Journal: American Journal of Cancer Research

Article Title: Two engineered site-specific antibody-drug conjugates, HLmD4 and HLvM4, have potent therapeutic activity in two DLL4-positive tumour xenograft models

doi:

Figure Lengend Snippet: ADCs inhibits cell proliferation and induces apoptosis in MDA-MB-231 and A549 xenograft models. A, B. Tumour inhibition rates of different dosage groups (n = 6). 5 mg/kg HLmD4 resulted in significant tumour growth inhibition in both models. The arrows indicate dosing days except H3L2 group. C, D. IHC staining of Ki-67 (anti-Ki67 antibody) for proliferation in paraffin sections of xenografted tumours. Scale bar = 50 mm. E, F. IHC staining of cleaved-caspase 3 (anti-cleaved caspase 3) for apoptosis in paraffin sections of xenografted tumour. Scale bar = 50 mm. G, H. Quantifcations of Ki67 or cleaved caspase 3 positive cells per field. Data are given as the mean ± SD (n = 3). *P < 0.05, **P < 0.001, ***P < 0.0001. NS: no significance.

Article Snippet: Human breast adenocarcinoma (MDA-MB-231) and human non-small cell lung cancer (A549) xenograft BALB/c nude mouse models were established by Keygene Biotech, China.

Techniques: Inhibition, Immunohistochemistry

Journal: American Journal of Cancer Research

Article Title: Two engineered site-specific antibody-drug conjugates, HLmD4 and HLvM4, have potent therapeutic activity in two DLL4-positive tumour xenograft models

doi:

Figure Lengend Snippet: ADCs block angiogenesis and indirectly inhibit tumour growth in MDA-MB-231 and A549 tumours. A, B. Tumour vessel number and perfusion were determined by an antibody to SMA (green) for mural cells and a CD31 antibody (red) for vessel staining. Scale bar = 50 mm. C, D. Quantifcations of mature (CD31+/α-SMA+) or immature (CD31+/α-SMA-) vessels per field. Data are given as the mean ± SD (n = 3). *P < 0.05, **P < 0.001, ***P < 0.0001. NS: no significance.

Article Snippet: Human breast adenocarcinoma (MDA-MB-231) and human non-small cell lung cancer (A549) xenograft BALB/c nude mouse models were established by Keygene Biotech, China.

Techniques: Blocking Assay, Staining

Journal: American Journal of Cancer Research

Article Title: Two engineered site-specific antibody-drug conjugates, HLmD4 and HLvM4, have potent therapeutic activity in two DLL4-positive tumour xenograft models

doi:

Figure Lengend Snippet: Engineered anti-DLL4 ADCs show lower toxicity than conventional ADC and small molecule drug in mouse safety studies. A. The plasma stability of ADCs was tested in BALB/c nude mouse (n = 6 animals/group, single i.v. dose on day 1). Changing values in blood over time relative to study day 1 were plotted. B, C. ICR mice (n = 5 animals/group, single i.v. dose on day 1) were given HLmD4, JmD4, HLvM4, H3L2, DM1 or Docetaxel at the indicated dose levels. Blood was drawn from mice on study days 6 and 12 for clinical chemistry (serum AST levels) and hematology (platelet counts). D, E. MDA-MB-231 or A549 xenograft BALB/c nude mouse models in different groups (n = 6) were weighed daily after dosing, and changes in body weight over time relative to study are plotted from day 1 to day 24. F. Survival rates of tumour-bearing mice in different groups (n = 6). In the MDA-MB-231 model and the A549 model, 5 mg/kg HLmD4 caused an effect to prolong evidently the length of survival. The arrows indicate dosing days except H3L2 group. Data are presented as the mean ± SD, **P < 0.01, ***P < 0.0001. NS: no significance.

Article Snippet: Human breast adenocarcinoma (MDA-MB-231) and human non-small cell lung cancer (A549) xenograft BALB/c nude mouse models were established by Keygene Biotech, China.

Techniques: Clinical Proteomics

Journal: Molecular Cancer Therapeutics

Article Title: Selective Inhibition of SIN3 Corepressor with Avermectins as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer

doi: 10.1158/1535-7163.mct-14-0980-t

Figure Lengend Snippet: Figure 6. Treatment with selamectin inhibits TNBC growth and metastasis in vivo. A, MMTV-Myc mouse mammary tumor cells were pretreated in vitro with vehicle or selamectin for 7 days. A total of 200,000 cells were inoculated into the inguinal mammary fat pads of FVB/N mice (n ¼ 10 per arm). Tumor volume (mm3) was calculated on the days indicated (, P ¼ 0.0017). B–D, 50,000 MMTV-Myc cells were inoculated into the flanks of FVB/N mice on day 0 and treated with selamectin (1.6 mg/kg/d) for 15 days (n ¼ 10 mice per arm). Tumor volume (B; , P < 0.0001), tumor mass (C; , P ¼ 0.0161), and number of lung metastases (D; , P ¼ 0.0224) in each group were measured. E–G, 4T1 cells (10,000 per mouse) were inoculated into the flanks of BALB/c mice. Tumors were allowed to grow for 10 days before surgical removal. Treatment was then initiated with selamectin (3.2 mg/kg/d for 30 days, n ¼ 4) or vehicle (n ¼ 5). Animals were sacrificed after 30 days and the total number of lung metastases were measured (E and F; , P ¼ 0.0017). Also measured were number of metastases according to size in each group (G; <1 mm: , P ¼ 0.0198; 1–2 mm: , P ¼ 0.0235; >2 mm: , P ¼ 0.0447). Error bars, mean SD. P, unpaired t test.

Article Snippet: Lung metastasis dissemination studies BALB/cmice were inoculated subcutaneously with 1 104 4T1 cells (triple-negative breast cancer mouse model; ATCC) into the interscapular space.When the tumors reached approximately 300 mm3 in volume, established primary tumors were surgically resected under anesthesia/analgesia (ketamine/xylazine) following IACUC guidelines.

Techniques: In Vivo, In Vitro