scholarly journals Calcium Signalling in Medulloblastoma: An In Silico Analysis of the Expression of Calcium Regulating Genes in Patient Samples

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1329
Author(s):  
Ahmed Maklad ◽  
Mohammed Sedeeq ◽  
Michael J. G. Milevskiy ◽  
Iman Azimi
Keyword(s):  
Calcium Signalling ◽  
Treatment Strategies ◽  
In Silico Analysis ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Malignant Brain Tumour ◽  
Tumour Metastasis ◽  
Regulator Genes ◽  
New Treatment ◽  
Silico Analysis

Dysregulation in calcium signalling is implicated in several cancer-associated processes, including cell proliferation, migration, invasion and therapy resistance. Modulators of specific calcium-regulating proteins have been proposed as promising future therapeutic agents for some cancers. Alterations in calcium signalling have been extensively studied in some cancers; however, this area of research is highly underexplored in medulloblastoma (MB), the most common paediatric malignant brain tumour. Current MB treatment modalities are not completely effective and can result in several long-lasting mental complications. Hence, new treatment strategies are needed. In this study, we sought to probe the landscape of calcium signalling regulators to uncover those most likely to be involved in MB tumours. We investigated the expression of calcium signalling regulator genes in MB patients using publicly available datasets. We stratified the expression level of these genes with MB molecular subgroups, tumour metastasis and patient survival to uncover correlations with clinical features. Of particular interest was CACNA1 genes, in which we were able to show a developmentally-driven change in expression within the cerebellum, MB’s tissue of origin, highlighting a potential influence on tumour incidence. This study lays a platform for future investigations into molecular regulators of calcium signalling in MB formation and progression.

scholarly journals Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

2021 ◽  
Author(s):  
Antonella Montinaro ◽  
Itziar Areso Zubiaur ◽  
Julia Saggau ◽  
Anna-Laura Kretz ◽  
Rute M. M. Ferreira ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Cancer Resistance ◽  
Therapeutic Approaches ◽  
Highly Effective ◽  
Drastic Increase ◽  
New Treatment

AbstractPrimary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.

Treatment Innovations of Opiate Dependence Treatment

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
W. van den Brink
Keyword(s):  
Partial Agonist ◽  
Treatment Strategies ◽  
Oral Morphine ◽  
Treatment Compliance ◽  
Psychosocial Interventions ◽  
Opiate Dependence ◽  
Treatment Modalities ◽  
List Type ◽  
Number Of Patients ◽  
New Treatment

Opiate dependence is a serious psychiatric disorder with substantial suffering for the patient, his environment and society as a whole. Currently available treatments include abstinence oriented treatment with naltrexone and substitutian treatments with methadone and buprenorphine. However, treatment compliance with naltrexone is very low resulting in low effectiveness. In addition, existing substituation treatments only show moderate effectiveness resulting in a large number of patients showing continued drug use and serious psychological, somatic and functional impairment.New treatment strategies involve:a.the development of long acting opiate antagonists (naltrexone) and partial agonist (buprenorphine) to improve treatment compliance and treatment retention,b.new substitution options such as slow release oral morphine (SROM), oral diacetylmorphine (heroin) and inhalable and injectable diacetyl morphine (heroin assisted treatment: HAT).Recently, a new approach using neurosurgical and neuromodulatory techniques has been advocated to help treatment refractory opiate dependent patients. Finally, certain combinations of farmacotherapy and psychosocial interventions have shown promise for future improvements.This presentation reviews the evidence of existing treatments for opiate dependence and explores the new treatment options for patients not fully responsive to the existing treatment modalities.

scholarly journals Immunotherapy: Newer Therapeutic Armamentarium against Cancer Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Saurabh Pratap Singh ◽  
Richa Singh ◽  
Om Prakash Gupta ◽  
Shalini Gupta ◽  
Madan Lal Brahma Bhatt
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Effective Means ◽  
Treatment Strategies ◽  
Antigen Expression ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Self Renewal ◽  
Primary Tumors

Mounting evidence from the literature suggests the existence of a subpopulation of cancer stem cells (CSCs) in almost all types of human cancers. These CSCs possessing a self-renewal capacity inhabit primary tumors and are more defiant to standard antimitotic and molecularly targeted therapies which are used for eliminating actively proliferating and differentiated cancer cells. Clinical relevance of CSCs emerges from the fact that they are the root cause of therapy resistance, relapse, and metastasis. Earlier, surgery, chemotherapy, and radiotherapy were established as cancer treatment modalities, but recently, immunotherapy is also gaining importance in the management of various cancer patients, mostly those of the advanced stage. This review abridges potential off-target effects of inhibiting CSC self-renewal pathways on immune cells and some recent immunological studies specifically targeting CSCs on the basis of their antigen expression profile, even though molecular markers or antigens that have been described till date as expressed by cancer stem cells are not specifically expressed by these cells which is a major limitation to target CSCs. We propose that owing to CSC stemness property to mediate immunotherapy response, we can apply a combination therapy approach by targeting CSCs and tumor microenvironment (TME) along with conventional treatment strategies as an effective means to eradicate cancer cells.

Cancer Drug Delivery

2016 ◽  
pp. 52-95
Author(s):  
Jai N. Patel ◽  
Jeryl Villadolid
Keyword(s):  
Drug Delivery ◽  
Supportive Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Cancer Drug ◽  
Cellular Mechanisms ◽  
Drug Dosing ◽  
New Treatment ◽  
Cancer Drug Delivery

Advancements in cancer drug delivery have led to the development of personalized oncology care through molecularly-driven targeted therapies. Understanding molecular and cellular mechanisms which drive tumor progression and resistance is critical in managing new treatment strategies which have shifted from empiric to biomarker-directed therapy selection. Biomarker-directed therapies have improved clinical outcomes in multiple malignancies as monotherapy and in combination with other treatment modalities, however the changing scope of treatment options presents new opportunities and challenges for research. Furthermore, pharmacogenetics may provide a rationale method of personalizing anticancer drug dosing and supportive care management for oncology patients. This chapter reviews biomarker classifications and pharmacogenetics in anticancer therapy and supportive care. Examples of biomarker-directed therapies and clinical assays, in addition to future directions of molecular profiling in oncology therapy management are discussed.

scholarly journals Cancer Drug Delivery

2017 ◽  
pp. 185-228
Author(s):  
Jai N. Patel ◽  
Jeryl Villadolid
Keyword(s):  
Drug Delivery ◽  
Supportive Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Cancer Drug ◽  
Cellular Mechanisms ◽  
Drug Dosing ◽  
New Treatment ◽  
Cancer Drug Delivery

Advancements in cancer drug delivery have led to the development of personalized oncology care through molecularly-driven targeted therapies. Understanding molecular and cellular mechanisms which drive tumor progression and resistance is critical in managing new treatment strategies which have shifted from empiric to biomarker-directed therapy selection. Biomarker-directed therapies have improved clinical outcomes in multiple malignancies as monotherapy and in combination with other treatment modalities, however the changing scope of treatment options presents new opportunities and challenges for research. Furthermore, pharmacogenetics may provide a rationale method of personalizing anticancer drug dosing and supportive care management for oncology patients. This chapter reviews biomarker classifications and pharmacogenetics in anticancer therapy and supportive care. Examples of biomarker-directed therapies and clinical assays, in addition to future directions of molecular profiling in oncology therapy management are discussed.

scholarly journals Possible Enhancement of Photodynamic Therapy (PDT) Colorectal Cancer Treatment when Combined with Cannabidiol

2020 ◽  
Vol 21 (2) ◽  
pp. 137-148 ◽  
Author(s):  
Nkune W. Nkune ◽  
Cherie A. Kruger ◽  
Heidi Abrahamse
Keyword(s):  
Colorectal Cancer ◽  
Photodynamic Therapy ◽  
Side Effects ◽  
Cannabis Sativa ◽  
Immune Therapy ◽  
Surgical Excision ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Secondary Spread ◽  
Tumour Metastasis

: Colorectal cancer (CRC) has a high mortality rate and is one of the most difficult diseases to manage due to tumour resistance and metastasis. The treatment of choice for CRC is reliant on the phase and time of diagnosis. Despite several conventional treatments available to treat CRC (surgical excision, chemo-, radiation- and immune-therapy), resistance is a major challenge, especially if it has metastasized. Additionally, these treatments often cause unwanted adverse side effects and so it remains imperative to investigate, alternative combination therapies. Photodynamic Therapy (PDT) is a promising treatment modality for the primary treatment of CRC, since it is non-invasive, has few side effects and selectively damages only cancerous tissues, leaving adjacent healthy structures intact. PDT involves three fundamentals: a Photosensitizer (PS) drug localized in tumour tissues, oxygen and light. Upon PS excitation using a specific wavelength of light, an energy transfer cascade occurs, that ultimately yields cytotoxic species, which in turn induces cell death. Cannabidiol (CBD) is a cannabinoid compound derived from the Cannabis sativa plant, which is found to exert anticancer effects on CRC through different pathways, inducing apoptosis and so inhibits tumour metastasis and secondary spread. This review paper highlights current conventional treatment modalities for CRC and their limitations, as well as discusses the necessitation for further investigation into unconventional active nanoparticle targeting PDT treatments for enhanced primary CRC treatment. This can be administered in combination with CBD, to prevent CRC secondary spread and so enhance the synergistic efficacy of CRC treatment outcomes, with less side effects.

scholarly journals Taxifolin Targets PI3K and mTOR and Inhibits Glioblastoma Multiforme

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Weiqi Yao ◽  
Hongyun Gong ◽  
Heng Mei ◽  
Lei Shi ◽  
Jinming Yu ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Treatment Strategies ◽  
Lipid Synthesis ◽  
In Silico Analysis ◽  
Acid Synthesis ◽  
Primary Brain Tumor ◽  
Input Signals ◽  
Regulate Cell Growth ◽  
Silico Analysis

Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, has a very poor prognosis. With increasing knowledge of tumor molecular biology, targeted therapies are becoming increasingly integral to comprehensive GBM treatment strategies. mTOR is a key downstream molecule of the PI3K/Akt signaling pathway, integrating input signals from growth factors, nutrients, and energy sources to regulate cell growth and cell proliferation through multiple cellular responses. mTOR/PI3K dual-targeted therapy has shown promise in managing various cancers. Here, we report that taxifolin, a flavanone commonly found in milk thistle, inhibited mTOR/PI3K, promoted autophagy, and suppressed lipid synthesis in GBM. In silico analysis showed that taxifolin can bind to the rapamycin binding site of mTOR and the catalytic site of PI3K (p110α). In in vitro experiments, taxifolin inhibited mTOR and PI3K activity in five different glioma cell lines. Lastly, we showed that taxifolin suppressed tumors in mice; stimulated expression of autophagy-related genes LC3B-II, Atg7, atg12, and Beclin-1; and inhibited expression of fatty acid synthesis-related genes C/EBPα, PPARγ, FABP4, and FAS. Our observations suggest that taxifolin is potentially a valuable drug for treating GBM.

scholarly journals New Aspects of Melasma/Novi aspekti melazme

2014 ◽  
Vol 6 (1) ◽  
pp. 5-18 ◽  
Author(s):  
Katerina Damevska
Keyword(s):  
Hormone Replacement Therapy ◽  
Recent Progress ◽  
Hormone Replacement ◽  
Treatment Strategies ◽  
Uv Exposure ◽  
Treatment Modalities ◽  
New Treatment ◽  
Topical Medications ◽  
Cosmetic Problem ◽  
Condition Today

Abstract Melasma is a common cosmetic problem and its severity ranges from minor pigmentation during pregnancy that resolves spontaneously, to a chronic, troublesome, disfiguring condition. Today, there are various treatment modalities for melasma, providing a different success rate. The need for an effective treatment for melasma is becoming more and more significant probably due to the current lifestyles with increased UV exposure, broad use of hormones for contraception and hormone replacement therapy, as well as increasing esthetic demands. The mainstay of treatment is regular use of sunscreens along with topical medications suppressing melanogenesis. This review summarizes recent progress in understanding the pathophysiology of melasma and implications for new treatment strategies.

scholarly journals Current Opinion and Knowledge on Peritoneal Carcinomatosis: A Survey among a Swiss Oncology Network

Chemotherapy ◽  
2018 ◽  
Vol 63 (3) ◽  
pp. 143-147 ◽  
Author(s):  
Fabian Grass ◽  
David Martin ◽  
Michael Montemurro ◽  
Patrice Mathevet ◽  
Anita Wolfer ◽  
...  
Keyword(s):  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Current Opinion ◽  
New Therapeutic Approaches ◽  
Case Vignettes ◽  
Colorectal Origin ◽  
New Treatment ◽  
Practice Knowledge

Aims of the Study: The present survey aimed to evaluate current opinion and practice regarding peritoneal metastasis (PM), satisfaction with available treatment options, and need for new therapeutic approaches. Methods: This was a qualitative study conducted between October 2016 and October 2017 in the Réseau Suisse Romand d’Oncologie including 101 members of various oncological specialties. Participants’ demographics, current practice, knowledge, and satisfaction regarding available treatment options and need for new treatment options were assessed by semantic differential scales through 33 closed questions with automatic reminders at 4-, 8-, 12-, and 16-week intervals. Results: Twenty-seven participants (27%) completed the survey. Participants were gastrointestinal or gynecologic oncologists and surgeons. Most participants (67%) evaluated their knowledge on PM as moderate, while 22% considered themselves as experts. Clinical usefulness of systemic chemotherapy and hyperthermic intraperitoneal chemotherapy was judged to be moderate to high for PM of ovarian and colorectal origin and moderate to poor for gastric origin. Satisfaction with available treatment options was 6/10 (interquartile range [IQR] 4–7) for ovarian, 5/10 (IQR 3–7) for colorectal, and 3/10 (IQR 1–3) for gastric PM. Treatment strategies varied widely for typical case vignettes. The need for new treatment modalities was rated as 8/10 (IQR 6–10). Conclusion: Usefulness of and satisfaction with available treatment options for PM were rated as moderate at best by oncological experts, and treatment strategies differed importantly among participants. There appears to be a clear need for standardization and new treatment modalities.

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