SERPINE1 and SERPINB7 as potential biomarkers for intravenous vitamin C treatment in non-small-cell lung cancer.

High dose intravenous vitamin C (IVC) has been proposed as a pro-oxidant anticancer agent. However, there is a lack of biomarkers that are specific for this treatment. Here, we explored profiles of gene expression responding to IVC treatment in non-small cell lung cancer (NSCLC) cells as an effort for potential biomarker discovery. Genome-wide RNA-seq was performed in human NSCLC cell lines treated with pharmacological concentrations of vitamin C(VitC) for differential expression of genes. The identified genes were analyzed for correlations with patient prognosis using data from the Kaplan-Meier Plotter and the Human Protein Atlas databases. Further, tumor samples from a retrospective study of 153 NSCLC patients were analyzed with immunohistochemistry for expression of targeted genes, and patient prognosis was correlated to these genes. Two genes, namely SERPINE1 and SERPINB7 were found to be downregulated in NSCLC cells following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that these 2 genes presented an unfavorable prognostic prediction of overall survival (OS) in NSCLC patients receiving standard of care. However, high expression level of these 2 genes were associated with prolonged OS in NSCLC patients receiving IVC in addition to standard of care. These data revealed that SERPINE1 and SERPINB7 have the potential to serve as predictive factors indicating favorable responses to IVC treatment in patients with NSCLC. Further validations are warranted.

A Retrospective Study of Gemcitabine and Carboplatin With or Without Intravenous Vitamin C on Patients With Advanced Triple-Negative Breast Cancer.

Background: This is a retrospective study to examine the effect of chemotherapy with or without intravenous vitamin C (IVC) on women with advanced triple-negative breast cancer (TNBC). Methods: From 2008 to 2016, a total of 113 patients with pathologically confirmed TNBC at Clifford Hospital were evaluated, and 70 patients were matched and divided into IVC (treatment group) and non-IVC groups (control group). The match was according to age, menopausal status, and metastatic sites. In the control group, 35 patients received gemcitabine and carboplatin. In the treatment group, 35 patients received the same chemotherapy plus IVC. Results: Baseline characteristics were not significantly different between the 2 groups. According to the criteria of RECIST 1.1 (Response Evaluation Criteria in Solid Tumors), enhanced computed tomography scan was compared after 2 cycles of chemotherapy. In the treatment group, 2/35 cases had a complete remission (CR), 15/35 cases had partial remission (PR), and 13/35 cases had stable disease (SD). The response rate was 48.6%. In the control group, there were no CR cases, 14/35 cases had PR, 14/35 cases had SD, and the response rate was 40.0% (P > .05). The median progression-free survival time and median overall survival time was 7 months (95% confidence interval [CI] =1.5-28.5 months) and 27 months (95% CI = 4-40 months) in the treatment group compared with 4.5 months (95% CI = 1.5-8 months) and 18 months (95% CI = 3-26 months) in the control group (P < .05). All patients experienced diverse reactions in the gastrointestinal tract and myelosuppression. The incidence of adverse reactions in the treatment group was significantly lower than that of the control group (P < .05). Conclusion: IVC may have an effect on improving the prognosis of patients with advanced TNBC.

The safety and pharmacokinetics of high dose intravenous ascorbic acid synergy with modulated electrohyperthermia in Chinese patients with stage III-IV non-small cell lung cancer.

Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no safety and pharmacokinetics data in Chinese cancer patients. We carried out a clinical trial to evaluate the safety and pharmacokinetics of those methods in patients with stage III-IV non-small cell lung cancer (NSCLC). Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I study. They were randomized allocated into 3 groups, and received doses 1.0, 1.2, 1.5g/kg AA infusions. Participants in the first group received intravenous AA (IVAA) when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. Pharmacokinetic profiles were obtained when they received solely IVAA and when IVAA in combination with mEHT. The process was applied 3 times a week (every other day, weekend days off) for 4weeks. We found that fasting plasma AA levels were significantly correlated with stage of the disease. Peak concentration of AA was significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IVAA-managed groups. IVAA synergy with simultaneous mEHT is safe and the concomitant application significantly increases the plasma AA level for NSCLC patients.

Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of peritoneal carcinomatosis with malignant ascites: A phase II randomized trial.

The purpose of this study was to develop a safe and non-toxic alternative to the conventional conservative treatment of peritoneal carcinomatosis with malignant ascites (PCMA) by investigating the efficacy and safety of local modulated electro-hyperthermia (mEHT) combined with the traditional Chinese medicine (TCM) 'Shi Pi' herbal decoction, compared with standard intraperitoneal chemoinfusion (IPCI). A randomized, controlled, single-center, open-label clinical trial (phase II) with two parallel groups (allocation ratio, 1:1) was conducted to investigate the efficacy and safety of mEHT+TCM (study group, SG) vs. standard IPCI (control group, CG) in patients with PCMA by intention-to-treat analysis. A total of 260 patients with PCMA were randomly allocated into the two groups (130/130); mEHT was applied for 60 min per session every second day for 4 weeks, for a total of 14 sessions. The TCM decoction was administered orally, at 400 ml daily. In CG, occlusive IPCI with cisplatin (30-60 mg) and fluorouracil (500-600 mg/m2) was applied twice, biweekly. The objective response rate (ORR), quality of life (QoL) and adverse event rate (AER) in the two groups were evaluated 1 month after treatment, analyzed and compared. The present study is registered on ClinicalTrials.gov (NCT02638051). No case was lost or excluded (0/260). The ORR in SG was 77.69% (101/130) vs. 63.85% (73/130) in CG (P<0.05). The QoL in SG was 49.23% vs. 32.3% in CG (P<0.05). The AER in SG was 2.3% (3/130) vs. 12.3% (16/130) in CG (P<0.05). All the adverse events were grade I. In conclusion, the combination of mEHT with TCM achieves better control of PCMA compared with standard IPCI, with less toxicity. Both components of the combination are non-toxic treatments easily tolerated by patients. Thus, this combined treatment may be preferred due to the better benefit-harm balance.