The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 106 MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm3, sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44+/CD24- or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an innovative therapeutic strategy in TNBC therapy by using sunitinib plus γ-secretase inhibitor to simultaneously target angiogenesis and CSC.

Thirty-five human neoplasms from various sites and of various histologic types and stages were examined with phosphorus-31 magnetic resonance spectroscopy in situ. The tumors included 13 squamous cell carcinomas of the head and neck (lymph nodes), eight Hodgkin lymphomas, six non-Hodgkin lymphomas, four carcinomas of the breast, one melanoma, one sarcoma, one neuroblastoma, and one mucoepidermoid sarcoma of the salivary glands. Thirty-four of the neoplasms had normal to slightly alkaline pH before irradiation. During fractionated radiation therapy, the pH stayed in a range of from near neutral to alkaline and rose to 7.6-8.0 at several time points of radiation therapy for some tumors. These results suggest that most tumor cells in human neoplasms are well oxygenated and that only a negligible fraction are chronic hypoxic cells. The fluctuating alkaline pH during radiation therapy occurred regardless of the responsiveness of the treated tumors.

In this work we review the dosimetric features of craniospinal axis irradiation in the areas of matching cranial and spinal fields, with reference to the normal structures within the spinal field. The implications of the use of photon or electron modalities for the spinal port were evaluated. A novel method of matching the cranial photon and the spinal electron fields involving a computer-aided junction design is presented. The technique involves moving the photon beam in three steps to degrade its penumbra to match that of the electron field. Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose-volume histogram study for an illustrative paediatric case were used to compare the dose to normal structures within the spinal field. Our results show that the use of electrons for the spinal field leads to better sparing of deep seated normal structures. In the case of bone marrow, the use of a customized bolus for the spinal field results in an improved dose distribution, making electrons potentially superior to photons for radiobiological reasons.

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