[A Patient with AFP-Producing Gastric Cancer and Stenosis Who Regained Oral Intake Capabilities after T-DXd Treatment].

We present the case of a 55-year-old man with HER2-positive, AFP-producing gastric cancer and multiple liver metastases. The patient consequently underwent 7 courses of SOX plus trastuzumab therapy, 3 courses of weekly PTX plus ramucirumab therapy, and 3 courses of nivolumab therapy, all of which resulted in PD. Obstruction due to tumor growth became noticeable 9 months after the start of the first treatment. Subsequently, the patient experienced malnutrition and systemic edema due to impaired oral intake. However, subsequent trastuzumab deruxtecan(T-DXd)therapy induced remarkable tumor shrinkage. Furthermore, oral intake became possible, and edema started subsiding. Thus, we report the course of a patient with AFP-producing gastric cancer and stenosis who regained oral intake capabilities after T-DXd treatment.

[Transverse Colectomy with D2 Lymph Node Dissection with a Small Incision Using Body Surface 3D-Simulation CT Colonography].

BACKGROUND: Laparoscopic transverse colectomy is technically difficult. In mini-laparotomy surgery, colectomy for midtransverse colon cancer can easily be performed, but exact D2 lymph node dissection is very difficult for a variety of vessels in the transverse colon. Using 3D-CT imaging, we present a case of D2 lymph node dissection where mini-laparotomy transverse colectomy was performedby a small incision similar to that usedin laparoscopic surgery. METHOD: The patient was a 60-yearoldwoman with early transverse colon cancer, which was locatedin the mid-transverse colon. Surgical treatment was plannedfor pT1b(1.5mm)andpVM1 in pathological findings after EMR. Using CT colonography(CTC), the location of the primary tumor was identified. Using simulation CTC(sCTC), composedof CTC and 3D imaging of the arteries andveins, the dominant artery was identified and D2 lymph node dissection was simulated. In addition, body surface 3D imaging and permeable surface 3D imaging of the abdominal trunk were performed. Using body surface 3D-sCTC, composedof sCTC and body surface 3D imaging, the minimum incision to enable D2 lymph node dissection was simulated. RESULT: Using sCTC, it was identified that the dominant artery was the right branch of the middle colic artery(MCA Rt)andthe accompanying vein was branchedfrom the gastrocolic trunk(GCT). D2 lymph node dissection to separate the branching root of MCA Rt and the accompanying vein was simulated. Next, surgical incision was simulated using body surface 3D-sCTC. Because the branching roots of MCA Rt andGCT were locatedabout 5 cm cranial from the upper rim of the navel, a 7 cm upper abdominal midline incision was designed in addition to a 2 cm umbilical incision. Mini-laparotomy transverse colectomy with a 7 cm incision was performedin accordance with the simulation. The operation time was 2 hours and5 1 minutes, andbloodloss was due to occult bleeding. The patient was discharged 7 days after surgery without complications, and the final diagnosis was pT1bN0M0, StageⅠwith no recurrence for 4 years and2 months after surgery. The cranial incision from the upper rim of the navel has shrank about 3 cm, and the umbilical incision is not noticeable. CONCLUSION: D2 lymph node dissection of minilaparotomy transverse colectomy can be a treatment option for early transverse colon cancer through using body surface 3DsCTC.

[Partial Gastrectomy for Elderly Patients with Early-Stage Gastric Cancer].

The aim of this study was to assess the impact of partial gastrectomy on postoperative outcomes in elderly patients with gastric cancer. Sixty -three consecutive elderly patients aged 75 years and older with histologically proven Stage ⅠA gastric adenocarcinoma who underwent partial gastrectomy(PG, n=7)or normal gastrectomy(NG, n=56)were investigated. PG was performed by segmental gastrectomy or local gastrectomy due to poor performance status, severe comorbidities, and social background instead of normal gastrectomy(distal, proximal, and total gastrectomy). Both body mass index(BMI)and body weight changes 12 months postoperatively were significantly higher in those who underwent PG(20.5 kg/m2 vs 18.4 kg/m2, p=0.043; and 96.6% vs 86.4%, p=0.016)despite being statistically similar preoperatively. The 5-year cause-specific survival rate of those who underwent PG was 100% excluding relapse cases. The 5-year overall survival rates were 86% in those who underwent PG and 67%in those who underwent NG, although they differed significantly. Partial gastrectomy may be a valid surgical procedure that may yield better prognosis compared to that with normal gastrectomy for elderly patients with Stage ⅠA gastric cancer.

[D2 Lymph Node Dissection in Mini-Laparotomy Transverse Colectomy Using Non-Contrast Simulation CT Colonography].

BACKGROUND AND PURPOSE: It is reported that simulation computed tomography colonography(S-CTC), which combines CTC and 3-dimensional(3D)vascular imaging, is useful in colorectal cancer surgery. However, it is difficult to create 3D vascular images using non-contrast CT. Laparoscopic transverse colectomy is said to be technically difficult. Mini-laparotomy surgery for mid-transverse colon cancer is quite easy to perform. However, exact D2 lymph node dissection is very difficult. We present a case of D2 lymph node dissection during mini-laparotomy transverse colectomy performed using S-CTC, which involves the creation of 3D vascular images using non-contrast CT. PATIENT AND METHOD: The patient was a 77-year-old man with transverse colon cancer located in the mid-transverse colon, cT2N0M0, Stage Ⅰ. He had coexisting chronic renal failure. Non-contrast CT was performed prior to surgery, and the images were processed using workstation Zaiostation2. RESULTS: Both the artery and the vein created from non-contrast CT could be visualized clearly until the marginal vessels. Using noncontrast S-CTC in combination with CTC and 3D artery imaging, it was identified that the dominant artery was the left branch of the middle colic artery(MCA Lt), while the right branch of the MCA(MCA Rt)and accessory MCA(AMCA)were 10 cm or more apart. The fusion of 3D artery and vein imaging made it evident that the vein accompanying MCA Lt branched from the superior mesenteric vein. Using non-contrast S-CTC, D2 lymph node dissection, dissection of the branching root of MCA Lt and the vein at the same level was simulated. Thus, mini-laparotomy transverse colectomy was performed through a 7 cm incision, in accordance with the simulation. CONCLUSION: Non-contrast S-CTC was useful for performing D2 lymph node dissection during mini-laparotomy transverse colectomy.

[A Case of Rectal Metastasis from Breast Cancer Diagnosed Two Years after Surgery].

We report a case of rectal metastasis from breast cancer.Colorectal metastasis from breast cancer is sometimes difficult to diagnose before surgery.A transanal needle biopsy was thought to be useful for a diagnosis and selection of treatment method.

Assessment for diagnosis of lymph node metastasis in esophageal cancer using endoscopic ultrasound elastography.

BACKGROUND: We performed endoscopic ultrasound real-time tissue elastography to more accurately diagnose lymph node metastasis of esophageal cancer. The aim of this study was to evaluate the ability of EUS elastography to distinguish benign from malignant lymph nodes in esophageal cancer patients. METHODS: The present study had two steps. As the first step (study 1), we developed diagnostic criteria for metastatic lymph nodes using elastography and verified the validity of the criteria. Three hundred and twenty-two lymph nodes from 35 patients treated by surgical resection were included in the study. As the second step (study 2), we preoperatively examined the lymph nodes of esophageal cancer patients with EUS elastography and compared its diagnostic performance with that of the conventional B-mode EUS images. A total of 115 lymph nodes from 31 patients were included. RESULTS: In study 1, lymph nodes were considered malignant if 50 % or more of the node appeared blue, or if the peripheral part of the lesion was blue and the central part was red/yellow/green. The sensitivity and specificity of the elastography were 79.7 and 97.6 % with an accuracy of 93.8 %, which was significantly higher than the values for conventional B-mode imaging. In study 2, the sensitivity and specificity of the EUS elastography were 91.2 and 94.5 % with an accuracy of 93.9 %, which was also significantly higher than the values for conventional B-mode EUS imaging. CONCLUSIONS: The present study demonstrated that EUS elastography is useful for diagnosing lymph node metastasis of esophageal cancer.

[Clinical evaluation of eribulin mesylate for the treatment of metastatic breast cancer].

BACKGROUND: Eribulin mesylate, a novel non-taxane inhibitor of microtubule dynamics, results in a significant improvement in the overall survival of heavily pretreated patients with metastatic breast cancer(MBC). In the present study, we aimed to clarify the efficacy and safety of eribulin mesylate for the treatment of MBC. PATIENTS AND METHODS: We examined 18 patients with MBC who received eribulin mesylate in our hospital from October 2011 to May 2013. The patients were assessed for therapeutic response and adverse events with this treatment; in addition, these parameters were assessed in patients undergoing a combination treatment of eribulin mesylate and trastuzumab. RESULTS: The mean age of the patients in this study was 68.7 years(range, 60-85 years). All patients exhibited metastases to lymph nodes and distant sites. The mean number of prior regimens was 4.4(range, 2-9). The mean number of cycles of eribulin mesylate treatment administered was 7.2(range, 2- 17). The objective response rate and clinical benefit rate(PR+long SD)were 33.3%(6/18)and 50.0%(9/18), respectively, and the median progression-free survival was 6 months. The Grade 3/4 adverse events occurring in the patients included neutropenia in 13 patients(72.2%), anemia in 1 patient(5.6%), anorexia in 1 patient(5.6%), stomatitis in 1 patient(5.6%), and peripheral neuropathy in 1 patient(5.6%). However, 3 elderly patients who received the combination treatment of trastuzumab and eribulin mesylate experienced no adverse events. CONCLUSIONS: eribulin mesylate appears to demonstrate an acceptable tumor response in patients with MBC, and it can be safely administered to elderly patients if myelosuppression is carefully managed.

Fat suppression strategies in MR imaging of breast cancer at 3.0 T: comparison of the two-point Dixon technique and the frequency selective inversion method.

PURPOSE: To compare two fat suppression methods in contrast-enhanced MR imaging of breast cancer at 3.0 T: the two-point Dixon method and the frequency selective inversion method. MATERIALS AND METHODS: Forty female patients with breast cancer underwent contrast-enhanced three-dimensional T1-weighted MR imaging at 3.0 T. Both the two-point Dixon method and the frequency selective inversion method were applied. Quantitative analyses of the residual fat signal-to-noise ratio and the contrast noise ratio (CNR) of lesion-to-breast parenchyma, lesion-to-fat, and parenchyma-to-fat were performed. Qualitative analyses of the uniformity of fat suppression, image contrast, and the visibility of breast lesions and axillary metastatic adenopathy were performed. RESULTS: The signal-to-noise ratio was significantly lower in the two-point Dixon method (P < 0.001). All CNR values were significantly higher in the two-point Dixon method (P < 0.001 and P = 0.001, respectively). According to qualitative analysis, both the uniformity of fat suppression and image contrast with the two-point Dixon method were significantly higher (P < 0.001 and P = 0.002, respectively). Visibility of breast lesions and metastatic adenopathy was significantly better in the two-point Dixon method (P < 0.001 and P = 0.03, respectively). CONCLUSION: The two-point Dixon method suppressed the fat signal more potently and improved contrast and visibility of the breast lesions and axillary adenopathy.

[A case of far advanced-esophageal squamous cell carcinoma successfully treated with docetaxel].

A 65-year-old man with dysphagia and hoarseness was admitted to our hospital. The upper gastrointestinal examinations revealed a tumor in the lower esophagus while the biopsy specimens revealed squamous cell carcinoma. The clinical diagnosis was esophageal cancer(Lt, type 2, cT3N4M0, cStage IVa). The patient underwent neoadjuvant-chemotherapy(5-fluorouracil/cisplatin). After one course, computed tomography(CT)showed rapid growth of the tumor and lymph nodes, resulting in a progressive disease. It was considered unresectable because of the direct invasion of the No. 1 lymph node to the liver. Then, three courses of docetaxel were administered as second-line chemotherapy, and CT revealed the markedly reduced size of the tumor and lymph nodes, resulting in a partial response. The tumor was now thought to be resectable. Subtotal esophagectomy could be performed and the postoperative course was uneventful. Histopathological findings showed no evidence of malignancy at the primary tumor(grade 3), although there were residual atypical keratinocytes in some lymph nodes. The patient is doing well without any signs of recurrence 21 months after the surgery.

miR-203 inhibits the migration and invasion of esophageal squamous cell carcinoma by regulating LASP1.

The expression of microRNA-203 (miR-203) in esophageal squamous cell carcinoma (ESCC) tissues is remarkably lower than that in non­ESCC tissues. We investigated how miR-203 could influence the development of ESCC cells. Our analyses revealed that miR-203 inhibited the migration and invasion of ESCC cells. Genome-wide gene expression data and target site inhibition assays showed that miR-203 appears to directly regulate LIM and SH3 protein 1 (LASP1). The knockdown of LASP1 resulted in inhibition of the migration and invasion of ESCC cells. Our results suggest that miR-203 and its target LASP1, may be associated with the progression of ESCC. In clinical ESCC specimens, the expression levels of miR-203, which were lower compared to those in normal tissues, were inversely correlated with the mRNA expression levels of LASP1. Moreover, we found that there was a significant correlation between the expression levels of miR-203 and the relapse­free survival. The identification of a cancer network regulated by miR-203 could provide new insights into the potential mechanisms of the progression of ESCC.

Diffusion-weighted MRI as an adjunct to mammography in women under 50 years of age: an initial study.

PURPOSE: To evaluate diffusion-weighted magnetic resonance (DW) imaging as an adjunct to mammography for the detection of small invasive breast cancer. MATERIALS AND METHODS: Institutional review board standards were followed for this retrospective study. We performed both breast DW imaging and mammography on 25 women under 50 years of age with pathologically proven T1 breast cancer and on 21 healthy women under 50 years of age. Four offsite radiologists blind to the clinical information independently interpreted the mammograms and DW images and then classified their confidence level regarding the presence of breast cancer. The composite area under receiver operating characteristic curve (AUC), of mammography alone, DW imaging alone, and the combination of DW imaging and mammography (DWI/Cal) were calculated. RESULTS: The AUC of composite ROC curves of mammography, DW imaging, DWI/Cal combination, was 0.79 (95% CI, 0.72-0.87), 0.86 (95% CI, 0.84-0.87), and 0.96 (95% CI, 0.92-1.00), respectively. CONCLUSION: DW imaging may be a useful adjunct to mammography in the detection of small invasive breast cancer in women under 50 years of age.

A phase 1/11 study of second-line chemotherapy with fractionated docetaxel and nedaplatin for 5-FU/cisplatin-resistant esophageal squamous cell carcinoma.

BACKGROUND/AIMS: There are few second-line regimens available for esophageal cancer. The use of fractionated docetaxel and nedaplatin as second-line chemotherapy was examined in this study. METHODOLOGY: Eligibility criteria were follows: histologically-proven squamous cell carcinoma, surgically unresectable disease, failure to respond to chemotherapy with 5-FU and cisplatin and no more than 2 prior chemotherapy regimens. A total of 12 patients were enrolled in this study. To reduce toxicities, fractionated docetaxel (50 mg/m² in day 1 and 8) and nedaplatin (50 mg/m² in day 8) were administered as second-line chemotherapy. RESULTS: Stable disease (SD) was observed in 4 cases (33%) and the disease control rate was 33%. Regarding toxicities, leukopenia was the most frequently observed (8 cases, 67%); however, there were no cases of grade 4 nonhematological toxicity. The 1-year overall survival was 26.7% and the median survival time was 7.8 months (95% CI=3.328-12.272 months). The 1-year progression-free survival was 0% and the median progression-free time was 2.0 months (95% CI=1.319-2.681). CONCLUSIONS: Combination chemotherapy using fractionated docetaxel and nedaplatin is safe and effective and appears to be a feasible regimen to use as second-line chemotherapy for FP-resistant advanced esophageal squamous cell carcinoma.

COX2 expression predicts resistance to chemoradiotherapy in esophageal squamous cell carcinoma.

PURPOSE: The overexpression of cyclooxygenase (COX)2 is correlated with carcinogenesis, tumor progression, and prognosis, and increased COX2 expression is correlated with radiation resistance. However, no correlation between the COX2 expression and resistance to chemoradiotherapy for esophageal squamous cell carcinoma has been characterized. The purpose of the present study was to evaluate whether COX2 expression is an indicator of resistance to chemoradiotherapy in esophageal squamous cell carcinoma and the feasibility of COX2 as a biomarker for CRT. METHODS: Fifty-eight patients who were diagnosed with esophageal squamous cell carcinoma from biopsy samples were enrolled in the present series. All patients underwent concurrent chemoradiotherapy in a neoadjuvant setting, followed by radical esophagectomy. COX2 expression was evaluated by immunohistochemical staining and statistically compared with the histopathologic findings in surgically resected specimens. RESULTS: The rate of responders was 87% for weak expression of COX2, 62% for moderate expression, and 30% for strong expression, and there was a close correlation between COX2 expression and the response rate (Kendall's τb = 0.396, P = 0.001). In the univariate analysis, negative or weak expression of COX2 was found to correlate significantly with CRT response (odds ratio, 6.296; 95% confidence interval (CI), 1.58-25.096; P = 0.010). In the multivariate analysis, weak expression of COX2 (30% or less) was found to be an independent prognostic factor (odds ratio, 6.534; 95% CI, 1.535-27.803; P = 0.011). CONCLUSIONS: The COX2 expression predicts resistance to chemoradiotherapy in esophageal squamous cell carcinoma, and it also is a feasible biomarker for evaluating the CRT response.

A case of small-cell esophageal cancer with chronic renal failure undergoing hemodialysis safely treated with cisplatin and etoposide.

A 54-year-old male undergoing hemodialysis was admitted to our hospital because of difficulty in swallowing. Esophagography and esophageal endoscopy revealed an irregular ulcerated lesion in the cervical esophagus. It was diagnosed as a small-cell esophageal cancer from the biopsy sample. Computed tomography showed a tumor infiltrating the trachea and a few lymph node metastases in the cervix, upper mediastinum, and abdomen. The patient was started on chemotherapy with cisplatin (CDDP) and etoposide (VP-16), which had been reported to be effective for small-cell lung cancer. The patient was treated with CDDP (80 mg/m(2)) on day 1 and VP-16 (100 mg/m(2)) on days 1, 3, and 5, every 4 weeks. On the days of chemotherapy, hemodialysis was started as soon as possible after completion of administration of the agents. No severe side effects were observed. After 4 courses of therapy, the patient achieved a partial response.

CHAP31 induces apoptosis only via the intrinsic pathway in human esophageal cancer cells.

OBJECTIVE: The antitumor mechanism of histone deacetylase (HDAC) inhibitors differs from conventional antitumor agents. HDAC inhibitors may be effective as novel therapeutic agents for esophageal squamous cell carcinoma (ESCC). This study describes the antiproliferative activity of CHAP31, a novel HDAC inhibitor. Furthermore, the molecular mechanism of CHAP31-induced apoptosis was investigated in ESCC. METHODS/RESULTS: The antitumor activity of CHAP31 was tested in esophageal cancer cell lines (T.Tn and TE2), and potent antitumor activity was observed in vitro and in vivo. In addition, CHAP31 induced apoptosis in esophageal cancer cells. Next, the mechanisms of CHAP31-induced apoptosis were examined using quantitative real-time RT-PCR and Western blotting. No processing of caspase 8 was observed, but CHAP31 induced the cleavage of caspase 9 and up-regulation of the Bax/Bcl-2 protein ratio. CONCLUSION: This study provides new and important information on the potent antitumor activity of CHAP31 and the apoptotic pathway induced by CHAP31 in human esophageal cancer cell lines T.Tn and TE2. In contrast to previous reports showing that apoptosis induced by HDAC inhibitors includes the extrinsic pathway, in our study, apoptosis induced by CHAP31 in the human esophageal cell lines T.Tn and TE2 involved only the intrinsic pathway.

Pre-operative dental brushing can reduce the risk of postoperative pneumonia in esophageal cancer patients.

BACKGROUND: The presence of pathogens in dental plaque is a risk factor associated with postoperative pneumonia in esophageal cancer patients. The effectiveness of pre-operative dental brushing to decrease the risk of postoperative pneumonia in esophageal cancer patients was evaluated prospectively. METHODS: A total of 86 thoracic esophageal cancer patients who underwent an esophagectomy were investigated. Patients were divided into 2 groups: the control group (41 patients) and the pre-operative dental brushing group (45 patients). The patients in the brushing group were assigned to brush their teeth 5 times a day. After the operation, the frequency of postoperative pneumonia and need for tracheostomy for pulmonary treatment was calculated. RESULTS: Postoperative pneumonia was decreased markedly from 32% to 9% (P = .013), and the frequency of postoperative pneumonia requiring tracheostomy decreased from 12% to 0% in the dental brushing group, respectively. Limiting the patients who had positive pathogenic bacteria in their dental plaque on their admission, the frequency of postoperative pneumonia was decreased from 71% (5 of 7 patients) in the control group to 17% (2 of 12 patients) in the dental brushing group (P = .045). CONCLUSION: Frequent pre-operative dental brushing is performed easily and seems to prevent postoperative pneumonia in esophageal cancer patients.

[Effect of practical use of preoperative immunonutrition with impact on prevention of postoperative pneumonia after esophagectomy].

To clarify the clinical benefits of administering immune-enhancing diet, Impact,we examined retrospectively the effect of preoperative immunonutrition with Impact on prevention of postoperative pneumonia after esophagectomy. In 47 patients without preoperative radiotherapy, no patient who preoperatively administered Impact>or=2,250 mL failed to develop pneumonia. The patients whose postoperative hospital stay was more than 30 days were administered Impact

Effects of carbon-ion radiotherapy combined with a novel histone deacetylase inhibitor, cyclic hydroxamic-acid-containing peptide 31 in human esophageal squamous cell carcinoma.

BACKGROUND: Carbon-ion radiotherapy has several potential advantages over X-rays. This therapy has been applied for various solid tumors including esophageal squamous cell carcinoma (SCC). However, some patients have shown resistance to this treatment. A new effective combined treatment strategy is required for improving the therapeutic effects. Histone deacetylase inhibitors (HDACIs) are new therapeutic candidates for cancer treatment. Several studies have evaluated the combination of X-rays and HDACIs, but, to date, no study has evaluated carbon-ion radiotherapy combined with HDACIs. MATERIALS AND METHODS: Radio-sensitization to carbon-ion radiotherapy when combined with a novel HDACI cyclic hydroxamic-acid-containing peptide 31(CHAP31) was assessed in human esophageal SCC both in vitro and in vivo. Changes of expression of genes related to DNA repair, by CHAP31 were assessed by quantitative real-time reverse transcriptional PCR analysis. RESULTS: CHAP31 induced sensitization to carbon-ion radiotherapy in vitro and tumor growth was significantly suppressed by the combination of carbon-ion radiotherapy with CHAP31 in comparison to either agent alone in in vivo experiments. CHAP31 inhibited the expression of genes related to DNA repair. CONCLUSION: CHAP31 sensitizes SCC cells to carbon-ion radiotherapy and this combinatory treatment may be a potentially useful therapeutic strategy for esophageal SCC.

Clinical and pathologic evaluation of the effectiveness of neoadjuvant chemoradiation therapy in advanced esophageal cancer patients.

BACKGROUND: Chemoradiation therapy (CRT) has the strongest antitumor effect against local tumors of esophageal cancer; however, no standard strategy has yet been established to achieve a clinical complete response (CR) after CRT. The aim of this study was to clarify when a decision can be made to perform further treatment for a clinical CR. METHODS: We evaluated 78 patients that underwent an esophagectomy after neoadjuvant CRT in our department between 1998 and 2007. The study investigated the clinical and pathologic results of neoadjuvant CRT. RESULTS: Of the 78 cases, 19 (24.3%) were a pathologic CR (Grade 3). Pathologic CR could be estimated in only 3 of 8 clinical CR cases (37.5%). On the other hand, 12 (20.7%) of the 58 clinical partial response (PR) cases achieved pathologic CR. Likewise, 4 cases (36.4%) achieved pathologic CR among the clinical no change/progressive disease (NC/PD) patients. CONCLUSIONS: The clinical evaluation for CRT does not reflect the pathologic effectiveness and, even if clinical CR was achieved, viable cancer cells were still present at the primary site in the majority of the population.

Combined effects of p53 gene therapy and leptomycin B in human esophageal squamous cell carcinoma.

BACKGROUND: p53 gene therapy has been examined in several clinical trials, however, the results of those trials have mostly been unsatisfactory due to the low efficacy of this therapy. Leptomycin B (LMB) is an antibiotic originally isolated from Streptomyces that has the ability to inhibit the export of proteins containing a nuclear export signal from the nucleus to the cytoplasm. Currently, it has been shown that p53 protein has a nuclear export signal. In this study, we assessed whether LMB augments the transduced p53 gene effect. METHODS: Antiproliferative effect of LMB was assessed in human esophageal squamous cancer cell lines. Accumulation of p53 protein into the nucleus by LMB was observed by fluorescence microscopy. The combined effect of p53 and LMB was evaluated in in vitro experiments. RESULTS: LMB induced cell death in a dose-dependent manner and p53 drastically accumulated in the nucleus after LMB treatment. The combinatory treatment of p53 gene and LMB significantly increases the efficiency compared to either agent alone. CONCLUSIONS: Our findings suggest that LMB has a potent ability to augment the effect of the tumor suppressor p53 in esophageal squamous cancer cell lines and that it is a promising component in p53 gene therapy.