scholarly journals Radiotherapy and the gut microbiome: facts and fiction

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jing Liu ◽  
Chao Liu ◽  
Jinbo Yue
Keyword(s):  
Gut Microbiome ◽  
Response To Treatment ◽  
Cancer Therapies ◽  
Functional Changes ◽  
Positive Effects ◽  
Combination Treatments ◽  
Important Player ◽  
Radiation Induced ◽  
Gastrointestinal Mucositis

AbstractAn ever-growing body of evidence has linked the gut microbiome with both the effectiveness and the toxicity of cancer therapies. Radiotherapy is an effective way to treat tumors, although large variations exist among patients in tumor radio-responsiveness and in the incidence and severity of radiotherapy-induced side effects. Relatively little is known about whether and how the microbiome regulates the response to radiotherapy. Gut microbiota may be an important player in modulating “hot” versus “cold” tumor microenvironment, ultimately affecting treatment efficacy. The interaction of the gut microbiome and radiotherapy is a bidirectional function, in that radiotherapy can disrupt the microbiome and those disruptions can influence the effectiveness of the anticancer treatments. Limited data have shown that interactions between the radiation and the microbiome can have positive effects on oncotherapy. On the other hand, exposure to ionizing radiation leads to changes in the gut microbiome that contribute to radiation enteropathy. The gut microbiome can influence radiation-induced gastrointestinal mucositis through two mechanisms including translocation and dysbiosis. We propose that the gut microbiome can be modified to maximize the response to treatment and minimize adverse effects through the use of personalized probiotics, prebiotics, or fecal microbial transplantation. 16S rRNA sequencing is the most commonly used approach to investigate distribution and diversity of gut microbiome between individuals though it only identifies bacteria level other than strain level. The functional gut microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, as well as metabolomics. Multiple ‘-omic’ approaches can be applied simultaneously to the same sample to obtain integrated results. That said, challenges and remaining unknowns in the future that persist at this time include the mechanisms by which the gut microbiome affects radiosensitivity, interactions between the gut microbiome and combination treatments, the role of the gut microbiome with regard to predictive and prognostic biomarkers, the need for multi “-omic” approach for in-depth exploration of functional changes and their effects on host-microbiome interactions, and interactions between gut microbiome, microbial metabolites and immune microenvironment.

scholarly journals Radiation-induced brain injury: current concepts and therapeutic strategies targeting neuroinflammation

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Casmir Turnquist ◽  
Brent T Harris ◽  
Curtis C Harris
Keyword(s):  
Radiation Therapy ◽  
Brain Injury ◽  
Primary Treatment ◽  
Hippocampal Neurogenesis ◽  
Treatment Modalities ◽  
Cancer Therapies ◽  
Radiation Induced ◽  
Cancer Types

Abstract Continued improvements in cancer therapies have increased the number of long-term cancer survivors. Radiation therapy remains one of the primary treatment modalities with about 60% of newly diagnosed cancer patients receiving radiation during the course of their disease. While radiation therapy has dramatically improved patient survival in a number of cancer types, the late effects remain a significant factor affecting the quality of life particularly in pediatric patients. Radiation-induced brain injury can result in cognitive dysfunction, including hippocampal-related learning and memory dysfunction that can escalate to dementia. In this article, we review the current understanding of the mechanisms behind radiation-induced brain injury focusing on the role of neuroinflammation and reduced hippocampal neurogenesis. Approaches to prevent or ameliorate treatment-induced side effects are also discussed along with remaining challenges in the field.

scholarly journals The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential Mechanistic Role in Disease Pathogenesis

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1405 ◽  
Author(s):  
Tomoko Kumagai ◽  
Farooq Rahman ◽  
Andrew Smith
Keyword(s):  
Gut Microbiome ◽  
Treatment Strategies ◽  
Bowel Injury ◽  
Pelvic Malignancy ◽  
Major Drawback ◽  
Prevention And Treatment ◽  
Radiation Induced ◽  
The Relationship ◽  
Shed Light

Radiotherapy has played a major role in both the curative and palliative treatment of cancer patients for decades. However, its toxic effect to the surrounding normal healthy tissue remains a major drawback. In cases of intra-abdominal and/or pelvic malignancy, healthy bowel is inevitably included in the radiation field, causing undesirable consequences that subsequently manifest as radiation-induced bowel injury, which is associated with significant morbidity and mortality. The pathophysiology of radiation-induced bowel injury is poorly understood, although we now know that it derives from a complex interplay of epithelial injury and alterations in the enteric immune, nervous, and vascular systems in genetically predisposed individuals. Furthermore, evidence supporting a pivotal role for the gut microbiota in the development of radiation-induced bowel injury has been growing. In this review, we aim to appraise our current understanding of radiation-induced bowel injury and the role of the microbiome in its pathogenesis as well as prevention and treatment. Greater understanding of the relationship between the disease mechanism of radiation-induced bowel injury and gut microbiome might shed light on potential future prevention and treatment strategies through the modification of a patient’s gut microbiome.

Measurements of Mcl-1 protein dependencies using dimerization-specific antibodies as predictive biomarkers for BH-3 mimetic class therapies in AML.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19505-e19505
Author(s):  
Michael H. Cardone ◽  
Andrew Kinloch ◽  
Mine Canakci ◽  
Jingping Ge
Keyword(s):  
Cell Lines ◽  
Protein Complexes ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Response To Treatment ◽  
Clinical Settings ◽  
Cancer Therapies ◽  
Protein Levels ◽  
Combination Treatments

e19505 Background: The anti-apoptotic Bcl-2 family proteins facilitate pro-survival and resistance to anti-cancer therapies. Measuring the function of these proteins has shown utility in predicting response to treatment. A biomarker platform that assesses the functionality of these proteins by measuring BH3 mediated signaling potential in individual patients’ cancers, could provide a potential guiding platform for treating AML. In AML venetoclax is becoming widely prescribed and highly effective in combination with other drugs. Recent data indicate that Mcl-1 dependence is a resistance factor to venetoclax and that methods for identifying this could provide guidance for combination treatments. We are developing a technology to directly measure the occurrence of heterodimers of Mcl-1, or Bcl-xL, bound to pro-apoptotic BH3-only protein Bim. These measurements are combined in algorithms developed to indicate the cancer cell apoptotic priming state and offer great potential for identifying best AML treatment options. Methods: Monoclonal antibodies against conformation-specific epitopes induced in Mcl-1/Bim and Bcl-xL/Bim protein complexes were made. Selective bonding of Heterodimer Specific Mcl-1 Bim (HSMCB) and Heterodimer Specific Bcl-xL Bim (HSBXB) mabs were confirmed using ELISA, fluorescence polarization, immunofluorescence microscopy and flow, and by immunohistochemistry in genetically defined cell lines and in AML patient biopsied samples. Results: We show that HSMCB signal depends on both Mcl-1 and Bim protein levels while HSBXB requires Bc-xL and Bim levels. The relative signals of HSMCB to unbound Mcl-1 signal ([HsMcB]/[Mcl-1]) provide a biomarker for Mcl-1 dependence. We carefully established binding metrics that correlate to drug response in cell lines. The pharmacological disruption of these complexes is monitored by the ratiometric readouts that serve as predictive biomarkers for BH-3 mimetic drugs in AML cells. Conclusions: Mcl-1 dependence is a predictive biomarker for venetoclax resistance and for response to Mcl-1 targeted therapies. Flow cytometric and IHC based measurements of a heterodimer complex offer a direct and simpler approach that harbors potential for use in clinical settings. Additional antibodies targeting Mcl-1/Bak and Bcl-2/Bim complexes are being tested.

Secondary gliosarcoma: a review of clinical features and pathological diagnosis

2010 ◽  
Vol 112 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Seunggu J. Han ◽  
Isaac Yang ◽  
Tarik Tihan ◽  
Susan M. Chang ◽  
Andrew T. Parsa
Keyword(s):  
Response To Treatment ◽  
Primary Glioblastoma ◽  
Key Word ◽  
Pubmed Search ◽  
Radiation Induced ◽  
Previously Treated ◽  
The Mean ◽  
Tumor Pathogenesis ◽  
Radiographic Presentation

Object Although secondary gliosarcoma after treatment of primary glioblastoma multiforme has been described, little is known of these rare tumors. In this article the authors review the literature on secondary gliosarcoma, with attention to clinical course and pathological features. Methods A PubMed search of the key word intracranial “gliosarcoma” with and without “radiation” or “radiotherapy” in humans was performed. The 204 citations yielded were screened for relevancy to gliosarcomas that occur after treatment of previous intracranial neoplasms. Results A search of the literature yielded 24 relevant articles, combined for a total of only 12 cases of secondary gliosarcoma and 12 cases of radiation-induced gliosarcoma. Of the 12 cases of secondary gliosarcoma, all were previously treated with surgery and radiotherapy (mean dose 50.7 Gy), with a mean survival of 13 months since time of gliosarcoma diagnosis (range 6.9–19.4 months). In the cases of radiation-induced gliosarcoma, the mean dose of previous radiotherapy was 51.3 Gy (median 54 Gy, range 24–60 Gy), and the mean survival since gliosarcoma diagnosis was 6.7 months (median 6 months, range 2–10 months). Conclusions Secondary gliosarcoma and radiation-induced gliosarcoma are exceedingly rare. The literature on secondary gliosarcoma illustrates a more favorable survival than for primary gliosarcoma but remains limited regarding clinical and radiographic presentation, response to treatment, and pathogenesis. The results of the present review also support the notion that secondary gliosarcomas and radiation-induced gliosarcomas are distinct entities, with longer survival and shorter latency of gliosarcoma induction seen in the former. Efforts to elucidate the role of radiotherapy in the induction of gliosarcomas may yield new insights into therapeutic risks of cranial radiation and CNS tumor pathogenesis.

Beyond Physical Exercise: The Role of Nutrition, Gut Microbiota and Nutraceutical Supplementation in Reducing Age-related Sarcopenia

2021 ◽  
Vol 14 ◽  
Author(s):  
Antara Banerjee ◽  
Francesco Marotta ◽  
Yashna Chabria ◽  
Sruthi Hari ◽  
Roberto Catanzaro ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Gut Microbiome ◽  
Physical Dependence ◽  
Nutritional Supplementation ◽  
Geriatric Population ◽  
Aged People ◽  
Positive Effects ◽  
Age Related ◽  
And Function

Sarcopenia, a commonly prevalent geriatric condition mainly characterized by progressive loss of the skeletal muscle mass that result in noticeable reduced muscle strength and quality. Most of the geriatric population of above 60 years of age are overweight leading to the accumulation of fat in the muscles resulting in abated muscle function. The increased loss of muscle mass is associated with high rates of disability, poor motility, frailty and mortality. The excessive degeneration of muscles is now also being observed in middle aged people. Therefore, geriatrics has recently started shifting towards the identification of early stages of the disability in order to expand the life span of the patient and reduce physical dependence. Recent findings have indicated that patients with increased physical activity are also affected by sarcopenia, therefore indicating the role of nutritional supplements to enhance muscle health which in turn helps to counteract sarcopenia. Various interventions with physical trainings haven’t provided substantial improvements of this disorder thereby highlighting the crucial role of nutritional supplementation in enhancing muscle mass and strength. Nutritional supplementation has not only shown to enhance the positive effects of physical interventions but also have a profound impact on the gut microbiome that has come forward as a key regulator of muscle mass and function. This brief review throws light upon the efficiency of nutrients and nutraceutical supplementation by highlighting their ancillary effects in physical interventions as well as improving the gut microbiome status in sarcopenic adults thereby giving rise to a multimodal intervention for the treatment of sarcopenia.

scholarly journals MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xanthene Miles ◽  
Charlot Vandevoorde ◽  
Alistair Hunter ◽  
Julie Bolcaen
Keyword(s):  
Dna Damage ◽  
Therapeutic Interventions ◽  
Cellular Damage ◽  
Current Status ◽  
Cancer Therapies ◽  
Downstream Signaling ◽  
Cycle Arrest ◽  
Radiation Induced ◽  
P53 Activation

Inhibition of the MDM2/X-p53 interaction is recognized as a potential anti-cancer strategy, including the treatment of glioblastoma (GB). In response to cellular stressors, such as DNA damage, the tumor suppression protein p53 is activated and responds by mediating cellular damage through DNA repair, cell cycle arrest and apoptosis. Hence, p53 activation plays a central role in cell survival and the effectiveness of cancer therapies. Alterations and reduced activity of p53 occur in 25-30% of primary GB tumors, but this number increases drastically to 60-70% in secondary GB. As a result, reactivating p53 is suggested as a treatment strategy, either by using targeted molecules to convert the mutant p53 back to its wild type form or by using MDM2 and MDMX (also known as MDM4) inhibitors. MDM2 down regulates p53 activity via ubiquitin-dependent degradation and is amplified or overexpressed in 14% of GB cases. Thus, suppression of MDM2 offers an opportunity for urgently needed new therapeutic interventions for GB. Numerous small molecule MDM2 inhibitors are currently undergoing clinical evaluation, either as monotherapy or in combination with chemotherapy and/or other targeted agents. In addition, considering the major role of both p53 and MDM2 in the downstream signaling response to radiation-induced DNA damage, the combination of MDM2 inhibitors with radiation may offer a valuable therapeutic radiosensitizing approach for GB therapy. This review covers the role of MDM2/X in cancer and more specifically in GB, followed by the rationale for the potential radiosensitizing effect of MDM2 inhibition. Finally, the current status of MDM2/X inhibition and p53 activation for the treatment of GB is given.

On the Methodology of Cartel agreements analysis

2014 ◽  
pp. 53-64 ◽  
Author(s):  
E. Andreyashchenko ◽  
A. Zazdravnykh
Keyword(s):  
Economic Models ◽  
Social Consequences ◽  
Positive Effects ◽  
Industrial Markets

This article is an attempt of summarizing key economic approaches to cartel agreements analysis, its stability, ways of estimating social consequences of cartel agreements. It is alleged that the traditional way of understanding the cartels’ role as completely negative is not accurate; this type of inter-corporate agreements may also bring positive effects on industrial markets. Typical limits of analytical apparatus, contradictions that appear while interpreting results of specific economic models are also represented in the article, as well as substantiation of a discrete role of pricing factor within the analysis of anti-competitive agreements.

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