Biomedical subjects

Hiroshi Okumura

Publications and source records attributed to Hiroshi Okumura.

At least 19 recordsLinked to original sources

PubMed2006

Carcinoembryonic antigen messenger RNA expression in blood predicts recurrence in esophageal cancer.

PURPOSE: The clinical significance of isolated tumor cells (ITC) in blood has not been clearly established, particularly during follow-up in cancer patients. We conducted a longitudinal analysis of the relationship between ITC in blood during follow-up and clinicopathologic findings in patients with esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN: Blood samples obtained from 106 patients were examined by real-time RT-PCR assay targeting carcinoembryonic antigen (CEA) mRNA. Follow-up examination every 3 months after surgery included testing for CEA mRNA and tumor markers, as well as imaging. RESULTS: Thirty-nine (36.8%) patients were positive for CEA mRNA expression. CEA mRNA positivity significantly correlated with tumor depth, lymph node metastasis, stage, and venous invasion. Recurrent disease was found in 34 of 106 (32.1%) cases. CEA mRNA was found in 28 (76.5%) patients experiencing relapse. Of these 28 patients, the number positive of CEA mRNA before detection by imaging, at the same time of detection by imaging, and after detection by imaging was 18 (52.9%), 8 (23.5%), and 2 (5.9%), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for CEA mRNA were higher than those for serum CEA or squamous cell carcinoma. Patients positive for CEA mRNA experienced significantly shorter disease-free interval than those with negative CEA mRNA (P < 0.001). According to multivariate analysis, CEA mRNA positivity was an independent factor for disease-free interval. CONCLUSIONS: Examination of CEA mRNA in peripheral blood during follow-up is useful for early detection of occult recurrence. We believe that CEA mRNA in blood will be a new marker for recurrence in esophageal squamous cell carcinoma.

Adult↗

PubMed2006

Expression of p53R2 is related to prognosis in patients with esophageal squamous cell carcinoma.

PURPOSE: The p53 gene and its family are important factors for carcinogenesis, prognosis, and chemoresistance in esophageal squamous cell carcinoma. A recently identified ribonucleotide reductase, p53R2, is regulated by p53 for supplying nucleotides to repair damaged DNA. In the present study, we analyzed the expression and clinicopathologic significance of p53 and p53R2 in esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN: We immunohistochemically investigated the relationship between p53 and p53R2 expressions in surgical specimens of primary tumors in 222 patients with esophageal squamous cell carcinoma. RESULTS: The positive expression rate of p53 was 47.1% and that of p53R2 was 61.7%. Positive p53R2 expression was significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis. In the p53-negative group, the 5-year survival rate was better in patients with negative p53R2 expression than in those with positive p53R2 expression. Multivariate analysis indicated that the negative expression of both p53 and p53R2 was an independent prognostic factor along with tumor depth nodal metastasis and stage. CONCLUSIONS: We showed that positive p53R2 expression was related to tumor development and that alteration of p53R2 expression in p53-negative tumors was closely related to prognosis. Evaluation of the expressions of p53 and p53R2 proteins should be useful for determining the tumor properties, including prognosis, in patients with esophageal squamous cell carcinoma.

Analysis of Variance↗

PubMed2006

2-Deoxy-D-ribose inhibits hypoxia-induced apoptosis by suppressing the phosphorylation of p38 MAPK.

An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-d-ribose, a degradation product of thymidine generated by TP enzymatic activity, partially prevented hypoxia-induced apoptosis. 2-Deoxy-d-ribose inhibited hypoxia-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) but not c-jun NH(2)-terminal kinase/stress-activated protein kinase in human leukemia HL-60 cells. 2-Deoxy-d-ribose also suppressed the levels of Bax attached to mitochondria under hypoxic conditions. SB203580, a specific inhibitor of the p38 MAPK, suppressed the hypoxia-induced apoptosis of HL-60 cells. These findings suggest that one of the molecular bases for resistance to hypoxia-induced apoptosis conferred by 2-deoxy-d-ribose is the inhibition of the p38 signaling pathway. The expression levels of TP are elevated in many malignant solid tumors and thus the 2-deoxy-d-ribose generated by TP in these tumors may play an important role in tumor progression by preventing hypoxia-induced apoptosis.

Apoptosis↗

PubMed2006

Small bowel obstruction secondary to Meckel diverticulum detected and treated laparoscopically--case report.

A 13-year-old man with no history of abdominal surgery was admitted to Saisei Kai Sendai Hospital complaining of acute abdominal pain. Abdominal computed tomography revealed distal small bowel obstruction of unknown etiology. Abdominal symptoms worsened and emergency surgery was performed. To determine the cause of bowel obstruction, laparoscopy was performed. At Trendelenburg position using endoscopic bowel forceps, the focus of the obstruction was explored. The dilated ileum was incarcerated at 10 cm proximal to the ileocecal region. Laparoscopic exploration revealed that the appendix was tightly attached to Meckel diverticulum (MD) and comprised an internal hernia orifice, in which the small bowel was incarcerated. Intra-abdominal surgical space was insufficient to release the bowel obstruction intracorporally. After a 5 cm of midline incision was made in the lower abdomen, a LAP-Disc (Hakko Co, Japan) was applied. Opening of the internal hernia orifice, normograde appendectomy, and resection of MD with a suturing instrument were performed. The hernia orifice between MD and the appendix was released and the incarcerated bowel was normalized. The patient was discharged without postoperative complications. Laparoscopic procedures are useful in identifying rare causes of bowel obstruction and to determine an appropriate access point for treatment.

Adolescent↗

PubMed2006

[A case of successful treatment by low-dose 5-fluorouracil and cisplatin for liver metastases of esophageal adenosquamous carcinoma].

Adenosquamous carcinoma of the esophagus is an uncommon type of esophageal tumor. In the present case, a 54-year-old man without symptoms was diagnosed with esophageal squamous cell carcinoma, based on endoscopic examination of a biopsy specimen. Endoscopy and barium roentgenography revealed a superficial plateau-type lesion, 2 cm in length, in the lower esophagus. Esophagectomy with lymphadenectomy was performed via a right thoraco-abdominal approach. The histological diagnosis was adenosquamous carcinoma with no lymph node metastasis. Three years after the surgery, multiple liver metastases were detected by computed tomography. The patient was treated with a combination of low-dose 5-fluorouracil(350 mg/body/day) and low-dose cisplatin (7 mg/body/day). Because the first course of chemotherapy was very effective and the number of liver metastases was reduced,a further 6 courses were administered. After 6 courses of chemotherapy, no liver metastases were detected. Based on the present findings, we recommend low-dose 5-fluorouracil/cisplatin therapy for liver metastasis from esophageal adenosquamous carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[A case of advanced rectal carcinoma, preoperative chemo-radiation therapy leading to histological complete response].

A 49-year-old male was admitted to Sendai Saiseikai Hospital with a complaint of upper abdominal pain. Perforative rectal cancer was diagnosed, and an emergency laparotomy was done. Transient colostomy and drainage for peritonitis were performed. Preoperatively rectal cancer was assessed to invade the sacral bone and prostate. A total of 50 Gy radiation therapy with low dose CDDP+5-FU chemotherapy was conducted for five weeks. Remarkable shrinkage of the tumor was found, and elective surgery for curative intent was done on April 2000. The tumor seemed to invade the adjacent tissues such as prostate and urine bladder, so extensive resection of the urine bladder and sacral bone was done in addition to abdominal perineal resection. Pathological exploration showed complete regression of the tumor and no tumor invasion to the prostate and sacral bone. He is well without tumor relapse. Once complete regression of the rectal cancer by chemo-radiation therapy has been achieved, relapse of the tumor was reported to be rare. Preoperative chemo-radiation therapy is an effective tool to control the advanced rectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Gene expression profiling of lymph node metastasis by oligomicroarray analysis using laser microdissection in esophageal squamous cell carcinoma.

We applied oligomicroarray analysis of 17086 genes to identify the genes related to lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The samples of cancer and non-cancerous paired tissue were taken from 16 patients with ESCC who underwent esophagectomy with lymph node dissection. Total ribonucleic acid was extracted from the cancer cells obtained by using laser microdissection and was amplified by T7 based-amplification for the application to the oligomicroarray. The oligomicroarray demonstrated 43 overexpressed genes, such as cell-cycle regulators, cell adhesion related genes, anti-apoptosis related genes, and 138 suppressed genes such as cell differentiation related and apoptosis related genes in ESCC cells with lymph node metastasis. Among them, 5 overexpressed genes (SPP-1, CKS2, CCT5, STMN1, NDUFB9) and one suppressed expression gene (GJB2) were selected in the gene profiles, and then the expressions of those genes were confirmed by real-time semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR) method for confirmation of the result not only in study cases but also in additional 21 cases. The gene expression by real-time semi-quantitative RT-PCR was in accordance with the microarray data. Although we were able to extract some genes related to nodal metastasis in ESCC, further examination is necessary in other genes as well as the interaction of stromal tissues.

Aged↗

PubMed2005

Predictive value of p53 and 14-3-3sigma for the effect of chemoradiation therapy on esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The p53 family regulates cell-cycle arrest, triggers apoptosis, repairs DNA damage caused by various genotoxic stresses, and protects cells from death upon irradiation. The purpose of the present study was to examine the expressions of p53 and one of the p53 family proteins, 14-3-3sigma, in biopsy specimens and to predict the clinical and histological responses to chemoradiation therapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We investigated with the relationship between p53 and 14-3-3sigma expressions in biopsy specimens obtained from 62 patients with ESCC and analyzed these patients' clinical and histological responses to CRT. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. RESULTS: Following CRT, 71.0% of patients showed a positive clinical response and 52.8% showed a positive histological response. The rate of positive expression was 43.5% for p53 and 58.1% for 14-3-3sigma. Statistically significant correlations were found between p53 expression and clinical response to CRT (P = 0.001) and histological response to CRT (P = 0.041), and between 14-3-3sigma expression and histological response to CRT (P = 0.01). Furthermore, in p53-positive tumors, CRT was more effective in tumors with 14-3-3sigma-positive expressions than those with 14-3-3sigma-negative expressions (P = 0.037). The survival rate of the patients with 14-3-3sigma-positive tumors was better than those with 14-3-3sigma-negative tumors in patients with p53-positive tumors (P = 0.047). CONCLUSIONS: We demonstrated that p53-negative or 14-3-3sigma-positive expressions were closely related to the response to CRT. It is clinically useful to examine the expression of these genes in biopsy specimens for predicting the CRT outcomes in patients with ESCC.

14-3-3 Proteins↗

PubMed2005

Clinical significance of nuclear expression of spleen tyrosine kinase (Syk) in gastric cancer.

Spleen tyrosine kinase (Syk) expression was immunohistochemically examined in 250 gastric cancer patients. The rate of positive Syk expression was 42.4%. Syk expression was significantly associated with T1 tumors, lymphatic invasion, venous invasion and lymph node metastasis (P<0.0001). The 5-year survival rate was significantly higher among patients with nuclear Syk expression than among those who were negative for Syk expression (P=0.0003). However, Syk expression was not an independent prognostic factor. Loss of Syk expression was closely related to the malignant property of gastric cancer in the context of tumor depth and lymph node metastasis, especially in early gastric cancer.

Adult↗

PubMed2005

Slug Expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma.

PURPOSE: The expression of E-cadherin correlates with the development, progression, and metastasis of esophageal squamous cell carcinoma (ESCC). Slug, a member of the snail family of transcriptional factors, is a newly identified suppressive transcriptional factor of E-cadherin. The purpose of the present study was to evaluate the clinical significance of E-cadherin and Slug expression in ESCC. EXPERIMENTAL DESIGN: Immunohistochemistry was used to investigate the expression of E-cadherin and Slug proteins in 203 patients with ESCC. The relationships between expression of these proteins and clinicopathologic factors, including prognosis, were analyzed. RESULTS: Positive expression of E-cadherin and Slug was observed in 43% and 48% of cases, respectively. The tumors with reduced E-cadherin expression or positive Slug expression invaded deeper, had more lymph node metastasis, and had more lymphatic invasion than the tumors with preserved E-cadherin expression or negative Slug expression. Slug expression significantly correlated with reduced E-cadherin expression. Sixty-seven of the 98 (68.4%) tumors with positive Slug expression had reduced E-cadherin expression (P = 0.0011). Patients with reduced E-cadherin expression or positive Slug expression had poor clinical outcomes. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were negative for Slug expression than for those who were positive for Slug expression (P = 0.035). Multivariate analysis indicated that E-cadherin expression and Slug expression were not independent prognostic factors. CONCLUSIONS: Evaluation of not only the expression of E-cadherin but also the co-expression of E-cadherin and Slug in preserved E-cadherin group is useful for predicting malignant properties of ESCC.

Aged↗

PubMed2005

Initial metastatic, including micrometastatic, sites of lymph nodes in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: It is important to identify the initial lymph node metastasis when performing less invasive surgery. The purpose of the present study was to analyze locations of solitary lymph node metastasis and micrometastasis in esophageal carcinoma. METHODS: We retrospectively analyzed the initial sites of lymph node metastasis in esophageal cancer. Sixty-five consecutive patients with solitary lymph node metastasis, and 33 pN0 patients with only lymph node micrometastasis detected by immunohistochemistry, were classified according to tumor location and tumor depth. RESULTS: The location of lymph node metastasis in the 22 patients with superficial cancer was limited to recurrent nerve nodes (RN) in the upper thoracic esophagus; RN, paraesophageal nodes (PE), or perigastric nodes (PG) in the middle or lower thoracic esophagus. Thirty-six patients with advanced cancer had lymph node metastasis at RN, PE, or PG locations, while in the remaining seven, lymph node metastasis was found in areas far from the primary tumor. Regarding the 33 patients with lymph node micrometastasis, the locations of micrometastasis were similar to those of solitary metastasis. CONCLUSIONS: Although less invasive surgery, such as reduction of lymphadenectomy, may be suitable for superficial cancer, it should be performed with special care in advanced cancer.

Aged↗

PubMed2005

Multiple primary carcinomas with esophageal squamous cell cancer: clinicopathologic outcome.

The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increased. The purpose of this study was to analyze clinicopathologic findings for MPC and for only esophageal cancer (OEC). Of 157 patients with MPCs, 60 had synchronous cancer and 97 metachronous cancer. Another 42 patients had antecedent esophageal cancer (AEC), and 55 patients had subsequent esophageal cancer (SEC). We retrospectively analyzed the clincopathologic findings for patients in these categories. The incidence of early-stage carcinoma was higher in patients with MPCs than in those with an OEC. Of patients with MPCs, those with metachronous cancer had a higher rate of early-stage carcinoma than those with synchronous cancer. The 5-year survival rates were not significantly different for MPC and OEC patients. Patients with metachronous cancer had a significantly better prognosis than those with synchronous cancer (p = 0.017); and in the metachronous cancer group the prognosis was significantly better for patients with AEC than for those with SEC (p = 0.0005). Meticulous follow-up after treatment of a first cancer should be required to detect other early-stage carcinomas.

Aged↗

PubMed2005

A case of leptomeningeal carcinomatosis from esophageal basaloid carcinoma diagnosed by quantitative reverse transcription-polymerase chain reaction for carcinoembryonic antigen.

We describe herein the case of a 68-year-old man who experienced leptomeningitis after esophagectomy from an esophageal basaloid carcinoma. Although the patient had a good operative course for the first 10 days after surgery, he suddenly had general convulsions with unconsciousness. He was placed on mechanical ventilation in an intensive care unit. Computed tomography and magnetic imaging resonance did not reveal any abnormal findings. No abnormal data in the cerebrospinal fluid were found by biochemical, virological, and cytological examination. The positive expression of carcinoembryonic antigen messenger ribonucleic acid in cerebrospinal fluid was detected by a quantitative reverse transcription-polymerase chain reaction method. Immunohistochemical staining using an anticytokeratin antibody confirmed the presence of tumor cells in the cerebrospinal fluid. Spontaneous breathing was recovered after treatment with systemic chemotherapy. Six months after surgery, computed tomography revealed multiple brain metastases. This case demonstrates that the quantitative reverse transcription-polymerase chain reaction method of analyzing carcinoembryonic antigen messenger ribonucleic acid may be a sensitive and useful method for determining leptomeningeal metastasis before the detection of tumors by cytological and imaging examinations in patients with cancer.

Aged↗

PubMed2005

Reconstruction of recurrent laryngeal nerve with involvement by metastatic node in esophageal cancer.

BACKGROUND: Recurrent laryngeal nerve paralysis represents one of the major complications in esophageal cancer surgery, and patients with esophageal cancer sometimes develop recurrent laryngeal nerve paralysis before treatment. We evaluated recurrent laryngeal nerve reconstruction in patients with lymph node metastasis infiltrating the recurrent laryngeal nerve. METHODS: Five patients with preoperative recurrent laryngeal nerve paralysis as a result of involvement of metastasis were enrolled in the present study. Ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck was performed in 4 patients and direct anastomosis of recurrent laryngeal nerve in the mediastinum in 1 patient. RESULTS: Six months after surgery, 3 patients who had undergone ansa cervicalis-recurrent laryngeal nerve anastomosis in the neck displayed good quality of life without hoarseness or aspiration. The patient who underwent direct anastomosis of the recurrent laryngeal nerve in the mediastinum experienced occasional aspiration and hoarseness. The remaining patient displayed poor condition because of recurrent lung tumor, and quality of life was decreased. CONCLUSIONS: If patients with recurrent laryngeal nerve paralysis before treatment can undergo potentially curative resection with lymph node dissection, including the metastatic lymph node infiltrating the recurrent laryngeal nerve, recurrent laryngeal nerve reconstruction should be performed to improve quality of life.

Adult↗

PubMed2005

Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells.

A major impediment to cancer treatment is the development of resistance by the tumor. P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) are involved in multidrug resistance. In addition to the extrusion of chemotherapeutic agents through these transporters, it has been reported that there are differences in the intracellular distribution of chemotherapeutic agents between drug resistant cells and sensitive cells. Cepharanthine is a plant alkaloid that effectively reverses resistance to anticancer agents. It has been previously shown that cepharanthine is an effective agent for the reversal of resistance in P-gp-overexpressing cells. Cepharanthine has also been reported to have numerous pharmacological effects besides the inhibition of P-gp. It has also been found that cepharanthine enhanced sensitivity to doxorubicin (ADM) and vincristine (VCR), and enhanced apoptosis induced by ADM and VCR of P-gp negative K562 cells. Cepharanthine changed the distribution of ADM from cytoplasmic vesicles to nucleoplasm in K562 cells by inhibiting the acidification of cytoplasmic organelles. Cepharanthine in combination with ADM should be useful for treating patients with tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Predictive value of COX-2 for the effect of chemoradiotherapy on esophageal squamous cell carcinoma.

Cyclooxygenase-2 (COX-2) displays anti-apoptotic functions related to angiogenesis or blocking of bcl-2 functions. COX-2 overexpression has been found in various human malignancies, including esophageal squamous cell carcinoma (ESCC). The present study examined correlations between expression of COX-2 mRNA and ESCC responses to chemoradiotherapy (CRT). Expression of COX-2 mRNA obtained from 29 biopsy specimens before CRT was quantified using reverse transcriptase-polymerase chain reaction (RT-PCR) using Sybr Green I on the Roche LightCycler system. CRT comprised 5-fluorouracil plus cisplatin and 40 Gy of radiation. Mean COX-2 mRNA score was significantly higher in tumors (1222) than in normal epithelium (50; p=0.05). Expression of COX-2 mRNA was high in 14 patients, low in 8 and absent in 7. The effective response to CRT was achieved in 18 patients. Mean COX-2 mRNA score was significantly higher in ineffective cases (2910) than in effective cases (190; p<0.05). CRT was more effective in patients with low COX-2 mRNA expression than in those with high expression. COX-2 mRNA expression in biopsy specimens was closely related to CRT effectiveness. Examination of COX-2 mRNA expression is useful for predicting the effect of CRT in patients with ESCC.

Adult↗

PubMed2005

[Radiation therapy leading to complete response of residual lymph node metastasis in advanced gastric cancer].

A 74-year-old male was admitted to Sendai Saiseikai Hospital with a complaint of upper abdominal pain. Gastrointestinal fibroscopy showed type 2 gastric cancer in the lower third of the stomach,and distal gastrectomy and D 2 lymph node dissection were performed. Metastatic lymph node 8 a had severely infiltrated the pancreas, and pancreatoduodenectomy was required to complete the curative surgery. However, because of preoperative complications of interstitial pneumonia, metastatic node 8 a remained untreated. Postoperatively, radiation therapy (38 Gy plus a boost of 18 Gy) for residual lymph node metastasis was performed over a one-month period. The metastatic node underwent complete regression following radiation therapy, and the patient was discharged without any adverse effects. He received TS-1 medication as postoperative adjuvant therapy. Four years have passed since the complete regression of the lymph node,and the patient has shown no signs of relapse. Therefore, our case suggests that postoperative radiation therapy can be a useful tool for treatment of residual lymph node metastasis in gastric cancer.

Aged↗

PubMed2004

Clinicopathological and biological characteristics of esophageal squamous cell carcinoma associated with head and neck cancer.

OBJECTIVE: Esophageal cancer has been reported to be frequently associated with cancer of the head and neck. The iodine dye method is reportedly useful to detect early esophageal cancer. The aim of this study was to clarify clinicopathological and biological characteristics of esophageal squamous cell carcinoma associated with head and neck cancer (HN group). METHODS: Thirty-seven patients of the HN group who underwent esophagectomy were examined clinicopathologically compared to 42 patients with esophageal cancer alone (SE group). All resected specimens were histologically studied after iodine dye staining, and p53 and cyclin D1 (CD1) expression were immunohistochemically examined in esophageal cancer. RESULTS: The HN group had more multiple iodine-unstained lesions and multiple primary cancers within the esophagus compared with the SE group (p = 0.0027, p = 0.067, respectively). There was no significant difference in smoking, drinking, family history and the other clinicopathological factors between the HN and SE groups. Coexpression of p53 and CD1 was found to be significant in the HN group (p = 0.03). CONCLUSIONS: The coexistence of multiple iodine-unstained lesions, multiple cancers in the esophagus and overexpression of p53 and CD1 is suggested as a risk factor for the HN group.

Aged↗