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Article: LGR5+ Intestinal Stem Cells Display Sex Dependent Radiosensitivity.

Zitter, Ryan C / Chugh, Rishi Man / Bhanja, Payel / Saha, Subhrajit

bioRxiv : the preprint server for biology

2023

Abstract: Radiosensitivity, the susceptibility of cells to ionizing radiation, plays a critical role in understanding the effects of radiation therapy and exposure on tissue health and regeneration. Identifying characteristics that predict how a patient may ... ...

Abstract	Radiosensitivity, the susceptibility of cells to ionizing radiation, plays a critical role in understanding the effects of radiation therapy and exposure on tissue health and regeneration. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data suggested a difference in male and female radiotherapy outcomes. Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity. In this manuscript, we demonstrated sex-specific differences in intestinal epithelial radiosensitivity. In mice models of abdominal irradiation, we observed a significant increase in oxidative stress and injury in males compared to females. Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation-induced toxicity. However, sex-specific differences in intestinal radiosensitivity are not dependent on sex hormones as we demonstrated similar sex-specific radiosensitivity differences in pediatric mice. In an ex-vivo study, we found that human patient-derived intestinal organoids (PID) derived from males showed higher sensitivity to irradiation compared to females as evidenced by loss of budding crypt, organoid size, and membrane integrity. Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation induced upregulation of mitochondrial oxidative metabolism in males compared to females' possible mechanism for radiosensitivity differences.
Language	English
Publishing date	2023-12-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.05.570158
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Article ; Online: LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity.

Zitter, Ryan C / Chugh, Rishi Man / Bhanja, Payel / Kimler, Bruce F / Saha, Subhrajit

Cells

2023 Volume 13, Issue 1

Abstract: Tissue radiosensitivity plays a critical role in the overall outcome of radiation therapy. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data ... ...

Abstract	Tissue radiosensitivity plays a critical role in the overall outcome of radiation therapy. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data have suggested a difference in male and female radiotherapy outcomes. Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity. In this manuscript, we demonstrated sex-specific differences in intestinal epithelial radiosensitivity. In a mouse model of abdominal irradiation, we observed a significant increase in oxidative stress and injury in males compared to females. Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation-induced toxicity. However, sex-specific differences in intestinal radiosensitivity were not dependent on sex hormones, as we demonstrated similar sex-specific radiosensitivity differences in pre-pubescent mice. In an ex vivo study, we found that patient-derived intestinal organoid (PID) from males showed higher sensitivity to radiation compared to females as evident from loss of budding crypts, organoid size, and membrane integrity. Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation-induced upregulation of mitochondrial oxidative metabolism in males compared to females, a possible mechanism for radiosensitivity differences.
MeSH term(s)	Humans ; Animals ; Female ; Male ; Mice ; Cell Division ; Cell Respiration ; Disease Models, Animal ; Radiation Injuries ; Radiation Tolerance ; Receptors, G-Protein-Coupled ; Stem Cells
Chemical Substances	Receptors, G-Protein-Coupled ; LGR5 protein, human
Language	English
Publishing date	2023-12-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13010046
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Article ; Online: Experimental Models to Study COVID-19 Effect in Stem Cells.

Chugh, Rishi Man / Bhanja, Payel / Norris, Andrew / Saha, Subhrajit

Cells

2021 Volume 10, Issue 1

Abstract: The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory ...

Abstract	The new strain of coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) emerged in 2019 and hence is often referred to as coronavirus disease 2019 (COVID-19). This disease causes hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), and is considered as the cause of a global pandemic. Very limited reports in addition to ex vivo model systems are available to understand the mechanism of action of this virus, which can be used for testing of any drug efficacy against virus infectivity. COVID-19 induces tissue stem cell loss, resulting inhibition of epithelial repair followed by inflammatory fibrotic consequences. Development of clinically relevant models is important to examine the impact of the COVID-19 virus in tissue stem cells among different organs. In this review, we discuss ex vivo experimental models available to study the effect of COVID-19 on tissue stem cells.
MeSH term(s)	COVID-19/pathology ; Cells, Cultured ; Humans ; Models, Theoretical ; Stem Cells/pathology
Language	English
Publishing date	2021-01-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10010091
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Article ; Online: Radiation-induced toxicity in rectal epithelial stem cell contributes to acute radiation injury in rectum.

Tirado, Felipe Rodriguez / Bhanja, Payel / Castro-Nallar, Eduardo / Olea, Ximena Diaz / Salamanca, Catalina / Saha, Subhrajit

Stem cell research & therapy

2021 Volume 12, Issue 1, Page(s) 63

Abstract: Background: Radiation-induced rectal epithelial damage is a very common side effect of pelvic radiotherapy and often compromise the life quality and treatment outcome in patients with pelvic malignancies. Unlike small bowel and colon, effect of ... ...

Abstract	Background: Radiation-induced rectal epithelial damage is a very common side effect of pelvic radiotherapy and often compromise the life quality and treatment outcome in patients with pelvic malignancies. Unlike small bowel and colon, effect of radiation in rectal stem cells has not been explored extensively. Here we demonstrate that Lgr5-positive rectal stem cells are radiosensitive and organoid-based transplantation of rectal stem cells mitigates radiation damage in rectum. Methods: C57Bl6 male mice (JAX) at 24 h were exposed to pelvic irradiation (PIR) to determine the radiation effect in pelvic epithelium. Effect of PIR on Lgr5-positive rectal stem cells (RSCs) was determined in Lgr5-EGFP-Cre-ERT2 mice exposed to PIR. Effect of PIR or clinically relevant fractionated PIR on regenerative response of Lgr5-positive RSCs was examined by lineage tracing assay using Lgr5-eGFP-IRES-CreERT2; Rosa26-CAG-tdTomato mice with tamoxifen administration to activate Cre recombinase and thereby marking the ISC and their respective progeny. Ex vivo three-dimensional organoid cultures were developed from Lgr5-EGFP-Cre-ERT2 mice. Organoid growth was determined by quantifying the budding crypt/total crypt ratio. Organoids from Lgr5-EGFP-ires-CreERT2-TdT mice were transplanted in C57Bl6 male mice exposed to PIR. Engraftment and repopulation of Lgr5-positive RSCs were determined after tamoxifen administration to activate Cre recombinase in recipient mice. Statistical analysis was performed using Log-rank (Mantel-Cox) test and paired two-tail t test. Result: Exposure to pelvic irradiation significantly damaged rectal epithelium with the loss of Lgr5+ve rectal stem cells. Radiosensitivity of rectal epithelium was also observed with exposure to clinically relevant fractionated pelvic irradiation. Regenerative capacity of Lgr5+ve rectal stem cells was compromised in response to fractionated pelvic irradiation. Ex vivo organoid study demonstrated that Lgr5+ve rectal stem cells are sensitive to both single and fractionated radiation. Organoid-based transplantation of Lgr5+ve rectal stem cells promotes repair and regeneration of rectal epithelium. Conclusion: Lgr5-positive rectal stem cells are radiosensitive and contribute to radiation-induced rectal epithelial toxicity. Transplantation of Lgr5-positive rectal stem cells mitigates radiation-induced rectal injury and promotes repair and regeneration process in rectum.
MeSH term(s)	Animals ; Humans ; Intestinal Mucosa ; Male ; Mice ; Organoids ; Radiation Injuries ; Receptors, G-Protein-Coupled/genetics ; Rectum ; Stem Cells
Chemical Substances	Receptors, G-Protein-Coupled
Language	English
Publishing date	2021-01-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-020-02111-w
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Article ; Online: Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal.

Chugh, Rishi Man / Bhanja, Payel / Olea, Ximena Diaz / Tao, Fang / Schroeder, Kealan / Zitter, Ryan / Arora, Tanu / Pathak, Harsh / Kimler, Bruce F / Godwin, Andrew K / Perry, John M / Saha, Subhrajit

International journal of molecular sciences

2022 Volume 23, Issue 10

Abstract: Radiation-induced loss of the hematopoietic stem cell progenitor population compromises bone marrow regeneration and development of mature blood cells. Failure to rescue bone marrow functions results in fatal consequences from hematopoietic injury, ... ...

Abstract	Radiation-induced loss of the hematopoietic stem cell progenitor population compromises bone marrow regeneration and development of mature blood cells. Failure to rescue bone marrow functions results in fatal consequences from hematopoietic injury, systemic infections, and sepsis. So far, bone marrow transplant is the only effective option, which partially minimizes radiation-induced hematopoietic toxicities. However, a bone marrow transplant will require HLA matching, which will not be feasible in large casualty settings such as a nuclear accident or an act of terrorism. In this study we demonstrated that human peripheral blood mononuclear cell-derived myeloid committed progenitor cells can mitigate radiation-induced bone marrow toxicity and improve survival in mice. These cells can rescue the recipient's hematopoietic stem cells from radiation toxicity even when administered up to 24 h after radiation exposure and can be subjected to allogenic transplant without GVHD development. Transplanted cells deliver sEVs enriched with regenerative and immune-modulatory paracrine signals to mitigate radiation-induced hematopoietic toxicity. This provides a natural polypharmacy solution against a complex injury process. In summary, myeloid committed progenitor cells can be prepared from blood cells as an off-the-shelf alternative to invasive bone marrow harvesting and can be administered in an allogenic setting to mitigate hematopoietic acute radiation syndrome.
MeSH term(s)	Acute Radiation Syndrome ; Animals ; Bone Marrow ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear ; Mice ; Peripheral Blood Stem Cells
Language	English
Publishing date	2022-05-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23105498
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Article: In-plane Extended Nano-coulter Counter (XnCC) for the Label-free Electrical Detection of Biological Particles.

Zhao, Zheng / Vaidyanathan, Swarnagowri / Bhanja, Payel / Gamage, Sachindra / Saha, Subhrajit / McKinney, Collin / Choi, Junseo / Park, Sunggook / Pahattuge, Thilanga / Wijerathne, Harshani / Jackson, Joshua M / Huppert, Mateusz L / Witek, Małgorzata A / Soper, Steven A

Electroanalysis

2022 Volume 34, Issue 12, Page(s) 1961–1975

Abstract: We report an in-plane extended nanopore Coulter counter (XnCC) chip fabricated in a thermoplastic via imprinting. The fabrication of the sensor utilized both photolithography and focused ion beam milling to make the microfluidic network and the in-plane ... ...

Abstract	We report an in-plane extended nanopore Coulter counter (XnCC) chip fabricated in a thermoplastic via imprinting. The fabrication of the sensor utilized both photolithography and focused ion beam milling to make the microfluidic network and the in-plane pore sensor, respectively, in Si from which UV resin stamps were generated followed by thermal imprinting to produce the final device in the appropriate plastic (cyclic olefin polymer, COP). As an example of the utility of this in-plane extended nanopore sensor, we enumerated SARS-CoV-2 viral particles (VPs) affinity-selected from saliva and extracellular vesicles (EVs) affinity-selected from plasma samples secured from mouse models exposed to different ionizing radiation doses.
Language	English
Publishing date	2022-06-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	384877-2
ISSN	1040-0397
ISSN	1040-0397
DOI	10.1002/elan.202200091
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Zs.A 4036: Show issues

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Article ; Online: BCN057 induces intestinal stem cell repair and mitigates radiation-induced intestinal injury.

Bhanja, Payel / Norris, Andrew / Gupta-Saraf, Pooja / Hoover, Andrew / Saha, Subhrajit

Stem cell research & therapy

2018 Volume 9, Issue 1, Page(s) 26

Abstract: Background: Radiation-induced gastrointestinal syndrome (RIGS) results from the acute loss of intestinal stem cells (ISC), impaired epithelial regeneration, and subsequent loss of the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight ...

Abstract	Background: Radiation-induced gastrointestinal syndrome (RIGS) results from the acute loss of intestinal stem cells (ISC), impaired epithelial regeneration, and subsequent loss of the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, sepsis, and mortality. The high radiosensitivity of the intestinal epithelium limits effective radiotherapy against abdominal malignancies and limits the survival of victims of nuclear accidents or terrorism. Currently, there is no approved therapy to mitigate radiation toxicity in the intestine. Here we demonstrate that BCN057, an anti-neoplastic small molecular agent, induces ISC proliferation and promotes intestinal epithelial repair against radiation injury. Methods: BCN057 (90 mg/kg body weight, subcutaneously) was injected into C57Bl6 male mice (JAX) at 24 h following abdominal irradiation (AIR) and was continued for 8 days post-irradiation. BCN057-mediated rescue of Lgr5-positive ISC was validated in Lgr5-EGFP-Cre-ERT2 mice exposed to AIR. The regenerative response of Lgr5-positive ISC was examined by lineage tracing assay using Lgr5-EGFP-ires-CreERT2-TdT mice with tamoxifen administration to activate Cre recombinase and thereby marking the ISC and their respective progeny. Ex vivo three-dimensional organoid cultures were developed from surgical specimens of human colon or from mice jejunum and were used to examine the radio-mitigating role of BCN057 on ISC ex vivo. Organoid growth was determined by quantifying the budding crypt/total crypt ratio. Statistical analysis was performed using Log-rank (Mantel-Cox) test and paired two-tail t test. Results: Treatment with BCN057 24 h after a lethal dose of AIR rescues ISC, promotes regeneration of the intestinal epithelium, and thereby mitigates RIGS. Irradiated mice without BCN057 treatment suffered from RIGS, resulting in 100% mortality within 15 days post-radiation. Intestinal organoids developed from mice jejunum or human colon demonstrated a regenerative response with BCN057 treatment and mitigated radiation toxicity. However, BCN057 did not deliver radio-protection to mouse or human colon tumor tissue. Conclusion: BCN057 is a potential mitigator against RIGS and may be useful for improving the therapeutic ratio of abdominal radiotherapy. This is the first report demonstrating that a small molecular agent mitigates radiation-induced intestinal injury by inducing ISC self-renewal and proliferation.
MeSH term(s)	Animals ; Gamma Rays/adverse effects ; Intestinal Diseases/metabolism ; Intestinal Diseases/pathology ; Intestinal Diseases/prevention & control ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Male ; Mice ; Radiation Injuries/metabolism ; Radiation Injuries/pathology ; Radiation Injuries/prevention & control ; Radiation-Protective Agents/chemistry ; Radiation-Protective Agents/pharmacology ; Stem Cells/metabolism ; Stem Cells/pathology
Chemical Substances	Radiation-Protective Agents
Language	English
Publishing date	2018-02-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-017-0763-3
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Article ; Online: Auranofin Protects Intestine against Radiation Injury by Modulating p53/p21 Pathway and Radiosensitizes Human Colon Tumor.

Nag, Dhrubajyoti / Bhanja, Payel / Riha, Randal / Sanchez-Guerrero, Giselle / Kimler, Bruce F / Tsue, Terance T / Lominska, Chris / Saha, Subhrajit

Clinical cancer research : an official journal of the American Association for Cancer Research

2019 Volume 25, Issue 15, Page(s) 4791–4807

Abstract: Purpose: The radiosensitivity of the normal intestinal epithelium is the major limiting factor for definitive radiotherapy against abdominal malignancies. Radiosensitizers, which can be used without augmenting radiation toxicity to normal tissue, are ... ...

Abstract	Purpose: The radiosensitivity of the normal intestinal epithelium is the major limiting factor for definitive radiotherapy against abdominal malignancies. Radiosensitizers, which can be used without augmenting radiation toxicity to normal tissue, are still an unmet need. Inhibition of proteosomal degradation is being developed as a major therapeutic strategy for anticancer therapy as cancer cells are more susceptible to proteasomal inhibition-induced cytotoxicity compared with normal cells. Auranofin, a gold-containing antirheumatoid drug, blocks proteosomal degradation by inhibiting deubiquitinase inhibitors. In this study, we have examined whether auranofin selectively radiosensitizes colon tumors without promoting radiation toxicity in normal intestine. Experimental design: The effect of auranofin (10 mg/kg i.p.) on the radiation response of subcutaneous CT26 colon tumors and the normal gastrointestinal epithelium was determined using a mouse model of abdominal radiation. The effect of auranofin was also examined in a paired human colonic organoid system using malignant and nonmalignant tissues from the same patient. Results: Both in the mouse model of intestinal injury and in the human nonmalignant colon organoid culture, auranofin pretreatment prevented radiation toxicity and improved survival with the activation of p53/p21-mediated reversible cell-cycle arrest. However, in a mouse model of abdominal tumor and in human malignant colonic organoids, auranofin inhibited malignant tissue growth with inhibition of proteosomal degradation, induction of endoplasmic reticulum stress/unfolded protein response, and apoptosis. Conclusions: Our data suggest that auranofin is a potential candidate to be considered as a combination therapy with radiation to improve therapeutic efficacy against abdominal malignancies.
MeSH term(s)	Animals ; Antirheumatic Agents/pharmacology ; Apoptosis ; Auranofin/pharmacology ; Cell Line, Tumor ; Cell Survival/drug effects ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Colonic Neoplasms/radiotherapy ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Endoplasmic Reticulum Stress/drug effects ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/injuries ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Protective Agents/pharmacology ; Radiation Injuries/pathology ; Radiation Injuries/prevention & control ; Radiation-Sensitizing Agents/pharmacology ; Tumor Suppressor Protein p53/metabolism ; Unfolded Protein Response/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Antirheumatic Agents ; CDKN1A protein, human ; Cyclin-Dependent Kinase Inhibitor p21 ; Protective Agents ; Radiation-Sensitizing Agents ; TP53 protein, human ; Tumor Suppressor Protein p53 ; Auranofin (3H04W2810V)
Language	English
Publishing date	2019-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-18-2751
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Article: Stressed Out - Therapeutic Implications of ER Stress Related Cancer Research.

Riha, Randal / Gupta-Saraf, Pooja / Bhanja, Payel / Badkul, Samyak / Saha, Subhrajit

Oncomedicine

2017 Volume 2, Page(s) 156–167

Abstract: The unfolded protein response (UPR) is an established and well-studied cellular response to the stress and serves to relieve the stress and reinstate cellular homeostasis. It occurs in the endoplasmic reticulum (ER), responsible of properly folding and ... ...

Abstract	The unfolded protein response (UPR) is an established and well-studied cellular response to the stress and serves to relieve the stress and reinstate cellular homeostasis. It occurs in the endoplasmic reticulum (ER), responsible of properly folding and processing of secretory and transmembrane proteins. It is extremely sensitive to alteration in homeostasis caused by various internal or external stressors which leads to accumulation of misfolded or unfolded proteins in the ER lumen. The UPR works by restoring protein homeostasis in the ER, either through the boosting of protein-folding and degradation capability or by assuaging the demands for such effects, and can cause the activation of cell death if unable to do so. Cancer cells have adapted to gain advantage from the UPR and keeping the cell away from apoptosis and promoting survival, including survival of the cancer stem cells and evading the immune system. Several components of the UPR are overexpressed in a malignant cell and are responsible for resistance from various chemotherapy options and radiotherapy, which are also responsible for causing ER stress and activating the UPR. In this review, we discuss the various ways in which UPR can aid different cancers to survive and evade therapy and highlight recent research, which exploits the UPR to confer sensitivity to these cancer cells against various drugs and radiation.
Language	English
Publishing date	2017-09-27
Publishing country	Australia
Document type	Journal Article
ISSN	2206-6349
ISSN	2206-6349
DOI	10.7150/oncm.22477
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Article: Low intensity focused ultrasound (LOFU) modulates unfolded protein response and sensitizes prostate cancer to 17AAG.

Saha, Subhrajit / Bhanja, Payel / Partanen, Ari / Zhang, Wei / Liu, Laibin / Tomé, Wolfgang / Guha, Chandan

Oncoscience

2014 Volume 1, Issue 6, Page(s) 434–445

Abstract: The hypoxic tumor microenvironment generates oxidative Endoplasmic Reticulum (ER) stress, resulting in protein misfolding and unfolded protein response (UPR). UPR induces several molecular chaperones including heat-shock protein 90 (HSP90), which ... ...

Abstract	The hypoxic tumor microenvironment generates oxidative Endoplasmic Reticulum (ER) stress, resulting in protein misfolding and unfolded protein response (UPR). UPR induces several molecular chaperones including heat-shock protein 90 (HSP90), which corrects protein misfolding and improves survival of cancer cells and resistance to tumoricidal therapy although prolonged activation of UPR induces cell death. The HSP90 inhibitor, 17AAG, has shown promise against various solid tumors, including prostate cancer (PC). However, therapeutic doses of 17AAG elicit systemic toxicity. In this manuscript, we describe a new paradigm where the combination therapy of a non-ablative and non-invasive low energy focused ultrasound (LOFU) and a non-toxic, low dose 17AAG causes synthetic lethality and significant tumoricidal effects in mouse and human PC xenografts. LOFU induces ER stress and UPR in tumor cells without inducing cell death. Treatment with a non-toxic dose of 17AAG further increased ER stress in LOFU treated PC and switch UPR from a cytoprotective to an apoptotic response in tumors resulting significant induction of apoptosis and tumor growth retardation. These observations suggest that LOFU-induced ER stress makes the ultrasound-treated tumors more susceptible to chemotherapeutic agents, such as 17AAG. Thus, a novel therapy of LOFU-induced chemosensitization may be designed for locally advanced and recurrent tumors.
Language	English
Publishing date	2014-06-03
Publishing country	United States
Document type	Journal Article
ISSN	2331-4737
ISSN	2331-4737
DOI	10.18632/oncoscience.48
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