This review was written to be included in the Special Collection 'Therapy Ultrasound: Medicine's Swiss Army Knife?' The purpose of this review is to provide basic presentation and interpretation of the fundamentals of hyperthermia biology, as it pertains to uses of therapeutic ultrasound. The fundamentals are presented but in the setting of a translational interpretation and a view toward the future. Subjects that require future research and development are highlighted. The effects of hyperthermia are time and temperature dependent. Because intra-tumoral temperatures are non-uniform in tumors, one has to account for differential biologic effects in different parts of a tumor that occur simultaneously during and after hyperthermia.

Supplementary Figures S1-S3; Tables S1, S2 from Gene Expression Profiles of Multiple Breast Cancer Phenotypes and Response to Neoadjuvant Chemotherapy

Supplementary Figures S1-S7.

GO term analysis from Estrogen-Related Receptor α Is Critical for the Growth of Estrogen Receptor–Negative Breast Cancer

Supplementary Figures 1-2 from Systemic Overexpression of Angiopoietin-2 Promotes Tumor Microvessel Regression and Inhibits Angiogenesis and Tumor Growth

AVI file - 34.5MB, Real-time intravascular release of doxorubicin from Dox-TSL and subsequent redistribution of drug in B16 melanoma tumor tissue. The video shows drug (red) delivered over the first 20min, at 20x magnification. The eNOS-GFPtg mouse model was used in this experiment, so the blood vessels are green. (Download before playing in IE8)

Supplemental Figure 3: Effects of radiation and MnTnBuOE-2-PyP5+ on tumor cells. (A) LN-18 and (B) LN-229 glioblastoma cell lines treated with or without 50 nM MnTnBuOE-2-PyP5+ in clonogenic survival assays prior to various doses of radiation.

Supplemental Figure 1: Western analysis of myelin within the corpus callosum. Signal intensity of myelin and actin were quantitated by Image J, averaged within groups, then normalized to the saline group .

Supplementary Movie 6 from The Pervasive Presence of Fluctuating Oxygenation in Tumors

S4. E-cadherin induces E- to N-cadherin switching in sarcoma cells.

Supplementary Movie 9 from The Pervasive Presence of Fluctuating Oxygenation in Tumors

Background Chaperon-mediated autophagy (CMA) has taken on a new emphasis in cancer biology. However, the roles of CMA in hypoxic tumours are poorly understood. We investigated the anti-tumour effects of the natural product ManA through the activation of CMA in tumour progression under hypoxia. Methods The effect of ManA on CMA activation was assessed in mouse xenograft models and cells. The gene expressions of HIF-1α, HSP90AA1, and transcription factor EB (TFEB) were analysed using The Cancer Genome Atlas (TCGA) datasets to assess the clinical relevance of CMA. Results ManA activates photoswitchable CMA reporter activity and inhibits Hsp90 chaperone function by disrupting the Hsp90/F 1 F 0 -ATP synthase complex. Hsp90 inhibition enhances the interaction between CMA substrates and LAMP-2A and TFEB nuclear localisation, suggesting CMA activation by ManA. ManA-activated CMA retards tumour growth and displays cooperative anti-tumour activity with anti-PD-1 antibody. TCGA datasets show that a combined expression of HSP90AA1 High /HIF1A High or TFEB Low /HIF1A High is strongly correlated with poor prognosis in patients with lung cancer. Conclusions ManA-induced CMA activation by modulating Hsp90 under hypoxia induces HIF-1α degradation and reduces tumour growth. Thus, inducing CMA activity by targeting Hsp90 may be a promising therapeutic strategy against hypoxic tumours.

Supplementary Figure 1 from Tumor Necrosis Factor-α Is a Potent Endogenous Mutagen that Promotes Cellular Transformation

Inflammatory breast cancer (IBC), an understudied and lethal breast cancer, is often misdiagnosed due to its unique presentation of diffuse tumor cell clusters in the skin and dermal lymphatics. Here, we describe a window chamber technique in combination with a novel transgenic mouse model that has red fluorescent lymphatics (ProxTom RFP Nu/Nu) to simulate IBC clinicopathological hallmarks. Various breast cancer cells stably transfected to express green or red fluorescent reporters were transplanted into mice bearing dorsal skinfold window chambers. Intravital fluorescence microscopy and the in vivo imaging system (IVIS) were used to serially quantify local tumor growth, motility, length density of lymph and blood vessels, and degree of tumor cell lymphatic invasion over 0–140 h. This short-term, longitudinal imaging time frame in studying transient or dynamic events of diffuse and collectively migrating tumor cells in the local environment and quantitative analysis of the tumor area, motility, and vessel characteristics can be expanded to investigate other cancer cell types exhibiting lymphovascular invasion, a key step in metastatic dissemination. It was found that these models were able to effectively track tumor cluster migration and dissemination, which is a hallmark of IBC clinically, and was recapitulated in these mouse models.

Supplementary Movie 5 from The Pervasive Presence of Fluctuating Oxygenation in Tumors

Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer toward practice changes. This review summarizes key topics discussed to advance research on the role of energy balance, including physical activity, body composition, and dietary intake, on cancer development, cancer outcomes, and healthy survivorship.

Supplemental Figure 2: Neurocognitive analysis of mice by Morris watermaze (A and B), novel object test (C and D), and fear conditioning (E and F). Tests were performed as described (29). (G and H) Distance and velocity during the novel object training and test periods and overall averages.