The gut microbiota impacts response to immunotherapy in cancer patients. We sought to evaluate the role of physiologic colonic fluorine-18-fluorodeoxyglucose (F-FDG) uptake, a test that was recently shown to reflect colonic bacterial load, as a possible predictor for response to immunotherapy. We carried out a retrospective study in metastatic melanoma patients who received the immune checkpoint inhibitor ipilimumab as first-line therapy. All patients underwent an F-FDG PET scan before treatment initiation. The primary outcome was defined as response to treatment according to the RECIST criteria. Regions of interest were drawn on each transaxial slice around the outer boundaries of the colon. Uptake was measured using maximum and mean standardized uptake value (SUV). A nonparametric test was used to compare SUV between response groups. The study included 14 melanoma patients, of whom two (14.3%) achieved a complete response (CR) following treatment, eight (57.1%) achieved a partial response (PR), and four (28.6%) developed progressive disease (PD). The mean SUVmax was 1.33±0.04, 2.2±0.46, and 3.33±2.67 for individuals with CR, PR, and PD, respectively. The difference between individuals with CR and those without CR (PR or PD) in total colonic SUVmax was statistically significant (P=0.03). Thus, physiologic colonic F-FDG uptake may predict CR to immunotherapy in metastatic melanoma patients.

P-glycoprotein (P-gp, multidrug resistance 1 (MDR1)) overexpression confers multidrug resistance to cancer cells, and P-gp in cell lines transfected with MDR1 or selected with chemotherapeutics significantly affect the anticancer drug efficacy. Although human cancer cell line panels consisting of defined tumor cell lines expressing endogenous P-gp have been used to screen drugs in pharmaceutical industries, endogenous P-gp affecting in vitro anticancer drug efficacy is unclear. We assessed the impact of P-gp expression on anticancer drug efficacy by using five colon cancer cell lines expressing varying endogenous P-gp levels and by selecting from the Cancer Cell Line Encyclopedia (CCLE). mRNA expression of MDR1 was considered as a surrogate of the protein expression of its gene product, P-gp, in CL-11, C2BBe1, and RKO cells, whereas P-gp protein expression in plasma membranes or crude membrane fractions was lower than expected from mRNA expression in CW-2 and CL-40 cells. The EC50 of paclitaxel and vinorelbine decreased in the presence of a P-gp inhibitor in CW-2 and CL-11 cells that highly express P-gp. No significant alterations in EC50 were observed in CL-40, C2BBe1, and RKO cells, which show lower P-gp expression. Accordingly, apparent in vitro efficacy of anticancer drugs could be underestimated if endogenous P-gp expression is higher than CL-11 cells. The effect of P-gp needs to be carefully evaluated in cell lines that highly express P-gp, which account for 1.5% of cancer cell lines, including all cancer types, and 14.5% of colon cancer cell lines in CCLE, considering protein expression levels in plasma membranes.

While particle carriers have potential to revolutionize disease treatment, using these carriers requires knowledge of spatial and temporal biodistribution. The goal of this study was to track orally administered particle uptake and trafficking through the murine gastrointestinal (GI) tract using multispectral optoacoustic tomography (MSOT). Polylactic acid (PLA) particles encapsulating AlexaFluor 680 (AF680) dye conjugated to bovine serum albumin (BSA) were orally gavaged into mice. Particle uptake and trafficking were observed using MSOT imaging with subsequent confirmation of particle uptake via fluorescent microscopy. Mice treated with PLA-AF680-BSA particles exhibited MSOT signal within the small bowel wall at 1 and 6 h, colon wall at 6, 12, and 24 h, and mesenteric lymph node 24 and 48 h. Particle localization identified using MSOT correlated with fluorescence microscopy. Despite the potential of GI tract motion artifacts, MSOT allowed for teal-time tracking of particles within the GI tract in a non-invasive and real-time manner. Future use of MSOT in conjunction with particles containing both protein-conjugated fluorophores as well as therapeutic agents could allow for non-invasive, real time tracking of particle uptake and drug delivery.

Raster-scan optoacoustic angiography at 532 nm wavelength with 50 μm lateral resolution at 2 mm diagnostic depth was used for quantitative characterization of neoangiogenesis in colon cancer models. Two tumor models of human colon adenocarcinoma (HT-29) and murine colon carcinoma (CT26) different in their histology and vascularization were compared. Tumors of both origins showed an inhomogeneous distribution of areas with high and low vascularization. Rapidly growing CT26 tumor demonstrated a higher rate of vessel growth from the periphery to the center. Peculiarities of the vascularity of tumor models revealed by optoacoustic imaging were confirmed by fluorescent microscopy with FITC-dextran and morphological analysis. The obtained results may be important for the investigation of tumor development and for improvement of colon cancer treatment strategies.

Curcumin is a widely researched and utilized natural product used for a variety of ailments including as a gastrointestinal aide and an anticancer agent. Curcumin however suffers from poor bioavailability. A strategy to circumvent poor bioavailability is to administer with an adjuvant or by synthetic modification. Herein we demonstrate the incorporation of curcumin into a self-degradable polymer by condensation with N,N'-di-Boc-L-cystine. The polymer is made self-degradable upon deprotection of the cystine amines. Degradation is confirmed by thermogravimetric analysis and differential scanning calorimetry. Curcumin retains its anti-cancer activity within the polymer showing activity against HT29 human colon cancer cells and DU-145 prostate cancer cells. The self-degrading polymer showed enhanced activity against HT29 cells compared to that of curcumin.

Objective To investigate the effect of miR-107 on the proliferation of colorectal cancer cells. Methods The expression of miR-107 was detected in colorectal cancer tissues and colorectal cancer cell lines by real-time quantitative PCR (qRT-PCR). miR-107 expression was up-regulated and down-regulated by the transfection of miR-107 mimic and miR-107 inhibitor in HT29 cells, respectively. The effect of miR-107 on the proliferation of HT29 cells was evaluated by MTT assay. The tumorigenic ability of HT29 cells was detected by soft-agar colony formation assay and nude mouse tumorigenic assay. The expression of cyclin D1 in HT29 cells was tested by Western blot analysis. Results The expression of miR-107 was significantly up-regulated in both colorectal cancer tissues and cells. Overexpression of miR-107 promoted the proliferation and tumorigenicity of HT29 cells, while the decrease of miR-107 expression inhibited the proliferation and tumorigenicity of HT29 cells. Overexpression of miR-107 up-regulated the expression of cyclin D1 in HT29 cells. Conclusion Overexpression of miR-107 in both colon cancer tissues and cells promotes the proliferation and tumor formation potential of HT29 cells via up-regulating cyclin D1 expression.