anticancer Drugs

The present review is focused on the current role of neoplastic stem and progenitor-like cells as primary targets in the pharmacotherapy of cancer as well as in the development of new anticancer drugs. We begin by summarizing the main characteristics of these tumor-initiating cells and key concepts that support their participation in therapeutic failure. In particular, we discuss the differences between the major carcinogenesis models (ie, clonal evolution vs cancer stem cell (CSC) model) with emphasis on breast cancer (given its importance to the study of CSCs) and their implications for the development of new treatment strategies. In addition, we describe the main ways to target these cells, including the main signaling pathways that are more activated or altered in CSCs. Finally, we provide a comprehensive compilation of the most recently tested drugs.

Immunotherapy: New insights in breast cancer treatment

2021 ◽  
pp. 1-10
Author(s):  
Bader Alshehri
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Treatment ◽  
Immune Evasion ◽  
Breast Tumor ◽  
Parp Inhibitor ◽  
Breast Cancer Treatment ◽  
New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

scholarly journals Silencing of MEG3 attenuated the role of lipopolysaccharides by modulating the miR-93-5p/PTEN pathway in Leydig cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xu Zhou ◽  
Jingliang He ◽  
Jinbo Chen ◽  
Yu Cui ◽  
Zhenyu Ou ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Leydig Cells ◽  
Treatment Strategies ◽  
Pten Expression ◽  
Luciferase Reporter ◽  
Western Blots ◽  
New Treatment ◽  
Lps Treatment

Abstract Background Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. Methods Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. Results Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. Conclusions This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.

scholarly journals The role of steroid hormones in breast cancer stem cells

2015 ◽  
Vol 22 (6) ◽  
pp. T177-T186 ◽  
Author(s):  
Bruno M Simões ◽  
Denis G Alferez ◽  
Sacha J Howell ◽  
Robert B Clarke
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Steroid Hormones ◽  
Normal Mammary Gland ◽  
Breast Cancer Stem Cells ◽  
Tumor Initiating Cells ◽  
Unit Of Selection ◽  
Selection For

Breast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity.

scholarly journals Clonal Evolution Characteristics and Reduced Dimension Prognostic Model for Non-Metastatic Metachronous Bilateral Breast Cancer

2021 ◽  
Author(s):  
Lingyu Li ◽  
Jiaxuan Li ◽  
Jiwei Jia ◽  
Hua He ◽  
Mingyang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Features ◽  
Risk Model ◽  
Clonal Evolution ◽  
Bilateral Breast Cancer ◽  
Treatment Strategies ◽  
Significant Heterogeneity ◽  
Prognostic Evaluation ◽  
Interval Time ◽  
Time To Build

Abstract Background:How to evaluate the prognosis and develop overall treatment strategies of metachronous bilateral breast cancer (MBBC) remains confused in clinical practice.Methods:Data from Surveillance, Epidemiology, and End Results (SEER) database and the first hospital of Jilin university were analyzed for breast cancer-specific cumulative mortality (BCCM) by competing risk model. Whole-exome sequencing was applied for 10 lesions acquired at spatial-temporal distinct regions from 5 patients to reconstruct clonal evolutionary characteristics of MBBC. Dimensional reduction (DR) cumulative incidence function (CIF) curves of MBBC features were established on different point in diagnostic interval time, to build a novel DR nomogram.Results:Significant heterogeneity in genome and clinical features of MBBC was widespread. The mutational diversity of contralateral BC (CBC) was significantly higher than that in primary BC (PBC), and the most effective prognostic MATH ratio was significantly correlated with interval time (R2=0.85, p < .05). In SEER cohort study (n=13304), the interval time was not only significantly affected the BCCM by multivariate analysis (p < .000), but determined the weight of clinical features (T/N stage, grade and ER status) on PBC and CBC in prognostic evaluation. Thus, clinical parameters after DR based on interval time were incorporated into the nomogram for prognostic predicting BCCM. Concordance index was 0.773 (95% CI, 0.769 to 0.776) in training cohort (n=8869), and 0.819 (95% CI, 0.813 to 0.826) in validation cohort (n=4435).Conclusions:Bilateral heterogeneous characteristics and interval time were determinant prognostic factors of MBBC. The DR nomogram may help clinical prognostic evaluation.

scholarly journals Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 968 ◽  
Author(s):  
Sunitha Kodidela ◽  
Kelli Gerth ◽  
Sanjana Haque ◽  
Yuqing Gong ◽  
Saifudeen Ismael ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Progressive Dementia ◽  
Hiv Patients ◽  
Age Related ◽  
Infected Cells ◽  
New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

scholarly journals Esophageal Cancer: Genomic and Molecular Characterization, Stem Cell Compartment and Clonal Evolution

Medicines ◽  
2017 ◽  
Vol 4 (3) ◽  
pp. 67 ◽  
Author(s):  
◽  
◽  
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Clonal Evolution ◽  
Basal Layer ◽  
Treatment Strategies ◽  
Squamous Carcinoma ◽  
Cellular Origin ◽  
Genetic Abnormalities ◽  
Genetic Landscape ◽  
New Treatment

Esophageal cancer (EC) is the eighth most common cancer and is the sixth leading cause of death worldwide. The incidence of histologic subtypes of EC, esophageal adenocarcinoma (EAC) and esophageal squamous carcinoma (ESCC), display considerable geographic variation. EAC arises from metaplastic Barrett’s esophagus (BE) in the context of chronic inflammation secondary to exposure to acid and bile. The main risk factors for developing ESCC are cigarette smoking and alcohol consumption. The main somatic genetic abnormalities showed a different genetic landscape in EAC compared to ESCC. EAC is a heterogeneous cancer dominated by copy number alterations, a high mutational burden, co-amplification of receptor tyrosine kinase, frequent TP53 mutations. The cellular origins of BE and EAC are still not understood: animal models supported a cellular origin either from stem cells located in the basal layer of esophageal epithelium or from progenitors present in the cardia region. Many studies support the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. The exact identification of these CSCs, as well as their role in the pathogenesis of EAC and ESCC remain still to be demonstrated. The reviewed studies suggest that current molecular and cellular characterization of EAC and ESCC should serve as background for development of new treatment strategies.

Molecular Pathways of Ischemic Stroke and Advanced Therapeutic Strategies

2018 ◽  
Vol 4 (1-2) ◽  
Author(s):  
Preeti Singh
Keyword(s):  
Ischemic Stroke ◽  
New Technologies ◽  
Treatment Strategies ◽  
Molecular Pathways ◽  
Therapeutic Approaches ◽  
Permanent Disability ◽  
Acute Cerebral Ischemia ◽  
Tremendous Progress ◽  
New Treatment

Ischemic stroke is a leading cause of death and permanent disability. This disease may affect any age group and especially in old age and pregnancy. All the responsible mechanisms are yet not completely understood. There is limited therapeutic intervention beyond prevention, yet tremendous progress in understanding cause of stroke at molecular level has been going on. A lot of advancement has occurred in the prevention and treatment of stroke during the past decade. In this review an update work of causeways of stroke and its therapeutic approaches have been discussed. The relevance of excitotoxicity (role of glutamate receptor), inflammation, ischemic penumbra, apoptosis, to delayed mechanisms and, damage and treatment strategies have been hasted out. Although the results among clinical studies, conflict regarding several experimental data of different therapies, and it may improve neurological outcome after acute cerebral ischemia. Along this several other interventions and new technologies such as stroke detector microwave helmet are being assessed and many other advanced techniques developed by researchers. Even the development of other novel and new treatment strategies (regarding molecular pathways and risk to benefit therapeutic ratio) for stroke are still required in future for better treatment.

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