Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors: its independency of p53 status
The usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a co...
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| Veröffentlicht in: | Journal of radiation research 2010-01, Vol.51 (1), p.27-35 |
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| creator | Masunaga, Shin-ichiro Tano, Keizo Nakamura, Jun Watanabe, Masami Kashino, Genro Takahashi, Akihisa Tanaka, Hiroki Suzuki, Minoru Ohnishi, Ken Kinashi, Yuko Liu, Yong Ohnishi, Takeo Ono, Koji |
| description | The usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without gamma-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53. |
| doi_str_mv | 10.1269/jrr.09072 |
| format | Article |
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Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without gamma-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.</description><identifier>ISSN: 0449-3060</identifier><identifier>ISSN: 1349-9157</identifier><identifier>EISSN: 1349-9157</identifier><identifier>DOI: 10.1269/jrr.09072</identifier><identifier>PMID: 19801892</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adjuvant chemotherapy ; Adjuvants ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Bromodeoxyuridine ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - therapy ; Cell Line, Tumor ; Cell Survival - drug effects ; Cell Survival - radiation effects ; Chemotherapy, Adjuvant - methods ; Cisplatin ; Cisplatin - administration & dosage ; Drug therapy ; Head and neck cancer ; Humans ; Hypoxia ; Immunofluorescence ; Leg ; Methenamine - administration & dosage ; Mice ; Mice, Nude ; p53 protein ; Radiation ; Radiation (Physics) ; Radiotherapy, Conformal - methods ; Solid tumors ; Squamous cell carcinoma ; Toxicity ; Treatment Outcome ; Tumor cells ; Tumor proteins ; Tumor Suppressor Protein p53 - metabolism ; Tumors</subject><ispartof>Journal of radiation research, 2010-01, Vol.51 (1), p.27-35</ispartof><rights>COPYRIGHT 2010 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-a46597d595d61b382e2418f3c7fa570df43ceaa2421589950f872cab41b894373</citedby><cites>FETCH-LOGICAL-c565t-a46597d595d61b382e2418f3c7fa570df43ceaa2421589950f872cab41b894373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19801892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Masunaga, Shin-ichiro</creatorcontrib><creatorcontrib>Tano, Keizo</creatorcontrib><creatorcontrib>Nakamura, Jun</creatorcontrib><creatorcontrib>Watanabe, Masami</creatorcontrib><creatorcontrib>Kashino, Genro</creatorcontrib><creatorcontrib>Takahashi, Akihisa</creatorcontrib><creatorcontrib>Tanaka, Hiroki</creatorcontrib><creatorcontrib>Suzuki, Minoru</creatorcontrib><creatorcontrib>Ohnishi, Ken</creatorcontrib><creatorcontrib>Kinashi, Yuko</creatorcontrib><creatorcontrib>Liu, Yong</creatorcontrib><creatorcontrib>Ohnishi, Takeo</creatorcontrib><creatorcontrib>Ono, Koji</creatorcontrib><title>Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors: its independency of p53 status</title><title>Journal of radiation research</title><addtitle>J Radiat Res</addtitle><description>The usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without gamma-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.</description><subject>Adjuvant chemotherapy</subject><subject>Adjuvants</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Bromodeoxyuridine</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - radiation effects</subject><subject>Chemotherapy, Adjuvant - methods</subject><subject>Cisplatin</subject><subject>Cisplatin - administration & dosage</subject><subject>Drug therapy</subject><subject>Head and neck cancer</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunofluorescence</subject><subject>Leg</subject><subject>Methenamine - administration & dosage</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>p53 protein</subject><subject>Radiation</subject><subject>Radiation (Physics)</subject><subject>Radiotherapy, Conformal - methods</subject><subject>Solid tumors</subject><subject>Squamous cell carcinoma</subject><subject>Toxicity</subject><subject>Treatment Outcome</subject><subject>Tumor cells</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><issn>0449-3060</issn><issn>1349-9157</issn><issn>1349-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkU2LFDEQhoO4uOPqwT8gAQ_iYcZ8dLo73pbFL1jYy-65qUkqTobupE3SsvMr_MubcQZEkApVSfG8RaiXkDecbbho9cd9ShumWSeekRWXjV5rrrrnZMWaepesZZfkZc57xkTHFHtBLrnuGe-1WJHfDxndMgbMmUZHd_gIE5bdYcSABUuCyQekkCkECna__IJQaIk0gfVQfKzdYKnxeR7rM9B6yg5pSQhlwsrWoTmO3tKyTDHlT9SXXCmLM9YUzOFIzErSXKAs-RW5cDBmfH2uV-Thy-f7m2_r27uv32-ub9dGtaqsoWmV7qzSyrZ8K3uBouG9k6ZzoDpmXSMNAohGcNVrrZjrO2Fg2_BtrxvZySvy_jR3TvHngrkMk88GxxECxiUPdZtcCSF5Jd-dyB8w4uCDi3Ur5kgP10q2XEnFRaU2_6FqWJy8iQGdr_1_BB9OApNizgndMCc_QToMnA1HV4fq6vDH1cq-PX922U5o_5JnG-UTVTKd2A</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Masunaga, Shin-ichiro</creator><creator>Tano, Keizo</creator><creator>Nakamura, Jun</creator><creator>Watanabe, Masami</creator><creator>Kashino, Genro</creator><creator>Takahashi, Akihisa</creator><creator>Tanaka, Hiroki</creator><creator>Suzuki, Minoru</creator><creator>Ohnishi, Ken</creator><creator>Kinashi, Yuko</creator><creator>Liu, Yong</creator><creator>Ohnishi, Takeo</creator><creator>Ono, Koji</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20100101</creationdate><title>Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors: its independency of p53 status</title><author>Masunaga, Shin-ichiro ; Tano, Keizo ; Nakamura, Jun ; Watanabe, Masami ; Kashino, Genro ; Takahashi, Akihisa ; Tanaka, Hiroki ; Suzuki, Minoru ; Ohnishi, Ken ; Kinashi, Yuko ; Liu, Yong ; Ohnishi, Takeo ; Ono, Koji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c565t-a46597d595d61b382e2418f3c7fa570df43ceaa2421589950f872cab41b894373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adjuvant chemotherapy</topic><topic>Adjuvants</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Bromodeoxyuridine</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - therapy</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - radiation effects</topic><topic>Chemotherapy, Adjuvant - methods</topic><topic>Cisplatin</topic><topic>Cisplatin - administration & dosage</topic><topic>Drug therapy</topic><topic>Head and neck cancer</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Immunofluorescence</topic><topic>Leg</topic><topic>Methenamine - administration & dosage</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>p53 protein</topic><topic>Radiation</topic><topic>Radiation (Physics)</topic><topic>Radiotherapy, Conformal - methods</topic><topic>Solid tumors</topic><topic>Squamous cell carcinoma</topic><topic>Toxicity</topic><topic>Treatment Outcome</topic><topic>Tumor cells</topic><topic>Tumor proteins</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Masunaga, Shin-ichiro</creatorcontrib><creatorcontrib>Tano, Keizo</creatorcontrib><creatorcontrib>Nakamura, Jun</creatorcontrib><creatorcontrib>Watanabe, Masami</creatorcontrib><creatorcontrib>Kashino, Genro</creatorcontrib><creatorcontrib>Takahashi, Akihisa</creatorcontrib><creatorcontrib>Tanaka, Hiroki</creatorcontrib><creatorcontrib>Suzuki, Minoru</creatorcontrib><creatorcontrib>Ohnishi, Ken</creatorcontrib><creatorcontrib>Kinashi, Yuko</creatorcontrib><creatorcontrib>Liu, Yong</creatorcontrib><creatorcontrib>Ohnishi, Takeo</creatorcontrib><creatorcontrib>Ono, Koji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of radiation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Masunaga, Shin-ichiro</au><au>Tano, Keizo</au><au>Nakamura, Jun</au><au>Watanabe, Masami</au><au>Kashino, Genro</au><au>Takahashi, Akihisa</au><au>Tanaka, Hiroki</au><au>Suzuki, Minoru</au><au>Ohnishi, Ken</au><au>Kinashi, Yuko</au><au>Liu, Yong</au><au>Ohnishi, Takeo</au><au>Ono, Koji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors: its independency of p53 status</atitle><jtitle>Journal of radiation research</jtitle><addtitle>J Radiat Res</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>51</volume><issue>1</issue><spage>27</spage><epage>35</epage><pages>27-35</pages><issn>0449-3060</issn><issn>1349-9157</issn><eissn>1349-9157</eissn><abstract>The usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors and its dependency on the p53 status of tumor cells were examined. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53), or with neo vector as a control (SAS/neo), were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. Then, they received hexamethylenetetramine (HMTA), intraperitoneally or continuously, combined with or without gamma-ray irradiation or cisplatin treatment. Immediately after treatment following HMTA, the response of quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (= P + Q) tumor cells was determined from the BrdU non-treated tumors. A higher toxicity of HMTA to Q cells than total cells, especially in SAS/neo, was made less clear by continuous administration. There was no apparent difference in the radio- and cisplatin-sensitivity enhancing effects by HMTA combination between SAS/neo and SAS/mp53 tumors, with a slightly greater effect in SAS/mp53. In both SAS/neo and SAS/mp53 tumors, continuous HMTA administration produced higher radio- and cisplatin-sensitivity enhancing effects than intraperitoneal single administration. Therefore, the use of HMTA as an adjuvant to radiation or cisplatin might be promising in curing solid tumors with large fraction of hypoxic cells and also with frequent loss-of-function in p53.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>19801892</pmid><doi>10.1269/jrr.09072</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adjuvant chemotherapy Adjuvants Animals Antineoplastic Agents - administration & dosage Antineoplastic Combined Chemotherapy Protocols - administration & dosage Bromodeoxyuridine Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - therapy Cell Line, Tumor Cell Survival - drug effects Cell Survival - radiation effects Chemotherapy, Adjuvant - methods Cisplatin Cisplatin - administration & dosage Drug therapy Head and neck cancer Humans Hypoxia Immunofluorescence Leg Methenamine - administration & dosage Mice Mice, Nude p53 protein Radiation Radiation (Physics) Radiotherapy, Conformal - methods Solid tumors Squamous cell carcinoma Toxicity Treatment Outcome Tumor cells Tumor proteins Tumor Suppressor Protein p53 - metabolism Tumors |
| title | Usefulness of hexamethylenetetramine as an adjuvant to radiation and cisplatin in the treatment of solid tumors: its independency of p53 status |
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