Breast cancer resistance protein impacts clinical outcome in platinum-based chemotherapy for advanced non-small cell lung cancer.

PURPOSE: The purpose of this study was to investigate the relationship between the level of expression of ATP-binding cassette (ABC) transporter proteins, and response to chemotherapy and prognosis in advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of ABC transporter proteins, including P-glycoprotein, multidrug resistance protein (MRP) 1, MRP2, MRP3, and breast cancer resistance protein (BCRP), was examined immunohistochemically in 72 formalin-fixed tumor samples from untreated stage IIIB or IV NSCLC patients. All of the patients received platinum-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival were compared in relation to expression of each of the ABC transporter proteins and clinicopathological factors. RESULTS: Expression of P-glycoprotein, MRP1, and MRP3 was not significantly associated with response to chemotherapy or survival. MRP2 expression was associated with overall survival (P = 0.002) but not with response to chemotherapy and PFS. By contrast, the response rate to chemotherapy of patients with BCRP-negative tumors was 44%, as opposed to 24% in patients with BCRP-positive tumors. Response rate was lower in BCRP-positive tumors, although this difference was not statistically significant (P = 0.08). BCRP-positive patients had also shorter PFS (P = 0.0003) and overall survival (P = 0.004) than BCRP-negative patients. Multivariate analysis confirmed BCRP status as an independent variable related to PFS (P = 0.001). CONCLUSIONS: Positive immunostaining for BCRP appears to be a predictor of survival in patients with advanced NSCLC. These findings indicate that BCRP may serve as a molecular target for reducing drug resistance to chemotherapy in advanced NSCLC patients.     

Dominant papillary subtype is a significant predictor of the response to gefitinib in adenocarcinoma of the lung.

PURPOSE: Gefitinib (IRESSA; AstraZeneca, Osaka, Japan) shows excellent antitumor activity against advanced non-small-cell lung cancer, especially for the treatment of adenocarcinoma. However, the predictive factors for the response to gefitinib are still controversial. The aim of this study was to identify the clinicopathological and immunohistochemical features that are favorable to the use of gefitinib in adenocarcinoma patients. EXPERIMENTAL DESIGN: Between June 2002 and October 2003, 36 adenocarcinoma patients who experienced a relapse after surgical resection were treated with gefitinib at our hospital. The histologic patterns of the tumors were divided into four distinctive subtypes according to the revised World Health Organization histologic classification, and the dominant histologic subtype for the maximum cut surface of each resected specimen was documented. Association between the response to gefitinib and the clinicopathological features or immunohistochemical expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, or c-erbB-2 were then investigated. RESULTS: A significant association between the response to gefitinib and dominant papillary subtype findings was observed (P = 0.0021); the survival time of papillary subtype patients was also significantly prolonged compared with that of non-papillary subtype patients (P = 0.03). No other clinicopathological features or the expression of EGFR, phosphorylated EGFR, or c-erbB-2 were associated with the response to gefitinib. CONCLUSIONS: The results of the present study indicate that dominant papillary subtype findings of lung adenocarcinomas can be an important predictor of the response to gefitinib. Thus, this type of adenocarcinoma might be susceptible to postoperative adjuvant treatment with gefitinib.     

The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas

Our study was designed to clarify the significance of silencing the E-cadherin gene, which is located on 16q22.1, due to CpG methylation during hepatocarcinogenesis. The CpG methylation status of primary hepatocellular carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, were assessed by digesting DNA with methylation-sensitive and non-sensitive restriction enzymes. CpG methylation around the promoter region of the E-cadherin gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis and 67% of HCCs examined. Immunohistochemical examination revealed reduced E-cadherin expression in 59% of HCCs examined. CpG methylation around the promoter region correlated significantly with reduced E-cadherin expression in HCCs (p < 0.05). CpG methylation around the promoter region, which increases during the progression from a precancerous condition to HCC, may participate in hepatocarcinogenesis through reduction of E-cadherin expression, resulting in loss of intercellular adhesiveness and destruction of tissue morphology. Int. J. Cancer 71:355-359, 1997. © 1997 Wiley-Liss Inc.     

Novel guide catheter for left coronary intervention via a right upper limb approach

We designed a novel guide catheter specifically for interventions to the left coronary artery via a right upper limb approach. The catheter has a novel first loop design which utilizes the angle between the right subclavian and innominate arteries for support. The first loop introduces the catheter into the correct position and generates powerful and coaxial back-up power. We report successful implantation of Palmaz-Schatz stents in five cases using this 6 Fr. catheter. Cathet. Cardiovasc. Diagn. 44:244–247, 1998. © 1998 Wiley-Liss, Inc.     

Morphological observation by intravascular ultrasound in superior vena cava syndrome after pacemaker implantation

We report a case of superior vena cava (SVC) syndrome that was assessed by intravascular ultrasound (IVUS). A highly echogenic eccentric lesion was demonstrated by IVUS. The use of IVUS also confirmed in vivo that SVC syndrome following pacemaker insertion occurs as a result of intimal thickening of the venous wall. © 1996 Wiley-Liss, Inc.     

Successful treatment of an unresectable rectal carcinoma with combined radio-chemo-immunotherapy resulting in complete remission

We administered multidisciplinary treatment to a 37-year-old man with poorly differentiated adenocarcinoma of the rectum which exhibited a fistula between the rectum and the urinary bladder; the tumor was considered unresectable because of extensive local spread at initial evaluation, including a laparotomy. The patient received radiotherapy, consisting of a total dose of 50 Gy, given as fractions of 2 Gy per day 4 days a week. Concurrently with the radiation, the patient also received twice daily a tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil] suppository (750 mg) and 5-fluorouracil ointment (2.5 g) applied to the perianal involved skin lesion. In addition, 5 KE of OK-432 was injected into the tumor nine times during the course of radiation. Because the tumor responded well to this radio-chemo-immunotherapy, the patient was discharged, and was treated only with tegafur suppositories for almost 3 years on an outpatient basis (total dose of tegafur, approximately 1500 g). As a result of the combined therapy, the tumor completely disappeared, while only the recto-urinary fistula remained. The patient has survived without recurrence for 50 months after his initial presentation, and his levels of carcinoembryonic antigen and immunosuppressive acidic protein have decreased from pretreatment values of 85 ng/ml and 1220 μg/ml, respectively, to 0.8 ng/ml and 459 μg/ml, respectively. Although this is only one case, it shows that appropriate multidisciplinary treatment may achieve excellent results even in patients with unresectable poorly differentiated adenocarcinomas of the rectum. Received: June 15, 1999 / Accepted: December 10, 1999     

A variable-number-tandem-repeat of the serotonin transporter gene and anxiety disorders.

1. A polymorphism of the variable-number-tandem-repeat (VNTR) in the second intron of the serotonin transporter (ST) gene, which has been reported to be associated with major depression, was studied in anxiety disorders. 2. The VNTR of the human ST gene was compared between 103 patients with anxiety and 106 controls. 3. The frequency of the allele containing 12 copies of the VNTR element (STin2.12) was significantly higher in the combined patient group (p = 0.027), and among patients with OCD (p = 0.0326), and GAD (p = 0.0123), in comparison with in controls. 4. The presence of the STin2.12 allele was significantly associated with the risk of combined anxiety disorders (odds ratio = 2.06, 95% CI 1.09-3.90), OCD (10.2, 1.34-77.4), and GAD (3.61, 1.23-10.6).