P4HA2 involved in SLUG-associated EMT predicts poor prognosis of patients with KRAS-positive colorectal cancer.

This study aimed to examine the immunohistochemical expression of epithelial-mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy.

Effect of Transcranial Direct Current Brain Stimulation of the Motor Cortex on Chemotherapy-Induced Nausea and Vomiting in Female Patients with Breast Cancer.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) is an adverse outcome associated with chemotherapy and is sometimes difficult to manage. This study aimed to examine the impact of a single session of transcranial direct current brain stimulation (tDCS; 2 mA) over the motor cortex for 20 minutes before chemotherapy in patients receiving a highly emetogenic chemotherapy. STUDY DESIGN: Prospective randomized double-blind sham-controlled study. SETTING: Academic medical center. METHOD: Sixty patients with breast cancer who were scheduled for chemotherapy treatment were selected and allocated randomly into two equal groups: a stimulation group and a sham group. tDCS was implemented over the primary motor area (M1) (2 mA) for 20 minutes. Patients' nausea was measured by a cumulative index of nausea, a visual analog scale for nausea (VAS-N), episodes of vomiting, and the Edmonton Symptoms Assessment Scale (ESAS) to assess symptoms like pain, malaise, and sense of well-being. Evaluation was done before stimulation and every 24 hours for 72 hours after the end of infusion of chemotherapy. RESULTS: The tDCS group showed a reduction in the cumulative index of nausea (P < 0.001, F = 50), the VAS-N (P < 0.001, F = 52), the ESAS malaise score (P < 0.001, F = 37.6), and the sense of well-being score (P < 0.001, F = 25) vs the sham group. Six patients (20%) in the tDCS group required rescue antiemtic therapy vs 14 patients (46.7%) in the sham group (P < 0.028). CONCLUSION: A single session of M1 tDCS is suggested as an effective adjuvant therapy to control CINV in female patients suffering from breast cancer and receiving highly emetogenic chemotherapy. Corroboratory studies are needed.