Journal: Nucleic Acids Research

Article Title: Spatially multiplexed RNA in situ hybridization to reveal tumor heterogeneity

doi: 10.1093/nar/gkz1151

Figure Lengend Snippet: Local RNA in situ hybridization. ( A ) Schematic overview of a microfluidic implementation of chromogenic RNA in situ hybridization. The initial preparation of the tissue section including paraffin removal (1), heat (2) and protease (3) pretreatment, as well as fixation was performed globally. The primary probe was then hybridized locally to the RNA of interest (4). In this case the detection of HER2 is shown with internal negative ( dapB ) and positive ( ActB ) controls. Finally, the amplification of the signal using preamplifier and amplifier strands (5), the binding of enzyme (6), and the enzymatic reactions (7) were performed globally on the whole slide. ( B ) Fluorescence images of RNA-ISH experiments detecting the gene expression of HER2 in cell pellet sections of the breast cancer cell lines MCF7 (left), SKBR3 (center) and BT474 (right). Probes directed against bacterial dapB and ActB were used as negative and positive controls, respectively. Scale bar: 100 μm.

Article Snippet: FFPE cell blocks of the cell lines MCF7, BT474 and SKBR3 (AMS Biotechnology, Abingdon, UK) with HER2 expression levels of 1+, 2+ and 3+, respectively, were used as references.

Techniques: RNA In Situ Hybridization, Amplification, Binding Assay, Fluorescence, Expressing

Journal: Nucleic Acids Research

Article Title: Spatially multiplexed RNA in situ hybridization to reveal tumor heterogeneity

doi: 10.1093/nar/gkz1151

Figure Lengend Snippet: Detection of HER2 expression status by RNA in situ hybridization using internal positive and negative controls. ( A ) Fluorescence images of the signals detected for HER2 , dapB , and ActB in a mammary carcinoma section. Scale bar: 100 μm. ( B ) Quantitative analysis of the fluorescence intensity of FISH signals detected for HER2 , dapB , and ActB integrated per sectioned cell for FFPE sections of the breast cancer cell lines MCF7, SKBR3, and BT474 (see Figure ) as well as the mammary carcinoma from (A). 100 ms excitation.

Article Snippet: FFPE cell blocks of the cell lines MCF7, BT474 and SKBR3 (AMS Biotechnology, Abingdon, UK) with HER2 expression levels of 1+, 2+ and 3+, respectively, were used as references.

Techniques: Expressing, RNA In Situ Hybridization, Fluorescence

Journal: Nucleic Acids Research

Article Title: Spatially multiplexed RNA in situ hybridization to reveal tumor heterogeneity

doi: 10.1093/nar/gkz1151

Figure Lengend Snippet: Single color multiplexed RNA-ISH for the detection of breast cancer biomarkers. ( A ) The primary probes for ER , PgR , and HER2 were delivered to spatially distinct regions of a mammary carcinoma section using a microfluidic chip (schematic in upper left corner). Fluorescence images of the signal detected for the breast cancer biomarkers ER , PgR and HER2 in a mammary carcinoma section. Scale bar: 100 μm. ( B ) Fluorescence intensity of FISH signals detected for ER , PgR and HER2 integrated per sectioned cell for FFPE sections of the breast cancer cell lines MCF7, SKBR3 and BT474 (see ) as well as the mammary carcinoma from (A). 500 ms excitation.

Article Snippet: FFPE cell blocks of the cell lines MCF7, BT474 and SKBR3 (AMS Biotechnology, Abingdon, UK) with HER2 expression levels of 1+, 2+ and 3+, respectively, were used as references.

Techniques: Fluorescence

Journal: Cancers

Article Title: High Antitumor Activity of the Dual Topoisomerase Inhibitor P8-D6 in Breast Cancer

doi: 10.3390/cancers14010002

Figure Lengend Snippet: Target control. MCF-7 ( A ) and SkBr3 ( B ) cells were treated with 10 µM P8-D6 (fluorophore: 462Ex/530Em) or control (PBS) for 10 h. P8-D6 were localized in vitro. ( i ): Cells were stained by CellTracker TM Deep Red Dye and Hoechst 33342. ( ii ) After fixation, topoisomerase I were detected. Fluorescence images show the fluorophore P8-D6 in green, membrane staining ( i ) or topoisomerase expression ( ii ) in red and nucleus staining in white. Scale bars, 50 µm. ( C ) Fluorescence intensity of P8-D6 in the nuclei was compared to PBS control. ( D ) BC cell lines and primary cells were lysed and protein expression was analyzed using western blot. HSP 90 was used as loading control.

Article Snippet: MCF-7 (1000/well), SkBr3 (1000/well), MDA-MB231 (2500/well), MDA-MB468 (500/well), BT-20 (18,750/well) and UF-182 (20,000/well) cells were seeded onto a 96-well Ultra-Low Attachment plate (Corning #4520).

Techniques: Control, In Vitro, Staining, Fluorescence, Membrane, Expressing, Western Blot

Journal: Cancers

Article Title: High Antitumor Activity of the Dual Topoisomerase Inhibitor P8-D6 in Breast Cancer

doi: 10.3390/cancers14010002

Figure Lengend Snippet: Antitumor responses in BC 2D monolayers. MCF-7, SkBr3, MDA-MB231, MDA-MB468, BT-20 (cell line) and UF-182 (primary cells) were treated with P8-D6, cisplatin, etoposide, topotecan and PBS as control. The relative caspase activity representing the rate of apoptosis were measured 48 h after treatment in MCF-7 ( A ), SkBr3 ( B ), MDA-MB231 ( C ), MDA-MB468 ( D ), BT-20 ( E ) and UF-182 ( F ) cells. Additionally, the anti-proliferative effects in the cells were visualized by microscopy after 24 h treatment. Scale bars, 50 µm ( G ). Heat map presents the IC50 values calculated by viability ( H ). P8-D6 was compared to cisplatin, epirubicin and topotecan. Data are means + SD one-way ANOVA, * ( p < 0.05), ** ( p < 0.01), *** ( p < 0.001), **** ( p < 0.0001), ns (non-significant).

Article Snippet: MCF-7 (1000/well), SkBr3 (1000/well), MDA-MB231 (2500/well), MDA-MB468 (500/well), BT-20 (18,750/well) and UF-182 (20,000/well) cells were seeded onto a 96-well Ultra-Low Attachment plate (Corning #4520).

Techniques: Control, Activity Assay, Microscopy

Journal: Cancers

Article Title: High Antitumor Activity of the Dual Topoisomerase Inhibitor P8-D6 in Breast Cancer

doi: 10.3390/cancers14010002

Figure Lengend Snippet: Growth changes in BC spheroids. For 3D culture, MCF-7, SkBr3, MDA-MB231, MDA-MB468, BT-20 (cell line) and UF-182 (primary cells) cells were cultured in ULA plates for 96 h. Subsequently, spheroids were treated with P8-D6 (10 µM, 1 µM, 0.5 µM, 0.1 µM), topotecan (10 µM, 1 µM) and PBS for 48 h. For the monitoring of growth changes and morphological changes, spheroids were imaged every 24 h by microscopy. MCF-7 ( A ), SkBr3 ( B ), MDA-MB231 ( C ), MDA-MB468 ( D ), BT-20 ( E ) and UF-182 ( F ). Scale bars, 500 µm.

Article Snippet: MCF-7 (1000/well), SkBr3 (1000/well), MDA-MB231 (2500/well), MDA-MB468 (500/well), BT-20 (18,750/well) and UF-182 (20,000/well) cells were seeded onto a 96-well Ultra-Low Attachment plate (Corning #4520).

Techniques: Cell Culture, Microscopy

Journal: Cancers

Article Title: High Antitumor Activity of the Dual Topoisomerase Inhibitor P8-D6 in Breast Cancer

doi: 10.3390/cancers14010002

Figure Lengend Snippet: Apoptosis induction in BC spheroids. For 3D culture, MCF-7, SkBr3, MDA-MB231, MDA-MB468, BT-20 (cell line) and UF-182 (primary cells) cells were cultured in ULA plates for 96 h. Subsequently, spheroids were treated with P8-D6 (10 µM, 1 µM, 0.5 µM, 0.1 µM), topotecan (10 µM, 1 µM) and PBS for 48 h. After treatment, the viability and caspase activity were analyzed in MCF-7 ( A ), SkBr3 ( B ), MDA-MB231 ( C ), MDA-MB468 ( D ), BT-20 ( E ) and UF-182 ( F ) spheroids. Data are means + SD ( n = 3) one-way ANOVA, * ( p < 0.05), ** ( p < 0.01), *** ( p < 0.001), **** ( p < 0.0001), ns (non-significant).

Article Snippet: MCF-7 (1000/well), SkBr3 (1000/well), MDA-MB231 (2500/well), MDA-MB468 (500/well), BT-20 (18,750/well) and UF-182 (20,000/well) cells were seeded onto a 96-well Ultra-Low Attachment plate (Corning #4520).

Techniques: Cell Culture, Activity Assay

Journal: Cancers

Article Title: High Antitumor Activity of the Dual Topoisomerase Inhibitor P8-D6 in Breast Cancer

doi: 10.3390/cancers14010002

Figure Lengend Snippet: Cell toxicity, live-dead staining and morphological changes in BC spheroids. For 3D culture, MCF-7, SkBr3, MDA-MB231, MDA-MB468, BT-20 (cell line) and UF-182 (primary cells) cells were cultured in ULA plates for 96 h. Subsequently, spheroids were treated with P8-D6 (10 µM, 1 µM, 0.5 µM, 0.1 µM), topotecan (10 µM, 1 µM) and PBS for 48 h. After treatment, the spheroids were stained with propidium iodide (red), calcein-AM (green) and Hoechst 33342 (blue) and imaged using NYONE ®® Scientific. MCF-7 ( A ), SkBr3 ( B ) and UF-182 ( C ). Scale bars, 500 µm. ( D ) During treatment, the cell toxicity was measured by fluorescence microscopy using CellTox™ Green (24 h, 48 h). Scale bars, 500 µm. These fluorescence signals were quantified (fluorescence intensity RFU) and presented in a heat map ( E ). ( F ) The P8-D6- (1 μM) or PBS-treated SkBr3 and UF-182 spheroids (48 h) were analyzed by scanning electron microscopy (SEM). Scale bars, 20 µm.

Article Snippet: MCF-7 (1000/well), SkBr3 (1000/well), MDA-MB231 (2500/well), MDA-MB468 (500/well), BT-20 (18,750/well) and UF-182 (20,000/well) cells were seeded onto a 96-well Ultra-Low Attachment plate (Corning #4520).

Techniques: Staining, Cell Culture, Fluorescence, Microscopy, CellTox Assay, Electron Microscopy

Journal: Membranes

Article Title: Liposomes Loaded with the Proteasome Inhibitor Z-Leucinyl-Leucinyl-Norleucinal Are Effective in Inducing Apoptosis in Colorectal Cancer Cell Lines

doi: 10.3390/membranes10050091

Figure Lengend Snippet: LLNle causes a concentration-dependent inhibition of survival in Caco-2, GP2d and LoVo cell lines. An MTT assay was performed after 72 h of treatment of the indicated cell culture, n = 4 replicas were performed and average values and SD are shown for each concentration indicated on the x -axis. An interpolation curve of survival values is shown for the GP2d cell line.

Article Snippet: CRC cell lines Caco-2 and LoVo were obtained from Banca Biologica and Cell Factory in IRCCS Ospedale Policlinico San Martino, belonging to the European Culture Collection’s Organization.

Techniques: Concentration Assay, Inhibition, MTT Assay, Cell Culture

Journal: Membranes

Article Title: Liposomes Loaded with the Proteasome Inhibitor Z-Leucinyl-Leucinyl-Norleucinal Are Effective in Inducing Apoptosis in Colorectal Cancer Cell Lines

doi: 10.3390/membranes10050091

Figure Lengend Snippet: LLNLe induces apoptosis in Caco-2, GP2d and LoVo cell lines. Cells were treated for 72 h with LLNle (1.7, 1.4 and 0.6 µM LLNle for Caco-2, GP2d and LoVo, respectively) or with DMSO used as a control. Cells were labeled with both the DNA-specific and cell-impermeant sytox-blue, and annexin-V APC and fluorescence emissions were analyzed by FCM. Early apoptotic (annexin-V APC + and sytox-blue − ) cells are indicated by red arrows while necrotic cells (annexin-V APC − and sytox-blue + ) are indicated by a black arrow.

Article Snippet: CRC cell lines Caco-2 and LoVo were obtained from Banca Biologica and Cell Factory in IRCCS Ospedale Policlinico San Martino, belonging to the European Culture Collection’s Organization.

Techniques: Control, Labeling, Fluorescence

Journal: Membranes

Article Title: Liposomes Loaded with the Proteasome Inhibitor Z-Leucinyl-Leucinyl-Norleucinal Are Effective in Inducing Apoptosis in Colorectal Cancer Cell Lines

doi: 10.3390/membranes10050091

Figure Lengend Snippet: LLNle-liposome inhibits CRC cell line survival. MTT analysis of Caco-2, GP2d, and LoVo cell line treated with LLNle, DMSO (used as a control for LLNle), LLNle-liposomes, Cxm-liposomes-LLNle, empty liposomes, and PBS (control for liposomes) for 72 h. LLNle-liposomes were diluted to achieve an LLNle final concentration in the culture medium equivalent to 2.5, 2.0 and 0.8 µM of free LLNle for Caco-2, GP2d and LoVo, respectively. All measurements here reported are presented as mean ± standard deviations (s.d.), n = 4. Details of the results of the statistical analysis are provided in .

Article Snippet: CRC cell lines Caco-2 and LoVo were obtained from Banca Biologica and Cell Factory in IRCCS Ospedale Policlinico San Martino, belonging to the European Culture Collection’s Organization.

Techniques: Control, Liposomes, Concentration Assay

Journal: Membranes

Article Title: Liposomes Loaded with the Proteasome Inhibitor Z-Leucinyl-Leucinyl-Norleucinal Are Effective in Inducing Apoptosis in Colorectal Cancer Cell Lines

doi: 10.3390/membranes10050091

Figure Lengend Snippet: LLNle-liposome inhibits proteasomal degradation of poly-ubiquitinated protein and induces apoptosis in CRC cell lines. Immunoblot analysis of whole-cell lysates of Caco-2, GP2d, and LoVo cell lines treated with LLNle, DMSO (used as control for LLNle), LLNle-liposomes, and PBS (control for LLNle-liposomes) for 72 h. LLNle-liposomes were diluted to achieve an LLNle final concentration in the culture medium equivalent to 1.7, 1.4 and 0.6 µM LLNle of free LLNle for Caco-2, GP2d and LoVo, respectively. All three cell lines display expression of ERBB1, the EGF receptor. A high molecular weight smear signal, corresponding to poly-ubiquitinated proteins, and the generation of the 89 kDa isoform of the protein PARP was detected by specific Ab only in LLNle-liposomes and LLNle treated samples. Tubulin was used as a loading control.

Article Snippet: CRC cell lines Caco-2 and LoVo were obtained from Banca Biologica and Cell Factory in IRCCS Ospedale Policlinico San Martino, belonging to the European Culture Collection’s Organization.

Techniques: Western Blot, Control, Liposomes, Concentration Assay, Expressing, High Molecular Weight

Journal: Theranostics

Article Title: Investigating the Intracellular Behaviors of Liposomal Nanohybrids via SERS: Insights into the Influence of Metal Nanoparticles

doi: 10.7150/thno.21173

Figure Lengend Snippet: Bright field image (A), SERS mapping (B) and merged image (C) of SKBR3 cells incubated with nanohybrids for 5 h. (D) SERS spectrum acquired from the SKBR3 cells. Scale bars for confocal images are 10 μm.

Article Snippet: After nanohybrids-loaded SKBR3 cells were supplemented with fresh culture medium, exocytosis prevailed gradually, leading to a decrease in the content of nanohybrids within SKBR3 cells as well as a reduction in the intensity of SERS signal.

Techniques: Incubation

Journal: Theranostics

Article Title: Investigating the Intracellular Behaviors of Liposomal Nanohybrids via SERS: Insights into the Influence of Metal Nanoparticles

doi: 10.7150/thno.21173

Figure Lengend Snippet: Colocalization between nanoparticles (labeled by SERS, red) and lipid bilayers (labeled by fluorescence, green) for 4 h (A-C), 8 h (D-F) and 12 h (G-I); 580-610 nm light was collected for fluorescence imaging of DiI and 800-1600 cm -1 Raman scattered light was collected for SERS imaging. (J) Average SERS spectrum of a single SKBR3 cell incubated with the nanohybrids for different times. (K) Colocalization quantification (>0.6 indicates substantial colocalization). Scale bars for confocal images are 10 μm.

Article Snippet: After nanohybrids-loaded SKBR3 cells were supplemented with fresh culture medium, exocytosis prevailed gradually, leading to a decrease in the content of nanohybrids within SKBR3 cells as well as a reduction in the intensity of SERS signal.

Techniques: Labeling, Fluorescence, Imaging, Incubation

Journal: Theranostics

Article Title: Investigating the Intracellular Behaviors of Liposomal Nanohybrids via SERS: Insights into the Influence of Metal Nanoparticles

doi: 10.7150/thno.21173

Figure Lengend Snippet: Effect of inhibitors on uptake of SKBR3 cells incubated with nanohybrids probed by SERS. In the intracellular experiments, 580-610 nm light was collected for fluorescence imaging of DiI (green) and 800-1600 cm -1 Raman scattered light was collected for SERS imaging (red). Scale bars for confocal images are 10 μm.

Article Snippet: After nanohybrids-loaded SKBR3 cells were supplemented with fresh culture medium, exocytosis prevailed gradually, leading to a decrease in the content of nanohybrids within SKBR3 cells as well as a reduction in the intensity of SERS signal.

Techniques: Incubation, Fluorescence, Imaging

Journal: Theranostics

Article Title: Investigating the Intracellular Behaviors of Liposomal Nanohybrids via SERS: Insights into the Influence of Metal Nanoparticles

doi: 10.7150/thno.21173

Figure Lengend Snippet: Confocal microscopy of SERS labeled nanohybrids (red) and fluorescence staining of organelle markers (green). Makers are DiI (membranes, A-C) and lyso-tracker green (lysosomes, D-F): 500-540 nm light was collected for the fluorescence imaging of Lysotracker Green, 580-610 nm light was collected for fluorescence imaging of DiI and 800-1600 cm -1 Raman scattered light was collected for SERS imaging. (G) Average SERS intensity of a single SKBR3 cell incubated with the nanohybrids for 4, 8 and 12 h. (H) Colocalization coefficients between nanohybrids and membranes (or lysosomes). Scale bars for confocal images are 10 μm.

Article Snippet: After nanohybrids-loaded SKBR3 cells were supplemented with fresh culture medium, exocytosis prevailed gradually, leading to a decrease in the content of nanohybrids within SKBR3 cells as well as a reduction in the intensity of SERS signal.

Techniques: Confocal Microscopy, Labeling, Fluorescence, Staining, Imaging, Incubation

Journal: Theranostics

Article Title: Investigating the Intracellular Behaviors of Liposomal Nanohybrids via SERS: Insights into the Influence of Metal Nanoparticles

doi: 10.7150/thno.21173

Figure Lengend Snippet: Confocal microscopy of NBD labeled liposomes (green) and fluorescence staining of organelle markers (red). Makers are DiI (membranes, A-C) and lysotracker red (lysosomes, D-F): 520-550 nm light was collected for fluorescence imaging of NBD, 580-610 nm light was collected for fluorescence imaging of DiI and 570-620 nm light was collected for fluorescence imaging of Lysotracker Red. (G) Average fluorescence intensity of a single SKBR3 cell incubated with the nanohybrids for 4, 8 and 12 h. (H) Colocalization coefficients between liposomes and membranes (or lysosomes). Scale bars for confocal images are 10 μm.

Article Snippet: After nanohybrids-loaded SKBR3 cells were supplemented with fresh culture medium, exocytosis prevailed gradually, leading to a decrease in the content of nanohybrids within SKBR3 cells as well as a reduction in the intensity of SERS signal.

Techniques: Confocal Microscopy, Labeling, Liposomes, Fluorescence, Staining, Imaging, Incubation

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: Athymic nu/nu female mice were inoculated subcutaneously on the right posterior leg with SKBr3 (HER2+/MUC4-) cells and on the left with JIMT1 (HER2+/MUC4+) cells. Imaging and treatments were initiated two weeks after inoculation when tumors reached approximately 0.5 cm 3 . Mice were randomized to four different groups: (1) the CS group receiving sweetened drinking water and i.p. saline injections ( n = 10), (2) the CT group receiving sweetened drinking water and trastuzumab injections (i.p., 5mg/kg ( n = 10), (3) the NS group receiving sweetened drinking water supplemented with NAC and saline i.p. injections ( n = 9), and (4) the NT group receiving sweetened drinking water supplemented with NAC and trastuzumab injections (i.p., 5mg/kg) ( n = 10). Imaging studies were conducted using a μPET-CT and each mouse was scanned three times, with an 18 F-FDG and 89 Zr-Trastuzumab PET-CT before treatment and an 18 F-FDG PET-CT post treatment. Images were recorded for 18 F-FDG at 1h and 89 Zr-Trastuzumab 6 days after injection respectively. After the last scan, animals were euthanized and an ex-vivo body distribution study was performed. A pathological examination was also conducted on a subset of animals from each cohort with immunostaining of HER2, MUC4, pAkt and Ki67.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques: Imaging, Positron Emission Tomography-Computed Tomography, Injection, Ex Vivo, Immunostaining

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: Standardized maximum uptake of 89 Zr-Trastuzumab in JIMT1 (HER2+/MUC4+; dot) and SKBr3 (HER2+/MUC4-; squares) tumors under NAC supplementation ( n = 19) and control ( n = 20) are shown in the graph with a 89 Zr-Trastuzumab PET axial image representative of the tumor (arrow) uptake under NAC exposure (NAC) and control (CTRL). All data points and mean ± SEM are shown, both expressed in SUV max with *** p < 0.001.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques:

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: The effect of the different treatment on JIMT1 (HER2+/MUC4+) and SKBr3 (HER2+/MUC4) tumors in dual-tumor-bearing mice randomized to the four treatment arms CS (Control+Saline; blue, n = 10), CT (Control+Trastuzumab; purple, n = 10), NS (NAC+Saline; green, n = 9) and NT (NAC+Trastuzumab; red n = 10) is represented per methodologies as follows: Tumor growth of JIMT1 ( A ) and SKBr3 ( B ) tumors monitored through caliper measurements. Data are represented as mean ± SEM, expressed in cm 3 for tumor volume, with *** p < 0.001.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques:

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: 18 F-FDG uptake of SKBr3 (HER2+/MUC4-) and JIMT1 (HER2+/MUC4+) tumors in dual-tumor-bearing mice randomized to the four treatment arms CS (Control+Saline; blue, n = 10), CT (Control+Trastuzumab; purple, n = 10), NS (NAC+Saline; green, n = 9) and NT (NAC+Trastuzumab; red n = 10) is represented. ( A ) The baseline 18 F-FDG uptake of JIMT1 and SKBr3 tumors preceding randomization is shown with future treatment group allocation. Representative 18 F-FDG PET/CT axial images(left) of the tumor (arrow) before and after treatment are shown together with the changes in 18 F-FDG uptake represented as percentage difference in SUV max (% ΔSUV max , right) for ( B ) JIMT1 and SKBr3 tumors in the different treatment arms. Data points as well as mean ± SEM are shown. Data are expressed in SUV max for the baseline 18 F-FDG uptake or as the percentage difference in SUV max (% ΔSUV max ) when comparing the effect of the different treatment arms; with ** p < 0.01 and *** p < 0.001.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques: Positron Emission Tomography-Computed Tomography

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: proliferation index Ki67 (left) and pAkt levels (right) for ( A ) JIMT1 (HER2+/MUC4+) and ( B ) SKBr3 (HER2+/MUC4-) tumors in dual-tumor-bearing mice randomized to the four treatment arms CS (Control+Saline; blue, n = 5), CT (Control+Trastuzumab; purple, n = 5), NS (NAC+Saline; green, n = 5) and NT (NAC+Trastuzumab; red n = 5). Data are shown as mean ± SEM expressed in % positive cells for Ki67 index values and IM scores for pAkt levels with *** p < 0.001.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques:

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: Ex vivo body distribution of 89 Zr-Trastuzumab uptake in JIMT1 (HER2+/MUC4+) and SKBr3 (HER2+/MUC4-) tumors in dual-tumor-bearing mice randomized to the four treatment arms CS (Control+Saline; blue, n = 10), CT (Control+Trastuzumab; purple, n = 10), NS (NAC+Saline; green, n = 9) and NT (NAC+Trastuzumab; red n = 10). Data are expressed in organ-to-blood ratio and represented as mean ± SEM with *** p < 0.001.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques: Ex Vivo

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: MUC4 (left) and HER2 (right) expression levels in ( A ) JIMT1 (HER2+/MUC4+) and ( B ) SKBr3 (HER2+/MUC4-) tumors in dual-tumor-bearing mice randomized to the four treatment arms CS (Control+Saline; blue, n = 5), CT (Control+Trastuzumab; purple, n = 5), NS (NAC+Saline; green, n = 5) and NT (NAC+Trastuzumab; red n = 5). Data are shown as mean ± SEM expressed in IM scores with *** p < 0.001.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques: Expressing

Journal: Oncotarget

Article Title: N-Acetylcysteine breaks resistance to trastuzumab caused by MUC4 overexpression in human HER2 positive BC-bearing nude mice monitored by 89 Zr-Trastuzumab and 18 F-FDG PET imaging

doi: 10.18632/oncotarget.17015

Figure Lengend Snippet: The side by side comparison of the association of HER2 expression levels ( left) and 89 Zr-Trastuzumab uptake (right) with ( A ) MUC4 is shown including both JIMT1 (HER2+/MUC4+) and SKBr3 (HER2+/MUC4-) tumors in dual-tumor-bearing mice randomized to the four treatment arms CS (Control+Saline), CT (Control+Trastuzumab), NS (NAC+Saline) and NT (NAC+Trastuzumab). ( B ) The side by side comparison of the association to 18 F-FDG PET metabolic response is limited to mice randomized to the trastuzumab treatment arms CT and NT are also represented. Data shown include both tumor types and are expressed in IM scores for HER2 and MUC4 expression, in SUV max for 89 Zr-Trastuzumab uptake and expressed as the percentage difference in SUV max (% ΔSUV max ) for 18 F-FDG metabolic response.

Article Snippet: Six-week-old athymic nu/nu female mice (Charles River) were inoculated subcutaneously on the right posterior leg with 3 × 10 6 SKBr3 cells and on the left with 1.5 × 10 6 JIMT1 cells suspended in 100μL of DMEM and Basement Membrane Extract (1:1; Cultrex, Trevigen).

Techniques: Expressing