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The purpose of this review is to provide up-to-date information regarding the effects of aerobic and resistance exercise training on the traditional blood lipid and lipoprotein profile. In addition, emerging coronary artery disease (CAD) risk factors, such as postprandial lipemia (PPL) and metabolic syndrome (MetS), are reviewed. Numerous studies report that aerobic exercise combined with weight loss significantly reduces blood cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG) while improving high-density lipoprotein cholesterol (HDL-C). Both aerobic and resistance training demonstrated a reduction in non-HDL-C independent of changes in body weight. Transient beneficial effects of a single session of aerobic exercise are observed for PPL. Nonetheless further research is needed to provide a better understanding of the potential mechanisms for reducing PPL. Exercise as an intervention for patients with MetS leads to improved CAD risk factors including atherogenic dyslipidemia, blood pressure, body composition, insulin sensitivity, and fat metabolism.

Chemotherapy has been known to cause severe side effects, including fatigue. While the mechanisms for chemotherapy induced fatigue (CIF) are likely to be multi-factorial in origin, it is thought that inflammation and anemia may play a role. The purpose of this study was to examine the effect of chemotherapy on fatigue in mice, and further, to begin to determine if inflammation and anemia may contribute to this response. For experiment 1, C57BL/6 mice were assigned to: vehicle (PBS), low (20 mg/kg), medium (40 mg/kg), or high (60 mg/kg) doses of 5-fluorouracil (5-FU). Voluntary physical activity (PA) was measured throughout the treatment period (day 1–5) as well as during the recovery period (day 6–14). In experiment 2, we examined the effects of 5-FU (60 mg/kg) on the inflammatory mediator MCP-1 and on markers of anemia (RBC, Hct and Hb). Finally, using MCP-1−/− mice we examined the role of MCP-1 on CIF (experiment 3). 5-FU reduced voluntary PA in a dose response manner (p < 0.05). Plasma MCP-1 was increased following 5-FU treatment on both days 5 (p = 0.10) and 14 (p < 0.05). In addition, RBCs, Hct and Hb were reduced with 5-FU on days 5 and 14 (p < 0.05). Both C57BL/6 and MCP-1−/− mice saw similar decrements in PA through the duration of the treatment period (days 1–5), however the MCP-1−/− mice recovered much earlier than wildtype mice. This study provides evidence of the dose response effect of a standard chemotherapy agent on fatigue and demonstrates a potential role of MCP-1 and presumably inflammation, and anemia.

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of diseasespecific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

Curcumin's benefits on tumorigenesis are thought to be mediated by its antiinflammatory activity; however, these effects have not been well characterized in a mouse model of colon cancer. We examined the effects of curcumin on intestinal inflammation in the Apc Min/þ mouse. Apc Min/þ mice were given a placebo or curcumin (2%) diet from 4 to 18 weeks of age (n ¼ 10/group). C57BL/6 mice were used as a wild-type control (n ¼ 10/ group). Intestines were analyzed for polyp burden (sections 1, 4, and 5) and for mRNA expression, and concentration of interleukin (IL)-1b, IL-6, tumor necrosis factor-a, and chemokine ligand 2 (CCL2) (sections 2 and 3). Plasma was collected for concentration of CCL2. Curcumin decreased total intestinal polyps by 75% (P < 0.05) in all size categories [>2 mm (65%), 1-2 mm (72%), <1 mm (82%); P < 0.05]. mRNA expression of IL-1b, IL-6, tumor necrosis factor-a, and CCL2 was elevated (P < 0.05) and curcumin blunted this increase (P < 0.05). Protein concentration of IL-1b, IL-6 (section 3), and CCL2 was increased (P < 0.05) and curcumin reduced this response for IL-1b (section 2) and CCL2 (P < 0.05). Curcumin also offset the increase in plasma CCL2 (P < 0.05). The benefits of curcumin in colon cancer may be at least in part mediated by its antiinflammatory activity.

Breast cancer affects roughly one in eight women over their lifetime and is a leading cause of cancer-related death in women. While outcomes have improved in recent years, prognosis remains poor for patients who present with either disseminated disease or aggressive molecular subtypes. Cancer immunotherapy has revolutionized the treatment of several cancers, with therapeutic vaccines aiming to direct the cytotoxic immune program against tumor cells showing particular promise. However, these results have yet to translate to breast cancer, which remains largely refractory from such approaches. Recent evidence suggests that the breast tumor microenvironment (TME) is an important and long understudied barrier to the efficacy of therapeutic vaccines. Through an improved understanding of the complex and biologically diverse breast TME, it may be possible to advance new combination strategies to render breast carcinomas sensitive to the effects of therapeutic vaccines. Here, we discuss past and present efforts to advance therapeutic vaccines in the treatment of breast cancer, the molecular mechanisms through which the TME contributes to the failure of such approaches, as well as the potential means through which these can be overcome.

Estrogen receptor (ER) is the most important factor in the pathophysiology of breast cancer. Consequently, modulation of ER activity has been exploited to develop drugs against ER+ breast cancer, such as tamoxifen, referred to as endocrine therapies. With deeper understanding of ER mechanism of action, posttranslational modifications (PTMs) are increasingly recognized as important in mediating ER activity. Some ER PTMs such as phosphorylation, are studied in the context of ligand-independent ER activity. However, they also play a pivotal role in defining the actions and outcome of the antiestrogen-bound ER. The complexity of these actions is increasing as new PTMs are identified, yet the functional consequences and clinical implications are not fully understood. This review will examine and summarize new emerging mechanistic knowledge and clinical data in breast cancer on how these PTMs affect antiestrogen-ER activity, with an emphasis on phosphorylation of serine 305 (S305). This phosphorylation site represents an integrated hub of oncogenic signaling to modulate ER conformation, dimerization, coregulators, and DNA binding to profoundly reduce sensitivity to endocrine therapy. Consequently, (i) S305 has the potential to become a useful marker of tamoxifen response, and (ii) blocking S305 phosphorylation defines a new therapeutic strategy to overcome tamoxifen resistance in breast cancer.

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