Fig. 1: Clinical activity of L-NMMA combined with docetaxel in chemorefractory MpBC patients. | Nature Communications

Fig. 1: Clinical activity of L-NMMA combined with docetaxel in chemorefractory MpBC patients.

From: NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression

Fig. 1

A Waterfall Plot showing change in target lesion/tumor volume, best response (RECIST), and baseline iNOS H-score expression status in the 13 patients with available data from post-baseline assessments. PD progressive disease, SD stable disease, PR partial response, and CR complete response. iNOS H-Score Metric (0–50: None, 51–100: low, 101–150: Moderate, >150: High) B Representative mammogram images at baseline (BL) and end of cycle 6 for Patient 100-048 (CR), showing shrinkage in target lesion size. C Hematoxylin and Eosin staining of BL tumor from 100-048 showing metaplastic squamous differentiation and end-of-treatment (EOT) tissue showing residual keratinized and fibrotic tissue. Scale bars represent 100 µM. Representative images of n = 3 tissue samples. D BL IHC staining of iNOS, PTEN, and phospho-Akt of tumor tissue from 100-048 and associated EOT iNOS, pAkt, and PTEN staining in residual tissue. Scale bars represent 100 µM. E iNOS H-score for BL and EOT tumors in indicated responders and non-responders. BL and EOT H-scores are indicated by red and blue box and whisker plots, respectively. R2-R4 indicates responder patients, and NR1-NR6 indicate non-responder patients. H-score analysis of 4–6 images per slide captured from tissues to cover entire tissue bed. The center bar indicates median, bounds of box represent lower and upper quartiles, and the whiskers indicate minimum and maximum of the dataset for each group. Statistical analysis by two-sided Student’s t test. F NOS2 alteration frequencies in various cancers from cBioPortal Combined Study Dataset (n = 179290). G NOS2 normalized gene expression in MpBC/metaplastic-like TNBC (n = 41, red dots) and non-MpTNBC (n = 137, blue dots) from the ARTEMIS dataset. The dot and error bars represent mean ± SD. Statistical analysis by two-sided Student’s t test. H Kaplan-Meier metastasis-free survival analysis of MpBC and non-MpTNBC tumors based on expression status [high (red line)/low (blue line)] of NOS2 from ARTEMIS dataset. I Gene set enrichment analysis of the top represented upregulated hallmark gene sets based on normalized enrichment score (NES) from RNA-sequencing data from TCGA in human MpBC tumors (n = 14) compared to invasive ductal carcinoma tumors (n = 814).

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