Capsaicin and Proton Differently Modulate Activation Kinetics of Mouse Transient Receptor Potential Vanilloid-1 Channel Induced by Depolarization.

The transient receptor potential vanilloid type 1 (TRPV1) channel is a non-selective cation channel expressed with transient receptor potential ankyrin type 1 (TRPA1) in small and medial size neurons of the dorsal root ganglions and trigeminal ganglions. TRPV1 is activated by capsaicin, thermal stimuli higher than 43°C, mechanical stress, and protons (H+). Although the TRPV1 channel does not have positively charged residues at regular intervals on its transmembrane segments, alterations in membrane potential also affect the state of TRPV1 channel. In the presence of capsaicin, voltage-dependent probability of opening of the TRPV1 channel and its kinetics have been examined, but the characteristics in the low pH remain unclear. To understand the voltage-dependency of the TRPV1 channel activation, we recorded capsaicin- and proton-induced mouse TRPV1 channel currents in a heterologous expression system. Outward current evoked by depolarizing square pulses in the presence of capsaicin or protons was fitted to a two-exponential function with a time-independent component. The voltage-dependent changes in amplitude of the three components displayed shallow curves and the changes in their ratio to the total current display similar tendencies in the presence of capsaicin and under the low pH. However, the fast and slow time constants in the presence of capsaicin were respectively 5- and 8-fold lower than those obtained under low pH conditions. These results suggest that the TRPV1 channel slowly drives the feed-forward cycle of pain sensation, and capsaicin and protons differently modulate the voltage-dependent TRPV1 channel gating.

Pathological responses to low-dose irradiation and Pepleomycin in Oral squamous cell carcinoma are predictive of Locoregional control.

BACKGROUND: The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence. METHODS: We retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3-4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato. RESULTS: Eight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively. CONCLUSIONS: The present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.

[Long-Term Effectiveness of Chemotherapy Containing mFOLFOX6 plus Panitumumab and 5-FU/l-LV plus Panitumumab after Primary Tumor Resection in a Case of Ascending Colon Carcinoma and Multiple Hepatic Metastases].

The patient was a 79-year-old man. He had ascending colon carcinoma and multiple hepatic metastases, and right hemicolectomy( D2)was performed in June 2012(SE, N1, P0, M1[H3], Stage Ⅳ). After surgery, 8 courses of mFOLFOX6 plus panitumumab biweekly, then, 5-FU/l-LV biweekly and panitumumab every 4 weeks were administered because he had wild- type KRAS. Before chemotherapy, his serum CEA level was 122 ng/mL, but the value decreased rapidly to a normal level after 7months. The hepatic metastases also decreased, and the lesion was only slightly observed on CT after 7months. Five years after the surgery, images and his CEA level are both normal, and the effectiveness is maintained. Even for right colon cancer, anti-EGFR antibodies might be effective if RAS is wild-type.

[Meckel's diverticulum duplication revealed by acute operation of ileus: a case report].

A 29-year-old man was admitted with abdominal pain. Peritonitis symptoms appeared on the day after of hospitalization and emeregency surgery was performed. A Meckel diverticulum adhered to the mesenterium of the sigmoid colon which was strangulated for a length of 30cm. Additionally, a second Meckel diverticulum was present on the oral side of the first one. The length of these were 3cm and 5cm, and the longer one caused the strangulation. The letter diverticulum contained a crab shell about 2cm in size, which was considered to be the cause of adhesion. Our search of the literature revealed only one report of two Meckel diverticula. This type of our case is extremely rare.