scholarly journals Anticancer Mechanism of Curcumin on Human Glioblastoma

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 950
Author(s):  
Shu Chyi Wong ◽  
Muhamad Noor Alfarizal Kamarudin ◽  
Rakesh Naidu
Keyword(s):  
Anticancer Agent ◽  
Treatment Options ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
The Core ◽  
Cycle Arrest ◽  
Tumor Cell Motility ◽  
Anticancer Mechanism ◽  
Potential Strategy ◽  
Median Survival Rate

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin’s anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility

2019 ◽  
Vol 18 (14) ◽  
pp. 1983-1990 ◽  
Author(s):  
V. Lenin Maruthanila ◽  
Ramakrishnan Elancheran ◽  
Ajaikumar B. Kunnumakkar ◽  
Senthamaraikannan Kabilan ◽  
Jibon Kotoky
Keyword(s):  
Biological Effects ◽  
Pleiotropic Effect ◽  
In Vivo Evaluation ◽  
Chemopreventive Agents ◽  
Cycle Arrest ◽  
Wide Range ◽  
Anticancer Mechanism ◽  
Metastasis Development

Emerging evidence present credible support in favour of the potential role of mahanine and girinimbine. Non-toxic herbal carbazole alkaloids occur in the edible part of Murraya koenigii, Micromelum minutum, M. zeylanicum, and M. euchrestiolia. Mahanine and girinimbine are the major potent compounds from these species. In fact, they interfered with tumour expansion and metastasis development through down-regulation of apoptotic and antiapoptotic protein, also involved in the stimulation of cell cycle arrest. Consequently, these compounds were well proven for the in-vitro and in vivo evaluation that could be developed as novel agents either alone or as an adjuvant to conventional therapeutics. Therefore, mahanine and girinimbine analogs have the potential to be the promising chemopreventive agents for the tumour recurrence and the treatment of human malignancies. In this review, an updated wide-range of pleiotropic anticancer and biological effects induction by mahanine and girinimbine against cancer cells were deeply summarized.

scholarly journals Senescence under appraisal: hopes and challenges revisited

2021 ◽  
Author(s):  
Camilla S. A. Davan-Wetton ◽  
Emanuela Pessolano ◽  
Mauro Perretti ◽  
Trinidad Montero-Melendez
Keyword(s):  
Cellular Senescence ◽  
Clinical Success ◽  
Immune Surveillance ◽  
Favourable Outcome ◽  
Cellular Growth ◽  
Therapeutic Approaches ◽  
Cycle Arrest ◽  
Therapeutic Development ◽  
The Right ◽  
Inflammation Resolution

AbstractIn recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can impact on multiple physiological and pathological processes such as wound healing, fibrosis, cancer and ageing. These unjustly called ‘zombie cells’ are indeed a rich source of opportunities for innovative therapeutic development. In this review, we collate the current understanding of the process of cellular senescence and its two-faced nature, i.e. beneficial/detrimental, and reason this duality is linked to contextual aspects. We propose the senescence programme as an endogenous pro-resolving mechanism that may lead to sustained inflammation and damage when dysregulated or when senescent cells are not cleared efficiently. This pro-resolving model reconciles the paradoxical two faces of senescence by emphasising that it is the unsuccessful completion of the programme, and not senescence itself, what leads to pathology. Thus, pro-senescence therapies under the right context, may favour inflammation resolution. We also review the evidence for the multiple therapeutic approaches under development based on senescence, including its induction, prevention, clearance and the use of senolytic and senomorphic drugs. In particular, we highlight the importance of the immune system in the favourable outcome of senescence and the implications of an inefficient immune surveillance in completion of the senescent cycle. Finally, we identify and discuss a number of challenges and existing gaps to encourage and stimulate further research in this exciting and unravelled field, with the hope of promoting and accelerating the clinical success of senescence-based therapies.

scholarly journals Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3708
Author(s):  
Bhaba K. Das ◽  
Aarthi Kannan ◽  
Quy Nguyen ◽  
Jyoti Gogoi ◽  
Haibo Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Aurora Kinase ◽  
Selective Inhibition ◽  
Potential Candidate ◽  
Cycle Arrest

Merkel cell carcinoma (MCC) is an often-lethal skin cancer with increasing incidence and limited treatment options. Although immune checkpoint inhibitors (ICI) have become the standard of care in advanced MCC, 50% of all MCC patients are ineligible for ICIs, and amongst those treated, many patients develop resistance. There is no therapeutic alternative for these patients, highlighting the urgent clinical need for alternative therapeutic strategies. Using patient-derived genetic insights and data generated in our lab, we identified aurora kinase as a promising therapeutic target for MCC. In this study, we examined the efficacy of the recently developed and highly selective AURKA inhibitor, AK-01 (LY3295668), in six patient-derived MCC cell lines and two MCC cell-line-derived xenograft mouse models. We found that AK-01 potently suppresses MCC survival through apoptosis and cell cycle arrest, particularly in MCPyV-negative MCC cells without RB expression. Despite the challenge posed by its short in vivo durability upon discontinuation, the swift and substantial tumor suppression with low toxicity makes AK-01 a strong potential candidate for MCC management, particularly in combination with existing regimens.

Understanding relevant immune mechanisms in gastrointestinal oncology

2021 ◽  
pp. 107815522199286
Author(s):  
Bulent Cetin ◽  
Ozge Gumusay
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Gastrointestinal Cancers ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Multiple Treatment ◽  
Gi Cancers ◽  
The Many

Rapid and successful drug development has resulted in multiple treatment options for gastrointestinal cancer, requiring careful decision making for individual patients. The general theme in modern immunology is that the field is moving beyond establishing the fundamental principles of immune response mechanisms to applying these propositions to understand human diseases and develop new therapies. Immunotherapy has contributed enormously to cancer treatments with a virtual explosion in novel therapeutics including checkpoint inhibitors and other recently developed immunomodulators and the development of novel therapeutic approaches. Although the majority of gastrointestinal (GI) cancers are generally considered poorly immunogenic, clinical trials have revealed that some of the patients with various gastrointestinal cancers are highly responsive to immune checkpoint inhibition-based therapies. We paid special attention to the clinical relevance of immunology and emphasized how newly developed therapies work, including what their strengths and pitfalls are. This review aims to enhance the interest of practitioners in the many specialties and subspecialties that the discipline influences and to assist them in understanding this increasing complexity.

New Therapeutics for Ulcerative Colitis

2021 ◽  
Vol 72 (1) ◽  
pp. 199-213
Author(s):  
Robert P. Hirten ◽  
Bruce E. Sands
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Disease ◽  
Clinical Remission ◽  
Treatment Options ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Stages Of Development ◽  
The Future ◽  
New Treatment ◽  
Novel Therapeutic

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.

Management of maxillary midline diastema with emphasis on etiology

2008 ◽  
Vol 32 (4) ◽  
pp. 265-272 ◽  
Author(s):  
Nikolaos Gkantidis ◽  
Olga-Elpis Kolokitha ◽  
Nikolaos Topouzelis
Keyword(s):  
Treatment Options ◽  
Mixed Dentition ◽  
Therapeutic Approaches ◽  
Need For Treatment ◽  
Treatment Plans ◽  
Treatment Objective ◽  
Laboratory Examinations ◽  
Genetic And Environmental Factors ◽  
Scientific Documentation ◽  
Normal Feature

The importance of the presence of a maxillary midline diastema resides in its position and the concern it causes to patients. This specific diastema has been attributed to genetic and environmental factors, even though it is often a normal feature of growth, especially in primary and mixed dentition. The need for treatment is mainly attributed to esthetic and psychological reasons, rather than functional ones. Although it is often the case, treatment plans should not be selected empirically but rather should be based on adequate scientific documentation. Possible therapeutic approaches include orthodontics, restorative dentistry, surgery and various combinations of the above. The ideal treatment should seek to manage not only the diastema in question but also the cause behind it. Irrespective of the treatment alternative selected, permanent retention of stable results should be considered as a treatment objective. The aim of this paper is to underscore the main etiological factors for the presence of a maxillary midline diastema and to illustrate the clinical and laboratory examinations required to recognize these factors. Furthermore, alternative treatment options are discussed depending on the etiology of the problem.

scholarly journals Nasopharyngeal Microbiota Profiles in Rural Venezuelan Children Are Associated With Respiratory and Gastrointestinal Infections

2020 ◽  
Author(s):  
Lilly M Verhagen ◽  
Ismar A Rivera-Olivero ◽  
Melanie Clerc ◽  
Mei Ling J N Chu ◽  
Jody van Engelsdorp Gastelaars ◽  
...  
Keyword(s):  
Treatment Options ◽  
Therapeutic Approaches ◽  
Gastrointestinal Infections ◽  
Differential Abundance ◽  
Associated Bacteria ◽  
16S Sequencing ◽  
Forest Models ◽  
Random Forest Models ◽  
Tract Infections ◽  
Klebsiella Spp

Abstract Background Recent research suggests that the microbiota affects susceptibility to both respiratory tract infections (RTIs) and gastrointestinal infections (GIIs). In order to optimize global treatment options, it is important to characterize microbiota profiles across different niches and geographic/socioeconomic areas where RTI and GII prevalences are high. Methods We performed 16S sequencing of nasopharyngeal swabs from 209 Venezuelan Amerindian children aged 6 weeks–59 months who were participating in a 13-valent pneumococcal conjugate vaccine (PCV13) study. Using random forest models, differential abundance testing, and regression analysis, we determined whether specific bacteria were associated with RTIs or GIIs and variation in PCV13 response. Results Microbiota compositions differed between children with or without RTIs (P = .018) or GIIs (P = .001). Several species were associated with the absence of infections. Some of these health-associated bacteria are also observed in developed regions, such as Corynebacterium (log2(fold change [FC]) = 3.30 for RTIs and log2(FC) = 1.71 for GIIs), while others are not commonly observed in developed regions, such as Acinetobacter (log2(FC) = 2.82 and log2(FC) = 5.06, respectively). Klebsiella spp. presence was associated with both RTIs (log2(FC) = 5.48) and GIIs (log2(FC) = 7.20). Conclusions The nasopharyngeal microbiota of rural Venezuelan children included several bacteria that thrive in tropical humid climates. Interestingly, nasopharyngeal microbiota composition not only differed in children with an RTI but also in those with a GII, which suggests a reciprocal interplay between the 2 environments. Knowledge of region-specific microbiota patterns enables tailoring of preventive and therapeutic approaches.

scholarly journals Finding a resveratrol analogue as potential anticancer agent with apoptosis and cycle arrest

2020 ◽  
Vol 143 (3) ◽  
pp. 238-241 ◽  
Author(s):  
Zhen-Hui Xin ◽  
Hui-Hui Yang ◽  
Yu-Han Gan ◽  
Ya-Li Meng ◽  
Ya-Peng Li ◽  
...  
Keyword(s):  
Anticancer Agent ◽  
Cycle Arrest

Treatment options for deciduous molar hypomineralization: a report of three cases

Dental Update ◽  
2019 ◽  
Vol 46 (6) ◽  
pp. 546-553
Author(s):  
Yasmy Quintero ◽  
Manuel Restrepo ◽  
Jenny Angélica Saldarriaga ◽  
Alexandra Saldarriaga ◽  
Lourdes Santos-Pinto
Keyword(s):  
Differential Diagnosis ◽  
Early Diagnosis ◽  
Treatment Options ◽  
Clinical Implications ◽  
Therapeutic Approaches ◽  
Enamel Defect ◽  
Delayed Treatment ◽  
Molar Incisor Hypomineralization ◽  
Permanent Molars ◽  
Deciduous Molar

Deciduous molar hypomineralization (DMH) is an enamel defect of systemic and multifactorial origin that affects the second deciduous molar. Currently, its treatment is based on guidelines for Molar Incisor Hypomineralization (MIH), a disturbance that affects permanent molars and may or may not be associated with permanent incisors. To date, there are no guidelines for DMH. Therefore, three different therapeutic approaches are presented to treat DMH, emphasizing the relevance of early diagnosis, differential diagnosis and treatment options, and tailored to take into account each patient's and parents' specific needs, as well as the involved tooth, severity of DMH, patients' symptoms and behaviour. CPD/Clinical Relevance: To understand the clinical implications of DMH since the diagnosis and delayed treatment of this enamel alteration could have important complications in both the primary and permanent dentition.

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