allopurinol and Esophageal-Neoplasms

The present study was conducted to evaluate the effect of allopurinol spray on stomatitis induced by chemotherapy for esophageal cancer. The chemotherapeutics used consisted of 5-FU + CDDP (FC) given to 40 patients and 5-FU + ND (FN) given to 9 patients. Allopurinol solution for spray was prepared using a gelatin agent as base. The allopurinol spray was used 3-5 times daily before and after chemotherapy. The Japan Society for Cancer Therapy's criteria for stomatitis were used. With FN-therapy, no stomatitis was observed. With FC-therapy, 9 of 40 patients developed stomatitis of grade 1 (8 patients) or grade 2 (1). The incidence of stomatitis was 18.4% with all therapies and 22.5% with FC-therapy. The average graded toxicity was 0.20 for all therapies and 0.25 for FC-therapy. These results suggest that allopurinol spray is markedly effective for the prevention of stomatitis induced by chemotherapy. In addition, allopurinol spray is portable and convenient, and resulted in less nausea or vomiting than mouthwash.

Topics: Aerosols; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Fluorouracil; Humans; Stomatitis

Twenty-three patients with advanced inoperable squamous cell carcinoma of the esophagus were treated with aminothiadiazole (A-TD) 125 mg/m2 weekly plus allopurinol daily in a phase II cooperative group trial. No patients responded to treatment; 17 patients progressed, three showed stable disease, and three were unevaluable. There were no life-threatening hematologic or metabolic toxicities. The median survival from study entry was 5 months. A-TD is not active in advanced squamous cell carcinoma of the esophagus.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Evaluation; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Survival Rate; Thiadiazoles

Hypoxia is one of most typical features in the tumor microenvironment of solid tumor and an inducer of endoplasmic reticulum (ER) stress, and HIF-1α functions as a key transcription factor regulator to promote tumor angiogenesis in the adaptive response to hypoxia. Increasing evidence has suggested that hypoxia plays an important regulatory role of ER homeostasis. We previously identified TMTC3 as an ER stress mediator under nutrient-deficiency condition in esophageal squamous cell carcinoma (ESCC), but the molecular mechanism in hypoxia is still unclear.. RNA sequencing data of TMTC3 knockdown cells and TCGA database were analyzed to determine the association of TMTC3 and hypoxia. Moreover, ChIP assay and dual-luciferase reporter assay were performed to detect the interaction of HIF-1α and TMTC3 promoter. In vitro and in vivo assays were used to investigate the function of TMTC3 in tumor angiogenesis. The molecular mechanism was determined using co-immunoprecipitation assays, immunofluorescence assays and western blot. The TMTC3 inhibitor was identified by high-throughput screening of FDA-approved drugs. The combination of TMTC3 inhibitor and cisplatin was conducted to confirm the efficiency in vitro and in vivo.. The expression of TMTC3 was remarkably increased under hypoxia and regulated by HIF-1α. Knockdown of TMTC3 inhibited the capability of tumor angiogenesis and ROS production in ESCC. Mechanistically, TMTC3 promoted the production of GTP through interacting with IMPDH2 Bateman domain. The activity of Rho GTPase/STAT3, regulated by cellular GTP levels, decreased in TMTC3 knockdown cells, whereas reversed by IMPDH2 overexpression. Additionally, TMTC3 regulated the expression of VEGFA through Rho GTPase/STAT3 pathway. Allopurinol inhibited the expression of TMTC3 and further reduced the phosphorylation and activation of STAT3 signaling pathway in a dose-dependent manner in ESCC. Additionally, the combination of allopurinol and cisplatin significantly inhibited the cell viability in vitro and tumor growth in vivo, comparing with single drug treatment, respectively.. Collectively, our study clarified the molecular mechanism of TMTC3 in regulating tumor angiogenesis and highlighted the potential therapeutic combination of TMTC3 inhibitor and cisplatin, which proposed a promising strategy for the treatment of ESCC.

Topics: Allopurinol; Carrier Proteins; Cisplatin; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Guanosine Triphosphate; Humans; Membrane Proteins; STAT3 Transcription Factor; Tumor Microenvironment; Vascular Endothelial Growth Factor A

In this series of experiments, we surveyed xanthine oxidase activity after microvascular transfer in the venous effluent after reperfusion of human rectus abdominis muscle (n = 8) and jejunum (n = 4). Enzyme activity was correlated with duration of ischemia and biochemical markers of cellular injury. Xanthine oxidase (XO) activity was measured spectrofluorometrically using a pterin assay, whereas cellular injury was measured with commercial creatinine phosphokinase activity assay and lipid peroxidation products using a spectrophotometer. The data demonstrated that XO activity was statistically significantly increased in muscle flaps kept at room temperature during ischemia compared with muscle flaps that were cooled (p < 0.05). Creatinine phosphokinase activity was also increased after 15 minutes of reperfusion in muscle flaps that were not cooled (p < 0.05). Two of the jejunal free flaps had ischemia times of > 1 hour and had elevated XO activity after reperfusion despite cooling (p < 0.05). Two other jejunal flaps had ischemia times of < 1 hour, but in one case, the XO activity was increased before harvest. The other case had no increase in XO activity.

Topics: Abdominal Muscles; Creatine Kinase; Esophageal Neoplasms; Female; Graft Survival; Humans; Jejunum; Leg Injuries; Lipid Peroxidation; Male; Mammaplasty; Pharyngeal Neoplasms; Postoperative Complications; Reperfusion Injury; Surgical Flaps; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Evaluation; Esophageal Neoplasms; Fluorouracil; Humans; Middle Aged

Forty patients with advanced squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, 5-FU (by continuous 5-day infusion), and allopurinol; 37 are evaluable for response. Thirteen remissions (35%) were obtained, including three complete and ten partial, with a median duration of 9 months. After chemotherapy, seven responding patients underwent a surgical procedure, which was radical in four. The most frequent side effects were nausea and vomiting. This regimen is effective and can be included in a multimodality approach.

Topics: Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Evaluation; Esophageal Neoplasms; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Palliative Care