Shinichi Asaka

Up-regulation of transcriptional factor E2F1 in papillary and anaplastic thyroid cancers

AbstractExpression of genes in the Rb-E2F signaling pathway is controlled by E2F transcriptional factors originally defined as molecules that bind to the promoter of E2 adenovirus. The E2F gene family consists of six members and is designated E2F1-6. The Rb-E2F signaling pathway is among the main regulators of the cell cycle, hence its importance in differentiation and oncogenesis. We document here up-regulation of E2F1, but not other members of the E2F gene family, in 15 of 18 primary papillary thyroid cancers examined (83%) in comparison to corresponding noncancerous thyroid tissues and in all of 11 anaplastic thyroid cancer (ATC) cell lines (100%). The E2F4gene, however, was down-regulated in 12 of the papillary thyroid cancers (67%). Immunohistochemical analysis with antibody to E2F1 revealed prominent intracellular E2F1 protein in most of the primary papillary cancers (16 of 18; 89%) but was not detectable in normal thyroid tissues. These data indicated that increased expression of the E2F1 gene might play a significant role in human thyroid carcinogenesis through derangement of the Rb-E2F signaling pathway.

Genetic Prognostic Index Influences Patient Outcome for Node-Positive Breast Cancer

PurposeTo establish a novel genetic prognostic index among node-positive breast cancer patients.MethodsUsing a cDNA microarray, the gene expression profiles of 20 primary breast cancers that had metastasis to four or more axillary lymph nodes were examined. Ten patients survived disease-free for more than 5 years (5S), while ten patients died of breast cancer within 5 years of surgery (5D).ResultsA set of genes characterizing each group was identified. Sixteen genes were underexpressed in 5D compared to 5S, and 15 genes were underexpressed in 5S in comparison to 5D. The prognostic index (PI) was established, which could predict the postoperative outcome with five genes that were commonly underexpressed in the 5D group; these genes encoded granulin (GRN), heat shock 90 kDa protein 1 beta (HSPCB), large tumor suppressor homolog 1 (LATS1), valosin-containing protein (VCP), and LIM-and-SH3 protein1 (LASP1).ConclusionThese five genes might play an important role in deciding the behavior of node-positive breast cancer. The PI system could thus predict the prognosis of node-positive breast cancer, and might therefore be able to provide valuable information for the prognosis of breast cancer patients.

Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer and recovory of its expression inhibits cell growth

Anaplastic thyroid cancer (ATC) is one of the most fulminant and foetal diseases in human malignancies. However, the genetic alterations and carcinogenic mechanisms of ATC are still unclear. Recently, we investigated the gene expression profile of 11 anaplastic thyroid cancer cell lines (ACL) and significant decreased expression of haemoglobin beta (HBB) gene in ACL. Haemoglobin beta is located at 11p15.5, where loss of heterozygosity (LOH) was reported in various kinds of cancers, including ATC, and it has been suggested that novel tumour suppressor genes might exist in this region. In order to clarify the meaning of decreased expression of HBB in ATC, the expression status of HBB was investigated with ACL, ATC, papillary thyroid cancer (PTC) and normal human tissues. Haemoglobin beta showed significant decreased expression in ACLs and ATCs; however, in PTC, HBB expressed equal to the normal thyroid gland. In addition, HBB expressed in normal human tissues ubiquitously. To validate the tumour-suppressor function of HBB, cell growth assay was performed. Forced expression of HBB in KTA2 cell, which is a kind of ACL, significantly suppressed KTA2 growth. The mechanism of downregulation of HBB in ATC is still unclear; however, our results suggested the possibility of HBB as a novel tumour-suppressor gene.

Adenocarcinoid of the Appendix: Report of Two Cases

Abstract.Adenocarcinoid of the appendix is a rare tumor with the histological features of both adenocarcinoma and carcinoid tumor. However, its biological behavior and malignant potential are still unclear. We treated two patients with this unusual tumor; a 60-year-old man and a 79-year-old woman. Both patients were initially diagnosed with acute appendicitis followed by an appendectomy. At surgery, the appendix was seen to be acutely inflamed without any macroscopic signs of tumor. Postoperative histological analysis revealed an adenocarcinoid tumor in the appendix, which had spread diffusely into its wall without forming a mass. Immunohistochemical staining with p53, MIB-1, bcl-2, and carcinoembryonic antigen suggested that neither of these tumors were particularly aggressive. Adenocarcinoid of the appendix is a rare tumor, which is very difficult to diagnose preoperatively and even macroscopically, making histological examination essential.

Impact of Branched-Chain Amino Acid-Enriched Nutrient on liver Cirrhosis with Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization in Barcelona Clinic Liver Cancer Stage B: A Prospective Study.

BACKGROUND In decompensated liver cirrhosis, hypoalbuminemia still persists even after they have been treated with branched-chain amino acid (BCAA) granules. We prospectively evaluated whether BCAA enriched nutrient switched from BCAA granules would increase the serum albumin level, and consequently extend the survival time after hepatocellular carcinoma (HCC) treatment. METHODS This study included 77 patients treated for liver cirrhosis with HCC. After the nutritional assessment, all patients initially received BCAA granules. In patients with unchanged or decreased serum albumin levels, BCAA granules were discontinued and BCAA enriched nutrient was started. Transcatheter arterial chemembolization (TACE) for HCC were performed in those with an improved Child-Pugh score. RESULTS TACE were performed following the aggressive intervention with BCAA nutritional education in 54 of 77 (70.1%) patients. Finally, survival time was significantly extended in the TACE group (P<0.0001). CONCLUSION Timely aggressive nutritional intervention in Barcelona Clinic Liver Cancer stage B HCC, namely, early partial replacement with BCAA enriched nutrient may consequently improve the treatment outcome of HCC.

Giant tumor of malignant fibrous histiocytoma (undifferentiated pleomorphic sarcoma) in the cervical esophagus: a case report

We herein report the case of a 50-year-old man with malignant fibrous histiocytoma (MFH) of the esophagus. The patient was admitted to our hospital because of cough, dysphagia, and weight loss. Esophagography and upper gastrointestinal endoscopy revealed a giant protruding lesion in the cervical esophagus. Total esophagectomy was performed with total laryngectomy and pharyngogastrostomy. The tumor was composed of proliferating spindle cells mixed with pleomorphic giant cells. The histopathological diagnosis was malignant fibrous histiocytoma of the esophagus. Although there have been several case reports of MFH of the alimentary tract, MFH of the esophagus is extremely rare. We recently experienced a case of this disease.

Lymphangiography Was Useful in Postoperative Intractable Chylothorax after Surgery for Esophageal Cancer: A Case Report

Postoperative chylothorax after surgery for esophageal cancer is a rare but serious complication. Treatment initially consists of conservative therapy and, if it fails to provide improvement, it is important to perform surgical treatment without delay. We report on a recent case of intractable chylothorax. This report describes a 72-year-old man with Stage III esophageal squamous cell carcinoma. Subtotal esophagectomy, through a right thoracoabdominal approach with two-field lymphadenectomy, and cervical esophagogastric anastomosis via the retrosternal route, were performed. On the 12th postoperative day, a diagnosis of chylothorax was made. Conservative treatment was initiated, but it proved to be ineffective. Therefore, ligation of the thoracic duct via a thoracotomy was performed, but this was not effective, either. Lymphangiography undertaken to identify the site of the leak in the thoracic duct enabled a diagnosis of an extremely rare double thoracic duct and identification of the site of the leak in the thoracic duct, thereby allowing curative direct ligation of the site. This case underscores the remarkable usefulness of lymphangiography in dealing with intractable postoperative chylothorax.

A case of surgical resection for superficial esophageal cancer with a single giant N4 cervical lymph node metastasis

Superficial thoracic esophageal cancer with a solitary metastasis to a lymph node outside the usual target area of lymphadenectomy is extremely rare. We report a case of superficial esophageal canc...

An Early Gastric Cancer Patient With Pleural Metastatic Recurrence

A 72-year-old male patient was diagnosed with depressed-type gastric cancer in the body of stomach [preoperative diagnosis: T2 (MP), N0, M0, P0, H0, cStage IB] and underwent distal gastrectomy and D2 dissection in January 2011. The pathological classification was T1b (SM), por2, 24 × 45 mm, ly3, v1, N2 (6/14), M0, P0, CY0, H0, fStage IIA. Continuous increase of serum carbohydrate antigen 19-9 (CA19-9) followed 1-year postoperative S-1 adjuvant chemotherapy, so S-1 was resumed despite not identifying the site of recurrence. In December 2012, pleural metastasis was suspected based on fluorine 18-fluorodeoxyglucose FDG standardized uptake value 14 × 23 mm in size on the right diaphragm (pleural cavity side) found on positron emission tomography-computed tomography. No other metastasis was found. Serum CA19-9 continued to increase. In April 2013, the patient underwent thoracoscopic removal of pleural metastasis on the right diaphragm (cytology of pleural effusion: class II). Pleural metastasis of gastric canc...

The Influence of Neoadjuvant Chemotherapy with Docetaxel, Nedaplatin and 5-Fluorouracil After Esophagectomy

BACKGROUND Neoadjuvant chemotherapy (NAC) with docetaxel, nedaplatin and 5-fluorouracil (5-FU) in esophageal cancer may adversely affect the postoperative clinical course following esophagectomy. PATIENTS AND METHODS We investigated the perioperative white blood cell count (WBC), C-reactive protein (CRP), serum albumin, body temperature (BT), heart rate (HR), respiratory rate (RR), water balance, partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio, postoperative complications and systemic inflammatory response syndrome (SIRS) in patients who underwent NAC or surgery alone (SA group). RESULTS In the NAC group, the preoperative WBC (p=0.015) and postoperative day (POD) 3 BT (p=0.049), as well as RR (p=0.037) were lower, whereas the POD 2 PaO2/FiO2 ratio was higher (p=0.047), compared to the SA group. No differences in the incidence of postoperative complications and SIRS were observed between the groups. CONCLUSION NAC using docetaxel, nedaplatin and 5-fluorouracil was tolerated and feasible in esophageal cancer.