Skip to main content
SpringerLink
Log in

Counteracting Hypoxia in Radio-Resistant Metastatic Lesions

  • Chapter
  • First Online:
Prostate Cancer: Shifting from Morphology to Biology

  • 1139 Accesses

Abstract

The identification of hypoxia-regulated genes and proteins, has provided the basis for the generation of new hypoxia-targeted drugs, conceived to re-oxygenate hypoxic tumor areas. In patients with advanced metastasizing prostate cancer (PC), these kinds of drugs are expected to optimize the effect of radiotherapy, reducing also its side effects. Immunohistochemistry, DNA, proteomic and, tissue array profiling, are increasingly providing us with exciting data, that could lead to the formulation of pre-treatment multimarker tests able to identify the individualized tumor response profiles to radiotherapy, basing on the specific cancer tissue hypoxia pattern and degree (Bussink et al., Radiother Oncol 67:3–15, 2003).

As an example, the recent discovery of the role of microRNA in PC tumor genesis points towards (Kulshreshtha et al., Cell Cycle 6(12):1426–1431, 2007) the, Inactivation of miRs affected by hypoxia as a promising synergistic therapeutic strategy for the radiotherapy-refractory subset of metastatic PC (Kulshreshtha et al., Cell Death Differ 15:667–671, 2008).

This chapter aims to give an outlook of the main hot-topics concerning the new trends of hypoxia-targeted molecular therapies for advanced metastasizing prostate cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aebersold DM, Burri P, Beer KT et al (2001) Expression of hypoxiainducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res 61:2911–2916

    PubMed  CAS  Google Scholar 

  • Anastasiadis AG, Ghafar MA, Salomon L et al (2002) Human hormone refractory prostate cancers can harbor mutations in the O(2)- dependent degradation domain of hypoxia inducible factor-1alpha (HIF-1alpha). J Cancer Res Clin Oncol 128:358–362

    PubMed  CAS  Google Scholar 

  • Anastasiadis AG, Bemis DL, Stisser BC, Salomon L, Ghafar MA, Buttyan R (2003) Tumor cell hypoxia and the hypoxia-response signaling system as a target for prostate cancer therapy. Curr Drug Targets 4(3):191–196

    PubMed  CAS  Google Scholar 

  • Aslan G, Cimen S, Yorukoglu K, Tuna B, Sonmez D, Mungan U et al (2005) Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer. Pathol Res Pract 201:593–598

    PubMed  CAS  Google Scholar 

  • Bakin RE, Gioeli D, Sikes RA, Bissonette EA, Weber MJ (2003) Constitutive activation of the Ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells. Cancer Res 63:1981–1989

    PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297. Review

    PubMed  CAS  Google Scholar 

  • Bashan N, Burdett E, Hundal HS, Klip A (1992) Regulation of glucose transport and GLUT1 glucose transporter expression by O2 in muscle cells in culture. Am J Physiol 262(3 Pt 1):C682–C690

    PubMed  CAS  Google Scholar 

  • Bussink J, Kaanders JHAM, Rijken PFJW et al (1999) Vascular architecture and microenvironmental parameters in human squamous cell carcinoma xenografts: effects of carbogen and nicotinamide. Radiother Oncol 50:173–184

    PubMed  CAS  Google Scholar 

  • Bussink J, Kaanders JHAM, van der Kogel AJ (2003) Tumor hypoxia at the micro-regional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers. Radiother Oncol 67:3–15

    PubMed  Google Scholar 

  • Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell’Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM (2004) MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 101:11755–11760

    PubMed  CAS  Google Scholar 

  • Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353:1793–1801

    PubMed  CAS  Google Scholar 

  • Cheng AM, Byrom MW, Shelton J, Ford LP (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290–1297

    PubMed  CAS  Google Scholar 

  • Chresta CM, Masters JR, Hickman JA (1996) Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high Bax: Bcl-2 ratio. Cancer Res 56:1834–1841

    PubMed  CAS  Google Scholar 

  • Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC, Colgan SP (2002) Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res 62:3387–3394

    PubMed  CAS  Google Scholar 

  • Costello LC, Franklin RB, Feng P et al (2005) Zinc and prostate cancer: a critical scientific, medical, and public interest issue (United States). Cancer Causes Control 16:901–915

    PubMed  Google Scholar 

  • Critz FA, Benton JB, Shrake P, Merlin ML (2013) 25-year disease-free survival rate after irradiation for prostate cancer calculated with the prostate specific antigen definition of recurrence used for radical prostatectomy. J Urol 189(3):878–883

    PubMed  Google Scholar 

  • Croce CM, Calin GA (2005) miRNAs, cancer, and stem cell division. Cell 122:6–7

    PubMed  CAS  Google Scholar 

  • Crosby ME, Devlin CM, Glazer PM, Calin GA, Ivan M (2009) Emerging roles of microRNAs in the molecular responses to hypoxia. Curr Pharm Des 15(33):3861–3866

    PubMed  CAS  Google Scholar 

  • Culig Z, Bartsch G (2006) Androgen axis in prostate cancer. J Cell Biochem 99:373–381

    PubMed  CAS  Google Scholar 

  • Cvetkovic D, Movsas B, Dicker AP et al (2001) Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer. Urology 57:821–825

    PubMed  CAS  Google Scholar 

  • Denhardt DT, Guo X (1993) Osteopontin: a protein with diverse functions. FASEB J 7:1475–1482

    PubMed  CAS  Google Scholar 

  • Dewhirst MW, Ong ET, Braun RD et al (1999) Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia. Br J Cancer 79:1717–1722

    PubMed  CAS  Google Scholar 

  • Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 25:1650–1659

    Google Scholar 

  • Ferrara N (1995) The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat 36:127–137

    PubMed  CAS  Google Scholar 

  • Forootan SS, Foster CS, Aachi VR et al (2006) Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer 118:2255–2261

    PubMed  CAS  Google Scholar 

  • Gilbert M, Knox S (1997) Influence of Bcl-2 overexpression on Na+/K(+)-ATPase pump activity: correlation with radiationinduced programmed cell death. J Cell Physiol 171:299–304

    PubMed  CAS  Google Scholar 

  • Godoy A, Watts A, Sotomayor P, Montecinos VP, Huss WJ, Onate SA, Smith GJ (2008) Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell. Endocrinology 149:2959–2969

    PubMed  CAS  Google Scholar 

  • Godoy A, Montecinos VP, Gray DR, Sotomayor P, Yau JM, Vethanayagam RR, Singh S, Mohler JL, Smith GJ (2011) Androgen deprivation induces rapid involution and recovery of human prostate vasculature. Am J Physiol Endocrinol Metab 300:E263–E275

    PubMed  CAS  Google Scholar 

  • Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC (1953) The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26:638–648

    PubMed  CAS  Google Scholar 

  • Harris AL (2002) Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2:38–47

    PubMed  CAS  Google Scholar 

  • Harrison L, Blackwell K (2004) Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy. Oncologist 9(suppl 5):31–40

    PubMed  Google Scholar 

  • Helmlinger G, Yuan F, Dellian M, Jain RK (1997) Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med 3:177–182

    PubMed  CAS  Google Scholar 

  • Henk JM (1986) Late results of a trial of hyperbaric oxygen and radiotherapy in head and neck cancer: a rationale for hypoxic cell sensitizers? Int J Radiat Oncol Biol Phys 12:1339–1341

    PubMed  CAS  Google Scholar 

  • Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011–1027

    PubMed  CAS  Google Scholar 

  • Höckel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biological and molecular aspects. J Natl Cancer Inst 93:266–276

    PubMed  Google Scholar 

  • Höckel M, Schlenger K, Knoop C, Vaupel P (1991) Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements. Cancer Res 51:6098–6102

    PubMed  Google Scholar 

  • Horsman MR, Overgaard J (2002) The oxygen effect and tumour microenvironment. In: Steel GG (ed) Basic clinical radiobiology. Arnold, London, pp 158–168

    Google Scholar 

  • Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC (2003) Differential roles of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α in hypoxic gene regulation. Mol Cell Biol 23:9361–9374

    PubMed  CAS  Google Scholar 

  • Huang A, Gandour-Edwards R, Rosenthal SA, Siders DB, Deitch RW, White RW (1998a) p53 and bcl-2 immunohistochemical alterations in prostate cancer treated with radiation therapy. Urology 51:346–351

    PubMed  CAS  Google Scholar 

  • Huang LE, Jie GU, Schau M, Bunn HF (1998b) Regulation of hypoxia-inducible factor-1a is mediated by an O2-dependent degradation domain via the ubiquitinproteasome pathway. Proc Natl Acad Sci USA 95:7989–7992

    Google Scholar 

  • Huang Y, Yu J, Yan C, Hou J, Pu J, Zhang G, Fu Z, Wang X (2012) Effect of small interfering RNA targeting hypoxia-inducible factor-1α on radiosensitivity of PC3 cell line. Urology 79(3):744.e17–744.e24

    Google Scholar 

  • Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070

    PubMed  CAS  Google Scholar 

  • Isa AY, Ward TH, West CML, Slevin NJ, Homer JJ (2006) Hypoxia in head and neck cancer. Br J Radiol 79:791–798

    PubMed  CAS  Google Scholar 

  • Jain RK (1999) Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng 1:241–263

    PubMed  CAS  Google Scholar 

  • Kaelin WG Jr (2005) ROS: really involved in oxygen sensing. Cell Metab 1:357–358

    PubMed  CAS  Google Scholar 

  • Kennedy AS, Raleigh JA, Perez GM et al (1997) Proliferation and hypoxia in human squamous cell carcinoma of the cervix: first report of combined immunohistochemical assays. Int J Radiat Oncol Biol Phys 37:897–905

    PubMed  CAS  Google Scholar 

  • Kenny PA, Bissell MJ (2003) Tumor reversion: correction of malignant behavior by microenvironmental cues. Int J Cancer 107:688–695

    PubMed  CAS  Google Scholar 

  • Kimbro KS, Simons JW (2006) Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocr Relat Cancer 13:739–749

    PubMed  CAS  Google Scholar 

  • Koukourakis MI, Giatromanolaki A, Sivridis E et al (2002) Hypoxiainducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int J Radiat Oncol Biol Phys 53:1192–1202

    PubMed  CAS  Google Scholar 

  • Koukourakis MI, Bentzen SM, Giatromanolaki A et al (2006) Endogenous markers of two separate hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial. J Clin Oncol 24:727–735

    PubMed  CAS  Google Scholar 

  • Kroemer G (2006) Mitochondria in cancer. Oncogene 25:4630–4632

    PubMed  CAS  Google Scholar 

  • Krutzfeldt J, Kuwajima S, Braich R, Rajeev KG, Pena J, Tuschl T, Manoharan M, Stoffel M (2007) Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res 35:2885–2892

    PubMed  CAS  Google Scholar 

  • Ku JH, Seo SY, Kwak C et al (2010) The role of survivin and Bcl-2 in zinc-induced apoptosis in prostate cancer cells. Urol Oncol 30:562–568

    PubMed  Google Scholar 

  • Kulshreshtha R, Ferracin M, Negrini M, Calin GA, Davuluri RV, Ivan M (2007) Regulation of microRNA expression the hypoxic component. Cell Cycle 6(12):1426–1431

    PubMed  CAS  Google Scholar 

  • Kulshreshtha R, Davuluri RV, Calin GA, Ivan MA (2008) microRNA component of the hypoxic response. Cell Death Differ 15:667–671

    PubMed  CAS  Google Scholar 

  • Le QT, Courter D (2008) Clinical biomarkers for hypoxia targeting. Cancer Metastasis Rev 27(3):351–362

    PubMed  CAS  Google Scholar 

  • Lekas A, Lazaris AC, Deliveliotis C, Chrisofos M, Zoubouli C, Lapas D et al (2006) The expression of hypoxia-inducible factor- 1alpha (HIF-1alpha) and angiogenesis markers in hyperplastic and malignant prostate tissue. Anticancer Res 26:2989–2993

    PubMed  CAS  Google Scholar 

  • Levy AP, Levy NS, Goldberg MA (1996) Hypoxia-inducible protein binding to vascular endothelial growth factor mRNA and its modulation by the von Hippel-Lindau protein. J Biol Chem 271:25492–25497

    PubMed  CAS  Google Scholar 

  • Ljungkvist ASE, Bussink J, Rijken PFJW, Kaanders JHAM, van der Kogel AJ, Denekamp J (2002) Vascular architecture, hypoxia, and proliferation in the first passage of xenografts of human head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 54:215–228

    PubMed  Google Scholar 

  • Lundgren K, Holm C, Landberg G (2007) Hypoxia and breast cancer: prognostic and therapeutic implications. Cell Mol Life Sci 64(24):3233–3247

    PubMed  CAS  Google Scholar 

  • Mabjeesh NJ, Willard MT, Frederickson CE, Zhong H, Simons JW (2003) Androgens stimulate hypoxia-inducible factor 1 activation via autocrine loop of tyrosine kinase receptor/phosphatidylinositol 30-kinase/protein kinase B in prostate cancer cells. Clin Cancer Res 9:2416–2425

    PubMed  CAS  Google Scholar 

  • Maxwell PH, Wiesener MS, Chang GW et al (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275

    PubMed  CAS  Google Scholar 

  • Merino M, Pinto A, González R et al (2011) Antiangiogenic agents and endothelin antagonists in advanced castration resistant prostate cancer. Eur J Cancer 47:1846–1851

    PubMed  CAS  Google Scholar 

  • Milosevic M, Chung P, Parker C, Bristow R, Toi A, Panzarella T et al (2007) Androgen withdrawal in patients reduces prostate cancer hypoxia: implications for disease progression and radiation response. Cancer Res 67:6022–6025

    PubMed  CAS  Google Scholar 

  • Moeller BJ, Dewhirst MW (2006) HIF-1 and tumour radiosensitivity. Br J Cancer 95:1–5. (Review)

    PubMed  CAS  Google Scholar 

  • Moll UM, Marchenko N, Zhang XK (2006) p53 and Nur77/TR3 – transcription factors that directly target mitochondria for cell death induction. Oncogene 25:4725–4743

    PubMed  CAS  Google Scholar 

  • Morales A, Miranda M, Sánchez-Reyes A, Biete A, Fernández-Checa JC (1998) Oxidative damage of mitochondrial and nuclear DNA induced by ionizing radiation in human hepatoblastoma cells. Int J Radiat Oncol Biol Phys 42:191–203

    PubMed  CAS  Google Scholar 

  • Movsas B, Chapman JD, Hanlon AL et al (2002) Hypoxic prostate/muscle pO2 ratio predicts for biochemical failure in patients with prostate cancer: preliminary findings. Urology 60:634–639

    PubMed  Google Scholar 

  • Muzandu K, Shaban Z, Ishizuka M, Kazusaka A, Fujita S (2005) Nitric oxide enhances catechol estrogen-induced oxidative stress in LNCaP cells. Free Radic Res 39:389–398

    PubMed  CAS  Google Scholar 

  • Nilsson MB, Zage PE, Zeng L et al (2010) Multiple receptor tyrosine kinases regulate HIF-1alpha and HIF-2alpha in normoxia and hypoxia in neuroblastoma: implications for anti-angiogenic mechanisms of multikinase inhibitors. Oncogene 29:2938–2949

    PubMed  CAS  Google Scholar 

  • Nordgren IK, Tavassoli A (2011) Targeting tumour angiogenesis with small molecule inhibitors of hypoxia inducible factor. Chem Soc Rev 40:4307–4317

    PubMed  CAS  Google Scholar 

  • Nordsmark M, Hoyer M, Keller J, Nielsen OS, Jensen OM, Overgaard J (1996) The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas. Int J Radiat Oncol Biol Phys 35:701–708

    PubMed  CAS  Google Scholar 

  • Orom UA, Kauppinen S, Lund AH (2006) LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene 372:137–141

    PubMed  CAS  Google Scholar 

  • Overgaard J, Horsman MR (1996) Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers. Semin Radiat Oncol 6:10–21

    PubMed  Google Scholar 

  • Overgaard J, Hansen HS, Overgaard M et al (1998) A randomized double blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5–85. Radiother Oncol 46:135–146

    PubMed  CAS  Google Scholar 

  • Overgaard J, Eriksen JG, Nordsmark M, Alsner J, Horsman MR (2005) Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised doubleblind placebo-controlled trial. Lancet Oncol 6:757–764

    PubMed  CAS  Google Scholar 

  • Park SY, Kim YJ, Gao AC, Mohler JL, Onate SA, Hidalgo AA et al (2006) Hypoxia increases androgen receptor activity in prostate cancer cells. Cancer Res 66:5121–5129

    PubMed  CAS  Google Scholar 

  • Park SE, Park JW, Cho YS et al (2007) HIF-1&;_ promotes survival of prostate cells at a high zinc environment. Prostate 67:1514–1523

    PubMed  CAS  Google Scholar 

  • Parker C, Milosevic M, Toi A et al (2004) Polarographic electrode study of tumour oxygenation in clinically localised prostate cancer. Int J Radiat Oncol Biol Phys 58:750–757

    PubMed  Google Scholar 

  • Pfeil K, Eder IE, Putz T, Ramoner R, Culig Z, Ueberall F et al (2004) Long-term androgen-ablation causes increased resistance to PI3K/Akt pathway inhibition in prostate cancer cells. Prostate 58:259–268

    PubMed  CAS  Google Scholar 

  • Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9:677–684

    PubMed  CAS  Google Scholar 

  • Quintero M, Mackenzie N, Brennan PA (2004) Hypoxia-inducible factor 1 (HIF-1) in cancer. Eur J Surg Oncol 30:465–468

    PubMed  CAS  Google Scholar 

  • Revelos K, Petraki C, Gregorakis A, Scorilas A, Papanastasiou M, Koutsilieris M (2005) Immunohistochemical expression of Bcl-2 is an independent predictor of time-to-biochemical failure in patients with clinically localized prostate cancer following radical prostatectomy. Anticancer Res 25:3123–3133

    PubMed  CAS  Google Scholar 

  • Rohwer N, Cramer T (2011) Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat 14:191–201

    PubMed  CAS  Google Scholar 

  • Romashkova JA, Makarov SS (1999) NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature 401:86–90

    PubMed  CAS  Google Scholar 

  • Rothermund CA, Gopalakrishnan VK, Eudy JD, Vishwanatha JK (2005) Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model. BMC Urol 5:5

    PubMed  Google Scholar 

  • Rugo RE, Schiestl RH (2004) Increases in oxidative stress in the progeny of X-irradiated cells. Radiat Res 162:416–425

    PubMed  CAS  Google Scholar 

  • Scherr DS, Vaughan ED Jr, Wei J, Chung M, Felsen D, Allbright R et al (1999) BCL-2 and p53 expression in clinically localized prostate cancer predicts response to external beam radiotherapy. J Urol 162:12–16

    PubMed  CAS  Google Scholar 

  • Schmaltz C, Hardenbergh PH, Wells A, Fisher DE (1998) Regulation of proliferation-survival decisions during tumor cell hypoxia. Mol Cell Biol 18:2845–2854

    PubMed  CAS  Google Scholar 

  • Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3:721–732

    PubMed  CAS  Google Scholar 

  • Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE (1991) Hypoxiainducible nuclear factors bind to an enhancer element located 30 to the human erythropoietin gene. Proc Natl Acad Sci USA 88:5680–5684

    PubMed  CAS  Google Scholar 

  • Senger DR, Galli SJ, Dvorak AM et al (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985

    PubMed  CAS  Google Scholar 

  • Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D (2003) Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 29:297–307

    PubMed  CAS  Google Scholar 

  • Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845

    PubMed  CAS  Google Scholar 

  • Srigley JR, Delahunt B, Evans AJ (2012) Therapy-associated effects in the prostate gland. Histopathology 60:153–165

    PubMed  Google Scholar 

  • Strohmeyer D, Strauss F, Rossing C et al (2004) Expression of bFGF, VEGF and c-met and their correlation with microvessel density and progression in prostate carcinoma. Anticancer Res 24:1797–1804

    PubMed  CAS  Google Scholar 

  • Szostak MJ, Kyprianou N (2000) Radiation-induced apoptosis: predictive and therapeutic significance in radiotherapy of prostate cancer (review). Oncol Rep 7:699–706

    PubMed  CAS  Google Scholar 

  • Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549

    PubMed  CAS  Google Scholar 

  • Vaupel P, Kelleher DK (2013) Blood flow and oxygenation status of prostate cancers. Adv Exp Med Biol 765:299–305

    PubMed  CAS  Google Scholar 

  • Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49:6449–6465

    PubMed  CAS  Google Scholar 

  • Vaupel P, Thews O, Hoeckel M (2001) Treatment resistance of solid tumors. Role of hypoxia and anemia. Med Oncol 18:243–259

    PubMed  CAS  Google Scholar 

  • Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103:2257–2261

    PubMed  CAS  Google Scholar 

  • Wang G, Reed E, Li QQ (2004) Apoptosis in prostate cancer: progressive and therapeutic implications (Review). Int J Mol Med 14:23–34

    PubMed  CAS  Google Scholar 

  • Watson ER, Halnan KE, Dische S et al (1978) Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix. Br J Radiol 51:879–887

    PubMed  CAS  Google Scholar 

  • Webster L, Hodgkiss RJ, Wilson GD (1995) Simultaneous triple staining for hypoxia, proliferation, and DNA content in murine tumours. Cytometry 21:344–351

    PubMed  CAS  Google Scholar 

  • Weiler J, Hunziker J, Hall J (2006) Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Ther 13:496–502

    PubMed  CAS  Google Scholar 

  • Wilson WR, Hay MP (2011) Targeting hypoxia in cancer therapy. Nat Rev Cancer 11:393–410

    PubMed  CAS  Google Scholar 

  • Wouters BG, van den Beucken T, Magagnin MG, Lambin P, Koumenis C (2004) Targeting hypoxia tolerance in cancer. Drug Resist Updat 7:25–40

    PubMed  CAS  Google Scholar 

  • Xie Y, Xu K, Dai B, Guo Z, Jiang T, Chen H et al (2006) The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs. Oncogene 25:70–78

    PubMed  CAS  Google Scholar 

  • Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198

    PubMed  CAS  Google Scholar 

  • Yasuda H (2008) Solid tumor physiology and hypoxia-induced chemo/radio-resistance: novel strategy for cancer therapy: nitric oxide donor as a therapeutic enhancer. Nitric Oxide 19(2):205–216

    PubMed  CAS  Google Scholar 

  • Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436:214–220

    PubMed  CAS  Google Scholar 

  • Zhivotovsky B, Joseph B, Orrenius S (1999) Tumor radiosensitivity and apoptosis. Exp Cell Res 248:10–17

    PubMed  CAS  Google Scholar 

  • Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D et al (1999) Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59:5830–5835

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Advanced Biomedical Sciences, Pathology Section, Faculty of Medicine and Surgery, University of Naples “Federico II”, via S. Pansini, n.5, 80131, Naples, Italy

    Stefania Staibano

Authors
  1. Stefania Staibano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefania Staibano .

Editor information

Editors and Affiliations

  1. Biomedical Advanced Sciences Pathology Section, University Federico II of Naples, Naples, Italy

    Stefania Staibano

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Staibano, S. (2013). Counteracting Hypoxia in Radio-Resistant Metastatic Lesions. In: Staibano, S. (eds) Prostate Cancer: Shifting from Morphology to Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7149-9_17

Download citation

Publish with us

Policies and ethics

Search

Navigation