Kiyotomi Maruyama

Akita University, Akita, Akita-ken, Japan

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Publications (52)94.56 Total impact

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    ABSTRACT: Cancer cells reportedly produce C-reactive protein (CRP) locally within tumors. The aim of this study was to determine whether tumoral CRP is associated with clinical outcome and recurrence in thoracic esophageal squamous cell cancer. The subjects included 73 Japanese patients with thoracic esophageal squamous cell cancer (pathological Stage IIA-IV) that had not been treated preoperatively with either chemotherapy or radiotherapy. Tumoral CRP expression in resected specimens of tumor tissue was assessed by immunohistochemistry. The survival rate following surgery, the rates and patterns of recurrence, and the serum CRP levels before treatment and at recurrence were analyzed in patients with and without tumoral CRP expression. Fifty-nine percent of the study participants (43/73) were positive for tumoral CRP expression, and the remaining 41% (30/73) were negative. No significant difference in clinicopathological factors was observed between the tumoral CRP-positive and CRP-negative groups; however, patients expressing tumoral CRP showed significantly poorer survival and recurrence rates. A multivariate analysis showed that tumoral CRP expression was an independent factor contributing to the likelihood of a poor outcome. Tumoral CRP is associated with a poor outcome in thoracic esophageal squamous cell cancer. Tumoral CRP could therefore be an important target for the treatment of this disease.
    Surgery Today 02/2012; 42(7):652-8. · 0.96 Impact Factor
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    ABSTRACT: In cases of thoracic esophageal cancer, multidirectional lymphatic flow from the tumor means that lymph node metastasis can occur in an area extending from the neck to the abdomen. To validate a method for limiting the performance of three-field lymphadenectomy only to patients who need it, we carried out a prospective study in which superparamagnetic iron oxide (SPIO)-enhanced lymphatic mapping was used to determine whether to perform neck lymph node dissection in patients with submucosal thoracic esophageal cancer. A total of 22 patients with clinically submucosal thoracic squamous cell esophageal cancer, without neck lymph node metastasis, were enrolled. SPIO was endoscopically injected into the peritumoral submucosal layer, after which its appearance in lymph nodes in the neck was evaluated using magnetic resonance imaging (MRI). Neck lymph nodes were then dissected based on the SPIO-enhanced MRI lymphatic mapping. Influx of SPIO into lymph nodes was detected in 21 patients (95% detection rate). SPIO flowed to the neck in 8 (36%) patients. Influx of SPIO into neck lymph nodes was unilateral in five patients and bilateral in three patients, and the lymph nodes were dissected accordingly. A cancer-involved node was identified in two of those patients. In 14 patients, we did not dissect neck nodes. Patients were followed up for 6 to 47 months. The neck lymph node recurrence rate was zero, and the overall recurrence rate was 5%. SPIO-enhanced lymphatic mapping may be useful for estimating the need for three-field lymphadenectomy with neck dissection.
    World Journal of Surgery 01/2012; 36(1):83-9. · 2.23 Impact Factor
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    ABSTRACT: Patients who have received subtotal esophagectomy for thoracic esophageal cancer must be closely monitored for second primary malignancies. The purpose of this study is to review and assess patients who developed a second primary esophageal cancer in the residual cervical esophagus. Between 1996 and 2010, 10 patients were diagnosed in our hospital with esophageal squamous cell cancer in the residual cervical esophagus after undergoing thoracic esophagectomy and were treated with endoscopic or surgical resection. Data from these patients were reviewed retrospectively. Seven of the 10 patients (70%) had multiple primary carcinoma lesions at the time of their esophagectomy. A second primary cancer in the residual cervical esophagus was detected in eight patients during follow-up endoscopic examinations while the patients were still asymptomatic. Seven of the patients underwent endoscopic resection for a superficial cancer. None of those patients experienced any complications, and all are currently alive and cancer-free. The remaining three patients underwent resection of the cervical esophagus with regional lymph node dissection. Two of those patients experienced severe complications; one subsequently died (hospital death) from pneumonia, 12 months after surgery, while the other died from recurrence of his cancer. The third patient is alive and cancer-free. Early detection of a second primary malignancy in the residual cervical esophagus followed by endoscopic resection is the best treatment strategy for patients who previously received subtotal esophagectomy for thoracic esophageal cancer. Surgical resection puts patients at high risk of mortality or morbidity.
    Diseases of the Esophagus 09/2011; 25(3):228-34. · 1.64 Impact Factor
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    ABSTRACT: Treatment of primary malignant melanoma of the esophagus remains challenging. We treated a 53-year-old man with pT4N2M0, Stage IVa malignant melanoma of the esophagus with esophagectomy followed by adjuvant chemotherapy. Six months later, computed tomography revealed a 12 cm disseminated tumor of the mesenterium, multiple peritoneal dissemination, and a large amount of ascites. We administered chemotherapy consisting of dacarbazine combined with cisplatin and nimustine, and radiotherapy(50 Gy)was applied to the disseminated mesenteric tumor. At another clinic, the patient was administered synchronous cellular immunotherapy consisting of dendritic cells pulsed with autologous tumor lysates and lymphokine-activated killer cells. The mesenteric tumor was extremely responsive to this trimodal treatment. Because recurrence occurred later within the left orbita muscle, we added 50 Gy of radiation to prevent blindness. The patient responded to this treatment and survived another 6 months with high quality of life. It is difficult to treat advanced malignant melanoma of the esophagus, and patient prognosis is extremely poor. In this patient, the recurrent tumors responded well to trimodal therapy consisting of chemotherapy, radiotherapy and cellular immunotherapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2011; 38(4):639-42.
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    ABSTRACT: Identification of reliable markers of radiosensitivity and the key molecules that enhance the susceptibility of esophageal cancer cells to anticancer treatments would be highly desirable. To identify molecules that confer radiosensitivity to esophageal squamous carcinoma cells, we assessed the radiosensitivities of the TE-5, TE-9 and TE-12 cloneA1 cell lines. TE-12 cloneA1 cells showed significantly greater susceptibility to radiotherapy at 5 and 10Gy than either TE-5 or TE-9 cells. Consistent with that finding, 24h after irradiation (5Gy), TE-12 cloneA1 cells showed higher levels of caspase 3/7 activity than TE-5 or TE-9 cells. When we used DNA microarrays to compare the gene expression profiles of TE-5 and TE-12 cloneA1 cells, we found that the mRNA and protein expression of insulin-like growth factor binding protein 3 (IGFBP3) and Bcl-2-associated athanogene 1 (BAG1) was five or more times higher in TE-12 cloneA1 cells than TE-5 cells. Conversely, knocking down expression of IGFBP3 and BAG1 mRNA in TE-12 cloneA1 cells using small interfering RNA (siRNA) significantly reduced radiosensitivity. These data suggest that IGFBP3 and BAG1 may be key markers of radiosensitivity that enhance the susceptibility of squamous cell esophageal cancer to radiotherapy. IGFBP3 and BAG1 may thus be useful targets for improved and more individualized treatments for patients with esophageal squamous cell carcinoma.
    Biochemical and Biophysical Research Communications 01/2011; 404(4):1070-5. · 2.28 Impact Factor
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    ABSTRACT: The mainstay treatment for benign esophageal stricture is dilation with medical therapy. Although dilation usually provides symptomatic relief, recurrent refractory strictures often occur. Here we describe the treatment of a patient with a diffuse esophageal stricture caused by severe acid exposure from frequent vomiting during treatment of a duodenal ulcer. Administration of a proton pump inhibitor without dilation relieved the diffuse stricture and completely restored esophageal motility in this patient.
    Esophagus 01/2011; 8(1):63-65. · 0.83 Impact Factor
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    ABSTRACT: Key molecules in the T helper (Th)1 and Th2 pathways underlie differential responses to the progression and surgical treatment of cancer. We investigated the relationship between Th1/Th2 cytokine polymorphism and prognosis in patients with thoracic esophageal squamous cell cancer. The study participants were 159 Japanese patients treated for thoracic esophageal squamous cell cancer with curative esophagectomy at Akita University Hospital. We determined the associations between prognosis following esophagectomy and genetic polymorphisms in Th1 cytokines (interleukin [IL]-2, Interferon-γ, IL-12β), and Th2 cytokines (IL-4, IL-10). IL-2 -330T>G genetic polymorphism was significantly associated with prognosis after esophagectomy. Univariate and multivariate analyses using a Cox proportional hazards model revealed that patients carrying the IL-2 -330G/G genotype had a significantly poorer prognosis than those carrying the T/G or T/T genotype. However, IL-2 -330T>G polymorphism was not associated with preoperative serum IL-2 levels. Moreover, interferon-γ, IL-12β, IL-4, and IL-10 genetic polymorphisms were not associated with prognosis after esophagectomy for thoracic esophageal squamous cell cancer. It is suggested that IL-2 -330T>G genetic polymorphism may be a predictive factor for prognosis in patients receiving esophagectomy for thoracic esophageal squamous cell cancer.
    Annals of Surgical Oncology 01/2011; 18(7):1995-2002. · 4.12 Impact Factor
  • The American surgeon 12/2010; 76(12):1442-4. · 0.92 Impact Factor
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    ABSTRACT: We investigated the effectiveness of chemoradiotherapy for the treatment of lymph node recurrence and hematogenous metastasis after esophagectomy for esophageal squamous cell carcinoma. Between 2001 and 2006, 216 patients with thoracic esophageal squamous cell carcinoma had curative esophagectomy. Of those, 23 with lymph node recurrence received chemoradiotherapy (50.0-68.8 Gy). In addition, five patients had isolated recurrences in a distant organ and received chemoradiotherapy (50.0-60.0 Gy). We analyzed outcomes from the radiotherapy for recurrent esophageal cancer. The 1-, 2-, and 5-year survival rates after recurrence for the 23 patients whose lymph node recurrence was treated with chemoradiotherapy were 52, 31, and 24%, respectively, and the median survival time was 13 months. Among the five patients with recurrent tumors in a distant organ, chemoradiotherapy produced a complete response in two patients, a partial response in one patient, and stable disease in two patients, giving an effectiveness rate of 60% (complete response + partial response). Chemoradiotherapy has a beneficial prognostic effect in patients with lymph node recurrence of esophageal squamous cell carcinoma. Chemoradiotherapy for a metastatic tumor in a distant organ may be the treatment of choice in cases where systemic chemotherapy has proven ineffective.
    Diseases of the Esophagus 10/2010; 24(3):166-71. · 1.64 Impact Factor
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    ABSTRACT: Stress hyperglycemia refers to the transient hyperglycemia seen during illness and is usually restricted to patients without previous evidence of diabetes. The influence of genetics on surgery-induced hyperglycemia remains only partially understood. The study participants were Japanese patients treated for thoracic esophageal cancer with curative esophagectomy at Akita University Hospital between 2003 and 2007. We determined the associations between esophagectomy-induced stress hyperglycemia (> or =30 mg/dl increases in blood glucose during surgery) and genetic polymorphisms for C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, -beta, interferon-gamma, transforming growth factor-beta1, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-6 receptors, IL-10, IL-12beta, adiponectin, and peroxisome proliferator-activated receptor-gamma. In 28 (46%) patients, blood glucose levels increased more than 30 mg/dl during surgery. Among the genetic polymorphisms tested, CRP -717C>T was significantly associated with stress hyperglycemia during esophagectomy. Multivariate logistic regression revealed that patients with the CRP -717T/T genotype had a significantly greater risk of developing surgery-induced hyperglycemia than those with the CRP -717C/T genotype. Stress hyperglycemia was also significantly associated with postoperative infectious complications and duration of intensive care unit stay. It is suggested that CRP -717 C>T genetic polymorphism may be a predictive factor for stress hyperglycemia in patients receiving esophagectomy for thoracic esophageal cancer.
    World Journal of Surgery 02/2010; 34(5):1001-7. · 2.23 Impact Factor
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    ABSTRACT: Regenerating gene (REG) I plays important roles in cancer cell biology. The purpose of this study was to determine whether REG I affects cytokine production in cancer cells. We transfected TE-5 and TE-9 squamous esophageal cancer cells with REG Ialpha and Ibeta and examined its effects on cytokine expression. We found that transfecting TE-5 and TE-9 cells with REG I Ialpha and Ibeta led to significantly increased expression of interleukin (IL)-6 mRNA and protein, but it had little or no effect on expression of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17A, interferon-gamma, tumor necrosis factor-alpha, granulocyte-colony stimulating factor or transforming growth factor-beta1. The elevated IL-6 expression seen in REG Ialpha transfectants was silenced by small interfering RNA-mediated knockdown. These finding suggest that REG I may act through IL-6 to exert effects on squamous esophageal cancer cell biology.
    Biochemical and Biophysical Research Communications 01/2010; 392(1):4-8. · 2.28 Impact Factor
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    ABSTRACT: We report 2 cases of small cell carcinoma of the esophagus treated with esophagectomy as a primary treatment and following chemotherapy. One patient (pT1N1M0) achieved long-term survival, while the other patient (pT1N1M1-lym) died 18 months after surgery. We used reports on 47 Japanese patients receiving esophagectomy as a primary treatment to determine when esophagectomy for small cell carcinoma of the esophagus is indicated. We conclude that esophagectomy as a local treatment provides relatively good long-term survival only in patients without lymph node involvement.
    European Surgical Research 01/2010; 45(1):41-4. · 0.75 Impact Factor
  • Satoru Motoyama, Kiyotomi Maruyama, Jun-ichi Ogawa
    Digestive surgery 11/2009; 26(5):371. · 1.37 Impact Factor
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    ABSTRACT: Cytokines play a major role in the organization of orchestrated responses to infections, and there is an emerging consensus that cytokine gene polymorphisms mediate individual variations in cytokine expression. Our aim in this study was to assess whether cytokine polymorphisms were associated with infectious complications following esophagectomy in a Japanese population. The study participants were Japanese patients treated with transthoracic esophagectomy without neoadjuvant treatment. DNA was extracted from blood samples, and genetic polymorphisms for interferon (INF)-gamma, tumor necrosis factor-alpha and -beta, transforming growth factor-beta1, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between gene polymorphisms and postoperative infection. Of the 110 patients studied, 18 (16%) developed a postoperative infection (pneumonia, 14 patients; pyothorax, 5; intraabdominal abscess, 1; neck abscess, 1; sepsis, 2). Although the characteristics of patients who developed postoperative infections did not differ, analysis of the genotypes using the Fisher exact test revealed a significantly (P = .0215) greater incidence of postoperative infections among those carrying the INF-gamma 874 (rs2430561) A/A and A/T genotypes. Moreover, univariate and multivariate logistic regression models showed patients carrying the INF-gamma 874A/T genotype were significantly more likely to develop postoperative infectious complications (odds ratio>3.4). Our findings suggest that the IFN-gamma 874A>T polymorphism is potentially predictive of the likelihood that patients undergoing esophagectomy for thoracic esophageal cancer will develop postoperative infections. This polymorphism may therefore have important clinical relevance and should be considered when treatment regimens are designed.
    Surgery 10/2009; 146(5):931-8. · 3.37 Impact Factor
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    ABSTRACT: Little is known about how C-reactive protein (CRP) genetic polymorphisms influence the rise in serum CRP levels seen after surgery. The purpose of this study was to assess the association between CRP polymorphisms and acute-phase serum CRP levels after esophagectomy for thoracic esophageal cancer. We enrolled 110 patients who underwent curative esophagectomy without neoadjuvant treatment between 2003 and 2008. Using peripheral blood samples collected from the patients, polymorphisms for CRP, tumor necrosis factor, interferon-gamma, tumor growth factor-beta1, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were all investigated to determine which, if any, affect postoperative serum CRP levels and clinical outcomes. Although preoperative serum CRP levels did not differ, 12 hours after esophagectomy, serum CRP levels were significantly higher in patients carrying the CRP 1059G/G genotype than in those with the 1059G/C genotype (111 +/- 35 mg/L versus 78 +/- 17 mg/L; p = 0.0266), and after 36 hours CRP levels remained higher in those with the 1059G/G genotype (217 +/- 63 mg/L versus 140 +/- 51 mg/L; p = 0.0020). Logistic regression models revealed that patients carrying the CRP 1059G/G genotype had a significantly higher likelihood of a postesophagectomy increase in serum CRP, although the CRP 1059G>C genetic polymorphism had no effect on clinical outcomes. None of the other cytokine genetic polymorphisms influenced postoperative serum CRP levels. Our findings suggest that the CRP 1059G>C genetic polymorphism is 1 determinant of serum CRP levels after major surgery.
    Journal of the American College of Surgeons 10/2009; 209(4):477-83. · 4.50 Impact Factor
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    ABSTRACT: Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis. The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and -beta, interferon (IFN)-gamma, transforming growth factor (TGF)- beta, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis. For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively. These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.
    Annals of Surgical Oncology 07/2009; 16(9):2479-85. · 4.12 Impact Factor
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    ABSTRACT: Heat shock protein (Hsp) 90 is a key regulator of a variety of oncogene products and cell-signaling molecules, and the therapeutic benefit of its inhibition in combination with radiation or chemotherapy has been investigated. In addition, hyperthermia has been used for many years to treat various malignant tumors. We previously described a system in which hyperthermia was induced using thermosensitive ferromagnetic particles (FMP) with a Curie temperature (Tc = 43 degrees C) low enough to mediate automatic temperature control, and demonstrated its antitumor effect in a mouse melanoma model. In the present study, we examined the antitumor effects of combining a Hsp90 inhibitor (geldanamycin; GA) with FMP-mediated hyperthermia. In cultured B16 melanoma cells, GA exerted an antitumor effect by increasing the cells' susceptibility to hyperthermia and reducing expression of Akt. In an in vivo study, melanoma cells were subcutaneously injected into the backs of C57BL/6 mice. FMP were then injected into the resultant tumors, and the mice were divided into four groups: group I, no treatment (control); group II, one hyperthermia treatment; group III, GA alone; and group IV, GA with hyperthermia. When exposed to a magnetic field, the temperature of tissues containing FMP increased and stabilized at the Tc. In group IV, complete regression of tumors was observed in five of nine mice (56%), whereas no tumor regression was seen in groups I-III. Our findings suggest that inhibition of Hsp90 with hyperthermia increases its antitumor effect. Thus, the combination of FMP-mediated, self-regulating hyperthermia with Hsp90 inhibition has important implications for the treatment of cancer.
    Cancer Science 02/2009; 100(3):558-64. · 3.48 Impact Factor
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    ABSTRACT: Following esophagectomy, tracheobronchial lesions (TBLs) can occur as a result of ischemia caused by extensive dissection around the tracheobronchus. In this study we assessed the causes and clinical features of these complications, paying particular attention to lymph node (LN)-related factors. Between January 2000 and March 2007, 305 consecutive patients underwent subtotal esophagectomy using a transthoracic approach with LN dissection for thoracic esophageal cancer. TBLs, including erosions, ulcers, and fistulae, without traumatic injury during the operation, were detected during bronchoscopic examinations performed twice daily after the operation. The correlation between TBLs and tumor or surgical factors were analyzed. TBLs were observed in 14 patients, accounting for an overall incidence of 5%; these included 6 fistulae, 5 ulcers, and 3 erosions. Cases with TBLs significantly more often involved three-field LN dissections (3FLD) than those without TBLs. Six (43%) patients with TBLs had more than four metastatic lymph nodes, while 9 (64%) had cervical and upper-mediastinal LN metastasis (p=0.034 and 0.041, respectively). More than 60 LNs were dissected from 10 (71%) patients with TBLs (p=0.021), and logistic regression analysis revealed that dissection of more than 60 lymph nodes and 3FLD were independent predictors of TBLs. Esophageal cancer patients requiring extensive LN dissection of more than 60 nodes and/or 3FLD have an increased risk of developing a TBL during their postoperative course.
    World Journal of Surgery 02/2009; 33(4):778-84. · 2.23 Impact Factor
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    ABSTRACT: Three-field lymph node dissection for thoracic esophageal cancer is associated with high morbidity and reduced quality of life after surgery. Consequently, minimized lymphadenectomy would be desirable, if appropriate. In the present study, we retrospectively analyzed the status of involved nodes and the direction of metastatic lymphatic flow from tumors into involved nodes to determine whether submucosal squamous cell esophageal cancers are potential candidates for minimized lymphadenectomy. We enrolled 199 patients who received esophagectomy with extensive lymph node dissection between 1989 and 2005 and retrospectively analyzed their prognoses, distribution of solitary metastatic lymph nodes, and the direction of metastatic lymphatic flow from the tumor, taking into consideration tumor location and depth. Of these patients with submucosal cancers, 83% had 1 or 2 involved nodes, and their esophageal cancer-specific 5-year survival rate was 66%. Solitary lymph node metastasis did not occur in neck lymph nodes in lower thoracic submucosal esophageal cancers, and the direction of metastatic lymphatic flow from the tumor was almost always in one direction. By contrast, T2-4 cancers with 2-4 involved nodes had bidirectional metastatic lymphatic flow from the tumor. There was a difference in the status of lymph node metastasis and the direction of metastatic lymphatic flow from tumors into involved nodes between submucosal and T2-4 thoracic squamous cell esophageal cancers. This analysis may be useful for developing an approach to minimized lymphadenectomy for thoracic esophageal cancers.
    World Journal of Surgery 12/2008; 33(3):512-7. · 2.23 Impact Factor
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    ABSTRACT: Identification of reliable markers of chemo- and radiosensitivity and the key molecules that enhance the susceptibility of squamous esophageal cancer cells to anticancer treatments would be highly desirable. To test whether regenerating gene (REG) I expression enhances chemo- and radiosensitivity in esophageal squamous cell carcinoma cells, we used MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays to compare the chemo- and radiosensitivities of untransfected TE-5 and TE-9 cells with those of cells stably transfected with REG Ialpha and Ibeta. We then used flow cytometry to determine whether REG I expression alters cell cycle progression. No REG I mRNA or protein were detected in untransfected TE-5 and TE-9 cells. Transfection with REG Ialpha and Ibeta led to strong expression of both REG I mRNA and protein in TE-5 and TE-9 cells, which in turn led to significant increases in both chemo- and radiosensitivity. Cell cycle progression was unaffected by REG I expression. REG I thus appears to enhance the chemo- and radiosensitivity of squamous esophageal cancer cells, which suggests that it may be a useful target for improved and more individualized treatments for patients with esophageal squamous cell carcinoma.
    Cancer Science 12/2008; 99(12):2491-5. · 3.48 Impact Factor