... had SD or PR up to 51+ weeks. ctDNA declined on treatment in 7/13 (54%) evaluable pts (3 complete, 4 >50% reductions) across doses. Conclusions: AZD5305 is a highly selective PARP1 inhibitor and trapper with excellent physiochemical properties and a wide therapeutic index. It led to maximal target...

... infiltration in tumor. We sought to determine the safety, recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage in patients with GN-refractory MPC. Methods: This phase 1, dose finding trial was conducted following preclinical study of IL-6...

... scale-up for commercial manufacturing. The “cold” immunosuppressive B16-F10 melanoma tumor model was used for comparing the efficacy of the bispecific candidates administered in a single i.v. dose. All three constructs showed statistically significant tumor size reduction compared to placebo or native...

... of cells selected for resistance with 25 µM cisplatin (Cis-R) compared with untreated parent A549. This dose was selected because we were unable to recover proliferating cultures with lower percentages of surviving. Cis-R spheroids exhibited a significant reduction in circularity that is indicative...

... of KRAS^G12C mutant MiaPaCa-2 tumor burden (p<0.001 single agents vs combination treatment). Residual tumor analysis showed a reduction in proliferation index (ki67), activation of pro-apoptotic caspases, and inhibition of mutant RAS effector signaling. Studies in additional KRAS^G12C xenograft...

.... Trotman LC , Niki M , Dotan ZA , Koutcher JA , Di Cristofano A , Xiao A , . Pten dose dictates cancer progression in the prostate . PLoS Biol 2003 ; 1 : E59 . 54. Bankhead P , Loughrey MB , Fernandez JA , Dombrowski Y...

...-resistant PDTX PY003 was established by administering lenvatinib orally at 30 mg/kg for four rounds. (B) The dose response curves showed that there was no tumor reduction upon sorafenib/lenvatinib administration, when compared with their corresponding mock controls. (C) Upon IPA analysis, top ten most de...

...-43 pharmacokinetic analysis JHU-LX44 tumor bearing mice were dosed with vehicle or 25 mg/kg INI-43 and animals were euthanized by inhalation overdose of CO2 in groups of 2 at 24 hours post-dose. Blood was collected by cardiac puncture using an acidified citrate dextrose (ACD)-coated syringe...

... lung and thyroid malignancies (70). Though generally well719 tolerated due to its high selectivity for RET over other kinases, a subset of patients may 720 require dose reductions or discontinue treatment due to adverse effects (70). Topical 721 administration would reduce the risks of systemic...

... evaluation. Data related to demographics, diagnosis, and cancer treatment (chemotherapeutic agents and cumulative doses; radiation therapy fields/doses, including scatter doses; surgical interventions) were abstracted from the medical record. All participants included in this investigation 5 completed...

... inhibitor PXB. E–G, Combining low-dose CTX with a Csf1r inhibitor (PXB) leads to a reduction in tumor burden in T12 and 2151R p53^−/− mouse tumors and stasis in T11. Number in parentheses shows the specific n values of biologically independent mice per treatment group. P value...

...)-resistant KYSE450 and YES2 cell lines were established by high-dose DDP induction. Specifically, parental cells were exposed to high-dose of DDP for 2 h and then cultured in complete medium. When cell growth was in the logarithmic phase, the cells were re-exposed to high-dose of the drugs. After 6-10 cycles...

... in the FTO gene to be significantly associated with T2DM in nearly 40,000 European adults ( 15 ). Obesity is a known risk factor for T2DM and the association between the SNPs and T2DM disappeared when correcting for body mass index (BMI), indicating the association of the SNPs with T2DM is mediated through...

...Erwin R. Boghaert; Megan C. Cox; Kedar S. Vaidya Antibody–drug conjugates (ADC) have emerged as one of the pillars of clinical disease management in oncology. The biggest hurdle to widespread development and application of ADCs has been a narrow therapeutic index. Advances in antibody technologies...

...-specific inhibitor due to the higher expression of the complementary enzymes that would not be inhibited. M5 measures the difference between target isozyme dominance in cancer versus its dominance in normal tissues (M5 = M3–M4), and we assume that the larger the difference the greater the therapeutic index...

... with the indicated doses of gemcitabine (5 days). Viability was determined by comparing nuclear counts at treatment endpoint compared to onset (data pooled from n = 2 experiments, two replicates per experiment). In B and G–I, statistical differences were calculated using unpaired t test...

... as described previously in “In vivo treatment strategy.” At day 28 after injection, mice were injected intraperitoneally with a high dose of gemcitabine (125 mg kg^–1) and culled after 15 minutes. Tumors and livers were collected and three pieces of at least 10 mg of each organ per mouse...

... of incubation, unengulfed apoptotic cells were washed away. The efferocytosis index was evaluated using FCM. Briefly, 5 × 10⁴ RAW264.7 cells were plated in a 35-mm petri dish with DMEM medium containing 10% FBS and cultured overnight. Annexin V-labeled apoptotic 4T1 cells were added at a ratio of 10...

... in triplicates) using Ba/F3 cells harboring different mutations with a nine-point dose. For wild-type EGFR, all culture and assays were performed in the presence of human recombinant epidermal growth factor (rhEGF at 10 ng/mL). C, The scatter plot of selectivity index, which was calculated from IC50 value ratios...

... carcinoma (MCC) cell lines MKL-1 and WaGa (68). MCC cell lines were subjected to increasing doses of etoposide or carboplatin in the presence and absence of anti-ABCB5 blocking antibodies, showing that blocking ABCB5 antibody led to increased sensitivity to these agents (68). Thus, targeting ABCB5...