Novel Treatment Targets in Sarcoma: More Than Just the GIST

2014 ◽  
pp. e488-e495 ◽  
Author(s):  
Alexander N. Shoushtari ◽  
Brian A. Van Tine ◽  
Gary K. Schwartz
Keyword(s):  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Molecular Classification ◽  
Metabolic Reprogramming ◽  
Treatment Targets ◽  
Rational Development ◽  
Novel Treatment ◽  
Wide Range ◽  
New Treatment ◽  
Novel Therapeutic Strategies

Sarcomas are rare tumors comprising a heterogeneous group of more than 50 histologic subtypes, the majority of which do not respond well to cytotoxic chemotherapy. This has fueled research into the distinct molecular mechanisms of tumorigenesis and disease progression for various sarcoma subtypes. Gastrointestinal stromal tumors and liposarcomas are presented as paradigms of molecular classification that have led to the rational development of novel therapeutic strategies for those tumors. Recent advances in understanding of growth signaling pathways, metabolic reprogramming, and immune therapy have identified new treatment targets for many sarcomas. These investigations will form the foundation for further improvements in our ability to care for patients with these tumors and may offer clinical insights into a wide range of other tumors.

scholarly journals Untargeted Metabolomics Reveal Defensome-Related Metabolic Reprogramming in Sorghum bicolor against Infection by Burkholderia andropogonis

Metabolites ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 8 ◽  
Author(s):  
Charity R. Mareya ◽  
Fidele Tugizimana ◽  
Lizelle A. Piater ◽  
Ntakadzeni E. Madala ◽  
Paul A. Steenkamp ◽  
...  
Keyword(s):  
Sorghum Bicolor ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Shikimic Acid ◽  
Dynamic Network ◽  
Metabolic Reprogramming ◽  
Disease Suppression ◽  
Untargeted Metabolomics ◽  
Wide Range ◽  
Burkholderia Andropogonis

Burkholderia andropogonis is the causal agent of bacterial leaf stripe, one of the three major bacterial diseases affecting Sorghum bicolor. However, the biochemical aspects of the pathophysiological host responses are not well understood. An untargeted metabolomics approach was designed to understand molecular mechanisms underlying S. bicolor–B. andropogonis interactions. At the 4-leaf stage, two sorghum cultivars (NS 5511 and NS 5655) differing in disease tolerance, were infected with B. andropogonis and the metabolic changes monitored over time. The NS 5511 cultivar displayed delayed signs of wilting and lesion progression compared to the NS 5655 cultivar, indicative of enhanced resistance. The metabolomics results identified statistically significant metabolites as biomarkers associated with the sorghum defence. These include the phytohormones salicylic acid, jasmonic acid, and zeatin. Moreover, metabolic reprogramming in an array of chemically diverse metabolites that span a wide range of metabolic pathways was associated with the defence response. Signatory biomarkers included aromatic amino acids, shikimic acid, metabolites from the phenylpropanoid and flavonoid pathways, as well as fatty acids. Enhanced synthesis and accumulation of apigenin and derivatives thereof was a prominent feature of the altered metabolomes. The analyses revealed an intricate and dynamic network of the sorghum defence arsenal towards B. andropogonis in establishing an enhanced defensive capacity in support of resistance and disease suppression. The results pave the way for future analysis of the biosynthesis of signatory biomarkers and regulation of relevant metabolic pathways in sorghum.

scholarly journals MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Afra Z. Daoud ◽  
Eoghan J. Mulholland ◽  
Grace Cole ◽  
Helen O. McCarthy
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Target Prediction ◽  
Pancreatic Disease ◽  
Response To Therapy ◽  
Wide Range ◽  
Mirna Expression Profiles ◽  
Novel Therapeutic Strategies

Abstract A severe lack of early diagnosis coupled with resistance to most available therapeutic options renders pancreatic cancer as a major clinical concern. The limited efficacy of current treatments necessitates the development of novel therapeutic strategies that are based on an understanding of the molecular mechanisms involved in pancreatic cancer progression. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the expression of multiple proteins in the post-translation process and thus have promise as biomarkers, prognostic agents, and as advanced pancreatic therapies. Profiling of deregulated miRNAs in pancreatic cancer can correlate to diagnosis, indicate optimal treatment and predict response to therapy. Furthermore, understanding the main effector genes in pancreatic cancer along with downstream pathways can identify possible miRNAs as therapeutic candidates. Additionally, obstacles to the translation of miRNAs into the clinic are also considered. Distinct miRNA expression profiles can correlate to stages of malignant pancreatic disease, and hold potential as biomarkers, prognostic markers and clinical targets. However, a limited understanding and validation of the specific role of such miRNAs stunts clinical application. Target prediction using algorithms provides a wide range of possible targets, but these miRNAs still require validation through pre-clinical studies to determine the knock-on genetic effects. Graphical abstract

E6 and E7 oncoproteins: Potential targets of cervical cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Cervical Lesions ◽  
Diagnostic Strategies ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.

High Altitude hypoxia

2020 ◽  
Vol 17 ◽  
Author(s):  
Asma Babar ◽  
Kifayatullah Mengal ◽  
Abdul Hanan Babar ◽  
Shixin Wu ◽  
Mujahid Ali Shah ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
High Altitude ◽  
Molecular Mechanisms ◽  
Strong Association ◽  
Haemoglobin Concentration ◽  
Metabolic Reprogramming ◽  
Molecular Networks ◽  
Whole Genome ◽  
Gene Expressions ◽  
Transcriptional Responses

: The world highest and largest altitude area is called the Qinghai-Tibetan plateau (QTB), which harbors unique animal and plant species. Mammals that inhabit the higher altitude regions have adapted well to the hypoxic conditions. One of the main stressors at high altitude is hypoxia. Metabolic responses to hypoxia play important roles in cell survival strategies and some diseases. However, the homeostatic alterations that equilibrate variations in the demand and supply of energy to maintain organismal function in a prolonged low O2 environment persist partly understood, making it problematic to differentiate adaptive from maladaptive responses in hypoxia. Tibetans and yaks are two perfect examples innate to the plateau for high altitude adaptation. By the scan of the whole-genome, EPAS1 and EGLN1 were identified as key genes associated with sustained haemoglobin concentration in high altitude mammals for adaptation. The yak is a much more ancient mammal which has existed on QTB longer than humans, it is, therefore, possible that natural selection represented a diverse group of genes/pathways in yaks. Physiological characteristics are extremely informative in revealing molecular networks associated with inherited adaptation, in addition to the whole-genome adaptive changes at the DNA sequence level. Gene-expression can be changed by a variety of signals originating from the environment, and hypoxia is the main factor amongst them. The hypoxia-inducible factors (HIF-1α and EPAS1/HIF-2α) are the main regulators of oxygen in homeostasis which play a role as maestro regulators of adaptation in hypoxic reaction of molecular mechanisms. (Vague) The basis of this review is to present recent information regarding the molecular mechanism involved in hypoxia that regulates candidate genes and proteins. Many transcriptional responses toward hypoxia are facilitated by HIFs that change the number of gene expressions and help in angiogenesis, erythropoiesis, metabolic reprogramming and metastasis. HIFs also activate several signals highlighting a strong association between hypoxia, the misfolded proteins’ accumulation in the endoplasmic reticulum in stress and activation of unfolded protein response (UPR). It was observed that at high-altitude, pregnancies yield a low birth weight ∼100 g per1000 m of the climb. (Vague) It may involve variation in the events of energy-demanding, like protein synthesis. Prolonged hypobaric hypoxia causes placental ER stress, which in turn, moderates protein synthesis and reduces proliferation. Further, Cardiac hypertrophy by cytosolic Ca2+ raises and Ca2+/calmodulin, calcineurin stimulation, NF-AT3 pathway might be caused by an imbalance in Sarcoplasmic reticulum ER Ca2, might be adaptive in beginning but severe later.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

Understanding Molecular Process and Chemotherapeutics for the Management of Breast Cancer.

2020 ◽  
Vol 14 ◽  
Author(s):  
Abhishek Kumar ◽  
Neeraj Masand ◽  
Vaishali M. Patil
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Molecular Classification ◽  
Neoplastic Disease ◽  
Molecular Process ◽  
The Past ◽  
Anti Cancer ◽  
Molecular Etiology ◽  
Near Future

Abstract: Breast cancer is the most common and highly heterogeneous neoplastic disease comprised of several subtypes with distinct molecular etiology and clinical behaviours. The mortality observed over the past few decades and the failure in eradicating the disease is due to the lack of specific etiology, molecular mechanisms involved in initiation and progression of breast cancer. Understanding of the molecular classes of breast cancer may also lead to new biological insights and eventually to better therapies. The promising therapeutic targets and novel anti-cancer approaches emerging from these molecular targets that could be applied clinically in the near future are being highlighted. In addition, this review discusses some of the details of current molecular classification and available chemotherapeutics

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

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