Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma

Moen, Ingrid; Tronstad, Karl Johan; Kolmannskog, Odd; Salvesen, Gerd; Reed, Rolf K.; Stuhr, Linda Elin Birkhaug

doi:10.1186/1471-2407-9-446

Cited by 41 publications

(49 citation statements)

References 38 publications

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“…In keeping with previous reports [20, 52, 53], we observed that development of resistance to 5FU treatment is typically associated with the detection of ischemic areas within MCTS, whereas progress toward the development of necrotic areas within MTCS appears to associate with increasing resistance to treatment only at the highest dose tested. Accordingly, sensitivity to 5FU is associated to the presence of high percentages of Ki-67 proliferating cells in “early” stage MCTS.…”

Section: Discussionsupporting

confidence: 92%

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

et al. 2016

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Culture of cancerous cells in standard monolayer conditions poorly mirrors growth in three-dimensional architectures typically observed in a wide majority of cancers of different histological origin. Multicellular tumor spheroid (MCTS) culture models were developed to mimic these features. However, in vivo tumor growth is also characterized by the presence of ischemic and necrotic areas generated by oxygenation gradients and differential access to nutrients. Hypoxia and necrosis play key roles in tumor progression and resistance to treatment. To provide in vitro models recapitulating these events in highly controlled and standardized conditions, we have generated colorectal cancer (CRC) cell spheroids of different sizes and analyzed their gene expression profiles and sensitivity to treatment with 5FU, currently used in therapeutic protocols. Here we identify three MCTS stages, corresponding to defined spheroid sizes, characterized by normoxia, hypoxia, and hypoxia plus necrosis, respectively. Importantly, we show that MCTS including both hypoxic and necrotic areas most closely mimic gene expression profiles of in vivo-developing tumors and display the highest resistance to 5FU. Taken together, our data indicate that MCTS may mimic in vitro generation of ischemic and necrotic areas in highly standardized and controlled conditions, thereby qualifying as relevant models for drug screening purposes.

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Section: Discussionsupporting

confidence: 92%

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

et al. 2016

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“…Typically, tumor cells are less well-oxygenated than normal tissues, and tumor hypoxia often leads to rapid tumor growth as well as resistance to radiotherapy and anticancer chemotherapy (15). Therefore, HBO may theoretically be used as an effective therapy for tumor treatment by reversing tissue hypoxia (16), as tumor cells can be stimulated resulting in an increased sensitivity to chemo-and radiotherapy, and the effect of chemo-and radiotherapy can be enhanced by HBO (17)(18)(19)(20). However, the effect of hyperbaric oxygen treatment alone on tumor treatment remains controversial (21).…”

Section: Discussionmentioning

confidence: 99%

Effects of hyperbaric oxygen treatment on gastric cancer cell line SGC7901

Ruan

Wang

et al. 2017

Biomedical Reports

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Abstract. Hyperbaric oxygen (HBO) has been previously identified as an effective adjunct treatment option for the management of brain injury, diabetic ulcers and chronic wounds. However, the roles of HBO as an adjunctive therapy for tumors remain controversial. The present research project was performed to explore the effects of HBO treatment on proliferation, autophagy and endoplasmic reticulum stress response of the gastric cancer cell line, SGC7901. The present study demonstrated that, after subjecting SGC7901 cells to HBO treatment, the increase in cell proliferation was significant, compared with that of the control group. In addition, there was a significant increase in LC3-phosphatidylethanolamine conjugate (LC3-II) level, as well as binding immunoglobulin protein level, and a significant decrease in CCAAT-enhancer-binding protein homologous protein level. These suggested that hyperbaric oxygen treatment alone may promote proliferation and cell survival of gastric cancer cell SGC7901, and inhibit apoptosis through regulating cell autophagy and oxidative stress. IntroductionWidely used in the clinic, hyperbaric oxygen (HBO) treatment has be shown to be an effective adjunct to management of brain injury (1), diabetic ulcers (2) and chronic wounds (3). However, the roles of HBO as an adjunctive therapy for tumors remains controversial. Some previous studies suggest that HBO therapy may improve postoperative outcome and outcome of radiotherapy and chemotherapy, especially proving beneficial for the treatment of radiotherapy (4,5). A combinatorial approach using chemotherapeutic drugs with HBO may enhance sensitivity of tumor cells to chemotherapeutic agents (6,7) and the application of HBO in chemotherapy for malignant lymphoma, brain tumor, lung cancer, gastric cancer and breast cancer may increase chemotherapeutic efficacy while decreasing treatment related toxicity (8). However, HBO treatment alone may stimulate the proliferation of tumor tissues (9). Other studies indicate that cancer cells in hypoxic conditions are more likely to metastasize and thus be more deadly (10-12). Meanwhile, hypoxic cells undergo a high rate of mutation to become a treatment-resistant genotype, and HBO treatment may improve it (13). The current study is to explore the effects of hyperbaric oxygen treatment alone on proliferation, autophagy and oxidative stress response of gastric cancer SGC7901 cells. Materials and methodsCell culture. Gastric cancer SGC7901 cell lines were purchased from the American Type Culture Collection (Manassas, VA, USA), inoculated in Dulbecco's modified Eagle's (high glucose) culture medium (Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) with 10% fetal bovine serum (Clark Bioscience, Richmond, VA, USA) and cultured in a 5% CO 2 incubator at 37˚C. HBO treatment.Prior to the experiment, the hyperbaric chamber was disinfected using UV techniques for 20 min, and cleaned using pure oxygen for 10 min. The cells were placed flat in the chamber under aseptic conditions for 90 min each time. The press...

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“…It has been shown that HBO therapy significantly lowers TIP (46) and repeated treatment gives a better therapeutic effect (47).…”

Section: Strategies Using the Physical Methodsmentioning

confidence: 99%

Releasing Pressure in Tumors: What Do We Know So Far and Where Do We Go from Here? A Review

et al. 2014

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Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment. It causes heterogenous intratumoral distribution of drugs and macromolecules. It also causes the development of hypoxia within tumor bulk, leading to reduced efficacy of therapeutic drugs and radiotherapy. Tumor pressure has been associated with increased metastatic potential and poor prognosis in some tumors. The formation of increased pressure in solid tumors is multifactorial. Factors known to affect tumor pressure include hyperpermeable tortuous tumor vasculatures, the lack of functional intratumoral lymphatic vessels, abnormal tumor microenvironment, and the solid stress exerted by proliferating tumor cells. Reducing this pressure is known to enhance the uptake and homogenous distribution of many therapies. Pharmacologic and biologic agents have been shown to reduce tumor pressure. These include antiangiogenic therapy, vasodilatory agents, antilymphogenic therapy, and proteolytic enzymes. Physical manipulation has been shown to cause reduction in tumor pressure. These include irradiation, hyperbaric oxygen therapy, hyper-or hypothermic therapy, and photodynamic therapy. This review explores the methods to reduce tumor pressure that may open up new avenues in cancer treatment. Cancer Res; 74(10); 2655-62. Ó2014 AACR.

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Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma

Cited by 41 publications

References 38 publications

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment

Effects of hyperbaric oxygen treatment on gastric cancer cell line SGC7901

Releasing Pressure in Tumors: What Do We Know So Far and Where Do We Go from Here? A Review

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