RESUMEN
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.
Asunto(s)
Calidad de Vida , Piel , Humanos , Celecoxib/efectos adversos , Resultado del TratamientoRESUMEN
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.
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Medicamentos Herbarios Chinos , Síndrome de Stevens-Johnson , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Factores Inmunológicos , Incidencia , Masculino , Persona de Mediana Edad , Piel , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/etiologíaRESUMEN
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.
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Factor de Transcripción Activador 3/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Células A549 , Factor de Transcripción Activador 3/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Femenino , Vía de Señalización Hippo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Taxus , Agua/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Proteínas Señalizadoras YAPRESUMEN
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.
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Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Recuento de Leucocitos , Pronóstico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Basófilos/efectos de los fármacos , Capecitabina , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Eosinófilos/efectos de los fármacos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Leucovorina/administración & dosificación , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Compuestos Organoplatinos/administración & dosificación , OxaloacetatosRESUMEN
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.
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Inhibidores Enzimáticos/farmacología , Neoplasias Pancreáticas/patología , Proteína Fosfatasa 2/antagonistas & inhibidores , beta Catenina/metabolismo , Antracenos/farmacología , Cantaridina/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Fosforilación , Sulfonamidas/farmacología , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/genéticaRESUMEN
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.