Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma

Background Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and c...

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Veröffentlicht in:Journal of neuro-oncology 2023-07, Vol.163 (3), p.693-705
Hauptverfasser: Kurdi, Maher, Fadul, Motaz M, Addas, Bassam M. J., Faizo, Eyad, Alkhayyat, Shadi, Bamaga, Ahmed K., Alsinani, Taghreed, Katib, Yousef, Okal, Fahad, Maghrabi, Yazid, Sabbagh, Abdulrahman J., Moshref, Rana, Albalawi, Sultan, Alkhotani, Alaa, Halawa, Taher F., Mulla, Nasser, Hakamy, Sahar, Baeesa, Saleh
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container_issue 3
container_start_page 693
container_title Journal of neuro-oncology
container_volume 163
creator Kurdi, Maher
Fadul, Motaz M
Addas, Bassam M. J.
Faizo, Eyad
Alkhayyat, Shadi
Bamaga, Ahmed K.
Alsinani, Taghreed
Katib, Yousef
Okal, Fahad
Maghrabi, Yazid
Sabbagh, Abdulrahman J.
Moshref, Rana
Albalawi, Sultan
Alkhotani, Alaa
Halawa, Taher F.
Mulla, Nasser
Hakamy, Sahar
Baeesa, Saleh
description Background Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated. Methods A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8 + T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed. Results The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8 + T-cell expression while 22% [n = 8] of cases have showed medium to high CD8 + T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14–106 days and 41–5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8 + T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8 + T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8 + T T-cell expression and SRC-1 gene downregulation had late recurrence. Conclusions Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.
doi_str_mv 10.1007/s11060-023-04385-5
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J. ; Faizo, Eyad ; Alkhayyat, Shadi ; Bamaga, Ahmed K. ; Alsinani, Taghreed ; Katib, Yousef ; Okal, Fahad ; Maghrabi, Yazid ; Sabbagh, Abdulrahman J. ; Moshref, Rana ; Albalawi, Sultan ; Alkhotani, Alaa ; Halawa, Taher F. ; Mulla, Nasser ; Hakamy, Sahar ; Baeesa, Saleh</creator><creatorcontrib>Kurdi, Maher ; Fadul, Motaz M ; Addas, Bassam M. J. ; Faizo, Eyad ; Alkhayyat, Shadi ; Bamaga, Ahmed K. ; Alsinani, Taghreed ; Katib, Yousef ; Okal, Fahad ; Maghrabi, Yazid ; Sabbagh, Abdulrahman J. ; Moshref, Rana ; Albalawi, Sultan ; Alkhotani, Alaa ; Halawa, Taher F. ; Mulla, Nasser ; Hakamy, Sahar ; Baeesa, Saleh</creatorcontrib><description>Background Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated. Methods A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8 + T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed. Results The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8 + T-cell expression while 22% [n = 8] of cases have showed medium to high CD8 + T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14–106 days and 41–5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8 + T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8 + T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8 + T T-cell expression and SRC-1 gene downregulation had late recurrence. Conclusions Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.</description><identifier>ISSN: 0167-594X</identifier><identifier>EISSN: 1573-7373</identifier><identifier>DOI: 10.1007/s11060-023-04385-5</identifier><identifier>PMID: 37402091</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adrenal Cortex Hormones - therapeutic use ; Astrocytoma ; Astrocytoma - drug therapy ; Astrocytoma - genetics ; Astrocytoma - metabolism ; Brain cancer ; Brain tumors ; CD8 antigen ; Cytotoxicity ; Down-regulation ; Edema ; Female ; Gene regulation ; Glioblastoma - drug therapy ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Humans ; Infiltration ; Lymphocytes T ; Male ; Medicine ; Medicine &amp; Public Health ; Metastases ; Middle Aged ; Neoplasm Recurrence, Local - drug therapy ; Neoplasm Recurrence, Local - genetics ; Neurology ; Nuclear Receptor Coactivator 1 - genetics ; Nuclear Receptor Coactivator 1 - metabolism ; Oncology ; Patients ; Retrospective Studies ; Statistical analysis ; Steroid receptor coactivator 1 ; Steroids ; Tumors ; World Health Organization</subject><ispartof>Journal of neuro-oncology, 2023-07, Vol.163 (3), p.693-705</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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J.</creatorcontrib><creatorcontrib>Faizo, Eyad</creatorcontrib><creatorcontrib>Alkhayyat, Shadi</creatorcontrib><creatorcontrib>Bamaga, Ahmed K.</creatorcontrib><creatorcontrib>Alsinani, Taghreed</creatorcontrib><creatorcontrib>Katib, Yousef</creatorcontrib><creatorcontrib>Okal, Fahad</creatorcontrib><creatorcontrib>Maghrabi, Yazid</creatorcontrib><creatorcontrib>Sabbagh, Abdulrahman J.</creatorcontrib><creatorcontrib>Moshref, Rana</creatorcontrib><creatorcontrib>Albalawi, Sultan</creatorcontrib><creatorcontrib>Alkhotani, Alaa</creatorcontrib><creatorcontrib>Halawa, Taher F.</creatorcontrib><creatorcontrib>Mulla, Nasser</creatorcontrib><creatorcontrib>Hakamy, Sahar</creatorcontrib><creatorcontrib>Baeesa, Saleh</creatorcontrib><title>Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma</title><title>Journal of neuro-oncology</title><addtitle>J Neurooncol</addtitle><addtitle>J Neurooncol</addtitle><description>Background Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated. Methods A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8 + T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed. Results The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8 + T-cell expression while 22% [n = 8] of cases have showed medium to high CD8 + T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14–106 days and 41–5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8 + T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8 + T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8 + T T-cell expression and SRC-1 gene downregulation had late recurrence. Conclusions Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. 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J. ; Faizo, Eyad ; Alkhayyat, Shadi ; Bamaga, Ahmed K. ; Alsinani, Taghreed ; Katib, Yousef ; Okal, Fahad ; Maghrabi, Yazid ; Sabbagh, Abdulrahman J. ; Moshref, Rana ; Albalawi, Sultan ; Alkhotani, Alaa ; Halawa, Taher F. ; Mulla, Nasser ; Hakamy, Sahar ; Baeesa, Saleh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-c43441d1b80e3c591f867c21a252c6aada6ff7b2b3d291edbc4bd66265e70e003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adrenal Cortex Hormones - therapeutic use</topic><topic>Astrocytoma</topic><topic>Astrocytoma - drug therapy</topic><topic>Astrocytoma - genetics</topic><topic>Astrocytoma - metabolism</topic><topic>Brain cancer</topic><topic>Brain tumors</topic><topic>CD8 antigen</topic><topic>Cytotoxicity</topic><topic>Down-regulation</topic><topic>Edema</topic><topic>Female</topic><topic>Gene regulation</topic><topic>Glioblastoma - drug therapy</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - metabolism</topic><topic>Humans</topic><topic>Infiltration</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neurology</topic><topic>Nuclear Receptor Coactivator 1 - genetics</topic><topic>Nuclear Receptor Coactivator 1 - metabolism</topic><topic>Oncology</topic><topic>Patients</topic><topic>Retrospective Studies</topic><topic>Statistical analysis</topic><topic>Steroid receptor coactivator 1</topic><topic>Steroids</topic><topic>Tumors</topic><topic>World Health Organization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kurdi, Maher</creatorcontrib><creatorcontrib>Fadul, Motaz M</creatorcontrib><creatorcontrib>Addas, Bassam M. 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J.</au><au>Faizo, Eyad</au><au>Alkhayyat, Shadi</au><au>Bamaga, Ahmed K.</au><au>Alsinani, Taghreed</au><au>Katib, Yousef</au><au>Okal, Fahad</au><au>Maghrabi, Yazid</au><au>Sabbagh, Abdulrahman J.</au><au>Moshref, Rana</au><au>Albalawi, Sultan</au><au>Alkhotani, Alaa</au><au>Halawa, Taher F.</au><au>Mulla, Nasser</au><au>Hakamy, Sahar</au><au>Baeesa, Saleh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma</atitle><jtitle>Journal of neuro-oncology</jtitle><stitle>J Neurooncol</stitle><addtitle>J Neurooncol</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>163</volume><issue>3</issue><spage>693</spage><epage>705</epage><pages>693-705</pages><issn>0167-594X</issn><eissn>1573-7373</eissn><abstract>Background Corticosteroid is commonly used before surgery to control cerebral oedema in brain tumours and is frequently continued throughout treatment. Its long-term effect of on the recurrence of WHO-Grade 4 astrocytoma remains controversial. The interaction between corticosteroid, SRC-1 gene and cytotoxic T-cells has never been investigated. Methods A retrospective cohort of 36 patients with WHO-Grade 4 astrocytoma were examined for CD8 + T-cell and SRC-1 gene expressions through IHC and qRT-PCR. The impact of corticosteroid on CD8 + T-cells infiltration, SRC-1 expression, and tumour recurrence was analyzed. Results The mean patients age was 47-years, with a male to female ratio 1.2. About 78% [n = 28] of the cases showed reduced or no CD8 + T-cell expression while 22% [n = 8] of cases have showed medium to high CD8 + T-cell expression. SRC-1 gene was upregulated in 5 cases [14%] and 31 cases [86%] showed SRC-1 downregulation. The average of total days and doses of administered corticosteroid from the preoperative period to the postoperative period was at range of 14–106 days and 41–5028 mg, respectively. There was no significant statistical difference in RFI among tumours expressing high or low CD8 + T-cells when corticosteroid was administered in recommended or exceeded doses [p-value = 0.640]. There was a significant statistical difference in RFI between CD8 + T-Cell expression and SRC-1 gene dysregulation [p-value = 002]. Tumours with high CD8 + T T-cell expression and SRC-1 gene downregulation had late recurrence. Conclusions Corticosteroid treatment can directly affect the SRC-1 gene regulation but does not directly influence cytotoxic T-cells infiltration or tumor progression. However, SRC-1 gene downregulation can facilitate late tumor recurrence.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>37402091</pmid><doi>10.1007/s11060-023-04385-5</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8979-3849</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adrenal Cortex Hormones - therapeutic use
Astrocytoma
Astrocytoma - drug therapy
Astrocytoma - genetics
Astrocytoma - metabolism
Brain cancer
Brain tumors
CD8 antigen
Cytotoxicity
Down-regulation
Edema
Female
Gene regulation
Glioblastoma - drug therapy
Glioblastoma - genetics
Glioblastoma - metabolism
Humans
Infiltration
Lymphocytes T
Male
Medicine
Medicine & Public Health
Metastases
Middle Aged
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - genetics
Neurology
Nuclear Receptor Coactivator 1 - genetics
Nuclear Receptor Coactivator 1 - metabolism
Oncology
Patients
Retrospective Studies
Statistical analysis
Steroid receptor coactivator 1
Steroids
Tumors
World Health Organization
title Dynamic interplay between corticosteroid treatment and the role of SRC-1 gene dysregulation in the progression of WHO-Grade 4 Astrocytoma
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