Background. Oxaliplatin and irinotecan are generally used to treat advanced colorectal cancer (CRC) patients. Antibiotics improve the cytotoxicity of oxaliplatin but not irinotecan in a colon cancer cell line in vitro. This study retrospectively assessed whether antibiotics improve the treatment efficacy of oxaliplatin- but not irinotecan-based therapy in advanced CRC patients. Patients and Methods. The medical records of 220 advanced CRC patients who underwent oxaliplatin- or irinotecan-based therapy were retrospectively reviewed. The oxaliplatin and irinotecan groups were further divided into antibiotic-treated (group 1) and antibiotic-untreated (group 2) subgroups. Results. In oxaliplatin groups 1 and 2, the response rate (RR) was 58.2% and 30.2%, while the disease control rate (DCR) was 92.5% and 64.2%, respectively; the median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI) = 7.5–12.2) and 7.0 months (95% CI = 17.0–26.0), respectively, and the median overall survival (OS) was 23.8 months (95% CI = 5.1–9.1) and 17.4 months (95% CI = 13.1–24.9), respectively. In irinotecan groups 1 and 2, the RR was 17.8% and 20.0%, while the DCR was 75.6% and 69.1%, respectively; the median PFS was 8.2 months (95% CI = 6.2–12.7) and 7.9 months (95% CI = 12.0–23.0), respectively, and the median OS was 16.8 months (95% CI = 5.9–10.6) and 13.1 months (95% CI = 10.4–23.7), respectively. Conclusion. To improve the treatment efficacy of oxaliplatin-based therapy in advanced CRC patients, adding antibiotics is a potential therapeutic option.

Patients with BRAF‐mutated colorectal cancer (CRC) have a poor prognosis despite recent therapeutic advances such as combination therapy with BRAF, MEK, and epidermal growth factor receptor (EGFR) inhibitors. To identify microRNAs (miRNAs) that can improve the efficacy of BRAF inhibitor dabrafenib (DAB) and MEK inhibitor trametinib (TRA), we screened 240 miRNAs in BRAF‐mutated CRC cells and identified five candidate miRNAs. Overexpression of miR‐193a‐3p, one of the five screened miRNAs, in CRC cells inhibited cell proliferation by inducing apoptosis. Reverse‐phase protein array analysis revealed that proteins with altered phosphorylation induced by miR‐193a‐3p were involved in several oncogenic pathways including MAPK‐related pathways. Furthermore, overexpression of miR‐193a‐3p in BRAF‐mutated cells enhanced the efficacy of DAB and TRA through inhibiting reactivation of MAPK signaling and inducing inhibition of Mcl1. Inhibition of Mcl1 by siRNA or by Mcl1 inhibitor increased the antiproliferative effect of combination therapy with DAB, TRA, and anti‐EGFR antibody cetuximab. Collectively, our study demonstrated the possibility that miR‐193a‐3p acts as a tumor suppressor through regulating multiple proteins involved in oncogenesis and affects cellular sensitivity to MAPK‐related pathway inhibitors such as BRAF inhibitors, MEK inhibitors, and/or anti‐EGFR antibodies. Addition of miR‐193a‐3p and/or modulation of proteins involved in the miR‐193a‐3p–mediated pathway, such as Mcl1, to EGFR/BRAF/MEK inhibition may be a potential therapeutic strategy against BRAF‐mutated CRC.

Cyanotic breath-holding spell is a benign and self-limiting disease of young children but occasionally associated with sudden, unexpected death. The authors report a rare case in a 2-year-old girl with a severe form that started after radical resection of a cervicomedullary ganglioglioma. She was admitted to our hospital because of delayed and unstable gait. Since magnetic resonance imaging showed a cervicomedullary tumor, she underwent a radical resection and histology showed the tumor to be a ganglioglioma. Postoperatively, the function of the lower cranial nerves and cerebellum deteriorated and hemiparesis on the left became apparent, but she returned to the preoperative state in a few months. In addition, mild sleep apnea (Ondine curse) and severe cyanotic breath-holding spells occurred. The former responded to medication but the latter failed and continued several times per day with a rapid onset and progression of hypoxemia, loss of consciousness, sweating and opisthotonos. Five months after the operation, the patient returned home with a portable oxygen saturation monitor equipped with an alarm. This case indicates that cyanotic breath-holding spell, as well as sleep apnea, is critical during the early postoperative period. This is the first report observing that such spells may occur as a complication of radical resection of a cervicomedullary tumor.

Local venous pain caused by dacarbazine (DTIC) injection is due to its photodegradation product 5-diazoimidazole-4-carboxamide (Diazo-IC). The production of Diazo-IC can be decreased by protecting the drug from light. Furthermore, the production of Diazo-IC reportedly increases with time; however, there are no studies reporting the association between the injection preparation time and local venous pain caused by the DTIC injection. We evaluated the e‹cacy of the following: (1) method used to shorten the injection preparation time and (2) method used to change the diluting solution for DTIC. We found that shortening the injection preparation time tended to decrease the local venous pain expression due to DTIC, and Veen F decreased the production of Diazo-IC compared with the normal saline and 5％ glucose solution. These results indicate that shortening the injection preparation time may be eŠective in preventing the local venous pain caused by the DTIC injection; moreover, using Veen F for DTIC may also reduce the pain.

The anticancer drug dacarbazine (DTIC) is photosensitive, and the photodegradation product 5-diazoimidazole-4-carboxamide (diazo-IC) induces adverse reactions including local venous pain during intravenous injection. In this study we evaluated the eŠectiveness of colored shields (orange and red) to protect against photodegradation of DTIC as determined by ascertaining the concentration of diazo-IC. Samples were prepared and stored under four conditions: (1) no shield; (2) covered with an aluminum (opaque) shield; (3) covered with an orange shield; and (4) covered with a red shield. The samples were exposed to natural light for a speciˆed time (0, 30, 60, 120, and 180 min) prior to measuring the concentration of diazo-IC by HPLC. We found that after 180 min, the diazo-IC concentration was 5.7±0.6 (S.D.) mg/mL with no shield and 1.9±0.2 mg/mL in both colored shield conditions. This production of diazo-IC under the colored shields was suppressed to a level similar to that under the aluminum shield (1.7±0.2 mg/mL). We also evaluated the eŠectiveness of NSAIDs (zaltoprofen, loxoprofen sodium, and diclofenac sodium) administered to mice prior to DTIC treatment on venous pain by counting their stretching and writhing reactions. Premedication with zaltoprofen signiˆcantly decreased expression of pain behavior in the DTIC-treated mice. These results suggest that storing DTIC under the protection of an orange or red shield is clinically beneˆcial because the shield prevents DTIC photodegradation, and that NSAIDs such as zaltoprofen are a promising premedication candidate for pain.