The Efficacy and Safety of the Shouzu Ning Decoction Treatment Versus Halometasone Plus Celecoxib Treatment in Patients With Grade 2 HFSR: A Randomized Clinical Trial.

OBJECTIVES: To compare the effects of the Shouzu Ning Decoction (SND) and Halometasone plus Celecoxib (Hal/Cxb) as therapy in patients with grade 2 hand-foot skin reaction (HFSR). MATERIALS AND METHODS: Fifty patients with grade 2 HFSR participated in a randomized, single-center, open-label study. Patients were randomly assigned in a 1:1 ratio to receive the SND or Hal/Cxb treatment, twice daily for 4 weeks, followed by 4 weeks of post-treatment follow-up. The primary endpoint was clinical remission of HFSR at the end of the fourth week (W4). The secondary endpoints were recurrence rate, quality of life (QoL), pain intensity, and safety. RESULTS: In this study, 46 patients successfully completed the study, and 4 patients were excluded. There was no statistically significant difference between the 2 groups on demographic and baseline clinical characteristics. In the SND group, 56.52% of patients showed clinical remission at W4, which was significantly superior to that achieved in the Hal/Cxb group (26.09%, P = .036). In addition, the HF-QoL score was statistically lower in the SND group compared to the Hal/Cxb group at W2 (P = .007), W3 (P = .005), and W4 (P = .005), respectively. In line with this, the inter-group difference in NRS score was statistically significant (P = .004). CONCLUSION: In the present study, SND treatment has been observed to be effective and well tolerated for patients with grade 2 HFSR. Thus, SND treatment could be considered a suitable option for HFSR patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027518. Registered on 17 Nov 2019.

Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients' health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient's skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.

Aqueous extract of Taxus chinensis var. mairei regulates the Hippo-YAP pathway and promotes apoptosis of non-small cell lung cancer via ATF3 in vivo and in vitro.

Taxus chinensis var. mairei (TC) is a traditional Chinese ornamental and medicinal plant, the leaves and twigs of which are used in anti-tumor therapy in southern China. However, the mechanism and role of aqueous extract of TC (AETC) in promoting apoptosis in non-small cell lung cancer (NSCLC) cell lines has remained unclear. In this research, we observed that AETC inhibited the suppression of the proliferation of NSCLC cells and highly inhibited the proliferation of NCI-1975 cells. Furthermore, AETC exerted minimal inhibitory effects on normal human lung epithelial cells and induced apoptosis in NCI-1975 and A549 cells. The findings of RNA sequencing, qRT-PCR, western blotting, and immunofluorescence showed that upregulated ATF3 expression and ATF3 gene knockdown, respectively, increased and decreased the anti-tumor effects of AETC associated with Hippo pathway inhibition and decreased YAP degradation. Furthermore, AETC reduced the tumor volume and weight in nude mice; upregulated ATF3, p-MOB1, and p-YAP (Ser397); and actively regulated cleaved PARP and cleaved caspase-9/8/3. These findings suggest that AETC induced NSCLC cell apoptosis via the ATF3-Hippo-YAP pathway in vivo and in vitro. We also found that AETC is non-toxic to normal cells and nude mice. Thus, AETC might represent a promising adjuvant for anti-tumor therapy against NSCLC.

Values of applying white blood cell counts in the prognostic evaluation of resectable colorectal cancer.

The count and classification of white blood cells (WBCs) may be used as prognostic markers in certain types of cancer. The present study investigated the prognostic potential of the counts of WBCs, including lymphocytes (LYs), monocytes (MOs), neutrophils (NEs), eosinophils (EOs) and basophils (BAs), in the prognosis of resectable colorectal cancer. The present study recruited 153 resectable colorectal cancer cases retrospectively, which were pathologically confirmed. All patients were divided into two groups, according to the median value of LY (low LY, ≤1.632x109/l or high LY, >1.632x109/l), MO (low MO, ≤0.330x109/l or high MO, >0.330x109/l), NE (low NE, ≤3.600x109/l or high NE, >3.600x109/l), EO (low EO, ≤0.085x109/l or high EO, >0.085x109/l), BA (low BA, ≤0.010x109/l or high BA, >0.010x109/l), or WBC (low WBC, ≤5.780x109/l or high WBC, >5.780x109/l). To evaluate the alterations in WBC counts following surgery and adjuvant chemotherapy; all samples received oxiplatin and capecitabine (XELOX) for 6­8 cycles or 5­fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) for 10­12 cycles. XELOX included oxaliplatin administered intravenously at a dose of 130 mg/m2 on day 1 and 850­1,250 mg/m2 capecitabine twice daily for days 1­14, repeated every 3 weeks. mFOLFOX6 included oxaliplatin administered intravenously at a dose of 85 mg/m2, 400 mg/m2 leucovorin and 400 mg/m2 5­FU on day 1 followed by 1,200 mg/m2/days continuous infusion for 2 days (in total, 2,400 mg/m2 over 46­48 h), repeated every 2 weeks. The present study investigated the post/pre­treatment of LY, MO, NE, EO, BA and WBC ratios (≤1 indicated that LY, MO, NE, EO, BA and WBC counts were not increased following therapy; whereas, >1 suggested increased counts). Kaplan­Meier curves were constructed to demonstrate overall survival (OS). A multivariate and univariate logistic regression analyses model was employed to identify the independent risk factors. Low pre­treatment BA counts were associated with larger tumor size (>5 cm); pre­treatment BA levels were positively associated with OS. Surgery significantly decreased the count of BAs and increased the count of EOs; whereas, no effect was observed on LYs, MOs, NEs or WBCs. Adjuvant chemotherapy markedly decreased the counts of LY, NE and WBC; whereas, no notable effects on MOs, EOs or BAs were observed. Whole course treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of LY, NE and WBC; however, increased the value of EO; no effects on the MO or BA counts were observed. An increased post­/pre­treatment NE ratio suggested poorer prognosis. Multivariate Cox regression analysis revealed that sex, tumor size, pre­treatment BA count and the post­/pre­treatment NE ratio were independent prognostic factors affecting OS. The results of the present study suggested that the pre­treatment BA count and post­/pre­treatment NE ratio may be potential prognostic factors for resectable colorectal cancer.

PP2A inhibitors suppress migration and growth of PANC-1 pancreatic cancer cells through inhibition on the Wnt/ß-catenin pathway by phosphorylation and degradation of ß-catenin.

Cantharidin is an active constituent of mylabris, a traditional Chinese medicine, and presents strong anticancer activity in various cell lines. Cantharidin is a potent and selective inhibitor of serine/threonine protein phosphatase 2A (PP2A). Our previous studies revealed the prospect of application of cantharidin, as well as other PP2A inhibitors, in the treatment of pancreatic cancer. However, the mechanisms involved in the anticancer effect of PP2A inhibitors have not been fully explored. The Wnt/ß­catenin pathway is involved in cell migration and proliferation and participates in the progression of pancreatic cancer. If ß­catenin is phosphorylated and degraded, the Wnt/ß­catenin pathway is blocked. PP2A dephosphorylates ß­catenin and keeps the Wnt/ß­catenin pathway active. In the present study, we found that PP2A inhibitor treatment induced phosphorylation and degradation of ß­catenin. The suppression on the migration and growth of PANC­1 pancreatic cancer cells could be attenuated by pretreatment with FH535, a ß­catenin pathway inhibitor. Microarray showed that PP2A inhibitor treatment induced expression changes in 13 of 138 genes downstream of the ß­catenin pathway. Real­time PCR further confirmed that FH535 attenuated the expression changes induced by PP2A inhibitors in 6 of these 13 candidate genes. These 6 genes, VEGFB, Dkk3, KRT8, NRP1, Cacnalg and WISP2, have been confirmed to participate in the migration and/or growth regulation in previous studies. Thus, the phosphorylation- and degradation-mediated suppression on ß­catenin participates in the cytotoxicity of PP2A inhibitors. Our findings may provide insight into the treatment of pancreatic cancer using a targeting PP2A strategy.

Cantharidin and norcantharidin inhibit the ability of MCF-7 cells to adhere to platelets via protein kinase C pathway-dependent downregulation of α2 integrin.

Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of circulating tumor cells with host platelets, where a surface coating of platelets protects tumor cells from mechanical trauma and the immune system. Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. Cantharidin and norcantharidin are potent protein phosphatase 2A (PP2A) inhibitors that exhibit in vitro and in vivo antitumor activity against several types of cancer, including breast cancer. We investigated whether cantharidin and norcantharidin could repress the ability of MCF-7 breast cancer cells to adhere to platelets. Using MTT, clone formation, apoptosis, adhesion and wound-healing assays, we found that cantharidin and norcantharidin induced apoptosis and repressed MCF-7 cell growth, adhesion and migration. Moreover, we developed a flow cytometry-based analysis of tumor cell adhesion to platelets. We proved that cantharidin and norcantharidin repressed MCF-7 cell adhesion to platelets through downregulation of α2 integrin, an adhesion molecule present on the surface of cancer cells. The repression of α2 integrin expression was found to be executed through the protein kinase C pathway, the activation of which could have been due to PP2A inhibition.