Synergistic Anti-tumor Effect of Dichloroacetate and Ivermectin.

We formerly reported that the combination of dichloroacetate, omeprazole, and tamoxifen blocked cancer progression by reducing lactic acid production and inducing superoxide production. Recently, ivermectin, a well-known anti-parasite drug, was reported to share the same mechanisms with them and have anti-tumor activity. Here, we present three patients in whom the combination of dichloroacetate, omeprazole (plus tamoxifen), and ivermectin dramatically relieved the symptoms accompanying cancer and sarcoma progression.

Cotreatment with dichloroacetate and omeprazole exhibits a synergistic antiproliferative effect on malignant tumors.

It has been reported that treating cancer cells with dichloroacetate (DCA), an approved treatment for congenital lactic acidosis, reverses the Warburg effect and inhibits tumor growth). Furthermore, omeprazole (OMP) is a well-known agent that enhances the effects of anticancer drugs. The aim of this study was to find clinically-used drugs that enhance the effects of DCA. The combination of DCA and OMP exhibited a more potent antitumor activity than DCA alone in HT1080 fibrosarcoma cells and RKO colon cancer cells, while the drugs did not affect the proliferation of WI-38 human fibroblasts. The inhibitory effect of DCA combined with OMP was reversed with vitamin E and Z-VAD-FMK; therefore conventional caspase-dependent cell growth inhibition through superoxide production was suggested as the mechanism for inhibition. The combination of these drugs also had an effect on HT1080 fibrosarcoma cells inoculated into mice. Since OMP and DCA may be administered orally and have been used clinically for several years without major side effects, we believe that this combination therapy could be readily translated to treat malignant tumors.

Co-treatment of dichloroacetate, omeprazole and tamoxifen exhibited synergistically antiproliferative effect on malignant tumors: in vivo experiments and a case report.

BACKGROUND/AIMS: Omeprazole (OPZ) and tamoxifen (TAM) strengthen the effects of anticancer drugs and dichloroacetate (DCA) inhibits tumor growth. This study assesses the synergistic effects of these drugs. METHODOLOGY: HT1080 human fibrosarcoma cells and WI-38 human fibroblasts were used as test and control cells, respectively. DCA, OPZ and TAM alone or in combination were applied and cells were counted after a one week culture. The combination of these drugs was prescribed to a cholangiocarcinoma patient and serum CA19-9 was monitored. RESULTS: DCA combined with OPZ and TAM exhibited more potent antitumor activity than DCA alone in HT1080 fibrosarcoma cells, but did not influence proliferation of WI-38 human fibroblasts. All these drugs induce caspase-dependent cell growth inhibition through superoxide production. Since they can be taken orally and have been used clinically without major side effects, it was thought that this combination therapy would be a readily translated strategy to treat malignant tumors. Under the patient's consent these three drugs were prescribed to a 51-year old female cholangiocarcinoma patient to whom neither gemcitabine+S-1 nor adoptive immunotherapy with natural killer cells was effective. Disease progression was successfully blocked (the rise of serum CA19-9 value) for three months, also confirmed by CT. CONCLUSIONS: Although findings are preliminary, this study is a sample of translational research. Since there is no consensus regarding treatment strategy of cholangiocarcinoma and chemotherapy has only limited efficacy, it is expected that it might open a new possibility of treatment.

The formulated growth of early gastric cancer.

Although the proportion of early gastric cancer is rising in the incidence of gastric cancer as a whole, its natural history is still under discussion. We report a patient who was diagnosed with early gastric cancer and who had undergone barium studies once a year for the three previous years. The exact, increasing size of the tumor could be measured at these four time points, and the data show, almost exactly, the line calculated by the formula S = 0.3 t2 [S = size (cm2) of the cancerous lesion, t = time (yr) elapsed from the beginning of the gastric cancer].

Midazolam sedation for upper gastrointestinal endoscopy: comparison between the states of patients in partial and complete amnesia.

BACKGROUND/AIMS: The amnesia produced by anesthesia is advantageous for unpleasant procedures like gastroscopy, and midazolam is one of the most commonly used anesthesias for endoscopy. However the proper use of midazolam from the viewpoint of complete amnesia has been discussed very little. METHODOLOGY: One hundred and thirty-three unselected patients about to undergo upper gastrointestinal endoscopy were premedicated with sufficient intravenous midazolam to cause enough sedation so that no response was evoked when calling their name. Pulse, arterial pressure, arterial oxygen saturation and the physical signs of patients were recorded continuously during the procedures. After the study, patients were given 0.25 mg of flumazenil and asked if they could recall the procedures. Those who could recall even part of the procedure were not regarded as achieving complete amnesia. The efficacy of the sedative was judged by the appearance of complete amnesia. RESULTS: From our regression analysis complete amnesia was achieved in 75.9% of the total patients. The differences of the blood pressure fall, pulse rate increase and arterial oxygen saturation fall between the patients with complete and partial amnesia were minute and did not cause serious complications. Regression analysis revealed the most important factors for the complete amnesia to be midazolam dose per body weight and habitual hypnotic use. CONCLUSIONS: There are no obvious disadvantages to producing complete amnesia with midazolam for upper gastrointestinal endoscopy. Habitual hypnotic use along with midazolam dose per body weight is the most influencing factor for that purpose.