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There is increasing global incidence of highly metastatic melanoma and therapeutic strategies like those focusing on the downstream beta-catenin/MITF axis of invading melanoma cells are urgently needed. Targeting endoplasmic reticulum (ER) stress can promote cancer cell death and inhibit epithelial mesenchymal transition (EMT) in metastatic tumors. This study aimed to determine if Honokiol could promote ER stress-dependent apoptosis and regulate metastatic melanoma. The therapeutic efficacy of Honokiol was assessed using the highly metastatic melanoma xenograft mouse model for peritoneal metastasis and evaluated by computed tomography imaging. The ER stress marker, Calpain-10, delineated a novel proteolytic cleavage enzyme, while CHOP/GADD153-regulated apoptosis was used for gene silencing to determine the role of the β-catenin/MITF axis in melanoma cells. The results showed that Honokiol effectively decreased peritoneal dissemination and organ metastasis via ER stress activation and EMT marker inhibition. Knockdown Calpain-10 or CHOP/GADD153 blocked all of the biological effects in Honokiol-induced β-catenin/MITF cleavage, ERSE or TCF/LEF luciferase activity, and β-catenin kinase activity. These findings suggest that Honokiol can significantly thwart the progression of highly metastatic melanoma using the β-catenin/MITF axis via prompt Calpain-10 and CHOP/GADD153 regulated cascades.

Tc-99m sestamibi (MIBI) has been used as a tumor-seeking agent. However, its role in detecting lymphomas has not been widely investigated. The aim of the present study was to determine the uptake and clearance characteristics of Tc-99m MIBI in vincristine-resistant lymphoma cell lines. In addition, thallium-201 (Tl-201) and gallium-67 (Ga-67) uptake and clearance characteristics were evaluated for comparison with Tc-99m MIBI. Drug-resistant lymphoma cell lines (monocyte-like, histiocytic lymphoma, human; B-lymphoma cell line, American Burkitt lymphoma, lymphoblastoid, human; Hodgkin's disease, lymphoid, human) were selected by multistep vincristine treatment up to 50 nM. After incubation of the radiotracers, Tc-99m MIBI, Tl-201 and Ga-67, in medium for 0, 10, 20, 30, 60 or 120 min, the uptake and clearance of each radiotracer were measured in the drug-resistant lymphoma cell lines. In addition, P-glycoprotein expression was determined by immunohistochemical study. In a comparison of the three radiotracers, the uptake of Tc-99m MIBI was the greatest in the studied wild-type lymphoma cell lines. Tc-99m MIBI uptake was much lower in drug-resistant tumor cell lines than in non-resistant cell lines. On the other hand, the uptake characteristics of Tl-201 did not differ between drug-resistant and non-resistant cells. Immunohistochemistry analyses of Ab-1 or JSB indicated that tumor cells expressed MDR-1 protein in all three cell lines. Tc-99m MIBI is a good radiotracer for detecting drug resistance in lymphoma cell lines.

The aim of this study was to investigate the relationships among technetium-99m tetrofosmin (Tc-TF) accumulation in untreated small cell lung cancer (SCLC), the expression of P-glycoprotein (Pgp) and multidrug resistance related protein-1 (MRP1), and the response to chemotherapy in patients with untreated SCLC. Thirty patients with SCLC were studied with chest scintigraphy 15 to 30 min after intravenous injection of Tc-TF before chemotherapeutic induction. Tc-TF chest scans were interpreted both visually and quantitatively. The response to chemotherapy was evaluated upon completion of chemotherapy. Immunohistochemical analyses were performed on multiple non-consecutive sections of biopsy specimens to detect Pgp and MRP1 expression. Fifteen patients with good response to chemotherapy had a significantly higher incidence (100.0%) of positive Tc-TF chest single photon emission computed tomography (SPECT) findings and negative Pgp or MPR expression than 15 patients with poor response (20%) (P

The purposes of this study were to predict the chemotherapy response of untreated malignant lymphomas (ML) using a technetium-99m tetrofosmin (Tc-TF) scan and to compare Tc-TF results with P-glycoprotein (Pgp) expression. Before undergoing chemotherapy, 25 patients with ML were enrolled in this study. Tc-TF scan was performed 10 min after intravenous injection of Tc-TF. Immunohistochemical analyses were performed on multiple sections of ML specimens to evaluate Pgp expression. The chemotherapy response was evaluated in the first 1–2 years after the completion of treatment. The mean tumor-to-background ratio of the 15 patients with good responses (3.23±0.56) was significantly higher than that of the ten patients with poor responses (1.18±0.11). All of the 15 patients with good responses had positive Tc-TF scan results, but negative Pgp expression. Among the ten patients with poor responses, all had negative Tc-TF scan results, but six had positive Pgp expression and four had negative Pgp expression. Significant differences in the incidences of good and poor responses were found between patients with positive Tc-TF scan results and patients with negative Tc-TF scan results and between patients with positive Pgp expression and patients with negative Pgp expression. No significant differences in the incidences of good and poor responses were found between Hodgkin's disease patients and non-Hodgkin's lymphoma patients, stage I–II patients and III–IV patients, patients aged >40 and patients aged ≤40 years, and patients with and without B symptoms. Compared with other prognostic factors, Tc-TF scan results and Pgp expression more accurately predict the chemotherapy response in patients with ML.

We prospectively studied a total of 24 patients with breast cancer to evaluate the relationship between the degree of accumulation of technetium-99m sestamibi (Tc-99m MIBI) and p-glycoprotein (Pgp) expression in tumor tissues. All 24 patients underwent Tc-99m MIBI scintimammography before surgery or biopsy. Immunohistochemical studies were performed on multiple non-consecutive sections of the same tumor using a Pgp specific monoclonal antibody, JSB-1. Planar images were started 10 min after injection of Tc-99m MIBI. Tumor to background (T/B) ratios calculated from the planar images were correlated with Pgp expression as determined by immunohistochemical studies. The T/B ratios were significantly lower for tumors in eight patients with positive Pgp expression (Group 1) than in 16 patients with negative expression (Group 2) (1.40+/-0.11 and 2.76+/-0.60, P0. 05). Our data confirmed that Tc-99m MIBI scintimammography is useful for determination of the presence of multidrug resistance due to Pgp expression in patients with breast cancer.