pirarubicin and Inflammation

Pirarubicin (THP) is widely used in clinical antitumor therapy, but its cardiotoxicity seriously affects the therapeutic effect in patients. In the study, we investigated the role of ring finger protein 10 (RNF10) in cardiotoxicity induced by THP.. A cardiac toxicity model in Sprague-Dawley (SD) rats induced by THP was established. Changes in diet, weight, electrocardiogram (ECG), and echocardiography were observed. Serum levels of brain natriuretic peptide (BNP), creatine kinase MB (CK-MB), cardiac troponin T (cTnT), and lactate dehydrogenase (LDH) were measured. The expression of RNF10 in myocardium was observed by immunohistochemistry. The expressions of RNF10, activator protein-1 (AP-1), mesenchyme homeobox 2 (Meox2), total nuclear factor (NF)-κB p65 (T-P65), phosphorylated NF-κB p65 (PP65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and mature IL-1β were detected by Western blot. A THP-induced H9c2 myocardial cell injury model was established. RNF10 was downregulated or overexpressed by RNF10 siRNA and a RNF10 lentiviral vector, respectively. Then, cell viability was measured. The expression of RNF10 in H9c2 cells was observed by immunofluorescence. All of the above signaling pathways were verified by Western blots.. THP caused a series of cardiotoxic manifestations in SD rats. Our studies suggested that THP caused cardiac inflammation by inhibiting the expression of RNF10, while overexpression of RNF10 antagonized the cardiotoxicity induced by THP.. Our study showed RNF10 improved THP-induced cardiac inflammation by regulating the AP-1/Meox2 signaling pathway. RNF10 may be a new target to treat THP-induced cardiotoxicity.

Topics: Animals; Arrhythmias, Cardiac; Cardiotoxicity; Carrier Proteins; Inflammation; Interleukin-6; Nerve Tissue Proteins; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

The side effects of chemotherapy drugs have been hindering the progress of tumor treatment. The liver is the metabolic site of most drugs, which leads to the frequent occurrence of liver injury. Classical chemotherapy drugs such as pirarubicin (THP) can also cause dose‑dependent hepatotoxicity, and the related mechanism is closely related to liver inflammation. Scutellarein (Sc) is a potential Chinese herbal monomer exhibiting liver protection activity, which can effectively alleviate the liver inflammation caused by obesity. In the present study, THP was used to establish a rat model of hepatotoxicity, and Sc was used for treatment. The experimental methods used included measuring body weight, detecting serum biomarkers, observing liver morphology with H&E staining, observing cell apoptosis with TUNEL staining, and detecting the expression of PTEN/AKT/NFκB signaling pathways and inflammatory genes with PCR and western blotting. However, whether Sc can inhibit the liver inflammation induced by THP has not been reported. The experimental results showed that THP led to the upregulation of PTEN and the increase of inflammatory factors in rat liver, while Sc effectively alleviated the aforementioned changes. It was further identified in primary hepatocytes that Sc can effectively inhabited PTEN, regulate AKT/NFκB signaling pathway, inhibit liver inflammation and ultimately protect the liver.

Topics: Animals; Apoptosis; Chemical and Drug Induced Liver Injury; Inflammation; NF-kappa B; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Rats; Signal Transduction

We present the response rate and adverse effects of our regimen of concurrent chemoradiotherapy with pirarubicin (THP) and 5-fluorouracil (5-FU) for oral and maxillary carcinoma.. Fifteen patients with oral (10 cases) or maxillary (5 cases) squamous cell carcinoma who underwent our concurrent chemoradiotherapy with the combination of intraarterial pirarubicin, intravenous continuous 5-fluorouracil, and radiation between March 2001 and February 2003 in our department were entered in this study. THP (5 mg/day) was infused into the lingual or maxillary artery one hour before radiation on days 1-5 and 8-12, while intravenous 5-FU (150 mg/m2/day) was instilled continuously on days 1-5, 8-12, 15-19, and 22-26 in accordance with the radiation schedule (2 Gy/day). Consequently, total doses of THP, 5-FU, and radiation were 50 mg, 3000 mg/m2 and 40 Gy, respectively. After the treatment series, response rate and adverse effects were evaluated.. Response rate achieved 100% (12 cases exhibited a complete response and the remaining 3 a partial response). Notably, all 10 patients with oral carcinoma exhibited complete response. The main adverse effects were leucopenia (6/15) and mucositis (6/15), both of which were acceptable.. This concurrent chemoradiotherapy is very useful for oral and maxillary carcinoma as a preoperative modality with remarkably high response rate and acceptable adverse events.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxorubicin; Female; Fluorouracil; Humans; Immunosuppressive Agents; Inflammation; Leukopenia; Male; Maxillary Neoplasms; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Radiotherapy, Adjuvant; Tomography, X-Ray Computed; Treatment Outcome