Journal: NAR Cancer

Article Title: EXO1 inhibition selectively kills replication repair-deficient cancer cells

doi: 10.1093/narcan/zcag029

Figure Lengend Snippet: (A ) Representative images for micronuclei induced by 24-h ART5537 treatment in eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells. Yellow arrows point to each micronucleus. Scale bar: 20 μm. ( B ) Quantification of cells with micronuclei for eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells in untreated condition or after 24-h treatment with either 2.5 or 5 μM ART5537 ( n = 3, quantification based on ≥399 nuclei per condition). Ordinary two-way ANOVA was performed on means from each biological replicate, with P -values denoted above columns. Mean with standard deviation is shown for each sample based on mean of the biological replicates. ( C ) Representative images for γH2AX signal induced by 24-h ART5537 treatment in eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells. Nuclei borders are denoted with dotted lines. Scale bar: 20 μm. ( D ) Quantification of mean intensity of γH2AX in eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells in untreated condition or after 24-h treatment with either 2.5 or 5 μM ART5537 ( n = 3, quantification based on ≥397 nuclei per condition). Ordinary two-way ANOVA was performed on means from each biological replicate (red line denotes overall mean), with P -values denoted above columns. ( E ) Representative images for RPA32-pS33 foci induced by 24-h ART5537 treatment in eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells. Nuclei borders are denoted with dotted lines. Scale bar: 20 μm. ( F ) Quantification of RPA-pS33 foci in eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells in untreated condition or after 24-h treatment with either 2.5 or 5 μM ART5537 ( n = 3, quantification based on ≥397 nuclei per condition). Ordinary two-way ANOVA was performed on means from each biological replicate (red line denotes overall mean), with P -values denoted above columns. ( G ) Immunoblotting of cell extracts from eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells following 24-h treatment with 5 μM ART5537. Samples were probed for phosphorylated levels of KAP1 and CHK2 with controls, and for beta-actin as loading control. ( H ) Quantification of clonogenic assay of eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cell lines with 1 μM TYMS inhibitor Pemetrexed ( n = 3). ( I ) Survival of eHAP iCas9 wild type, FANCG KO, and ZRSR2 KO cells treated with ART5537 without or with TYMS inhibitor Pemetrexed ( n = 3); ordinary two-way ANOVA with Tukey’s test.

Article Snippet: Compounds developed for EXO1 inhibition [compound 20, compound 29 (ART5537), and compound 30] [ ] were a generous gift from Artios Ltd, while ATM inhibitor (KU-55933), PARP inhibitor olaparib (AZD2281), PARP inhibitor veliparib (ABT-888), and TYMS inhibitor Pemetrexed ( LY231514 ) were purchased from Selleckchem.

Techniques: Standard Deviation, Western Blot, Control, Clonogenic Assay

Journal: BMC Cancer

Article Title: Real-world evidence for first-line intrathecal pemetrexed in leptomeningeal metastases from solid tumors: a retrospective cohort study

doi: 10.1186/s12885-026-15915-5

Figure Lengend Snippet: Overall Survival (OS) of patients with Leptomeningeal Metastasis (LM) from the whole cohort and Kaplan–Meier estimates based on clinical characteristics. A The median OS (mOS) of all the patients after diagnosis of LM was 8.0 months. B Patients with high Karnofsky Performance Status scores had better mOS (> 60 versus ≤ 60: 9.0 versus 5.0 months, hazard ratio [HR]: 0.60, P = 0.005). C Patients who had extensive systemic disease with few treatment options had slightly higher mOS (8.0 versus 6.0 months, HR: 0.65, P = 0.014). D Patients who received more than six times of intrathecal pemetrexed (IP) had better mOS (> 6 versus ≤ 6: 14.0 versus 5.0 months, HR: 0.41, P < 0.001). E Patients with response for IP treatment had better mOS (effective versus non-effective: 8.0 versus 4.0 months, HR: 0.50, P < 0.001). F Continued negative cerebrospinal fluid cytology after treatment was associated with longer survival (mOS 11.0 versus 5.0 months, HR: 0.42, P < 0.001)

Article Snippet: Pemetrexed (Alimta, Eli Lilly and Company, 100 mg) was dissolved in a 0.9% sodium chloride solution (3–5 mL) and prepared into a 50-mL mixture.

Techniques: Biomarker Discovery

Journal: BMC Cancer

Article Title: Real-world evidence for first-line intrathecal pemetrexed in leptomeningeal metastases from solid tumors: a retrospective cohort study

doi: 10.1186/s12885-026-15915-5

Figure Lengend Snippet: The Overall Survival (OS) of patients with Leptomeningeal Metastasis (LM) from the Non-Small-Cell Lung Cancer (NSCLC) cohort and Kaplan–Meier estimates based on clinical characteristics. A The median OS (mOS) of all the patients after diagnosis of leptomeningeal metastasis (LM) was 6.0 months. B Patients with local treatment had better mOS (8.0 versus 3.0 months, hazard ratio [HR]: 0.58, P = 0.023). C Patients who received more than six times of intrathecal pemetrexed (IP) had better mOS (> 6 versus ≤ 6: 16.0 versus 4.0 months, HR: 0.33, P < 0.001). D Patients with response for IP treatment had better mOS (effective versus non-effective: 11.0 versus 3.5 months, HR: 0.46, P < 0.001). E Continued negative cerebrospinal fluid cytology after treatment was associated with longer survival (mOS 12.0 versus 4.0 months, HR: 0.41, P < 0.001)

Article Snippet: Pemetrexed (Alimta, Eli Lilly and Company, 100 mg) was dissolved in a 0.9% sodium chloride solution (3–5 mL) and prepared into a 50-mL mixture.

Techniques: Biomarker Discovery