Influence of the hypoxic subvolume on the survival of patients with head and neck cancer

Stadler, Peter F.; Becker, Axel; Feldmann, Horst Jürgen; Hänsgen, Gabriele; Dunst, Jürgen; Würschmidt, Florian; Molls, M.

doi:10.1016/s0360-3016(99)00115-7

Cited by 243 publications

(147 citation statements)

References 12 publications

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“…HSV (pO 2 < 5 mmHg) has not been recognized as a prognostic factor in advanced cervix carcinoma previously. However, our observation is consistent with the results from a similar study of squamous cell carcinoma of the head and neck (Stadler et al, 1999). In this study, oxygen tension was measured in primary tumours in 26 patients and in lymph-node metastases in 33 patients, and multivariate Cox regression analysis identified HSV (pO 2 < 5 mmHg) as a significant prognostic factor for overall survival.…”

Section: Discussionsupporting

confidence: 92%

Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis

et al. 2000

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Summary Poor outcome of treatment in advanced cervix carcinoma has been shown to be associated with poor oxygenation of the primary tumour. Hypoxia may cause radiation resistance and promote lymph-node metastasis. The purpose of the study reported here was to investigate whether hypoxia-induced treatment failure in advanced cervix carcinoma is primarily a result of hypoxia-induced radiation resistance or the presence of hypoxia-induced lymph-node metastases at the start of treatment. Thirty-two patients with squamous cell carcinoma of the uterine cervix were included in the study. Radiation therapy was given with curative intent as combined external irradiation and endocavitary brachytherapy. The oxygenation status of the primary tumour was measured prior to treatment using the Eppendorf pO 2 Histograph. Pelvic and para-aortal lymph-node metastases were detected by magnetic resonance imaging at the time of initial diagnosis. The primary tumours of the patients with metastases (n = 18) were significantly more poorly oxygenated than those of the patients without metastases (n = 14). Multivariate Cox regression analyses involving biological and clinical parameters identified the tumour subvolume having pO 2 values below 5mmHg (HSV (pO 2 < 5mmHg) as the only significant, independent prognostic factor for locoregional control, disease-free survival and overall survival. The probabillities of locoregional control, disease-free survival and overall survival were significantly lower for the patients with HSV (pO 2 < 5 mmHg) above the median value than for those with HSV (pO 2 < 5 mmHg) below the median value. On the other hand, the outcome of treatment was not significantly different for the patients with metastases and the patients without metastases at the start of treatment, irrespective of clinical end-point. Consequently, treatment failure was primarily a result of hypoxia-induced radiation resistance rather than hypoxia-induced lymph-node metastasis, suggesting that novel treatment strategies aiming at improving tumour oxygenation or enhancing the radiation sensitivity of hypoxic tumour cells may prove beneficial in attempts to improve the radiation therapy of advanced cervix carcinoma.

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Section: Discussionsupporting

confidence: 92%

Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis

et al. 2000

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“…However, it is apparent that upregulation of HIF-1 transactivates antiproliferative and proapoptotic genes (Bacon and Harris, 2004). Regions of hypoxia are known to exist within many solid tumours and the extent of tumour hypoxia is regarded as an important prognostic factor influencing neoplastic aggression, resistance to therapy and overall patient survival (Hockel et al, 1998;Stadler et al, 1999;Knowles and Harris, 2001;Harris, 2002). This suggests that antitumorigenic proteins that are hypoxically upregulated are either non-functional or the tumour escapes from negative signalling.…”

Section: Introductionmentioning

confidence: 99%

Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by histone deacetylation and methylation in colorectal cancer

et al. 2006

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Hypoxia, via the hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2), upregulates many genes involved in cell survival. However, proapoptotic pathways are also induced. BCL-2/adenovirus E1B-19 kDa-interacting protein 3 (BNIP3) represents a paradigm of a cell death protein that is hypoxically upregulated via HIF-1 in most cancers. We found that in contrast to many other cell types, 6/8 colorectal cancer (CRC) cell lines show little hypoxic induction of BNIP3 despite an intact HIF signalling system. Colorectal tumour tissue also loses BNIP3 expression relative to matched normal samples. Downregulation of hypoxic BNIP3 in CRC cells was independent of the expression of other BCL-2 family members, or BNIP3L. That BNIP3 plays a functional role in hypoxic survival in CRC cells was demonstrated by the fact that CRC cell lines that do not upregulate BNIP3 or have been treated with BNIP3 RNA interference were insensitive to hypoxia-induced cell death. Promoter methylation and histone deacetylation were shown to silence BNIP3 in these CRC cell lines. Of significance, hypoxic induction of BNIP3 was restored in 4/6 cell lines by trichostatin-A treatment alone. These data suggest that BNIP3 plays an important role in hypoxic cell death and epigenetic mechanisms selectively silence its expression in CRC.

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“…Okrem rádiorezistencie, indukuje nádo-rová hypoxia expresiu génov nádoro-vých buniek, ktoré spôsobujú zvýšenú agresivitu týchto nádorov, manifestujúcu sa genetickou instabilitou, stratou apoptotického potenciálu, zvýšeným metastatickým potenciálom a rezistenciou voči chemoterapii [9][10][11].…”

Section: Nádorová Hypoxia Ako Príčina Rádiorezistencie Nádorov Hlavy unclassified

Relation between Carbonic Anhydrase IX Serum Level, Hypoxia and Radiation Resistance of Head and Neck Cancers

Rosenberg¹,

Pastoreková²,

Zaťovičová³

et al. 2014

Klin Onkol

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1 Oddelenie radiačnej onkológie, FNsP J. A. Reimana Prešov, Slovensko 2 Virologický ústav SAV, Bratislava, Slovensko 3 Ústav simulačného a virtuálneho medicínskeho vzdelávania, LF UK v Bratislave, Slovensko 4 Oddelenie bio medicínskej fyziky, Fakulta matematiky, fyziky a informatiky UK v Bratislave, Slovensko 5 Vysoká škola zdravotníctva a sociálnej práce sv. Alžbety, Bratislava, Slovensko SúhrnVýchodiská: Hypoxia lokálne pokročilých karcinómov hlavy a krku je jednou z hlavných príčin ich rádiorezistencie, ktorá sa klinicky manifestuje perzistenciou reziduálnej nádorovej choroby po liečbe rádioterapiou. Detekcia nádorovej hypoxie teda môže byť dôležitým prediktorom efektivity liečby. Karboanhydráza IX (carbonic anhydrase IX -CA IX) je proteín, kódovaný rovnomenným génom, ktorého expresia sa v nádorových tkanivách za hypoxických podmienok zvyšuje. CA IX preto predstavuje endogénny marker nádorovej hypoxie, identifi kovateľný v nádo-rových tkanivách a jeho rozpustnú extracelulárnu doménu je možné detekovať aj v telesných tekutinách pacienta. Primárnym cieľom tejto štúdie bolo zistiť, či existuje korelácia medzi séro-vou hladinou CA IX a reziduálnou nádorovou chorobou po liečbe. Sekundárnym cieľom bolo zistiť, ako sa mení sérová hladina CA IX počas frakcionovanej rádioterapie. Materiál a metódy: Táto prospektívna monocentrická klinická štúdia hodnotila súbor 30 pacientov s lokálne pokročilými skvamocelulárnymi karcinómami hlavy a krku, liečených rádioterapiou alebo konkomitantnou chemorádioterapiou s kuratívnym zámerom. Sérová koncentrácia rozpustnej formy CA IX sa vyšetrovala z venóznej krvi pomocou sendvičovej enzýmovej imunoanalýzy (ELISA) pred zahájením rádioterapie, v polovici rádioterapie, pri skončení rádioterapie a šesť týždňov po jej ukončení. Výsledky: Zistili sme výraznú variabilitu nameraných hladín CA IX v sledovanej populácii v rozsahu 0-1 696 pg/ ml. Významné zmeny v strednej hodnote koncentrácie CA IX sme v priebehu rádioterapie a po nej nezistili. U 11 pacientov (36,7 %) sa liečbou dosiahla kompletná remisia ochorenia. U týchto pacientov sme zaznamenali v priemere nižšie predliečebné hodnoty CA IX v porovnaní s pacientmi s perzistenciou reziduálnej nádorovej choroby (37,57 vs 77,47; p = 0,154). Záver: Naše výsledky ukazujú, že sérová hladina CA IX sa u pacientov s lokálne pokročilými nádormi hlavy a krku v priebehu frakcionovanej rádioterapie významne nemení. Zistený vzťah medzi sérovou hladinou CA IX a reziduálnou nádorovou chorobou po rádioterapii je potrebné potvrdiť na väčšom súbore pacientov. Kľúčové slovánádory hlavy a krku -hypoxia -karboanhydráza IX -rádioterapia -reziduálny nádor Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do bi omedicínských časopisů.The Editorial Board declares that the manuscript met the ICMJE "uniform requirements" for biom...

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Influence of the hypoxic subvolume on the survival of patients with head and neck cancer

Cited by 243 publications

References 12 publications

Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis

Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis

Selective silencing of the hypoxia-inducible factor 1 target gene BNIP3 by histone deacetylation and methylation in colorectal cancer

Relation between Carbonic Anhydrase IX Serum Level, Hypoxia and Radiation Resistance of Head and Neck Cancers

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